Long-term effects of exposures to developmental toxins during infancy
by DP Meulenberg
Section 1: Seeking to learn outcomes of alternative types of infant feeding, as indicated by different kinds of evidence: See below.
Section 1.a: Quality levels of medical evidence:
The study type that is by far the most common, observational, is considered by experts in medical evidence to lead only to evidence of low or (occasionally) medium quality, often leading to false conclusions. These studies almost entirely investigate only near-term effects of alternatives. Many professional reviewers, in attempting to learn from results of research, won't even consider observational studies. For details, see Section 1.a.
Summary of Section 1.b: Randomized trials, the gold standard: When people choose or decide not to choose an intervention, such as breastfeeding, that introduces confounding due to different types of people choosing one or the other alternative, varying according to (a) socio-economic status, (b) smokers or not, (c) living in more-polluted versus less polluted areas, etc. In contrast, studies based on randomized interventions and controls are recognized to be able to provide high-quality evidence. Such evidence, now available from large, recently-completed studies extending to age 16, tends to conflict with typical findings from observational studies;
For details and sources related to the above, see the full text in Section 1.b.
Summary of Section 2: Exposures to developmental toxins during infancy, a period of vulnerability of long-term development:
Section 2.a: Dramatic increases of toxins in the environment in the 20th century: For all of human history until relatively recently, toxins in the environment were of relatively little concern for infant nutrition. But, beginning in about the middle of the 20th century, exposures to developmental toxins in the environment greatly increased, and that affected nutrition of infants.
Preview of Figure 1
This was the first time in human history when toxic chemicals from industry and from new combustion processes (including burning of plastics) became widespread in the environment and substantially present in infant food.
Section 2.b, summary: PCBs and dioxins: Toxic to neurological development, and carcinogenic:
Children who have grown up in developed and many developing countries during the more recent decades would have been likely, during their vulnerable developmental periods, to have been exposed to unprecedentedly large amounts of these chemicals, especially in their food; exposures to some of those substances in early childhood have been authoritatively recognized to have significant effects later in life.
Sections 2.c, d and e, summary: Special vulnerability of early development:
The first two years of life are referred to by WHO as "the most critical period" for development of the central nervous system. The first 12 months after birth are the period when the brain is going through its most active, and most sensitive, stages of development. PCBs and dioxins are both recognized to disrupt early development. Typical infants tend to be exposed to those and other developmental toxins in high concentrations.
Sections 2.g -h summary:: The Promotion of Breastfeeding Intervention Trial (PROBIT) is the largest randomized, controlled trial (recognized to be the highest-quality study type) ever conducted in the area of health effects of human lactation. This study found improvements in breastfed children during infancy but decreasing longer-term benefits.
Section 3 summary: Randomized study results:
Section 3.a: A very noteworthy but almost unnoticed adverse outcome: In the PROBIT study, involving two groups that were well matched in many respects, after 16 years the following was found: three times as many of the children who had received one specific popular type of infant feeding (compared with controls) were unable or unwilling to take a test that 99% of the studied children were willing and able to take. Inability to take the test would indicate obvious mental impairment; and unwillingness to take the test would indicate a probable psychological impairment involving significantly reduced likelihood of becoming cooperative, rule-following, normally-compensated members of society.
For details and sources related to the above, see the full text in Section 3.
Section 3.b summary: There have been very few other randomized studies dealing with alternative types of infant feeding. In what was probably the most significant finding, allergies were found to be greatly reduced by introducing variety into infant feeding.
Summary of Section 4:
Section 4.a: Very likely related to the adverse outcomes described in Section 3.a are developmental toxins such as PCBs and dioxins, which are received by typical infants in doses greatly exceeding established safe levels at a time of special vulnerability of neurological development.
Considering that far more males than females have been affected by autism and ADHD, which have greatly increased in recent decades, it is of interest that both PCBs and dioxins have been found in studies to have adverse developmental effects on males but far less so on females.
Many experts consider animal tests to provide evidence about effects of toxins that is highly relevant to humans. An experiment with rats exposed to PCBs in doses similar to those often received by typical human infants showed the infant rats to have effects considered by a highly-respected researcher to resemble characteristics of autism.
For details and sources related to the above, see the full text in Sections 4.a and 4.b
Section 4.c summary: Other developmental toxins have been becoming prevalent in human milk in recent decades, including PBDE flame retardants, which are especially high in the U.S. PBDEs are known to have adverse neurobehavioral effects particularly during the postnatal period. Other developmental toxins, also, including pollutants that convey PCBs and dioxins, have been found to have adverse effects specifically following postnatal exposures.
Section 4.d summary:: Some studies have found breastfeeding duration to be associated with autism prevalence, including in dose-response relationships. A 2011 study that investigated data from all 50 U.S. states and 51 U.S. counties found that "exclusive breast-feeding shows a direct epidemiological relationship to autism," and also, "the longer the duration of exclusive breast-feeding, the greater the correlation with autism."
For details and sources related to the above, see the full text in Section 4.d.
Section 5 summary: Long-term effects of developmental exposures to these toxins, in various areas:
Section 5.a: Beginning in the late 1960's, breastfeeding gained greatly in popularity.
Now, a half-century later, is a good time to take stock and see what outcomes can be summarized following that major change in infant feeding.
Beginning in the 1970's, several childhood disorders began to increase substantially. Among others, obesity in U.S. children more than tripled between 1976 and 2007. In the recent PROBIT research, overweight and obesity were found to be more prevalent among children who were more breastfed; the authors provided good reasons to deduce that the earlier (observational) studies would have been led to erroneous findings by confounding factors and short study durations.
Considerable scientific research has found that higher PCB levels in children, which are basically determined by breastfeeding, have the effect of reducing activity; inactivity is clearly linked with obesity.
For details and sources related to the above, see the full text in Section 5.a.
Section 5.b summary: Other disorders have also been greatly increasing during the period when breastfeeding was greatly increasing. A major sibling study found that worse outcomes in asthma were consistently, positively associated with breastfeeding duration, across all methods of comparing the data. Prevalence of diabetes among children and young adults increased dramatically since the 1970's; PCBs are considered to be diabetogenic. Allergies have doubled, tripled or quadrupled since the 1970's.
Preview of Figure 10a
A highly-published scientist, summarizing data from the CDC, stated in a 2015 publication that we are in the midst of an epidemic of brain-based disorders, including ADHD. Dramatic increases among children apparently began in the 1970s, when breastfeeding began increasing rapidly.
For details and sources related to the above, see the full text in Section 5.b
Section 6: Toxic exposures of infants -- remembered versus actual
A: Chemical exposures that far exceed
established safe levels
Appendix B: Increase of serious asthma among U.S. children in recent decades
Appendix C: Chemical exposures determined to exceed safe levels even more than previously thought
Appendix D: The Hygiene hypothesis/ microbial-deprivation hypothesis
Appendix E: Failure of the authors to comment on what appears to be substantial adverse outcome of more breastfeeding
Appendix H: Ongoing sources of PCBs, dioxins and PBDEs, including in traffic emissions
Appendix I: More about PBDEs
Appendix J: Low quality of evidence from observational studies
Appendix K: A possibly unique pathway of widespread infant exposure to developmental toxins in doses exceeding established safe levels
Appendix L: Exposures of mothers to toxins and times of exposures of the developing infant to those toxins
Appendix M: Basis for recommending against breastfeeding in case of nuclear accident, which would have predated the Chernobyl meltdown
Appendix N: Increased risk of metabolic syndrome among the more-breastfed PROBIT group, especially males, at 11.5 years of age
Appendix O: “Recall bias” as a problem in observational studies
Appendix P: Long-term accumulation of body burden of dioxins
Appendix Q: Other reasons to be skeptical about findings of studies in a matter, such as breastfeeding, about which strong opinions are widely held
Appendix R: Very misleading statement by the U.S. CDC on toxins in breast milk
Appendix S: Additional indications of inaccuracy in typical studies such as those dealing with breastfeeding
Determining the true effects of breastfeeding in modern times has been a problematic challenge; that is especially true given that the study type that has until recently almost always been at the basis of research into effects of breastfeeding, observational study,1 is considered by leading experts in medical evidence to yield only evidence of low or (sometimes) medium quality. (See Appendix J) Evidence from that study type has a recognized tendency to lead to false conclusions for various reasons, including confounders; such confounders include the characteristics of mothers (normally of higher socio-economic status4) who choose to breast feed -- better home environments (related to smoking, pollution levels, etc.) and better health-related habits5,7 -- versus environments and practices of mothers who choose not to breastfeed.
On the basis of a large and consistent body of evidence from observational studies showing that use of hormone replacement therapy (HRT) was associated with a 40–60% lower incidence of coronary heart disease, several medical associations in the mid-1990's officially recommended HRT for post-menopausal women;2 that is, they did so until about 2002 when results came in from long-term randomized studies; those studies found that HRT actually led to worse health outcomes. Until that time, it had not yet been generally recognized that observational studies were so greatly subject to erroneous findings, as compared with randomized trials, which are recognized to be the highest-quality type.3 The original results favoring HRT had been arrived at even after adjustments had been made in the observational studies (as is normal) in attempting to correct for numerous potential confounders.3a
A publication of the Institute of Medicine (of the U.S. National Academy of Sciences) discussed the dramatic discrepancies that were found when randomized trials were compared with observational studies on the same topic.3c The authors devoted a large paragraph to the problem of selection bias that is inherent in observational studies, ending with, "Although a variety of statistical methods can be used to attempt to reduce the impact of selection bias, there is no way that analysis can be used to correct for unknown factors that may be associated with prognosis. Thus, it is generally acknowledged that 'adjustment' in the analysis cannot be viewed as a substitute for a study design that minimizes this bias." (Emphasis is added here because it is often believed that adjustment can lead to good evidence even though a study is merely observational.) The Institute's authors then continued by pointing out that, in addition to selection bias, "observational studies are also particularly subject to detection bias, performance bias, and information biases."3c All of those biases are in addition to the well-known existence of publication bias, which is especially likely to be problematic if a study's findings do not conform to prevailing beliefs among publisher staff, peer reviewers, and/or researchers themselves.
In addition to the HRT case, there have been numerous other examples of medical recommendations, established on the basis of observational studies, having been found to be in error when tested later by randomized trials.3a,3b A 2019 systematic search of randomized clinical trials found 396 medical reversals described in three leading medical journals alone; the practices said to be reversed were described as established medical practices, and all were reviewed by four physicians; those 396 were said to add to a previously-reported list of 146 reversals published in just one journal during 2001-2010.3d,3f Reversals have included routine invasive treatments for degenerative conditions of the knee, prescription of (often addictive) opioids for pain,3e and stenting for stable coronary artery disease.3b
Additional discussion of fundamental problems in typical observational studies and their poor record will be found in Section 6 and in Appendix J. Small randomized controlled trials (RCTs) have been contradicted, but apparently no large RCTs have been contradicted. (see Appendix J) This will be an important point to remember later when discussing findings of a genuinely large RCT.
With all of the above in mind, note that a major 2011 publication of the U.S. Surgeon General, while strongly recommending breastfeeding, acknowledged that "research on the health outcomes of different modes of infant feeding is limited to observational studies…."1 (That was apparently written before results of the recent randomized trials had become known.) So recommendations to breastfeed were based on studies of a type that is now recognized to have a poor record of correct findings.
Section 1.b: Randomized trials: In typical studies, better child health is often found to be associated with breastfeeding; but the outcomes are likely to actually be caused by the underlying confounders that affected the decision to breastfeed, as discussed in Section 1.a. Randomization of an intervention (such as breastfeeding), as was employed in the PROBIT studies (Section 2.g), is the accepted means to avoid such confounding.
According to the U.S. Agency for Healthcare Research and Quality, “many reviewers admit only RCTs (randomized controlled trials) into a systematic review and eliminate other study designs from further consideration.”7c If “many” professionals who review studies (with intention of generalizing about what has been learned) won’t even so much as consider findings of observational (non-randomized: see Appendix J) studies, that says a great deal about the reputation of such studies for arriving at conclusions that have later been found to be incorrect. Such an unfavorable reputation is well deserved (see Section 1.a).
There is a question as to whether evidence from non-randomized studies might be thought to be of some value if randomized trials have not been carried out in a particular area, on the assumption that low- or-sometimes-medium-quality evidence might be better than no evidence. The committee writing for the Institute of Medicine took up that question in their 2011 publication quoted earlier,3c and its answer was unequivocal: " The committee did not find evidence to support a recommendation about substituting observational data in the absence of data from RCTs." In other words, the committee of the Institute of Medicine concluded that, if the evidence is only observational, there is no reason to consider that evidence to be of value.
Given the above, bear in mind that the studies that provided the basis for recommendations to breastfeed were entirely observational, according to the author(s) of the U.S. Surgeon General's 2011 breastfeeding-promoting document.1 So there is clearly good reason to look closely at the randomized trials that have been published in recent years.
Consideration of the best type of evidence regarding the effects of breastfeeding is especially important given the reasons to be worried about feeding human milk to infants, particularly as the predominant or exclusive food:
a) Typical human milk in many contemporary countries is recognized to have contained developmental toxins in concentrations far exceeding established safe doses in recent decades (see Section 2 below); and
b) there have been many serious health declines that have taken place among children and young people since breastfeeding started increasing in the late 1960s (Sections 5 and 6), health declines for which satisfactory explanations have apparently not been found.
It would be logical to consider whether there is a causal link between (a) and (b) above. When doing so, the recognized best type of evidence (from randomized studies) should be looked at closely, and the major susceptibility to false conclusions of the other types of studies (Section 1.a) should kept in mind.
Evidence from relevant, recently-completed RCTs will be discussed in Sections 2.g, 3, and 5.a, and the findings do not look favorable for breastfeeding. The reader might wish to skip forward to those sections; this article, before going on to those discussions, will delve into some relevant information to explain why effects of breastfeeding would tend to be adverse, as revealed by high-quality (randomized) studies and as further substantiated by a large amount of historical data.
Section 2.a: Dramatic increases of toxins in the environment in the 20th century:
There appears to be no reason to doubt the generalization that, for all of human history until well into the 20th century, human milk was the ideal food for infants.
But, beginning in about the middle of the 20th century, exposures to developmental toxins in modern environments greatly increased. A basic element of much of the economic development that took place since then, and an important contributor to environmental toxins, has been production of chemicals, which rose dramatically during the last three-quarters of a century.
Beginning in the years following World War II, there were major environmental increases of chemicals to which humans became exposed;7ais especially strong about increases in exposures of Americans to dioxins and PCBs (the two toxins of principal concern in this article) beginning in the 1940's.7b Chemicals enter the human environment not only via the well-known routes (smokestacks, etc.) but also via off-gassing from materials in older buildings,8 from pollutants in landfills and on land, and via emissions from many widespread forms of combustion; included in the latter category are both diesel- and gasoline-powered vehicles,8a,8b,9d and wildfires.9 Dioxin releases are known to generally increase with chlorine content of the combustibles,9b,9d so the rapid increase in uses of plastics (which typically contain chlorine) beginning after 19459c would have greatly increased dioxin emissions from the previously fairly harmless practice of backyard burning, beginning not long after that increase of plastics.9 Similarly, the huge increases in vehicular traffic over the course of the 20th century, with accompanying scores-to-100-fold increases in dioxin levels within a few hundred feet of major traffic locations,8b would have had a major impact on toxic emissions close to people.
So children who have grown up in developed and many developing countries during the more recent decades would have been likely, during their vulnerable developmental periods, to have been exposed to unprecedentedly large amounts of certain environmental pollutants such as PCBs and dioxins, compared with children in earlier times. Not surprisingly, the U.S. ATSDR (Agency for Toxic Substances and Disease Registry) points out that lower levels of dioxins are observed in people in less-industrialized countries.7b
Discussing the pathway for pollutants from the environment to developing children, the American and Danish experts, P. Grandjean and A. A. Jensen (who are authors or coauthors of 481 and 127 scientific studies and articles respectively), pointed out in 2004 the following: "these substances have caused contamination of human milk only during the last half century, and long-term health impacts are now being discovered." Specific chemicals to which they referred were PCBs, dioxins, and brominated flame retardants (PBDEs).9a
Dioxins and PCBs in human milk
For original source of the above, go to van den Berg et al., WHO/UNEP Global Surveys of PCDDs, PCDFs and DDTs in human milk and benefit-risk evaluation of breastfeeding, at https://www.ncbi.nlm.nih.gov/pubmed/27438348
The study that is the source of the above charts had eight authors; Martin van den Berg is shown in PubMed as author or co-author of 107 scientific articles, and H Fiedler is shown with 517. There is considerable other evidence that supports the findings indicated in these charts (see Appendix A). For a discussion of developmental effects of PCBs and dioxins, see Section 2.b below.
Note that infant formula has been found to be essentially free of these toxins (see beginning of Section 4). We should also note that the toxicity standards that were in effect during the 2000-2010 surveys, results of which are shown in the charts above, have been subsequently replaced by far stricter standards (see Appendix C); so the updated exceedances of established safe intakes of these toxins, according to the best currently-available evidence and research methods, are many times the already major exceedances shown in the charts above. There is also substantial other evidence, from the U.S. and other developed countries, indicating that exposures of breastfed infants to both PCBs and dioxins during the 2000's have exceeded established safe levels by scores to hundreds of times.10
Seeing the above, a reasonable initial reaction might be, "Toxins are everywhere, we can't avoid them." There is some truth to that, but toxins in concentrations that exceed established safe levels are exceptional; and human milk is apparently the only widespread source of human exposure to toxins in such concentrations. Professionals who ought to be knowledgeable on this topic do not dispute the very high levels of recognized carcinogens and developmental toxins in human milk, and they are apparently unable to suggest any other possible pathway for widespread exposure of infants to toxins in unsafe doses (see Appendix K). A widespread yet specific pathway for exposure of infants to developmental toxins in recognized hazardous concentrations is uniquely unfavorable and ought to be a matter of serious concern.
It is logical to point out the fact that, despite all of the above, the medical community recommends that mothers should breastfeed for at least six months, with very few exceptions. In explanation of that apparent paradox, it should be pointed out that medical recommendations to breastfeed have been in place since the late 1900's, and the above extensive information about serious toxins in human milk was not published until the 2000's. The recommendations to breastfeed originated before the publication of the high-quality studies and the considerable historical data that have indicated worsening of child health while breastfeeding increased (Sections 3 through 6 of this article). Also, the extremely high rate of erroneous findings in observational studies (the study type on which breastfeeding recommendations were based) was apparently not yet well recognized until into the 2000's. (Section 1.a) So recommendations to breastfeed were established at a time when that would have been the right decision, based on the information generally available as of that time. And doctors in the more recent years would be expected to be very reluctant to acknowledge, even to themselves, that they have for many years been giving advice that has recently been found to be harmful.
The American Academy of Pediatrics does not dispute the considerable evidence about toxins' commonly being at high levels in human milk. (see Appendix K) But in its entire large position paper on breastfeeding, the AAP gives no indication of consideration of those toxins in typical human milk; the closest they come to this topic is to exceptional cases, such as when an individual mother receives unusual exposures.60f The AAP's failure to even discuss the undisputed matter of generally-high levels of developmental toxins in human milk, while recommending human milk as the exclusive infant food, ought to raise a red flag to anybody concerned about human health. That is especially true considering the many serious declines in health of children and young people that have been taking place as breastfeeding increased in recent decades. (see Sections 3 and later)
Section 2.b: PCBs and dioxins: Toxic to neurological development, carcinogenic, and persistent: PCBs are ranked by the U.S. Agency for Toxic Substances and Disease Registry (ATSDR) as being among the top 5 priority hazardous substances.11 Dioxin is "often called the most toxic man-made chemical," as stated in a document of the EPA, with no question expressed about the correctness of that assessment.12 PCBs and dioxins are chemically related; both are lipophilic (attracted to fat, which is why they become attracted to human milk), both are considered to be “persistent” in the environment and in the body, and both are considered by the International Agency for Research on Cancer (IARC) to cause cancer in humans.12b
A large team of German scientists and physicians, prospectively studying 171 healthy mother-infant pairs and publishing in 2001, found "negative associations between (human) milk PCB and mental/motor development ... at all ages, becoming significant from 30 months onwards." Also, "negative associations with PCB increased with age."12a A separate research team reached a similar conclusion in a 2011 publication, citing evidence from "several prospective cohort studies" including their own.13 (Prospective studies are for good reasons considered to be a study type of much higher quality compared with the more typical retrospective studies -- see Section 6) A 2019 review article reached a similar conclusion about developmental toxicity of PCBs, referring to evidence from both animal research and "a wealth" of human epidemiological data, and explaining that "developmental exposures to PCBs interfere with the organization of neural networks."14 (It is difficult to imagine an outcome more likely to impair than disorganization of neural networks.) For more information about adverse effects of PCBs on mental development, see Section 4.
The reader may be puzzled to see references to findings of observational (non-RCT) studies above, considering the unfavorable reputation of that general category as discussed earlier. But the studies referred to just above are of the very best subtypes of observational studies: prospective (see Section 6) and epidemiological (see epidemiologic in Section 4.d); and they are in accord with long-term results of randomized studies as will be discussed later. And animal studies are almost by nature randomized, not merely observational.
According to the EPA, dioxins have effects in multiple tissues and organs at various life stages, including developmental, reproductive, cardiovascular, and endocrine, among others, as well as being carcinogenic.12 Lactational exposures of monkey offspring to "low levels" of dioxin have been found to affect cognitive development, as stated by the U.S. Institute of Medicine.45c
Distinctly long-term effects of PCBs and dioxins: These toxins have serious long-term effects that would be unlikely to be observed in typical studies, which normally deal with outcomes in early childhood.14f In a 2009 study,14a mice were administered PCBs in doses that result in a plasma PCB level that is comparable to the levels found in some human populations that have received brief exposures to PCBs;14b the outcome was that permeability of the blood-brain barrier became two to four times the normal level, depending on which specific type of PCB was administered. (Animal studies are considered to provide good indications of effects that toxins would have on humans, but typically to greatly understate the effect that the toxin would have on humans -- see below Figure 5). A study with human brain tissues arrived at a very similar conclusion.14g Dioxins, also, were found (in another study) to increase the permeability of blood-brain barriers in mice as a result of exposure specifically during development of the barrier.14d (Development of that barrier in humans is recognized to continue for six months after birth.)
Considering all the chemicals that have become prevalent in typical environments and in human blood streams in recent decades,14c it should be apparent that subnormal shielding of the brain from these chemicals could have serious neurological consequences. But the effects would normally be long term; probably not observable in typical studies, which cover just a few early-childhood years,14f but very possibly becoming serious eventually; this would especially be the case as the maturing child increasingly receives exposures to (a) pollution from traffic emissions and other sources, (b) drugs, both legal and illegal, and (c) chemicals in workplaces.
The German study mentioned above, which found that "negative associations with PCB increased with age," may well have been observing effects of the children's brains' being exposed to progressively more toxins over time, by way of cumulative effects stemming from the original weakening of the blood brain barrier.
Another result of PCB exposure that would have predominantly long-term consequences is reduced activity, as found in the study by Jacobson et al. (1990) and in several other studies discussed below figure 9a, later. Reduced activity would not normally be seen as harmful in the usual early-childhood studies, but it is likely to have contributed to the greatly-increasing rates of childhood obesity of recent decades; and both inactivity and obesity are independent risk factors for diabetes,14e another long-term outcome that has greatly increased among children and young people in recent decades.58
Much more about long-term, developmental effects of these toxins will be presented in Section 2.c, not far below.
Distinctly near-term nature of the evidence that is cited in support of breastfeeding: In the position paper on breastfeeding of the American Academy of Pediatrics, it is of interest to look at the studies provided to support the benefits of breastfeeding. Of the first 10 studies provided to indicate better outcomes for breastfed children, all 10 measured the outcomes in infancy or early childhood.14f This is in addition to the fact that they are all observational studies, with all that means about the low quality of evidence provided by such studies (Section 1.a). All of the above leads to the generalization that follows:
The case for breastfeeding appears to be based entirely on observational evidence, mainly gathered during early childhood; it does not properly consider long-term adverse effects for which there is now high-quality evidence.
Section 2.c: Special vulnerability of early development:
Exposures to environmental chemicals during early childhood have been increasingly recognized to have major effects later in life, as discussed in the Faroes Statement, which was by 23 authors from around the world, many of whom were highly-published experts; this statement was an outcome of a conference sponsored by seven health- and environment-related agencies of the U.S. and European governments and WHO. Those authors were deeply concerned about the special "susceptibility of early development" to environmental toxins, specifically including endocrine disrupters, which include PCBs and dioxins;17a,17 they referred to the embryo, fetus and small child as "highly vulnerable populations," pointing out that chemical exposures during early life may predispose to disease during adolescence and adult life.15 The Committee on Developmental Toxicology of the National Academy of Sciences describes adverse developmental effects specifically of early exposures to dioxin, in the way it "alters the expression of several dozen genes, one or more of which might result in an adverse developmental outcome." 15a (The reader may wish to review in Figure 1.a how high dioxins are in typical human milk.) Gene expression (activation, affecting development), vulnerable as it is to effects of dioxin, continues after birth; according to a publication of the National Scientific Council on the Developing Child, "many organs, including the brain, are most vulnerable to the influence of these substances on gene expression during the period of fetal and infant development, when basic organ systems are being built."15b
Thyroid disruption is an area that is particularly relevant to long-term effects of PCBs and dioxins. According to a publication of WHO, "Normal thyroid function is crucial for development, and any disruption of thyroid hormone action may have disastrous consequences in children's health." Continuing, the authors note that "The first two years of life when the central nervous system (including the brain) is rapidly developing are the most critical period."16 According to the U.S. ATSDR, PCBs and dioxins are both endocrine disruptors that can interfere with thyroid function or thyroid hormone action.17 Evidence of thyroid disruption by PCBs is especially strong;17a the ATSDR devotes a large paragraph, including 40 references to scientific studies as evidence, describing the various ways in which "PCBs can disrupt the production and disposition of thyroid hormones."17 Remember from above the WHO statement about the adverse developmental consequences that can result from thyroid disruption. Also remember (from Figure 1.a) the major exposures of breastfed children to PCBs and dioxins during what WHO refers to as "the most critical period" for development, during the first two years of life.
Section 2.d: Means by which these toxins become concentrated before infants are exposed to them: As mentioned, PCBs, dioxins and similar chemicals are lipophilic, meaning they are attracted to fat, which is why they become concentrated in breast milk. The U.S. ATSDR, in support of its statement that "the amount of PCBs transferred to offspring is expected to be higher during lactation than during gestation," refers to a laboratory experiment as an example: "In female rats administered PCBs before gestation, an average of 0.003% of the administered dose was transferred to the fetus, whereas 5% was transferred to sucklings."18 That works out to lactational transfer of PCBs over 1600 times greater than gestational transfer, resulting from the same original prenatal exposure; this is a ratio that the ATSDR obviously considers to be relevant to how human lactational exposure compares with human gestational exposure to PCBs. Studies of humans have found lactational transfers of developmental toxins to be hundreds of times greater than gestational transfers.19 See the beginning of Section 4 about infant formula being essentially free of these toxins. And see the next subsection (2.e) about the vulnerability of neurological development to toxins during the early postnatal period.
Declining levels of these toxins? PCBs and dioxins have been declining in many countries' overall environments since the 1970's; but they are called persistent for good reason, and they continue to be emitted by many widely-distributed processes and structures to which people are closely exposed, including vehicular combustion, backyard burning, and older buildings -- See Appendix H. As shown in surveys from the 2000's in Figure 1.a above and in the accompanying text, those toxins are still present in typical human milk in concentrations far exceeding established safe levels, decades after their emissions started to decline. A German study found that, in 2003 after dioxins in breast milk had substantially declined and then practically leveled out over preceding decades, a breastfed infant would still take in dioxins in the range of 100 times the intake of an adult.19a And, while PCBs and dioxins declined, other chemicals with similar toxic properties, such as PBDEs, increased dramatically in environments and in human milk. (see Figure 6 and Appendix I)
Within the first two years that are recognized by WHO to be the most critical time for overall neurological development (Section 2.c), there is a period that merits even greater concern: the first 12 months after birth are the period when the development of the brain appears to be going through its most active, and most vulnerable, stages of development.
found at https://developingchild.harvard.edu/resources/inbrief-science-of-ecd/
If one looks at the part of this chart that applies to the first 12 months after birth, it is apparent that those months include very active brain development and therefore major vulnerability to developmental toxins.
In a publication of the National Academies Press, the authors state that "toxic exposures at a particular time would differentially affect the structures undergoing peak development."20 Observe above multiple peaks of the brain's development, specifically formation of connections, during the first year after birth.
Studies have demonstrated that PCBs interfere with formation of connections and normal patterns of connectivity in the developing brain.20a
We should also consider the very substantial overall growth that takes place in the brain during this period; the brain approximately doubles in volume during the first year after birth.22 Given that, note that, according to the NIH, "research shows that endocrine disruptors (which include PCBs and dioxins17a,17) may pose the greatest risk during prenatal and early postnatal development when organ and neural systems are forming."
For several additional studies indicating distinctly postnatal vulnerability to developmental toxins from the environment, including multiple comparisons in which equivalent prenatal exposures were found to have little or no effect, see Section 4.c later.
The especially high vulnerability of the first year after birth doesn't mean that serious harm from developmental toxins would already be apparent in early childhood. Remember from Section 2.b the long-term harm from these toxins that may become apparent only much later.
The Promotion of Breastfeeding Intervention Trial (PROBIT) is the largest randomized study ever conducted in the area of human lactation.23 The Republic of Belarus was chosen as the location for the trial because postpartum infant care practices in its maternity hospitals and clinics in the 1990's were similar to those in North America and Western Europe 20-30 years earlier; that, combined with compatible compositions of infant formula, relatively low rates of infant and child mortality and infection, and strict hygienic standards, allowed study of the potential health effects of prolonged and exclusive breastfeeding in developed countries.23,24
The PROBIT study found breastfeeding to be associated with reduction of infections in the gastrointestinal tract during infancy. Reduction of infection during infancy by breastfeeding is as expected, given the transmission of immune cells that takes place via human milk. The major question in relation to the effects of those immune cells is the likely negative effect on development of the child's own immune system, a long-term adverse effect that could result from shielding the infant from immunity-stimulating infections during development. The "hygiene hypothesis" or "microbial deprivation hypothesis" would be relevant to that. (See Appendix D)
At 6.5 years of age, children who were part of the breastfeeding promotion group had better results in IQ scores; but when the children were tested at age 16, the only significantly higher result for the more-breastfed group was for verbal IQ. And at that age the verbal IQ advantage was small (1.4 points) and less than one-fifth as high as it had been at age 6.5,25 raising the question as to whether even that remaining difference would disappear by adulthood. The authors of the study at the 16-year stage said that better verbal function in breastfed children might be explained by, among other things, more verbal exchange during breastfeeding compared with bottle feeding. They also pointed out that the decreasing magnitude of breastfeeding effects with advancing child age is consistent with the results of a recent meta-analysis.
Section 2.h: Null long-term results from breastfeeding, or worse: The same randomized PROBIT groups were also examined for various other comparative health effects at age 11.5, leading to what the authors called "null results," as opposed to the hypothesized beneficial effects of greater breastfeeding.24 Effects on asthma and allergy, specifically, were found to be null in the initial results; but three test sites in the experimental group and three in the control group showed suspiciously high results, which were reasonably attributable to incorrect procedures during the study. When results from those six sites were excluded, "the relative odds of positive skin prick tests (indicating sensitivity to allergens) were twofold to threefold higher in the experimental (more-breastfed) group than in the control group." The authors concluded, in a very understated way, "The fact that most atopic outcomes have increased in incidence over the past several decades, simultaneous with the renaissance in breast feeding, strongly suggests that breast feeding does not have a potent protective effect at the population level." 24a
Also at 11.5 years, a branch of the PROBIT studies compared risk of metabolic syndrome (cardiometabolic risk) between the more-breastfed and less-breastfed groups, starting with the hypothesis that breastfeeding would be demonstrated to have a protective effect. However, the experimental group, with major increases in both duration and exclusivity of breastfeeding, showed results that "were generally in the opposite direction to the hypothesized protective effects." 56c There was a 49% higher risk of metabolic syndrome among the more-breastfed males than among the control males. See Appendix N for discussion of this matter.
When investigating a risk factor (such as metabolic syndrome) that indicates risk of cardiovascular disease,56s it is completely logical to show results for males separately from females; according to the American Heart Association, men have substantially higher risk of having a diagnosed heart attack or fatal coronary heart disease, with a more-than two-fold male-female difference between ages 45 and 64.56t So special attention should be devoted to the 49% higher risk of metabolic syndrome not among females but among the more-breastfed males (odds ratio, 1.49, vs. 0.94 in females, as shown in this study just above Table 2; 1.0 is the level of no increased risk). Reporting male and female risks separately is especially appropriate considering the major contents of chemicals in human milk (Figure 1.a) that have been found to affect males much more than females. (Figure 5 and accompanying text) And the reason to suspect a connection between human milk and a risk factor for cardiovascular disease is strong considering the following: epidemiological and laboratory studies have shown that exposure to PCBs (Figure 1.a) can lead to diabetes, hypertension, and obesity; all of which are risk factors for cardiovascular disease.56u
There is also new evidence in the most recent (16-year) phase of the PROBIT studies that carries immense significance regarding effects of breastfeeding, but which has thus far apparently not been discussed in publications. See below.
Section 3.a: Surprising outcome of the largest randomized trial in this area: A serious adverse effect, which has drawn little attention: Inserted below is a passage from the above-mentioned PROBIT study25 that states, without comment, something that deserves major attention with regard to effects of breastfeeding:
To spell out plainly something that is easy to pass by (as seen in the normal, non-underlined version of the above) without noticing its major significance:
-- Being presented here is information about 16-year-olds' taking or not taking a test that 99% of the studied children were willing and able to take;
-- 0.5% of the control group were unable or unwilling to take the test, whereas
-- 1.4% of the intervention group (the more-breastfed group) were unable or unwilling to take the test.
This research was basically intended to find differences in cognitive outcomes between the two groups, which were well matched in important respects except for the major difference in breastfeeding exposures. One substantial difference was found in the outcomes: a three-times-as-high percentage of the more-breastfed 16-year-olds were unable or unwilling to take a computerized test that 99% were willing and able to take.
Doing some simple math, that means that there was an excess of about 64 members of the high-breastfeeding group (0.9% x 706626) who were unwilling or unable to take the test, This excess is as compared with the number who would not have taken the test if the 0.5% unable/unwilling percentage of the control group had applied to the highly-breastfed group. That ought to cause people to stop and think.
The reasons for not taking the test were described in general terms as inability or unwillingness. Whether it was for inability or unwillingness, the non-taking would very likely reflect some kind of serious long-term impairment. Mental retardation / intellectual disability affects roughly one percent of the U.S. population27 and would account for some large part of the adverse outcomes here. For those who were unwilling, that was apparently also a serious matter, since 99% of the 16-year-olds were willing to take the test; what comes to mind regarding the refusers is Oppositional Defiant Disorder (ODD), which was first introduced as a disorder by the American Psychiatric Association in 1980;28 ODD often co-occurs with autism,29 diagnoses of which have increased dramatically in recent decades. According to a publication of The National Academies Press, ODD is a marked impairment; "children with ODD experience greater school failure and more suspensions and expulsions; they are less successful at peer relationships. With increasing age, symptoms shift from impairment and disruption of family and school life, to societal infractions and encounters with the legal system."30 Other authors state that "adults and adolescents with a history of ODD have a greater than 90% chance of being diagnosed with another mental illness in their lifetime. They are at high risk of developing social and emotional problems as adults, including suicide and substance use disorders."30a
So, in this largest study of breastfeeding's health effects of the type (randomized controlled trial) that is recognized to be the gold standard of study types, it was found as follows:
A dramatically increased percentage of the more-breastfed children were either intellectually disabled or demonstrated what appears to be higher risk of problems in school and seriously reduced likelihood of becoming mentally stable, self-supporting citizens. They are likely to become long-term burdens on their parents and on society. The significance of such impairment seems to greatly overshadow any beneficial effects of breastfeeding that were found as of that age. (see Section 2.g)
The authors of the study in which this result was found (major difference between the two groups in ability or willingness to take the test) did not comment about this finding's possible unfavorable implications; see Appendix E for discussion of that matter.
Section 3.b: Other randomized trials of relevance: Aside from other PROBIT studies, which will be discussed in the next section, apparently the only other randomized trials that have been conducted on health effects of breastfeeding have been as follows:
-- The randomized trial of exclusive breastfeeding in relation to allergies, which is represented in Figure 10a in Section 5.b; this found that later allergies were greatly reduced when exclusiveness of breastfeeding was interrupted by additionally feeding infants with potentially allergenic foods;
-- A 2001 study in Honduras on effects of exclusive breastfeeding for four versus six months.56d Infants breastfed for six months crawled sooner than infants in the less-breastfed group, which the authors considered to be a more favorable outcome for the more-breastfed infants. They did not discuss other considerations as follows:
a) Essentially all non-human land mammals develop more rapidly than homo sapiens, and all of those animals also have shorter lifespans than humans. If slower development, and a more gradual life course, weren't advantageous to humans in the long run, we probably would not have evolved to have slower development.
b) Even in the near term, faster development does not appear to be favorable. In a 2012 Swiss study that investigated the relationship between timing of meeting infant motor milestones and later development, that team's findings indicated that "early motor development is not essentially related to later outcomes in healthy children;" they said that this was in agreement with the findings of another recent study.56p
-- A 2001 study that included randomized trials (Singhal et al.) found that breast milk consumption during the neonatal period was associated with lower mean arterial blood pressure in 13-16-year-old children who had been born prematurely.56e Based on findings from a study that dealt with 35-64-year-olds, the authors interpreted that to be a favorable outcome for breastmilk feeding. They did not mention a very plausible unfavorable interpretation of that study, as follows: The mean arterial blood pressure of the formula-fed children (86.1 mm HG) was almost exactly in the center of a range that is considered to be normal and healthy (70-100);56h any significant deviation from that figure in either direction, as was found in the breast-milk-fed children, would shift the child's blood pressure closer toward exiting the healthy range. Low mean arterial blood pressure can lead to depression as well as to other adverse effects,56j,56k and can even be life-threatening.56g Also, low mean arterial blood pressure can result from endocrine (hormone) problems;56j,56k in relation to that, we should bear in mind that dioxins and PCBs, both of which are very high in human milk (Figure 1.a), are both known to be endocrine disrupters.17,17a So breast milk may well be reducing blood pressure by way of causing endocrine problems, and the resulting reduced blood pressure may contribute to various adverse outcomes including depression.57m In times such as recent decades, when youth suicide has become a substantial and growing problem,21m anything that might contribute to risk of depression in young people should be of serious concern. So, based on this randomized study, we can reasonably hypothesize that endocrine-disrupting chemicals that are high in human milk may lead not only to children's blood pressure moving toward falling outside the healthy range, but potentially also to more serious consequences.
-- A 2016 study of young people born pre-term (would show up in a search for randomized studies, but its authors acknowledged that it was not fully randomized and that there was substantial loss to follow-up.56f
-- In what was apparently the only other randomized study on health effects of breastfeeding, it was found (not surprisingly) that formula feeding was associated with far lower transmission of HIV to infants.60j
So the studies using research methods recognized to be the gold standard, after being read carefully, appear to have led to results that only add to the questions about the benefits of breastfeeding. Additional evidence about PROBIT findings, indicating significantly adverse effects of breastfeeding in other areas such as mental outcomes and obesity, will be presented later in Section 5.a.
Section 4.a: What might cause the mental or psychological impairment of such a disproportionate percentage of the highly-breastfed children (as indicated in Section 3.a)?
As explained in Section 2, industrial chemicals have become much more widespread in environments of developed countries, beginning not long before the middle of the 20th century. (Figure 1) And that has meant entry into human milk of developmental toxins (Figure 1.a), to which infants are heavily exposed at a time of major vulnerability of their neurological development. (Figure 2 and accompanying text).
According to a major document of the American Academy of Pediatrics published in 2012, referring specifically to PCBs, PBDEs, and major types of pesticides, "Infant formula is free of these residues...." (then going on to explain how that result comes about).31 . Dioxin has been found to be present in infant formula in concentrations less than one percent of those in human milk.32
Evidence of adverse neurodevelopmental effects of PCBs and dioxins was initially discussed in Section 2.b. In addition to that, bear in mind that
-- two kinds of impairment, diagnoses of which have increased dramatically in recent decades, are autism and ADHD, and
-- far more males than females are affected by those two disorders.
Therefore it is relevant to look into male-female differences in neurological effects of PCBs and dioxins, as will be discussed below.
Section 4.b: Highly relevant studies:
Observe below the sex difference in mental impairment that has been found, in an experiment with rats, to occur following developmental exposure to PCBs.
Note that developmental exposures to PCBs had dramatic adverse effects on learning ability of males but only minimal effects on females. So PCBs seem to fit well as a possible cause of the cognitive impairments that have overwhelmingly been affecting male children in recent decades. Studies of human exposures to dioxins, also, have found adverse effects on males but not females.32a
Experiments with animals have obvious advantages regarding kinds of tests that can be conducted, under controlled laboratory conditions, tests that would not be carried out with humans. There is good reason to believe that effects observed in animals would be similar to effects that those chemicals would have on human infants.33 According to a consensus statement signed by 57 scientists, researchers and health professionals, including many who are highly published experts, "The concordance between human and animal neurotoxicity assessment is remarkable as demonstrated for lead, mercury and PCB's."34
But there is also good basis to believe that animal studies under-estimate the effects on humans; according to a 2002 article by a research team that included three MD's, "animal studies commonly underestimate human vulnerability to neurotoxicants because of the obvious difficulty testing uniquely human cognitive, language, and behavioral functions within animal models. In the case of lead, mercury, and PCBs, animal studies underestimated the levels of exposure that cause effects in humans by 100- to 10,000-fold....." Continuing, "current testing protocols also underestimate toxic threats by exposing subjects to only one chemical at a time, although children are exposed to complex mixtures of chemicals throughout development. It is now well established that such multiple chemical exposures can be far more damaging, or cause damage at lower levels of exposure, than single exposures generally addressed in animal models."35
As published in the journal, Proceedings of the National Academy of Sciences, biological evidence of a link between PCBs in breast milk and autism was provided in a 2007 study (Kenet et al.) carried out in the laboratory of and with guidance from M.M. Merzenich, a member of both the U.S. National Academy of Sciences and the Institute of Medicine.36 According to Dr. Merzenich, "PCB intoxication was achieved by feeding the rat mother just enough of the poison to match the levels of PCB recorded in nursing human mothers in high-PCB-exposure areas of the U.S.," which he indicated to be "all over the country."37
According to a summary of the above study published by the National Scientific Council on the Developing Child (which works in close collaboration with the Center on the Developing Child at Harvard University),38 "the key mechanism that the brain uses for learning new skills in all animal species and humans" was found to be impaired, in this study.39 Dr. Merzenich also pointed out that, as a result of these PCB exposures, "the brain remained into adulthood in a very primitive underdeveloped state."
Section 4.c: Other relevant developmental toxins, and the period of greatest vulnerability:
-- PBDEs: Dr. Merzenich stated that, in addition to PCBs, we should also be concerned about PBDEs, which are "close cousins" of PCBs and "very structurally similar" to the specific type of PCBs used in the experiment;40 PBDEs, like PCBs, accumulate especially in fat and breast milk40b and are also endocrine disruptors.40a Dr. Merzenich concluded, "If human fetal and infant effects parallel rat impacts, we would predict that there would be a correlation between the PCB/PBDE levels in human breast milk -- and in infant blood -- with the probability of autism onset."
The EPA states that "the most sensitive outcome of PBDE exposure is adverse neurobehavioral effects following exposure during the postnatal period."112 There is a popular belief that postnatal exposures are of minor significance compared with prenatal exposures, so readers should note well the above EPA statement about the special importance of postnatal exposure; also remember the substantial earlier related text (Section 2.e) concerning special postnatal vulnerability of neurological development, and see more below on that topic.
Multiple studies have found that vulnerability of neurological development to toxins in air pollution is distinctly high in the year after birth: In a 2020 study of early-life exposures to pollutants in relation to autism (McGunn et al.), it was found that exposure to fine particle air pollution (PM2.5) during the first year after birth was positively associated with later autism diagnoses, whereas prenatal exposures to PM2.5 were not.112a Two studies published in 2019, including a review/meta-analysis, found that postnatal exposures to air pollution were much more associated with ASD than were prenatal exposures.112g
Note that PCBs and dioxins are by-products of most forms of combustion (including normal vehicle operation).112k That means that those chemicals contribute to the toxicity of air pollution, postnatal exposures to which have been distinctly associated with autism (see above). According to the ATSDR, "dioxins have an affinity for particulates," and they "may be found in particulates released from the combustion of most types of organic material …"112h Those contents would be expected to become part of the mother's body burden of dioxins, since particles in that diameter range are inhalable and PM2.5 can be absorbed into the blood.112c In addition to the infants' direct inhalation of the toxins, the toxic contents absorbed by full-size (mothers') lungs could also be channeled to infants via lactation. (Figure 1.a)
A 2015 publication based on the SEED study found that autism diagnoses were doubled among children who had received increased exposures to air pollution during the first year after birth, whereas there was no increase among children whose mothers had received the same increased exposures during gestation.112d As in the case of the McGunn et al. study discussed above, the pollution of concern (traffic emissions) contains PCBs and dioxins, as well as PBDEs;8a,8b,9d,112f the pollutants would have been taken in by mothers and transferred to infants (Figure 1.a), adding to the infant's own intakes.
The Volk et al. 2013 traffic pollution study found that risk of autism was more than three times as high among children with elevated first-year postnatal exposure to traffic pollution, compared with much lower increased risk among children with elevated prenatal exposures.112e
Section 4.d: The relationship between autism and breastfeeding, as found in various studies:
Considering the link suggested by Dr. Merzenich (Section 4.c above) between autism and some background exposures to PCBs and PBDEs, typically received in high doses via breastfeeding, note that many studies have found autism prevalence to be associated with duration of breastfeeding, including in dose-response relationships. See below.
A 2011 study that investigated data from all 50 U.S. states and 51 U.S. counties found that "exclusive breast-feeding shows a direct epidemiological relationship to autism," and also, "the longer the duration of exclusive breast-feeding, the greater the correlation with autism."41
Note that, according to the EPA, "Epidemiologic studies of exposed human populations provide the most convincing evidence of human health effects."42 Similarly, a publication of the National Academy of Sciences states, "Positive human epidemiologic data are the strongest evidence in evaluating any human-health risk."42a Also, a dose-response relationship between an exposure and a health outcome is considered to be especially significant evidence to support a finding of cause and effect. One example of a dose-response relationship, as found in an epidemiologic study by a well-published scientist (R.J. Shamberger), was quoted in the previous paragraph: "the longer the duration of exclusive breast-feeding, the greater the correlation with autism." This finding was even more significant in that it was based on data for most of the population of a major, diversely-populated continent (all 50 U.S. states), and it was also found in relation to numerous smaller-scale units (51 U.S. counties).
Additional support for a causal connection between breastfeeding and autism was provided by three additional, relatively recent studies, with a dose-response relationship being apparent in the overall view of those three studies, with increasing odds of autism in parallel with greater durations of breastfeeding.
-- In a 2009 U.K. study, the duration of breastfeeding that was assessed was four weeks versus less than four weeks. 65% of the autism cases had received exclusive breastfeeding for at least four weeks; that should be compared with only about 28% of the general U.K. infant population receiving that much breastfeeding. That meant a 130% higher odds of having had the larger amount of breastfeeding, among those with autism.44
-- In a 2010 American study in Kentucky by an MD/PhD team, the duration of breastfeeding used for comparison was six months. 37% of autism cases had received that much breastfeeding, compared with 13% of the controls, indicating an approximately 185% (37% / 13%) greater likelihood that the autism cases would have had more breastfeeding. The p-value was .003, indicating that, given the evidence found in the study, there was extremely low probability that the finding was a result of chance occurrence.45
The reader may wish to go back over the above studies to see what appears to be a dose-response relationship: the greater the duration of exposure, the greater the percentage of autism increase.
A dose-response relationship (in relation to different intensities of breastfeeding) can also be seen in a 2015 U.S. study (Husk et al.46). The authors found an increased-odds figure of 1.03 (a 3% increase) for current autism diagnosis with each additional month of "any" breastfeeding. The adjusted odds ratio for autism diagnosis was greater for exclusive breastfeeding, at 1.04 for each additional month.47
Also, the finding in the randomized PROBIT study described in Section 3 might be seen as an indication of a positive relationship between more breastfeeding and greater likelihood of autism. Incidence of autism has apparently not been specifically assessed in the PROBIT studies, but the finding concerning greatly increased inability or unwillingness to take the standard test, among children who had received more breastfeeding, could be considered to be an indication in that study of the mental impairment and the oppositional/defiant behavior that are common in people with autism.29,,47a, 47d
For additional descriptions of studies of the relationship between autism and breastfeeding, see Section 4.a of www.pollution-effects.info/..
Section 5: Long-term effects of developmental exposures to these toxins, in various areas
Note that dioxins are carcinogens, in addition to having other long-term effects.
Beginning in the late 1960's, breastfeeding (which by that time contained unhealthful as well as beneficial substances) gained greatly in popularity:
Note the especially major increases in long-term breastfeeding.
We will discuss (just ahead) increases that have been occurring over recent decades in obesity, asthma, allergies, ADHD, brain disorders and childhood cancer while increases have been occurring in infant exposures to developmental toxins and carcinogens.
Section 5.a: Beginning in the 1970's, several childhood disorders began to increase substantially.
The increase in breastfeeding in the U.S. was especially notable after 1970, but it actually started gradually in the late 1960's, following a low period in the early 1960's.48 Breastfeeding in most countries of Western Europe also increased greatly, apparently beginning in the 1970's,48a,49 although data for before 1980 is scarce.
A publication of former Surgeon General Regina Benjamin pointed out that research on the health outcomes of different modes of infant feeding was limited to observational studies.51 (Apparently results of PROBIT studies were not yet known as of her writing.) Evidence from observational studies is recognized by highest authorities on medical evidence to be mainly of low quality (see Section 1 ); that is as opposed to the recently-completed (PROBIT) randomized trials, which are recognized to be able to provide high-quality evidence (as discussed earlier, in Section 1.b); those studies have found predominantly unfavorable effects of breastfeeding. (Section 3 as well as below).
The PROBIT study,
with over 17,000 mother-infant pairs, was a randomized trial on the health
effects of breastfeeding, publishe
d in the Journal of the American
Medical Association. The children's outcomes were followed at stages up
to age 16. The researchers gathered data concerning an experimental group
whose breastfeeding rates were greatly increased by major promotion of
breastfeeding, comparing that with data from a control group whose
breastfeeding was relatively minimal. In addition to the results described
in Sections 2.g-2.h and 3, which were very mixed toward
breastfeeding, the study also found that risk of overweight/ obesity at age 16
was increased among children who had received more breastfeeding.52 A recent major sibling study, another
means of avoiding the confounding that is normal in observational studies, also
found that obesity increased with greater breastfeeding.53
The above contradictions of a typical belief about breastfeeding's effects fit well with what has actually happened with obesity prevalence in the U.S. in recent decades, while breastfeeding has been greatly increasing. Note that breastfeeding in the U.S., especially for 6 months or more, increased dramatically after 1970 (Figure 8, not far above); in relation to that, see (below) what happened in obesity of American children following the breastfeeding increases:
The more-than-tripling of child obesity during these years is compatible with the dramatic increases in breastfeeding that took place after the 1960s.
Non-increasing obesity among those born before the late 1960s:
Looking at the first two assessment periods shown in the chart below, notice that 18-to-29-year-olds in those years would have been born before the period of breastfeeding increases.
Notice that obesity was not increasing among those people who were born before breastfeeding increased. (This is seen in the first two periods shown above). Then, in the first assessment period in which a large part of this age group would have been born in the late 1960s and later (when breastfeeding was increasing greatly), obesity was increasing rapidly.
In explanation of how breastfeeding could lead to obesity, note the findings of the Jacobson et al. 1990 study,54 as follows: "reduced activity (of children) was associated with both 4-year PCB body burden and its principal determinant, exposure to PCB-contaminated breast milk." (There is ample evidence indicating that major PCB contamination is a normal characteristic of contemporary human milk and that PCBs are persistent in the body; see Figure 1.a and the text following it.) The most-exposed children were found in this study to be ”about 2-3 times more likely to be rated 'usually quiet and inactive.' " The children who were observed were mostly from Great Lakes fish-eating populations, with merely slightly-above-average PCB exposures.55 Three animal studies have also found reduced -- often greatly reduced -- activity to be an effect of postnatal PCB exposure, including at upper-background levels.56 (Concerning the relevance and value of such studies, see "Experiments with animals" in Section 4.b) The causal connection between reduced activity and increases in obesity probably needs no explanation. But the recognition of breastfeeding history as the principal determinant of (activity-reducing) PCB levels in children over a period of years is worthy of emphasis.
Section 5.b: Other disorders also increasing, as breastfeeding increased:
Asthma: See below:
Although the above chart is not specifically about children, other CDC data as of 1999 shows that serious cases of asthma had increased substantially specifically in the youngest age groups; serious asthma cases declined greatly among those not affected by increases in breastfeeding (those over age 35); and cases increased moderately among those who were born while breastfeeding was increasing but who were well past the exposures of infancy (age 15-34). (see Appendix B.)
In the sibling study mentioned earlier, which minimized the confounding that is typically caused by between-family differences in exposures to smoking, living in areas of bad air quality, etc., poorer outcomes in asthma were found to be consistently, positively associated with breastfeeding duration, across all methods of comparing the data.53
Allergies, mainly affecting children, are reported to have doubled or tripled since the 1970s.56a Peanut allergies among U.S. children, occasionally fatal, are reported to have more than quadrupled;56b these allergies are responsible for more deaths from anaphylaxis, or constriction of the airways, than any other food allergy.(although deaths are very rare.) Children who develop a peanut allergy generally do not outgrow it and must be vigilant to avoid peanuts for the rest of their lives.56q Allergies have also increased among adults, but not to the extent reported for children.56n,56o
Remember from Section 1 that randomized trials are generally recognized to be the gold standard of study types. Notice in the charts above, adapted from a randomized trial published in 2016,56r that peanut and egg allergies were substantially reduced when exclusiveness of breastfeeding was interrupted by a large minority of mothers in a test group (left-hand charts); and allergies were dramatically reduced among infants all of whom were fed potentially allergenic foods in addition to human milk, in accordance with the study's protocol.
Diabetes: According to the president of the American Diabetes Association in 2002, type 2 diabetes as of that year had "changed from a disease of our grandparents and parents to a disease of our children." At that time it was on its way to being what she called a "new epidemic" among children and young adults.58 Considering when the children must have been born who made up the new epidemic among children and young adults as of 2002, major increases in diabetes very likely occurred among those who were beginning to be born somewhere around 1970. Observe in Figure 8 (repeated just below) how being born around 1970 and later relates to the time of the major increases in breastfeeding. This statement by a high authority on diabetes made a clear point about disease increase among people born after about 1970 (the approximate time when breastfeeding started increasing), while no problems were mentioned regarding those born earlier. Increases in diabetes are an unsurprising accompaniment to the increases in obesity, discussed above. Also note that PCBs (see Figure 1.a) are considered to be diabetogenic.58a
Epidemic of brain-based disorders: A highly-published Canadian scientist (Bruce P. Lanphear), summarizing data from the U.S. CDC, stated in a 2015 publication that "these data indicate that we are in the midst of an epidemic of brain-based disorders," with ADHD prominent among the rapidly-increasing disorders among children.59 As reported in a 2008 publication of the U.S. Center for National Health Statistics, “Over the past three decades in the United States, behavioral and learning disorders have emerged as major chronic conditions affecting the development of school-aged children and adolescents.”60 So 1978 would be the approximate year when large numbers of children increasingly affected by those disorders would have been recently entering their school years; those early-years-schoolchildren with declining mental health would have started being born in the late 1960s and early 1970s.
Section 6: Toxic exposures of infants -- remembered versus actual:
The American Academy of Pediatrics points to observational studies that have found breastfeeding to be associated with reduced leukemia.60f Aside from the matter of the generally low quality of evidence from observational studies (see Section 1), there is a problem that applies especially to studies that rely on retrospective reports of breastfeeding histories -- that is, most studies of child health outcomes related to breastfeeding. In a large meta-analysis, with 85% of the studies relying on mothers' recollections of their children's feeding at a time in the past, the predominant finding was of reduction of childhood cancer with breastfeeding; but the authors identified four studies that worked with breastfeeding data that was actually recorded during infancy, and all four of those studies found either no effects or significantly adverse effects of breastfeeding; see Appendix O. Research has found that responses to survey questions about past practices are very often inaccurate; five studies were cited in support of that statement, in a 2015 journal article.60a In a Boston hospital survey, 0.7% of mothers breastfed exclusively for six months, but 22% reported having done so in a later questionnaire.60b "Social desirability bias" in responses is so widely recognized as a problem in surveys that numerous different methods for trying to deal with the problem have been reported in two separate reviews published on the subject.60c,60d So it should not be surprising that many studies based on such faulty maternal recollections have concluded with findings of favorable relationships between breastfeeding and childhood cancer, even though human milk has very high contents of carcinogens (Figure 1.a); those dubious findings about breastfeeding in relation to leukemia also conflict with very substantial historical data showing higher or lower breastfeeding rates to have been directly associated with higher or lower incidence of childhood cancer. (see upcoming sections)
As mentioned, professionals who ought to be knowledgeable on this topic do not dispute the very high levels of carcinogens in human milk (Figure 1.a and accompanying text), nor do they suggest any other possible pathway for widespread exposures of infants to toxins in unsafe doses (Appendix K).
Section 8: Final Thoughts
Section 8.a: An important question to think about:
Considering the following:
a) infants have increasingly been fed a substance (human milk) that is authoritatively recognized to have begun in recent decades to contain known developmental toxins and carcinogens in concentrations greatly exceeding established safe doses (Fig. 7),
b) there have been
increases in childhood cancer and other diseases in recent decades, the causes
of which are largely unknown but which are closely, specifically associated
with breastfeeding history in many disease areas (Sections 4.b
and later), and
c) the only studies that have found favorable effects of breastfeeding have been of a type that leading experts in medical evidence recognize can result in false conclusions (Section 1).
Given the above, how do we know that breastfeeding isn't leading to harmful effects, overall?
Bear in mind that many authoritative sources who ought to be knowledgeable on the subject do not know of any pathway other than breastfeeding by which children are widely exposed to toxins beyond established safe levels. (Appendix K)
Section 8.b: A brief look at the health of those least exposed to the pathway relevant to all of the above:
Americans born when extended breastfeeding was unusual (those born during the 1960's -- see below and reference 119) -- have had many better health outcomes in early middle age compared with those born both before and since that time.
In the case of deaths connected with the opioid epidemic, as in many other cases, the group mainly born in the 1960's (the 45-54 group in this case) stands out as being far less affected than other groups in the central age range.
For much more information about health outcomes among the least-breastfed age group, see Section 5 of www.pollutionaction.org/shorter-lives.htm .
Actually, a better question would be, "is it time for a first-time-ever, balanced consideration of the case for breastfeeding in industrialized countries?" Good evidence indicates that there has not yet been a rational consideration of this important matter, paying suitable attention to evidence of adverse effects of the toxins that are authoritatively recognized to be present in human milk.
The American Academy of Pediatrics would probably be the logical U.S. organization to carry out a proper examination of this question, given its area of medical specialization. But what it has published in this regard ignores the possibility of adverse effects of breastfeeding aside from isolated cases; it gives no indication of consideration of the serious toxins that are authoritatively recognized to be present in typical human milk in concentrations greatly exceeding established safe levels.60f (But the AAP does not dispute the considerable evidence about toxins at high levels in human milk -- see Appendix K.) So the AAP is clearly not a likely source of a balanced consideration of this matter based on any semblance of "the whole truth."
The American Academy of Family Physicians (AAFP) takes a somewhat different approach in that they acknowledge the (undisputed) presence of toxins in human milk. But the statement at the center of their document on this matter60h is, by considerable evidence, untrue; when this is pointed out, they make no attempt to provide evidence to support it. (No supporting evidence is provided in the original text, either.) The untrue statement in their breastfeeding document reads, "By using formula, they (mothers) do not reduce exposure to environmental toxins." The author of this article wrote to the appropriate vice president of the AAFP in July of 2019 (return receipt requested and received), pointing to considerable authoritative evidence that contradicts their statement about formula not having less toxins, and asking "if the AAFP can provide any scientific evidence" to support its statement on this matter; the only stipulation was that there be indication of comparison of concentrations of toxins between the two feeding types. There has been no response as of eight months later.
So, if we are seeking a rational, truth-based analysis of the pros and cons of breastfeeding, the AAP and AAFP are not likely sources of such a thing. (Similarly, other organizations that have also been recommending breastfeeding for many years are unlikely to be open-minded toward evidence indicating that they have been wrong.)
Until such time as there is an authoritative re-evaluation of the benefits versus adverse effects of breastfeeding, by professionals who do not have a long-standing commitment to one side of the issue, mothers should be informed of scientific reasons to question the desirability of breastfeeding.
(b) The immune cells transferred from the mother via breastfeeding are important in areas where modern sanitation is likely to be minimal (as in many less-developed countries); but those maternal immune cells may actually be harmful in countries in which infants are already largely protected from microbes; the added immune cells will cause further reduction of the challenges that are likely to be beneficial in stimulating development of the child's own immune system. This is in accordance with the Hygiene hypothesis, sometimes called the Microbial-deprivation hypothesis; see Appendix D; this hypothesis has received additional support in a 2020 study's finding of inverse association between more-serious infections in early childhood and risk of leukemia.120 And this could help explain why asthma (an immune system disorder) has dramatically increased among children (Figure 10) following the major increases in breastfeeding (Figure 8).
As the author of the above, my role has not been to carry out original research, but instead it has been to read through very large amounts of scientific research that has already been completed on the subjects of environmental toxins and infant development, and then to summarize the relevant findings; my aim has been to put this information into a form that enables readers to make better-informed decisions related to these matters. The original research articles and government reports on this subject (my sources) are extremely numerous, often very lengthy, and are usually written in a form and stored in locations such that the general public is normally unable to learn from them.
My main qualification for writing these publications is ability to find and pull together large amounts of scientific evidence from authoritative sources and to condense the most significant parts into a form that is reasonably understandable to the general public and also sufficiently accurate as to be useful to interested professionals. My educational background included challenging courses in biology and chemistry in which I did very well, but at least as important has been an ability to correctly summarize in plain English large amounts of scientific material. I scored in the top one percent in standardized tests in high school, graduated cum laude from Oberlin College, and stood in the top third of my class at Harvard Business School.
There were important aspects of the business school case-study method that have been helpful in making my work more useful than much or most of what has been written on this subject, as follows: After carefully studying large amounts of printed matter on a subject, one is expected to come up with well-considered recommendations that can be defended against criticisms from all directions. The expected criticisms ingrain the habits of (a) maintaining accuracy in what one says, and (b) not making recommendations unless one can support them with good evidence and logical reasoning. Established policies receive little respect if they can't be well supported as part of a free give-and-take of conflicting evidence and reasoning. That approach is especially relevant to the position statements on breastfeeding of the American Academy of Pediatrics60f and the American Academy of Family Physicians60h, which statements cite only evidence that has been
(a) selected, while in no way acknowledging the considerable contrary evidence,92 and
(b) of a kind that has been authoritatively determined to be of low quality. (See the paragraphs dealing with observational studies.)
When a brief summary of material that conflicts with their breastfeeding positions is repeatedly presented to the physicians' associations, along with a question or two about the basis for their breastfeeding recommendations, those associations never respond. That says a great deal about how well their positions on breastfeeding can stand up to scrutiny.
The credibility of the contents of the above article is based on the authoritative sources that are referred to in the references: The sources are mainly U.S. government health-related agencies and reputable academic researchers (typically highly-published authors) writing in peer-reviewed journals; those sources are essentially always referred to in footnotes that follow anything that is said in the text that is not common knowledge. In most cases a link is provided that allows easy referral to the original source(s) of the information. If there is not a working link, you can normally use your cursor to select a non-working link or the title of the document, then copy it (control - c usually does that), then paste it (control - v) into an open slot at the top of your browser, for taking you to the website where the original, authoritative source of the information can be found.
The reader is strongly encouraged to check the source(s) regarding anything he or she reads here that seems to be questionable, and to notify me of anything said in the text that does not seem to accurately represent what was said by the original source. Write to firstname.lastname@example.org. I will quickly correct anything found to be inaccurate.
Comments or questions on the above are invited, including criticisms if they are specific, and will usually receive a response. At the next link are past comments and questions from a number of readers, including eight doctors, followed by our responses. Some of the doctors have been critical but others have been substantially in agreement with us (including one with children with asthma, one who says she has delivered thousands of babies, and one with a son with autism); they put into briefer, everyday language and personal terms some important points that tend to be immersed in detail when presented in our own publications. Topics discussed in that section include about having breast milk tested for toxins and about means of trying to achieve milk that is relatively free of toxins, including the "pump and dump" option. To read the above, go to www.pollutionaction.org/comments.htm
In criticisms, please point out any specific passages that you feel are not accurately based on authoritative sources (as cited) or that do not logically follow from the evidence presented. Note that the author of this article feels no obligation to present the pro-breastfeeding case as long as the medical associations and other promoters of breastfeeding fail to inform parents about the developmental toxins that are, without dispute, present in high concentrations in human milk. Please e-mail criticisms or other comments to email@example.com. Most will receive a reply.
For a more complete statement about the author and Pollution Action, please go to www.pollutionaction.org.
Shenandoah, VA, USA
that far exceed established safe levels:
The American Academy of Pediatrics and the American Academy of Family Physicians, both of which strongly advocate breastfeeding, do not deny that PCBs and dioxins are transferred to infants via breastfeeding in quantities that far exceed established safe levels. In an August, 2018 letter to the AAP, the author of this article wrote the following, based on considerable evidence from authoritative sources, which were cited: "PCBs have been found to be present in human milk in doses 63 to 270 times the minimal risk level established by the U.S. Agency for Toxic Substances and Disease Registry.4,6 Dioxins have been found to be present in typical U.S. human milk in concentrations exceeding the EPA's RfD (estimated reasonably safe dose) by scores to hundreds of times.5,6 PCBs have been found to have long-term effects including cancer7,9 and damage to the blood-brain barrier; 8 dioxins have been found to have long-term effects including cancer, heart disease, reproductive abnormalities, and immunity deficits.9,10 "
The letter requested a response from the AAP that would contradict the above based on scientific evidence, and offered $5,000 to compensate for the time required to write a response. (The financial offer was due to the lack of response to several earlier, similar letters to both the AAP and the American Academy of Family Physicians.) Return receipt for the letter was requested and received from the U.S. Postal Service, and (despite offer to place the funds in escrow to assure payment upon receipt of reply) as of over six months later, no response has been received. Any organization that promotes breastfeeding (such as the AAP) should have responded if the statements quoted just above were not well-substantiated or if there existed scientific evidence that could contradict the substance of the letter that was received.
Likewise, there has
been no reply to a similar letter to the AAP (dated Oct. 5, 2018)
stating, "Of toxins with recognized long-term effects, none are known to
be ingested or inhaled by U.S. infants in doses beyond established safe levels,
except for toxins that are transferred via breast milk." Again,
there was an ample financial offer to compensate for a science-based,
contradictory response, return receipt for the letter was received, and again
(after over six months) there has been no response and no sign of disagreement
with the statement in quotes.
For additional sources about authoritatively-established safe doses of these chemicals and actual exposures in the U.S. and other countries, see reference no. 10 below.
Appendix B: Increase of serious asthma among U.S. children in recent decades:
Notice above that serious cases of asthma
-- increased greatly in the age group (0-4) most closely affected by the increases in breastfeeding,
-- declined greatly among those over age 35, those unaffected by the post-mid-1960s increases in breastfeeding (as of this chart's data period), and
-- increased moderately among those who were born after the mid-1960's but whose breastfeeding exposures were many years in the past.
Appendix C: Chemical exposures determined to exceed safe levels even more than previously thought:
In 2001, the European Commission's Scientific Committee on Food set a safe level for dioxins and dioxin-like PCBs that was similar to the level determined by WHO in 2001, which was the standard that was in effect during the WHO surveys results of which are shown in Figure 1.a.93 However, in November of 2018, the European Food Safety Authority (EFSA) issued a revised statement of tolerable intake that was seven times lower than that established in 2001 by its predecessor Committee, based on new data and on improved assessment methods.94
Appendix D: The Hygiene hypothesis/ microbial-deprivation hypothesis
Breastfeeding transmits immune cells from the mother to the baby, which help protect the infant from microbes. But there is an important reverse side to that coin, related to the major recent reduction in stimuli of the kind needed for a child's own immune system to develop properly. It is well established, in the underlying principle of most vaccinations, that the immune system develops its own capacities in response to challenges. It has recently been learned that some microbial challenges need to occur very soon after birth in order to properly promote development of the child's immune system (see below).
For over 99% of the evolutionary history of Homo Sapiens, sanitation did not exist; our forebears until late in the 19th Century knew nothing about protecting infants from bacteria. Before modern sanitation, clean water, pasteurized milk, vaccinations, and refrigeration came into existence, transmission of immune cells via breastfeeding promoted survival and increase of our species. Primitive conditions still prevail in many countries, and the immune cells in human milk still serve the original purpose in those countries.
However, it is safe to say that most infants' exposures to microbes in developed countries have already been reduced to extremely low levels in relation to what our species became adapted to.
Of great relevance here is the "hygiene hypothesis" described in a web page of the U.S. Food and Drug Administration, according to which proper infant development depends on "the necessary exposure to germs required to 'educate' the immune system so it can learn to launch its defense responses to infectious organisms. In the period immediately after birth the child's own immune system must take over and learn how to fend for itself." (emphasis added) The FDA continues, "The 'hygiene hypothesis' is supported by epidemiologic studies."95 "The young immune system is strengthened by exposure to everyday germs so that it can learn, adapt, and regulate itself," according to the director of the Laboratory for Human Biology Research at Northwestern University.96 Various studies have recently added to the evidence along the above lines; "these studies show the critical importance of proper immune conditioning by microbes during the earliest periods of life," according to another expert in the field. 97 The reader may want to try to figure out where shielding provided by microbe-destroying cells from outside the infant's own body, received via breast milk beginning right after birth, fits into the picture of necessary exposure of the infant to challenges from germs right after birth.
A study found on the NIH's website discusses "the microbial exposure which may be critical for immune priming" and suggests it would be helpful to re-name the "hygiene hypothesis" as "microbial deprivation hypothesis."98
Appendix E: Failure of the authors to comment on what appears to be substantial adverse outcome of more breastfeeding:
That could be an accommodation to a perceived prevailing attitude that will not accept the idea that breastfeeding can have adverse effects. Researchers may think that, in order for their work to be acceptable to the establishment (and therefore to sources of future research grants), it is better not to present evidence that is negative toward breastfeeding. Basis for such a concern can be found by doing an internet search for "position on breastfeeding of U.S. government" (or probably position of most other governments as well). Despite the findings in recent years of high levels of developmental toxins in human milk (see Figure 1.a), the recent findings by way of superior research methods of lack of benefits of breastfeeding (see Section 2), and the many studies that have found adverse effects of breastfeeding (see Section 4), one will find uniformly strong promotion of breastfeeding by the establishment, with no acknowledgement of possible drawbacks except in rare cases. That indicates the apparent attitude and the lack of openness to conflicting evidence on the part of the people who control the purse strings for most research.
So, to promote openness toward considering all evidence about what is best for developing children, there is a need to explore some of the many compelling reasons why breastfeeding could -- and almost certainly does -- have adverse health effects.
Appendix H: Ongoing sources of PCBs, dioxins and PBDEs, including in traffic emissions and older buildings, to which people are closely exposed: In a 2013 U.S. study of PCB concentrations in carpet dust in homes at various distances from possible pollution sources, PCB concentrations were found to be about five times as high in homes within 600 yards from major roads in Los Angeles as they were in homes that were over 1100 yards from those roads;104 a study in the Czech Republic found even more extreme differences in traffic-affected soils compared with soils in reference areas.8b In a study in Colombia, measurements of PCBs and dioxins taken near vehicular sources were found to be almost six times as high as measurements made over a mile farther away.105 Similar results concerning PCBs in traffic emissions were found in a study in Stockholm, Sweden.106 PCBs also continue to be released from old equipment (such as transformers and capacitors) that is either still in use or is being emitted from waste sites, and from buildings built between 1949 and 1978, in all of which they were typically intentionally and heavily used.106a
Dioxins: A 2009 Czech study found "dramatic decreases" in concentrations of pollutants (including dioxins) in soil according to distances from roadways. Concentrations next to roadways were found to be as high as in industrially-polluted areas; and the concentrations of dioxins were found to decrease, stepwise, with progressive distances from roadways up to the last distance measured.107
PBDEs are apparently produced in vehicle emissions in even greater amounts than PCBs. A Taiwanese study found that concentrations of PBDEs in vehicle exhausts were 17 to 140 times as high as concentrations of PCBs, in the different vehicles tested.108 (When reading that, remember from above how high PCBs have been found to be in vehicle emissions.) In a 2010 study, the PBDE emission rate from tailpipe exhaust of just one unleaded-gas-fueled vehicle was found to be about four times higher than that from one U.S. house and garage.109 Bear in mind that U.S. houses, usually containing many flame-retardant-treated furnishings and electronics, are themselves substantial sources of PBDE dust.110
Appendix I: More about PBDEs:
PBDEs are chemical relatives of PCBs and best known as flame retardants. They are similar to PCBs in that they are toxins that can cause impairment, being listed in the TENDR group of the six toxins of greatest concern.111 In a discussion of PBDEs, the EPA refers to those toxins' adverse neurobehavioral effects following exposure during the postnatal period." (The italics were added here to reinforce the point that these chemicals are known to have adverse neurodevelopmental effects resulting from exposures occurring after birth; that emphasis was added because prenatal exposures seem to draw inappropriately predominant attention.) The EPA clearly sees those effects of PBDEs as being serious; they refer to neurobehavioral effects of postnatal PBDE exposures as being a "critical endpoint of concern." 112
Appendix J: Low quality of evidence from observational studies:
The leading authorities on medical evidence have determined that evidence from observational (non-randomized) studies is predominantly of low quality, with evidence from only exceptional ones reaching a medium level of quality. One such determination has been provided by Dr. Gordon Guyatt and an international team of 14 associates;113 Dr. Guyatt is chief editor of the American Medical Association's Manual for Evidence-based Clinical Practice, in which 26 pages are devoted to examples of studies (almost all of which were observational) that were later refuted by high-quality studies.114
A similar assessment of the generally low quality of evidence from observational studies has been provided by the other chief authority on medical evidence, Dr. David Sackett,115 writing about "the disastrous inadequacy of lesser evidence," in reference to findings from observational studies.116 Dr. Sackett was said by the British Medical Journal to have been "widely regarded as 'the father of evidence-based medicine.'"117
A team of MD's, in an article in the AMA Journal of Ethics, studied the matter brought up by John P.A. Ioannidis (MD, PhD) in the latter's 2005 article entitled, "Why most published research findings are false." The authors were in agreement with what Ioannidis wrote, and they discussed which type of studies (among 45 highly-cited medical studies in prominent journals) was especially subject to false conclusions; it was found that 5 out of 6 observational studies were later contradicted, compared with only 23% of randomized trials; and they noted that the only predictor of contradiction in the randomized trials was small sample size.3b A June, 2020 search of Pubmed and Google Scholar on this topic yielded only one publication alleging contradiction among large RCTs,3g but three out of the four possibly-contradicted "large" RCTs discussed were actually in the size range (under 1000 cases) that other authors who studied far more RCTs considered to be in the small-size category.3b In his book, Wrong, Why experts keep failing us…, David H. Freedman stated that even large RCTs had been contradicted; but when the principal author of this article asked Freedman (in his online book's comments section) to provide evidence in support of that statement, Freedman was initially unable to come up with any good examples of contradicted RCTs with study populations numbering in the thousands (as is the case with typical larger RCTs3b), and concluded saying that he might get back to the question in the future. (April 22, 2020 response to post, at https://freedman.com/wrong/#comment-10146) No additional response has been received as of 10 months later. So it appears to be safe to say, until evidence to the contrary may become available, that apparently no large RCTs have been contradicted.
Observational studies of health effects of breastfeeding are especially subject to false conclusions because of
a) known confounding by socio-economic status (see Section 1.a),
b) inaccurate, biased data, which is especially likely to occur in retrospective (that is, most) studies of breastfeeding (see Section 6;
c) reverse causality: poor growth (itself associated with later adiposity and metabolic risk) or agitated behavior during feeding (itself likely to predict later mental problems) may be causes of formula supplementation or weaning;1a,1c and
d) selective publication;1a,1b aside from selective publication's being recognized in peer-reviewed literature as a special problem in research on breastfeeding,1a it appears that screening out of contrary information regarding breastfeeding is encouraged and practiced at the highest levels of medicine; this can be seen in the policy statement on breastfeeding of the American Academy of Pediatrics,60f which cites numerous studies that are favorable to breastfeeding but refers to none of the many negative studies60g and does not mention the word "toxin" even once, despite ample undisputed evidence about presence of developmental toxins in high concentrations in human milk. (Figure 1.a and accompanying text)
Appendix K: Very likely a unique pathway of widespread infant exposure to developmental toxins in doses exceeding established safe levels:
As can be seen in Figure 1.a and accompanying text, with considerable authoritative supporting evidence, breastfeeding is a pathway for ingestion of multiple developmental toxins by infants, with PCBs and dioxins at especially high levels. But it is more than just a pathway; it is almost certainly the only pathway by which infants are widely exposed to developmental toxins in doses exceeding established safe levels. The author of this article has written relevant letters of inquiry to appropriate officials at:
a) the American Academy of Pediatrics,
b) the American Academy of Family Physicians,
c) the entire science team at the major autism-advocacy organization, Autism Speaks,
d) the U.S. Agency for Toxic Substances and Disease Registry (ATSDR), and
e) the U.S. Centers for Disease Control and Prevention (CDC).
Those letters asked whether the addressees or their organizations were aware of
a) any toxins that are believed to widely reach infants in doses well in excess of a recognized safe level (e.g., EPA's RfD), aside from the several such toxins that are ingested by means of breast milk, or
b) any other pathway of infant exposure to toxins in concentrations exceeding established safe levels.
As of six or more months later, none of the five replies that were received suggested any other such toxins or other pathway.
Related to this are the very large differences between concentrations of toxins in breast milk and those in the main alternative infant feeding. The toxins being discussed here are present in infant formula in concentrations usually less than 1% as high as their concentrations in human milk. (See Section 4 above and also near the beginnings of each of the subsections of Section 3 of www.pollution-effects.info)
Appendix L: Exposures of mothers to toxins and times of exposures of the developing infant to those toxins:
The period of adverse exposures of developing children to pesticides or other substances is often said to be prenatal, with no mention of postnatal exposure. However, prenatal exposure of the mother typically merely adds to a mother’s accumulated body burden of toxins, contributing to a much greater postnatal exposure that will occur later for breastfed infants; remember the ATSDR's illustrative example of the laboratory experiment in which the following was observed: after a maternal dose of PCB administered before gestation, postnatal exposure of rat sucklings to those PCBs via lactation was over 1600 times greater than fetal exposure (see earlier). Also note that dioxins are closely related to PCBs – both are persistent, lipophilic organochlorine compounds that accumulate in the body.
Also note in Figure 11 that dioxin toxic equivalency levels in infants as of time of birth are very low, indicating low exposures during gestation; but the dioxin levels very rapidly increase among breastfed children right after birth, indicating that the postnatal exposures of breastfed children are far greater than prenatal.
Appendix M: Basis for recommending against breastfeeding in case of nuclear accident, which would have predated the Chernobyl meltdown:
"Experts on the thyroid gland have warned that after exposure of the mother to radioactive iodine, infants should not be breast-fed because radioactive iodine passes through the mother's milk to the nursing infant." (Miller and Zanzonico: Radioiodine Fallout and Breast-Feeding, Radiation Research 164 (2005) The above quote is from an article published in 2005, but
-- two of the studies cited by those authors as the basis for the above content were published before the Chernobyl accident (in 1986) and a third one was published in 1986;
-- another study, in the internationally-known journal, Pediatrics, published a few years before the Chernobyl accident, found that fully half of certain radioactive material administered to a mother (as part of medical treatment) was excreted in her (pumped) breast milk within the first 24 hours; (Pittard et al., Radioactive excretion in human milk following administration of technetium Tc 99m macroaggregated albumin, Pediatrics, 1982, at https://www.ncbi.nlm.nih.gov/pubmed/6212905 )
-- another study indicated that the ready passage of radioactive iodine via breastfeeding was established knowledge at least as far back as 1955 (Miller and Weetch, The excretion of radioactive iodine in human milk. CABI/ CabDirect, 1955, at https://www.cabdirect.org/cabdirect/abstract/19561402176)
-- still another study, on the topic of nuclear medicine and the nursing mother and published in the British Medical Journal in 1985, pointed out the finding in various studies that "selective uptake may result in iodine concentrations in milk being 40 times those in plasma." (Coakley and Mountford, Nuclear medicine and the nursing mother, British Medical Journal, 1985, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1416365/) (Bear in mind that the iodine discussed here is considered to be a vehicle for radioactivity.) This remarkable finding, published in a prestigious journal just a year before the Chernobyl accident, would probably have been fresh in the minds of many medical professionals at the time of the accident, leading to medical advice not to breastfeed for a significant period after the surge in radioactivity.
Appendix N: Increased risk of metabolic syndrome among the more-breastfed PROBIT group, especially males, at 11.5 years of age:
When investigating a risk factor (such as metabolic syndrome) that indicates risk of cardiovascular disease,56s it is completely logical to show results for males separately from females; according to the American Heart Association, men have substantially higher risk of having a diagnosed heart attack or fatal coronary heart disease, with a more-than two-fold male-female difference between ages 45 and 64.56t So special attention should be devoted to the 49% higher risk of metabolic syndrome not among females but among the more-breastfed males (odds ratio, 1.49, vs. 0.94 in females, as shown in this study just above Table 2; 1.0 is the level of no increased risk). Reporting male and female risks separately is especially appropriate considering the major contents of chemicals in human milk (Figure 1.a) that have been found to affect males much more than females. (Figure 5 and accompanying text) And the reason to suspect a connection between human milk and a risk factor for cardiovascular disease is strong considering the following: epidemiological and laboratory studies have shown that exposure to PCBs (Figure 1.a) can lead to diabetes, hypertension, and obesity; all of which are risk factors for cardiovascular disease.56u
Appendix O: “Recall bias” as a problem in observational studies: In a 2005 meta-analysis of 26 publications on the association between breastfeeding and childhood cancer, 85% of the studies relied on the mothers’ long-term recall of feeding history, and those studies overwhelmingly found that breastfeeding was associated with reduced cancer. (Martin et al., Breast‐feeding and childhood cancer: A systematic review with metaanalysis, IJC Epidemiology, 2005, at https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.21274) But, of the four studies in that meta-analysis that were based on feeding data gathered during the children’s infancies, not one found any statistically significant association of breastfeeding with reduced cancer. One of those study teams had access to an especially complete record of the breastfeeding histories (those for every child born in Sweden), on which to base its finding of a substantial increase in non-Hodgkins lymphoma in relation to breastfeeding; and there was a dose-response relationship for that finding. (Hardell and Dreifaldt, Breast-feeding duration and the risk of malignant diseases in childhood in Sweden, European Journal of Clinical Nutrition, 2001, at https://www.nature.com/articles/1601142.pdf )
The other studies using prospectively-gathered feeding data:
McKinney et al., Pre- and perinatal risk factors for childhood leukaemia and other malignancies: a Scottish case control study, British Journal of Cancer, 1999, at https://www.nature.com/articles/6690609.pdf
Murray et al., Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study, British Journal of Cancer, 2002, at
Golding et al.. Factors associated with childhood cancer in a national cohort study. Br J Cancer 1990;
Appendix P: Long-term accumulation of body burden of dioxins:
Exposures of breastfed infants to pesticides are much more than merely a pass-through of current exposures of the mother. According to most studies that have been conducted on this topic, dioxins that are excreted in human milk result from mobilization of accumulations that have built up in a woman's adipose tissue over many years. (LaKind, Recent global trends and physiologic origins of dioxins and furans in human milk, Journal of Exposure Science & Environmental Epidemiology, 2007, at https://www.nature.com/articles/7500543
Also Furst: Dioxins, polychlorinated biphenyls and other organohalogen compounds in human milk, Mol Nutr Food Res, 2006 A publication of the National Academies Press, from the Institute of Medicine, refers to a woman’s “body burden” of dioxins, which is reduced during breastfeeding. (Case Study 13: Dioxin Toxicity." Institute of Medicine. 1995. Environmental Medicine: Integrating a Missing Element into Medical Education. Washington, DC: The National Academies Press. doi: 10.17226/4795, at https://www.nap.edu/read/4795/chapter/25#337. “nursing females decrease their body burden of TCDD through lactation.”) Documents of the European Commission state, "Toxicity of dioxins is related to the amount accumulated in the body during lifetime." (Fact Sheet on dioxin in feed and food, European Commission, 2001, at
https://ec.europa.eu/commission/presscorner/detail/en/MEMO_01_270) and "the average concentration (of dioxins in the body) increases progressively from year to year. " (Compilation of EU Dioxin Exposure and Health Data, Report produced for the European Commission, 1999, In Executive Summary of Task 5 (4/5-way down from top), at https://ec.europa.eu/environment/archives/dioxin/pdf/dioxin.pdf) (Also See Appendix L about this process.) And, according to the ATSDR, "lactation provides an efficient mechanism for decreasing the body burden of these compounds," since lipophilic compounds (such as dioxins) concentrate in maternal milk. (Toxicological profile for chlorinated dibenzo-p-dioxins, ATSDR, U.S. Dept. of Health and Human Services, 1998, Section 188.8.131.52, at https://www.atsdr.cdc.gov/toxprofiles/tp104.pdf)
Appendix Q: Other reasons to be skeptical about findings of studies in a matter, such as breastfeeding, about which strong opinions are widely held: According to U.K. authorities on scientific research, in addition to the biases that affect observational studies as referred to in Section 1.a, other common kinds of bias (which could favor breastfeeding) include "cherry-picking of findings that support a researcher's own position," publication bias, and pressure to attract funding and to publish regularly, for career progression.7g There are strong pro-breastfeeding biases in organizations whose senior members are likely to influence awarding of research grants as well as selecting which articles to publish, which would be quite apparent to researchers who are seeking funding and trying to publish; these biases are indicated by
-- public statements on breastfeeding by the medical establishment that distort the truth as part of an effort to promote breastfeeding (see Appendix S just ahead), and
-- pro-breastfeeding statements by the U.S. CDC in support of which no evidence is offered despite good reasons to believe that they are not true. (See Appendix R below)
Appendix R: Very misleading statement by the U.S. CDC on toxins in breast milk:
A web page of the CDC states, "While some women may have detectable levels of chemical agents in their breast milk, no established “normal” or “abnormal” levels exist to aid in clinical interpretation." (CDC web page at
https://www.cdc.gov/breastfeeding/breastfeeding-special-circumstances/environmental-exposures/index.html ) The reader is invited to review the chart below from a high-quality scientific study, and the text below it, and possibly also the large amount of authoritative information about toxins in human milk in studies cited at reference no.10, and then count the several different ways in which the above CDC statement is basically incompatible with evidence.
Fig. 1.a reviewed
Dioxins and PCBs in human milk
For original source of the above, go to van den Berg et al., WHO/UNEP Global Surveys of PCDDs, PCDFs and DDTs in human milk and benefit-risk evaluation of breastfeeding, at https://www.ncbi.nlm.nih.gov/pubmed/27438348
There is considerable other evidence that supports the findings indicated in these charts (see Appendix A). Also note that the toxicity standards that were in effect during the 2000-2010 surveys, results of which are shown above, have been subsequently replaced by much stricter standards (see Appendix C); so the updated exceedances of established safe intakes of these toxins, according to the best currently-available evidence and research methods, are many times the already major exceedances shown in the charts above. There is also substantial other evidence, from the U.S. and other developed countries, indicating that exposures of breastfed infants to both PCBs and dioxins during the 2000's have exceeded established safe levels by scores to hundreds of times.10
The CDC also states, "To date, effects on the nursing infant have been seen only where the mother herself was clinically ill from a toxic exposure." The phrase, "have been seen only where…," in order to deserve respect, should only be made after a thorough consideration of long-term effects, some evidence of which consideration ought to be given; but none is provided by the CDC. The reader is invited to review Sections 3 to 6 (earlier in this article) and to see what has actually occurred in important disease prevalences while breastfeeding has increased. Then, on the (fairly safe) assumption that long-term effects were not adequately investigated, consider whether the above CDC statement constitutes anything other than promotion of an opinion in the absence of actual evidence.
Appendix S: Additional indications of low quality in typical studies such as those dealing with breastfeeding, and nonrational bias in the medical establishment:
Contents of Section 1 are only part of the reason why the many studies cited by medical associations as evidence for beneficial effects of breastfeeding merit only minimal credibility. A respected physician and scientist, John P.A. Ioannidis, Professor of Medicine at Stanford University and member of the U.S. National Academy of Medicine,64a authored an article entitled, "Why Most Published Research Findings Are False," in which he states that "claimed research findings may often be simply accurate measures of the prevailing bias;" he provides considerable evidence for that conclusion.64b There can be little doubt about the prevalence of fundamental, nonrational bias among key medical associations on the subject of breastfeeding when, for instance, the American Academy of Pediatrics, in its policy statement on breastfeeding, does not mention the word "toxin" even once;60f that is despite the very large amount of authoritative evidence indicating considerable toxins in human milk in concentrations far exceeding established safe levels;60m much less does the AAP mention any of the numerous studies that have found adverse effects of breastfeeding.60g Deep-seated bias is also apparent when the American Academy of Family Physicians makes the false statement (in its position statement on breastfeeding) as follows: "By using formula, they (mothers) do not reduce exposure to environmental toxins;" 60h the AAFP makes no attempt to support that statement with evidence either together with the statement or when challenged on it. (Section 8.d)
The reader is also encouraged to
-- review all of the many diseases and disorders among children and young adults that have been greatly increasing since the 1970's (Sections 5 and later) and also
-- remember the major increases in breastfeeding that have occurred since the late 1960's (Figure 8), and then
-- reflect on the fact that the medical establishment publicly states that almost all of those diseases and disorders are reduced by breastfeeding.60k
It should be apparent from the above (including the preceding Appendix R) that bias in favor of breastfeeding, intense enough to lead to suppression of contrary views and facts where they are able to do so, is pervasive in the medical establishment and in the U.S. government's health establishment.
1) The Surgeon General's Call to Action to Support Breastfeeding 2011, p. 33, at www.surgeongeneral.gov/library/calls/breastfeeding/calltoactiontosupportbreastfeeding.pdf
Also Patel et al., Cohort Profile: The Promotion of Breastfeeding Intervention Trial (PROBIT), Int J Epidemiol. 2014 Jun; at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052126
1a) Martin et al., Effects of Promoting Longer-Term and Exclusive Breastfeeding on Cardiometabolic Risk Factors at Age 11.5 Years, A Cluster-Randomized, Controlled Trial, Circulation (journal), at https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.113.005160
1b) Owen et al., Effect of breast feeding in infancy on blood pressure in later life: systematic review and meta-analysis. BMJ. 2003
1c) Children with autism at significant risk for feeding problems and nutritional deficits, Woodruff Health Sciences Center | Feb. 4, 2013 at http://www.news.emory.edu/stories/2013/02/autism_nutritional_deficits/
Lucas et al., Dysregulated Breastfeeding Behaviors in Children Later Diagnosed With Autism, J Perinat Educ. 2015; 24(3): 171–180 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720870/
Also see Section 6.c, "Early weaning in relation to autism" at http://www.pollution-effects.info/.
2) Gary Taubes, Do We Really Know What Makes Us Healthy? The New York Times Magazine, Sept. 16, 2007, at http://www.nytimes.com/2007/09/16/magazine/16epidemiology-t.html?_r=0
3) Lawlor et al, Commentary: The hormone replacement-coronary heart disease conundrum: is this the death of observational epidemiology? International Journal of Epidemiology, v. 33, Issue 3, June 2004, Oxford University Press, at https://academic.oup.com/ije/article/33/3/464/716652
3a) Maki et al., Limitations of Observational Evidence: Implications for Evidence-Based Dietary Recommendations, Advances in Nutrition, 2014, at https://academic.oup.com/advances/article/5/1/7/4558018 In the section, "Implications for Evidence-Based Reviews…", the authors refer to "the frequency with which results from RCTs have failed to confirm hypotheses suggested by observational evidence…."
3b) Huded et al., When Research Evidence is Misleading, AMA Journal of Ethics, 2013, at https://journalofethics.ama-assn.org/article/when-research-evidence-misleading/2013-01
3c) Institute of Medicine: "Standards for Finding and Assessing Individual Studies," Chapter 3, pp. 134-5, in Finding What Works in Health Care: Standards for Systematic Reviews. 2011. Washington, DC: The National Academies Press. At https://www.nap.edu/read/13059/chapter/5#134
3d) Perez et al., A comprehensive review of randomized clinical trials in three medical journals reveals 396 medical reversals, eLife, 2019, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559784/
3e) Haslam et al., Medical Reversals in Family Practice: A Review, Curr Ther Res Clin Exp, 2020, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063107/
3f) Prasad et al., A Decade of Reversal: An Analysis of 146 Contradicted Medical Practices, Mayo Clinic Proceedings, 2013, at https://www.mayoclinicproceedings.org/article/S0025-6196(13)00405-9/fulltext
3g) Solo-Rivera and Agos, Tight Glycemic Control in the Pediatric Intensive Care Unit, J Pediatr Intensive Care. 2016, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512400/
4) The Surgeon General's Call to Action to Support Breastfeeding 2011, Table 2, at www.surgeongeneral.gov/library/calls/breastfeeding/calltoactiontosupportbreastfeeding.pdf
5) Simpson et al., A meta-analysis of the association between adherence to drug therapy and mortality, BMJ 2006; 333 doi: at http://www.bmj.com/content/333/7557/15
6) Gary Taubes, Do We Really Know What Makes Us Healthy? The New York Times Magazine, Sept. 16, 2007, at http://www.nytimes.com/2007/09/16/magazine/16epidemiology-t.html?_r=0
Also see O'Neil and 7 others, Observational evidence and strength of evidence domains: case examples, Biomed Central: Systematic Reviews, at https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/2046-4053-3-35
7) This can be verified by going to the websites of the AAP (American Academy of Pediatrics at 60f), AAFP (American Academy of Family Physicians 60h) and ACOG (American Congress of Obstetricians and Gynecologists) and seeing their breastfeeding position papers.
7a) Sperm Counts Continue to Fall, Ashley Fetters, The Atlantic, Oct. 12, 2018, athttps://www.theatlantic.com/family/archive/2018/10/sperm-counts-continue-to-fall/572794/
7b) ATSDR Toxic Substances Portal: Addendum to the Profile, 1998: Toxicological Profile for Chlorinated Dibenzo-p-dioxins (CDDs), pp. 378 ff, at https://www.atsdr.cdc.gov/ToxProfiles/tp.asp?id=366&tid=63
Also ATSDR: Toxicological Profile for Chlorinated Dibenzo-P-Dioxins, at https://www.atsdr.cdc.gov/toxprofiles/tp104.pdf, p. 2
Also see Section 2.a in http://www.pollutionaction.org/shorter-lives.htm.
7d) "Methodological Issues" section in Zahm and Ward, Pesticides and Childhood Cancer, Envir Health Perspect, 1998, at https://www.ncbi.nlm.nih.gov/pubmed/9646054
7e) Duncan and Sears, Breastfeeding and allergies: time for a change in paradigm? Genetics and epidemiology, 2008, at https://journals.lww.com/co-allergy/Abstract/2008/10000/Breastfeeding_and_allergies__time_for_a_change_in.7.aspx
7f) CDC: History of the Surgeon General's Reports on Smoking and Health, at https://www.cdc.gov/tobacco/data_statistics/sgr/history/index.htm
7g) Reproducibility and reliability of biomedical research: Improving research practice, Symposium report, Oct. 2015, The Academy of Medical Sciences (UK) and Medical Research Council, at https://acmedsci.ac.uk/policy/policy-projects/reproducibility-and-reliability-of-biomedical-research
7h) Freedman: Lies, Damned Lies, and Medical Science, The Atlantic, Nov. 2010, at https://www.theatlantic.com/magazine/archive/2010/11/lies-damned-lies-and-medical-science/308269/
8) MacIntosh et al., Mitigation of building-related polychlorinated biphenyls in indoor air of a school, Environ Health. 2012; 11: 24, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3353159/
European Commission: Science for Environment Policy: Building materials used between 1950 and 1980 in Europe may contribute to PCB air pollution, 15 Apr. 2016, at http://ec.europa.eu/environment/integration/research/newsalert/pdf/building_materials_used_1950_1980_in_europe_may_contribute_to_pcb_air_pollution_453na2_en.pdf
8a) 2,3,7,8-Tetrachlorodibenzo-P-dioxin, U.S. National Library of Medicine, at https://pubchem.ncbi.nlm.nih.gov/compound/15625#section=Use-and-Manufacturing
8b) Sidlova et al., Dioxin-Like and Endocrine Disruptive Activity of Traffic-Contaminated Soil Samples, Archives of Environmental Contamination and Toxicology, 200, at https://link.springer.com/article/10.1007%2Fs00244-009-9345-4
9) EPA: An Inventory of Sources and Environmental Releases of Dioxin-Like Compounds in the United States for the Years 1987, 1995, and 2000, EPA/600/P-03/002F November 2006, Table 1-12, at https://cfpub.epa.gov/ncea/dioxin/recordisplay.cfm?deid=159286 ; under Downloads, choose to download the Dioxin Inventory of Sources (Optimized Report).
At the EPA "An Inventory of Sources...." listed above, see p. xliv and Section 6.5, "Backyard Barrel Burning."
Tox Town: Polyvinyl Chloride (PVC), at https://toxtown.nlm.nih.gov/text_version/chemicals.php?id=84
New York Times: In Rural Areas, the Heat Is on Over Practice of Trash Burning, By Lisa W. Foderaro, MARCH 7, 2005 , at https://www.nytimes.com/2005/03/07/nyregion/in-rural-areas-the-heat-is-on-over-practice-of-trash-burning.html?pagewanted=all
9a) P Grandjean and AA Jensen, Breastfeeding and the Weanling's Dilemma Am J Public Health. 2004 July; 94(7): 1075. PMCID: PMC1448391 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1448391/
9b)Thomas and Spiro, An estimation of dioxin emissions in the United States, Toxicological and Environmental Chemistry, 1995, at https://www.tandfonline.com/doi/abs/10.1080/02772249509358202
9c) Freinkel: A Brief History of Plastic's Conquest of the World, Scientific American, at https://www.scientificamerican.com/article/a-brief-history-of-plastic-world-conquest/
9d) Dopico and Gomez, Review of the current state and main sources of dioxins around the world, Journal of the Air & Waste Management Assn., 2015, at https://www.tandfonline.com/doi/full/10.1080/10962247.2015.1058869?src=recsy
10) Re: EPA's RfD for dioxin: At www.epa.gov/iris/supdocs/dioxinv1sup.pdf in Section 4.3.5, at end of that section, "...the resulting RfD in standard units is 7 10−10 mg/kg-day." (that is, O.7 pg of TEQ/kg-d)
Re: breastfed infants' exposures to dioxins, in U.S. and internationally:
- Arisawa et al., Background exposure to PCDDs/PCDFs/PCBs and its potential health effects : a review of epidemiologic studies, The Journal of Medical Investigation Vol. 52 2005, at https://www.jstage.jst.go.jp/article/jmi/52/1%2C2/52_1%2C2_10/_pdf
- Lorber et al., Infant Exposure to Dioxin-like Compounds in Breast Milk, Vol. 110 No. 6, June 2002, Environmental Health Perspectives at http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=54708#Download, indicating 242 pg of TEQ/kg-d at initiation of breastfeeding.
Also see Patandin et al. in ref 84c for other U.S. information.
- Focant et al., Levels of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls in human milk from different regions of France, Science of The Total Environment, Volumes 452-453, 1 May 2013, Pages 155-162 abstract at http://www.sciencedirect.com/science/article/pii/S0048969713002404
- Yang J, et al., PCDDs, PCDFs, and PCBs concentrations in breast milk from two areas in Korea: body burden of mothers and implications for feeding infants. Chemosphere. 2002 Jan;46(3):419-28. At www.ncbi.nlm.nih.gov/pubmed/11829398
- Bencko V et al., Exposure of breast-fed children in the Czech Republic to PCDDs, PCDFs, and dioxin-like PCBs. Environ Toxicol Pharmacol. 2004 Nov;18(2):83-90. Abstract at http://www.ncbi.nlm.nih.gov/pubmed/21782737/
- Nakatani T, et al., Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in human milk in Osaka City, Japan Arch Environ Contam Toxicol. 2005 Jul;49(1):131-40. Epub 2005 Jun 22. Found at http://www.ncbi.nlm.nih.gov/pubmed/15983863
- Deng B, et al., Levels and profiles of PCDD/Fs, PCBs in mothers' milk in Shenzhen of China: estimation of breast-fed infants' intakes.Environ Int. 2012 Jul;42:47-52.. At www.ncbi.nlm.nih.gov/pubmed/21531025
- Chovancov J, et al., PCDD, PCDF, PCB and PBDE concentrations in breast milk of mothers residing in selected areas of Slovakia Chemosphere. 2011 May;83(10):1383-90. doi: 10.1016/j. At www.ncbi.nlm.nih.gov/pubmed/21474162
- J Grigg, Environmental toxins; their impact on children's health, Arch Dis Child 2004;89:244-250 doi:10.1136/adc.2002.022202 at http://adc.bmj.com/content/89/3/244.full
-- Oregon Department of Environmental Quality Environmental Cleanup Program, Oct. 2010, 10-LQ-023, p. D2-4 (near very end) at http://www.deq.state.or.us/lq/pubs/docs/cu/HumanHealthRiskAssessmentGuidance.pdf The doses of PCBs that a breastfeeding infant may be expected to receive, given breast milk PCB concentrations measured in the literature, are presented in table 1. These doses range from 0.0019 to 0.0081 mg/kg/day and are 63-270 times higher than ATSDR's minimal risk level (0.00003 mg/kg/day) for PCB exposures that last between 15 and 364 days.
12) EPA: HEALTH CONSEQUENCES OF DIOXIN EXPOSURE, at https://cfpub.epa.gov/si/si_public_record_Report.cfm?Lab=NHEERL&dirEntryId=171623
12a) Jens Walkowiak et al., Environmental exposure to polychlorinated biphenyls and quality of the home environment: effects on psychodevelopment in early childhood. Lancet 2001: 358: 1602-07 Abstract at https://www.sciencedirect.com/science/article/pii/S0140673601066545
12b) IARC Monographs Volume 107: Polychlorinated Biphenyls and Polybrominated Biphenyls at https://www.iarc.fr/news-events/iarc-monographs-volume-107-polychlorinated-biphenyls-and-polybrominated-biphenyls/
Also IARC web page on dioxin at https://monographs.iarc.fr/wp-content/uploads/2018/06/mono100F-27.pdf
13) Winneke, Developmental aspects of environmental neurotoxicology: lessons from lead and polychlorinated biphenyls, J Neurol Sci. 2011 Sep 15; Epub 2011 Jun 15. at http://www.ncbi.nlm.nih.gov/pubmed/21679971
14) Pessah et al., Neurotoxicity of polychlorinated biphenyls and related organohalogens, Acta Neuropathologica, 2019 (Review article) (p. 376, 370 and conclusion)
14a) Seelbach et al., Polychlorinated Biphenyls Disrupt Blood–Brain Barrier Integrity and Promote Brain Metastasis Formation, Environ Health Perspect. 2010 Apr; 118(4): 479–484. Published online 2009 Oct 28. At https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854723/
14d) Miyazaki et al., The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the development and function of the blood–brain barrier, Neurotoxicology, 2016, at https://pubmed.ncbi.nlm.nih.gov/26582458/
14e) Qin et al., Does physical activity modify the risk of obesity for type 2 diabetes: a review of epidemiological data, Eur J Epidemiol, 2010, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807936/
14f) Of the first 10 studies provided in the American Academy of Pediatrics' Policy Statement on Breastfeeding to indicate better outcomes for breastfed children, all 10 measured the outcomes in infancy or early childhood. American Academy of Pediatrics, Policy Statement, Breastfeeding and the Use of Human Milk, at https://pediatrics.aappublications.org/content/129/3/e827, as accessed May 4, 2020. Starting with footnote number 13.
15) Grandjean et al., The Faroes Statement: Human Health Effects of Developmental Exposure to Chemicals in Our Environment, Basic and Clinical Pharmacology and Toxicology, Volume 102, Issue 2, February 2008 at http://onlinelibrary.wiley.com/doi/10.1111/j.1742-7843.2007.00114.x/full
15a) Committee on Developmental Toxicology, Board on Environmental Studies and Toxicology, in Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000) , Commission on Life Sciences, The National Academies Press, p. 56
15b) Early Experiences Can Alter Gene Expression and Affect Long-Term Development, Working Paper 10 of The National Scientific Council on the Developing Child, Center on the Developing Child at Harvard University, 2010, at https://developingchild.harvard.edu/wp-content/uploads/2010/05/Early-Experiences-Can-Alter-Gene-Expression-and-Affect-Long-Term-Development.pdf
16) Endocrine disrupters and child health, Possible developmental early effects of endocrine disrupters on child health, at https://apps.who.int/iris/bitstream/handle/10665/75342/9789241503761_eng.pdf;jsessionid=6C174B18182AABB475365AA1BC52E5AF?sequence=1 p. 51
WHO: Endocrine disrupters and child health, Possible developmental early effects of endocrine disrupters on child health, p. 17, at https://apps.who.int/iris/bitstream/handle/10665/75342/9789241503761_eng.pdf;jsessionid=6C174B18182AABB475365AA1BC52E5AF?sequence=1
ATSDR: Toxicological Profile for Chlorinated Dibenzo-P-Dioxins, at https://www.atsdr.cdc.gov/toxprofiles/tp104.pdf, p. 279
17a) Nagayama et al., Postnatal exposure to chlorinated dioxins and related chemicals on thyroid hormone status in Japanese breast-fed infants, Chemosphere. 1998 Oct-Nov;37(9-12):1789-93.at http://www.ncbi.nlm.nih.gov/pubmed/9828307
18) U.S. ATSDR, Persistent chemicals found in breast milk, Appendix A, p. 180, at https://www.atsdr.cdc.gov/interactionprofiles/ip-breastmilk/ip03-a.pdf
19a) Furst: Dioxins, polychlorinated biphenyls and other organohalogen compounds in human milk, Mol Nutr Food Res, 2006
20) Pesticides in the Diets of Infants and Children, p. 60, Commission on Life Sciences, National Research Council, National Academy Press, Washington, D.C. 1993, at http://www.nap.edu/openbook.php?record_id=2126
20a) Panesar et al., Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?, Toxics, 2020, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560399/
21) Sampaio and Truwit, Myelination in the Developing Brain, in Nelson and Luciana, Eds., Handbook of Developmental Cognitive Neuroscience, MIT Press, 2001
21a) Swaab, Sexual orientation and its basis in brain structure and function, PNAS, 2008, at https://www.pnas.org/content/105/30/10273
21b) A study published in the American Journal of Public Health found that male bisexuality/ homosexuality is associated with a seven-fold increased odds of suicide attempt. Remafedi et al., The Relationship between Suicide Risk and Sexual Orientation: Results of a Population-Based Study, American Journal of Public Health, 1998, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1508407/pdf/amjph00013-0059.pdf
21c) Roselli, Neurobiology of gender identity and sexual orientation, J Neuroendocrinol, 2018, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677266/
21d) Pasterski et al., Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys, Hormones and Behavior, 2015, at https://www.sciencedirect.com/science/article/pii/S0018506X15000033?via%3Dihub
21e) Hines et al., Early androgen exposure and human gender development, Biol Sex Differ, 2015, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350266/
Lamminmaki et al., Testosterone measured in infancy predicts subsequent sex-typed behavior in boys and in girls, Hormones and Behavior, 2012, at https://www.sciencedirect.com/science/article/abs/pii/S0018506X1200044X
21f) Human Neurons Continue to Migrate After Birth, Research Finds; UCSF Study Reveals Previously Unrecognized Stage of Brain Development. By Nicholas Weiler, University of California San Francisco, 2016, at https://www.ucsf.edu/news/2016/10/404486/human-neurons-continue-migrate-after-birth-research-finds)
21g) Walker and Gore, Endocrine-Disrupting Chemicals and the Brain, From: Endocrine-Disrupting Chemicals: From Basic Research to Clinical Practice, Edited by: A. C. Gore © Humana Press Inc., at http://eknygos.lsmuni.lt/springer/631/63-109.pdf
21h) Gore, Neuroendocrine targets of endocrine disruptors, Hormones, 2010, at http://www.hormones.gr/539/article/article.html
21j) Leijs, Toxic effects of dioxins, PCBs and PBDEs in adolescents, Univ. of Amsterdam Digital Academic Repository, at https://pure.uva.nl/ws/files/1295744/74345_07.pdf
Also Rinaldi, Dioxins modulate estrogen receptor signalling and adversely affect body's responses to hormones, The Scientist.com, 2003, at https://www.the-scientist.com/research-round-up/dioxins-estrogen-connection-51586
21k) Encyclopedia Britannica at https://www.britannica.com/science/androgen
21m) In 2001, the Harvard Institute of Economic Research devoted an entire publication to the subject indicated by its title: "Explaining the Rise in Youth Suicide." (Harvard Institute of Economic Research: Explaining the Rise in Youth Suicide, 2001, Harvard University, at https://canadiancrc.com/pdfs/harvard_discussion_paper_no_1917.pdf)
Since then, suicides in the U.S. grew a total of 31%, between 2001 and 2017. (NIH web page: Suicide, Figure 1 and separate text, accessed 5/27/2019 at https://www.nimh.nih.gov/health/statistics/suicide.shtml
21n) Rice and Barone, Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models, Environ Health Perspect, 2000, at https://ehp.niehs.nih.gov/doi/abs/10.1289/ehp.00108s3511
22a) NIH website on endocrine disruptors at www.niehs.nih.gov/health/topics/agents/endocrine
23) Patel et al., Cohort Profile: The Promotion of Breastfeeding Intervention Trial (PROBIT), Int J Epidemiol. 2014 Jun; at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052126/
24) Martin et al., Effects of Promoting Longer Term and Exclusive Breastfeeding on Cardiometabolic Risk Factors at Age 11.5 Years: A Cluster-Randomized, Controlled Trial, Circulation, 2014, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946966/
24a) Kramer et al., Effect of prolonged and exclusive breast feeding on risk of allergy and asthma: cluster randomised trial, BMJ, 2007, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2034727/
25) Yang et al., Breastfeeding during infancy and neurocognitive function in adolescence: 16-year follow-up of the PROBIT cluster-randomized trial, PloS Med, 2018, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909901/
26) 6967 was the number in the intervention group who took the test (Table 1 of Yang et al., above) The original number would have been 7066, if subtracting 1.4% would leave 6967
27) Van Naarden Braun et al., Trends in the Prevalence of Autism Spectrum Disorder, Cerebral Palsy, Hearing Loss, Intellectual Disability, and Vision Impairment, Metropolitan Atlanta, 1991-2010, PLoS One. 2015; 10(4): e0124120, Published online 2015 Apr 29. doi: 10.1371/journal.pone.0124120 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414511/
28) Pardini et al., Building an Evidence Base for DSM-5 Conceptualizations of Oppositional Defiant Disorder and Conduct Disorder: Introduction to the Special Section, J Abnorm Psychol, 2013, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826598/
29) Gadow et al., Oppositional Defiant Disorder as a Clinical Phenotype in Children with Autism Spectrum Disorder, J. Autism Dev Disord, 2008, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784313/
30) Ch.7 Clinical Characteristics of Oppositional Defiant Disorder and Conduct Disorder, The National Academies Press, Mental Disorders and Disabilities Among Low-Income Children (2015), p. 153, at https://www.nap.edu/read/21780/chapter/11#152
30a) Riley et al., Common Questions About Oppositional Defiant Disorder, Am Fam Physician, 2016, at https://www.ncbi.nlm.nih.gov/pubmed/27035043
31) American Academy of Pediatrics: Pediatric Environmental Health, 3rd Edition, 2012, p. 200
32) Infant Exposure to Dioxin-like Compounds in Breast Milk Lorber and Phillips Vol. 110., No. 6 June 2002, Environmental Health Perspectives at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240886/pdf/ehp0110-a00325.pdf, 242 pg at initiation; this should be compared with data from following: U.K. Food Standards Agency Food Survey Information Sheet 49/04 Mar. 2004, Dioxins and Dioxin-Like PCBs in Infant Formulae, found at www.food.gov.uk/multimedia/pdfs/fsis4904dioxinsinfantformula.pdf
Compatible figures were found in Weijs PJ, et al., Dioxin and dioxin-like PCB exposure of non-breastfed Dutch infants, Chemosphere 2006 Aug;64(9):1521-5. Epub 2006 Jan 25 at www.ncbi.nlm.nih.gov/pubmed/16442144
32a) Boys but not girls with elevated dioxin exposure were found to have decreased communication scores. (Tai et al., Effects of Perinatal Dioxin Exposure on Development of Children during the First 3 Years of Life, J Pediatr., 2016 Aug; at https://www.ncbi.nlm.nih.gov/pubmed/27189679) Boys but not girls had significantly lower neurodevelopmental scores in relation to elevated total dioxin exposures via breastfeeding.(Nishijo et al., 2,3,7,8-Tetrachlorodibenzo-p-dioxin in breast milk increases autistic traits of 3-year-old children in Vietnam. Mol Psychiatry. 2014 Nov; at https://www.ncbi.nlm.nih.gov/pubmed/24637425)
33) WHO, Persistent Organic Pollutants: Impact on Child Health, p. 6, at http://whqlibdoc.who.int/publications/2010/9789241501101_eng.pdf
34) Collaborative on Health and the Environment's Learning and Developmental Disabilities Initiative: Scientific Consensus Statement on Environmental Agents Associated with Neurodevelopmental Disorders, 2008, at https://www.healthandenvironment.org/docs/xaruploads/LDDIStatement.pdf
35) Stein et al., In Harm's Way: Toxic Threats to Child Development, Journal of Developmental & Behavioral Pediatrics: February 2002 - Volume 23 - Issue 0 - pp S13-S22 at http://journals.lww.com/jrnldbp/Fulltext/2002/02001/In_Harm_s_Way__Toxic_Threats_to_Child_Development.4.aspx
Also see Patandin et al., Dietary Exposure to Polychlorinated Biphenyls and Dioxins from Infancy until Adulthood: A Comparison between Breast-feeding, Toddler, and Longterm Exposure, Environmental Health Perspectives * Volume 107, Number 1, January 1999, at https://repub.eur.nl/pub/8983
36) Kenet et al., Perinatal exposure to a noncoplanar polychlorinated biphenyl alters tonotopy, receptive fields, and plasticity in rat primary auditory cortex, 2007, The National Academy of Sciences of the USA, 7646-7651, PNAS, May 1, 2007, vol. 104, no. 18, at http://www.pnas.org/content/104/18/7646.full.pdf at http://www.pnas.org/content/104/18/7646.full.pdf
Re Dr. Merzenich: see http://www.brainhq.com/world-class-science/science-team/dr-michael-merzenich
37) Merzenich, What underlies the documented increase in autism incidence? Results of a new study, from On the Brain, by Dr. Michael Merzenich, 26 April 2007, at http://www.onthebrain.com/2007/04/underlies-documented-increase-autism-incidence-results-new-study
Also: Breastfeeding, Brain Development and Chemical Poisons: Neuroscientist Michael Merzenich, by Jeff Miller on May 18, 2007, at https://www.ucsf.edu/news/2007/05/3817/merzenich: "...the levels of PCBs to which the laboratory rats were exposed proportionately equal the levels now being found in the breast milk of women all over the country."
39) National Scientific Council on the Developing Child, Science Briefs: Prenatal and Infant Exposure to an Environmental Pollutant Damages Brain Architecture and Plasticity (2007). at http://www.policyarchive.org/handle/10207/20626
40) University of California at San Francisco: Breastfeeding, Brain Development and Chemical Poisons: Neuroscientist Michael Merzenich, By Jeff Miller, May 18, 2007 at https://www.ucsf.edu/news/2007/05/3817/merzenich See Appendix Y in http://www.pollution-effects.info/ for excerpts of transcript of interview with Dr. Merzenich
40a) Trasande et al., Burden of disease and costs of exposure to endocrine disrupting chemicals in the European Union: an updated analysis, Andrology, 2016 Jul, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244983/
40b) EPA web page on PBDEs at https://www.epa.gov/sites/production/files/2015-05/documents/biomonitoring-pbdes.pdf
41) Shamberger, R.J., Autism rates associated with nutrition and the WIC program, J Am Coll Nutr. 2011 Oct;30(5):348-53. Abstract at www.ncbi.nlm.nih.gov/pubmed/22081621 An image of part of the article is shown below, since it may be expensive for many readers to see the complete study; readers may be satisfied to see the chart provided below, taken from the article.)
42) EPA, The Effects of Great Lakes Contaminants on Human Health, Report to Congress, Section III, p. 12 (bottom) and again on p. 16, at http://nepis.epa.gov/Exe/ZyNET.exe/2000BSHI.txt?ZyActionD=ZyDocument&Client=EPA&Index=1995%20Thru%201999&Docs=&Query=&Time=&EndTime=&SearchMethod=1&TocRestrict=n&Toc=&TocEntry=&QField=&QFieldYear=&QFieldMonth=&QFieldDay=&UseQField=&IntQFieldOp=0&ExtQFieldOp=0&XmlQuery=&File=D%3A%5CZYFILES%5CINDEX%20DATA%5C95THRU99%5CTXT%5C00000002%5C2000BSHI.txt&User=ANONYMOUS&Password=anonymous&SortMethod=h%7C-&MaximumDocuments=1&FuzzyDegree=0&ImageQuality=r75g8/r75g8/x150y150g16/i425&Display=p%7Cf&DefSeekPage=x&SearchBack=ZyActionL&Back=ZyActionS&BackDesc=Results%20page&MaximumPages=10&ZyEntry=20
42a) Ch. 6 Risk Assessment (Overall Conclusions section) in Possible Health Effects of Exposure to Residential Electric And Magnetic Fields, 1997, U.S. National Academy of Sciences, National Academies Press, at https://www.ncbi.nlm.nih.gov/books/NBK232740/
Merriam-Webster at https://www.merriam-webster.com/dictionary/epidemiological?pronunciation&lang=en_us&dir=e&file=epidem07
43) Dodds et al., The Role of Prenatal, Obstetric and Neonatal Factors in the Development of Autism, J Autism Dev Disord (July 2011) 41:891-902 DOI 10.1007/s10803-010-1114-8, Table 6, at http://link.springer.com/article/10.1007/s10803-010-1114-8?no-access=true This article is available only by subscription or $40 payment, so the reader might be satisfied to see the screenshots of charts from the study, below:
44) Whitely et al., Trends in Developmental, Behavioral and Somatic Factors by Diagnostic Sub-group in Pervasive Developmental Disorders: A Follow-up Analysis, Table 9, Autism Insights 2009:1 3-17 at https://www.researchgate.net/publication/51018617_Trends_in_Developmental_Behavioral_and_Somatic_Factors_by_Diagnostic_Sub-group_in_Pervasive_Developmental_Disorders_A_Follow-up_Analysis . This study found that 65% of autism cases had been exclusively breastfed for at least four weeks; the authors looked at a comparison figure of 55%, but that figure was unrealistically high, since it came from a study (Pontin et al.) of breastfeeding by mothers largely from "more affluent families," who breastfeed at unusually high rates in the U.K.; but the Whitely et al. authors did not indicate that their study group was more affluent than average. For breastfeeding prevalence data that would apply to the general U.K. population, the authors of the Pontin study referred the reader to Infant Feeding 1995 (Foster et al.); examination of the data in that book reveals that a figure in the upper 20%'s would apply for the equivalent period (just after four weeks). That is also as was found in the U.K. Infant Feeding Survey - UK, 2010 Publication date: November 20, 2012, Chapter 2, Figure 2.13, at http://www.hscic.gov.uk/catalogue/PUB08694/ifs-uk-2010-chap2-inc-prev-dur.pdf
45) Breastfeeding and Autism P. G. Williams, MD, Pediatrics, University of Louisville, and L. L. Sears, PhD, presented at International Meeting for Autism Research, May 22, 2010, Philadelphia Marriot https://imfar.confex.com/imfr/2010/webprogram/Paper6362.html) This study found a 37% rate of breastfeeding at six months among children diagnosed with autism, as compared with 13% in the control group.
46) Husk et al., Breastfeeding and Autism Spectrum Disorder in the National Survey of Children's Health, Epidemiology. 2015 Jul;26(4):451-7. Table 3 and accompanying text. Abstract at http://www.ncbi.nlm.nih.gov/pubmed/25872161
Notice above the low period of breastfeeding in the early 1960's, followed by a gradual increase. Other evidence shows that breastfeeding rates were much higher in the 1950's and earlier (reference 119), and also after 1970 (Figure 8), compared with during the 1960's.
51) The Surgeon General's Call to Action to Support Breastfeeding, 2011, U.S. Department of Health and Human Services, Washington, D.C., at https://www.cdc.gov/breastfeeding/resources/calltoaction.htm
52) Martin et al., Effects of promoting longer-term and exclusive breastfeeding on adolescent adiposity, blood pressure, and longitudinal growth trajectories: evidence from the PROBIT cluster-randomized trial, JAMA Pediatr, 2017, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576545
53) Colen and Ramey, Is Breast Truly Best? Estimating the Effect of Breastfeeding on Long-term Child Wellbeing in the United States Using Sibling Comparisons, Soc.Sci.Med. 2014, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077166/
None of the regression coefficients in this study reached statistical significance, but the true effects of breastfeeding may well be worse for the child than as found in this study; the authors pointed out that, despite the usefulness of the discordant sibling method of comparison, there could still be bias in favor of the breastfed infants: "All of the scenarios we can call to mind in which siblings are differently fed favor the breastfed sibling -- for example, sibling A is born full-term and breastfed while sibling B is born preterm and bottle-fed." (A significant positive relationship has been found between pre-term birth and bottle feeding.57) So the true effects of breastfeeding could well be even worse than as found in this high-quality study.
54) Jacobson et al., Effects of Exposure to PCBs and Related Compounds on Growth and Activity in Children, Neurotoxicology and Teratology, 1990, Vol. 12, pp. 319-326, at http://ac.els-cdn.com/089203629090050M/1-s2.0-089203629090050M-main.pdf?_tid=5f238b74-1d4f-11e7-8a29-00000aacb35d&acdnat=1491761419_84450b69c691bfdc5ffd9534957f7940
55) Kostyniak et al., Relation of Lake Ontario Fish Consumption, Lifetime Lactation, and Parity to Breast Milk Polychlorobiphenyl and Pesticide Concentrations, Environmental Research, 1999, at http://www.sciencedirect.com/science/article/pii/S0013935198939391. Great Lakes fish-eaters have been found to have PCB levels about 35% higher than non-fish-eaters for some of the various forms of PCBs.
56) Koja et al., Changes of gross behavior
with polychlorinated biphenyls (PCB) in
immature rats [in Japanese]. Kagoshima
Daigaka Igaka Zasshi. 1978 Cited in Tilson et al. (below)
Koja et al., Effects of polychlorinated
biphenyls (PCB) on the gross
behavior of immature rats and the influence
of drugs upon them [in Japanese].
Kagoshima Daigaka Igaka Zasshi 1979;31:
315-319. Cited in Tilson et al. (below)
Tilson HA et al., Polychlorinated biphenyls and the developing nervous system: cross-species comparisons.
Neurotoxicol Teratol. 1990; at https://pubmed.ncbi.nlm.nih.gov/2115098/
Also Johansen et al., Postnatal exposure to PCB 153 and PCB 180, but not to PCB 52, produces changes in activity level and stimulus control in outbred male Wistar Kyoto rats, Behavioral and Brain Functions, BioMed Central Ltd. 2011, at https://behavioralandbrainfunctions.biomedcentral.com/articles/10.1186/1744-9081-7-18 One of the experiments was by a team of researchers who said that the concentrations of the toxins found in their test animals' brains were "about the same order of magnitude as observed in infants less than 1 year old."
56a) Bieber, "Atopic dermatitis" N Engl J Med. 2008 Apr 3; 358(14):1483-94, at
Also see article in USA Today, posted 8/7/2005, "Allergy sensitivity doubles since 1970s" found at https://www.peanutallergy.com/boards/allergy-sensitivity-doubles-since-1970s
Also see Management of Atopic Dermatitis in the Pediatric Population Andrew C. Krakowski, MD et al., Found at http://pediatrics.aappublications.org/content/122/4/812.long
56b) Feed Your Kids Peanuts, Early and Often, NY Times, Jan. 5, 2017, at https://www.nytimes.com/2017/01/05/well/eat/feed-your-kids-peanuts-early-and-often-new-guidelines-urge.html
56c) Martin et al., Effects of Promoting Longer-Term and Exclusive Breastfeeding on Cardiometabolic Risk Factors at Age 11.5 Years, A Cluster-Randomized, Controlled Trial, Circulation, at https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.113.005160
56d) Dewey et al., Effects of Exclusive Breastfeeding for Four versus Six Months on Maternal Nutritional Status and Infant Motor Development: Results of Two Randomized Trials in Honduras, The Journal of Nutrition, 2001, at https://academic.oup.com/jn/article/131/2/262/4687018
56e) Singhal, Early nutrition in preterm infants and later blood pressure: two cohorts after randomised trials, The Lancet, 2001, at https://www.sciencedirect.com/science/article/pii/S0140673600040046
56f) Lewandowski et al., Breast Milk Consumption in Preterm Neonates and Cardiac Shape in Adulthood, Pediatrics, 2016
56g) Low blood pressure (hypotension), web page of Mayo Clinic at https://www.mayoclinic.org/diseases-conditions/low-blood-pressure/symptoms-causes/syc-20355465
56h) Healthline.com web page on mean arterial pressure at https://www.healthline.com/health/mean-arterial-pressure#high-map
56j) Healthline web page on low blood pressure at https://www.healthline.com/health/hypotension#symptoms
56k) American Heart Assn. web page on low blood pressure at https://www.heart.org/en/health-topics/high-blood-pressure/the-facts-about-high-blood-pressure/low-blood-pressure-when-blood-pressure-is-too-low
56m) Depression, the Thyroid, and Hormones (page of WebMD) at https://www.webmd.com/depression/guide/depression-the-thyroid-and-hormones#1
Also see Endocrine (hormone) disruption in Section 2.e of http://www.pollutionaction.org/suicide-increase.htm.
56n) Gupta et al., Prevalence and Severity of Food Allergies Among US Adults, JAMA Network Open, 2019, at https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2720064
56o) Adult-Onset Food Allergies Increasing, Confusing, WebMD Health News, at https://www.webmd.com/allergies/news/20190111/adult-onset-food-allergies-increasing-confusing
56p) Jenni et al., Infant motor milestones: poor predictive value for outcome of healthy children, Acta Pediatrica, 2012, at https://onlinelibrary.wiley.com/doi/full/10.1111/apa.12129
56q) RC Rabin, Feed Your Kids Peanuts, Early and Often, New Guidelines Urge, The New York Times, Jan. 5, 2017, at https://www.nytimes.com/2017/01/05/well/eat/feed-your-kids-peanuts-early-and-often-new-guidelines-urge.html
56r) Perkin et al., Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants, NEJM. 2017, at https://www.nejm.org/doi/full/10.1056/NEJMoa1514210
56s) American Heart Association, "Why Metabolic Syndrome Matters", at https://www.heart.org/en/health-topics/metabolic-syndrome/why-metabolic-syndrome-matters
56t) Mosca et al., Sex/Gender Differences in Cardiovascular Disease Prevention What a Difference a Decade Makes, Circulation, 2012, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362050/
56u) Perkins et al., Polychlorinated Biphenyls and links to Cardiovascular Disease, Environ Sci Pollut Res Int, 2016, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609220/#:~:text=Chlorinated%20organic%20pollutants%2C%20such%20as,factors%20for%20developing%20cardiovascular%20disease.
57) Chiang et al., Receipt of Breast Milk by Gestational Age - United States, 2017, MMWR Morb Mortal Wkly Rep. 2019 Jun, at https://www.ncbi.nlm.nih.gov/pubmed/31170123?deliveryName=USCDC_1296-DM10201
58) Type 2 Diabetes in Children and Young Adults: A "New Epidemic" Francine Ratner Kaufman, MD CLINICAL DIABETES Volume 20, Number 4, 2002 at http://clinical.diabetesjournals.org/content/20/4/217.full.pdf+html
Also see Trends in Hospitalizations for Diabetes Among Children and Young Adults United States, 1993-2004 JOYCE M. LEE et al., at http://care.diabetesjournals.org/content/30/12/3035.full.pdf+html
Also, a Univ. of Michigan article published in 2008 reported, "Recent studies suggest that there have been dramatic increases in type 2 diabetes among individuals in their 20s and 30s...." (at http://www2.med.umich.edu/prmc/media/newsroom/details.cfm?ID=422), which is compatible with origins of the epidemic in infant development beginning in the 1970's.
58a) Ruiz et al., Disparities in Environmental Exposures to Endocrine-Disrupting Chemicals and Diabetes Risk in Vulnerable Populations, Diabetes Care, 2018, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741159/
59) Lanphear, The Impact of Toxins on the Developing Brain, Annu. Rev. Public Health 2015., at https://www.annualreviews.org/doi/pdf/10.1146/annurev-publhealth-031912-114413
60) Pastor et al., Diagnosed attention deficit hyperactivity disorder and learning disability: United States 2004-2006, National Center for Health Statistics, 2008, at http://www.cdc.gov/nchs/data/series/sr_10/Sr10_237.pdf
60a) Merckle and Octobre, Do Survey Respondents Lie? Inconsistent Responses and the Biographical Illusion in a Longitudinal Survey on Adolescents’ Leisure Outings, Revue Francaise de Sociologie, 2015 (both authors affiliated with French universities), at https://www.cairn-int.info/article-E_RFS_563_0561--do-survey-respondents-lie.htm
60b) Greiner, Exclusive breastfeeding: measurement and indicators, International Breastfeeding Journal, 2014, at https://internationalbreastfeedingjournal.biomedcentral.com/articles/10.1186/1746-4358-9-18
60c) Nederhof, Methods of coping with social desirability bias: A review, European Journal of Social Psychology, 1985, at https://onlinelibrary.wiley.com/doi/abs/10.1002/ejsp.2420150303
60d) van de Mortel, Faking it: social desirability response bias in self report research, Australian journal of advanced nursing, Vol. 26, No. 4, at http://ajan.com.au/Vol25/Vol_25-4_vandeMortel.pdf
Also see Bland et al., Maternal recall of exclusive breast feeding duration, Arch Dis Child, 2003, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1719625
Also Agampodi et al., Duration of exclusive breastfeeding; validity of retrospective assessment at nine months of age, BMC Pediatrics, 2011, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189116/
60f) Breastfeeding and the Use of Human Milk, AAP Section on Breastfeeding, Pediatrics, 2012, at https://pediatrics.aappublications.org/content/129/3/e827.full#content-block
60h) American Academy of Family Physicians: Breastfeeding (Policy Statement) at http://www.aafp.org/about/policies/all/breastfeeding.html
60j) Nduati et al., Effects of Breastfeeding and Formula Feeding on Transmission of HIV-1: A Randomized Clinical Trial, JAMA Network, 2000, at https://jamanetwork.com/journals/jama/fullarticle/192449
61) Steenland et al., Dioxin Revisited: Developments Since the 1997 IARC Classification of Dioxin as a Human Carcinogen, Environ Health Perspect, 2004, at https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.7219
62) Hooiveld et al., Second Follow-up of a Dutch Cohort Occupationally Exposed to Phenoxy Herbicides, Chlorophenols, and Contaminants, American Journal of Epidemiology, 1998, Table 7, at https://academic.oup.com/aje/article/147/9/891/68169
63) Steenland et al., Revisited: Developments since the 1997 IARC Classification of Dioxin as a human carcinogen. Environ. Health Perspect. 2004;112:1265–1268. doi: 10.1289/ehp.7219. [PMC free article]
64) SEER 9 areas and US Mortality Files (National Center for Health Statistics, CDC), at https://seer.cancer.gov/csr/1975_2016/browse_csr.php
64b) Ioannidis, Why Most Published Research Findings Are False, PloS Med, 2005, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182327/
64c) Cancer.gov web page at https://seer.cancer.gov/statfacts/html/common.html
64d) Institute of Medicine (US) and National Research Council (US)::Childhood Cancer Survivorship: Improving Care and Quality of Life, 2 The Epidemiology of Childhood Cancer, National Academies Press, 2003, at https://www.ncbi.nlm.nih.gov/books/NBK221740/
65) Morokuma et al., The Vernix Caseosa is the Main Site of Dioxin Excretion in the Human Foetus, Scientific Reports, 2017, at https://www.nature.com/articles/s41598-017-00863-9
Also Figure 3 of Suzuki et al., Distribution of PCDDs/PCDFs and Co=PCBs in Human Maternal Blood, Cord Blood, Placenta, Milk and Adipose Tissue, Biosci. Biotechnol. Biochem., 2005
66)ATSDR, U.S. Dept. of Health and Human Services, 1998, p. 206, at https://www.atsdr.cdc.gov/toxprofiles/tp104.pdf
67) Toxicological Profile for Chlorinated Dibenzo-P-Dioxins, ATSDR, U.S. Dept. of Health and Human Services, 1998, Section 184.108.40.206, at https://www.atsdr.cdc.gov/toxprofiles/tp104.pdf
68) World Trade Center Health Program: Minimum Latency & Types or Categories of Cancer, p.9, at https://www.cdc.gov/wtc/pdfs/policies/WTCHP-Minimum-Cancer-Latency-PP-01062015-508.pdf (The reader may need to access the above via the page at https://www.cdc.gov/wtc/policies.html and the topic beginning "Minimum Latency and Types…"}
Also (for 1-year minimum latency figure) Childhood Cancer Survivorship: Improving Care and Quality of Life, National Academies Press, at https://www.ncbi.nlm.nih.gov/books/NBK221740/
69) Eguchi et al., MLL Chimeric Protein Activation Renders Cells Vulnerable to Chromosomal Damage: An Explanation for the Very Short Latency of Infant Leukemia, Genes, Chromosomes and Cancer, 2006, at https://onlinelibrary.wiley.com/doi/pdf/10.1002/gcc.20338
70) M. Greaves: Molecular Genetics, Natural History and the Demise of Childhood Leukemia (section headed "Post-natal genetic events"), European Journal of Cancer, 1999, at https://www.ejcancer.com/article/S0959-8049(98)00433-X/fulltext
70a) Eldridge and Paul, Overview of cancer latency periods, Verywell Health, at https://www.verywellhealth.com/what-is-cancer-latency-period-4057124
70b) WHO: Principles for evaluating health risks in children associated with exposure to chemicals, Environmental Health Criteria 237, at http://www.inchem.org/documents/ehc/ehc/ehc237.pdf , pp. 3, 120
71) The Surgeon General's Call to Action to Support Breastfeeding 2011, p. 8, at www.surgeongeneral.gov/library/calls/breastfeeding/calltoactiontosupportbreastfeeding.pdf
72) Steliarova-Boucher et al., Geographical patterns and time trends of cancer incidence and survival among children and adolescents in Europe since the 1970s (the ACCIS project): an epidemiological study, The Lancet, 2004, at https://www.sciencedirect.com/science/article/pii/S0140673604175508
Also Kaatsch, Epidemiology of childhood cancer, Cancer Treatment Reviews, 2010, at https://www.cancertreatmentreviews.com/article/S0305-7372(10)00023-X/fulltext
73) Steliarova-Foucher et al., Time trends of cancer incidence in European children (1978–1997): Report from the Automated Childhood Cancer Information System project, EJC, 2006, at https://www.sciencedirect.com/science/article/abs/pii/S0959804906004709
73a) Stellarova-Foucher et al., International incidence of childhood cancer, 2001–10: a population-based registry study, The Lancet Oncology, 2017, at https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17
74) Schmidt et al., Incidence of Childhood Central Nervous System Tumors in the Nordic Countries, Pediatr Blood Cancer 2011;56:65–69, at https://onlinelibrary.wiley.com/doi/abs/10.1002/pbc.22585
75) Hjalgrim et al., Age- and Sex-Specific Incidence of Childhood Leukemia by Immunophenotype in the Nordic Countries, JNCI: Journal of the National Cancer Institute, 2003, at https://academic.oup.com/jnci/article/95/20/1539/2520493
76) Shah and Coleman, Increasing incidence of childhood leukaemia: a controversy re-examined, British Journal of Cancer, 2007, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360402/
77) Crowther et al., Eds., The Resurgence of Breastfeeding, 1975–2000, The transcript of a Witness Seminar held by the Wellcome Trust Centre for the History of Medicine at UCL, London, on 24 April 2007, at https://discovery.ucl.ac.uk/id/eprint/15855/1/15855.pdf , Figure 11.
78) Johannesen et al., Trends in Incidence of Brain and Central Nervous System Tumors in Norway, 1970–1999, Neuroepidemiology, 2004, at https://www.ncbi.nlm.nih.gov/pubmed/15084778 Their study period covered the years 1970-1999, but the authors noted a "leveling off during the 1990s," so by far the largest part of the increase in tumors must have taken place during the 1970s and 1980s.
80) Hjalmars et al., Increased incidence rates but no space–time clustering of childhood astrocytoma in Sweden, 1973–1992, ACS Journals, 2000, at https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/%28SICI%291097-0142%2819990501%2985%3A9%3C2077%3A%3AAID-CNCR27%3E3.0.CO%3B2-4
81) As of 1970, only 35% of Swedish mothers had breastfed for at least two months, Berfenstam and Olsson, Early Child Care in Sweden, Taylor and Francis, p. 60; but by 1987 about 77% breastfed for three months -- see Figure 14 and also see.Yngve and Sjostrom, Breastfeeding in countries of the European Union and EFTA: current and proposed recommendations, rationale, prevalence, duration and trends, Public Health Nutrition, 2001, at http://www.ernaehrungsdenkwerkstatt.de/fileadmin/user_upload/EDWText/TextElemente/Kinder/Breastfeeding_Europe_4Sup_631_2001.pdf
82) Bunin et al., Increasing incidence of childhood cancer: report of 20 years experience from the Greater Delaware Valley Pediatric Tumor Registry, Paediatric and Perinatal Epidemiology, at https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-3016.1996.tb00054.x
83) Italian Cancer Figures - Report 2012, Cancer in children and adolescents, AIRTUM Working Group and AIEOP Working Group, Epidemiol Prev 2013; pp. 11, 12, at http://www.epiprev.it/materiali/2013/EP2013_I1S1_001.pdf
84) Isaevska et al., Cancer incidence rates and trends among children and adolescents in Piedmont, 1967–2011, PloS One, 2017, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524393/ "Incidence rates in Italy mostly increased in the 1980’s until mid 1990’s."
85) Table 1 of Colodro Conde et al., Relationship Between Level of Education and Breastfeeding Duration Depends on Social Context: Breastfeeding Trends Over a 40-Year Period in Spain, Journal of Human Lactation, 2011, at https://www.um.es/registrogemelos/pdf/breastfeeding%20trends.pdf Be sure to look in the ">6 mo" column.
86) Results section of Peris-Bonet et al., Childhood cancer incidence and survival in Spain, Ann Oncol, 2010, at https://www.researchgate.net/publication/51443337_Childhood_cancer_incidence_and_survival_in_Spain
87) Goujon et al., Spatial and temporal variations of childhood cancers: Literature review and contribution of the French national registry, Cancer Med, 2018, especially Table 4, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198217/#cam41774-sup-0001
87a) Associated Press: Public health crisis in Mexico as breastfeeding rates drop, experts claim, June 6, 2013, at https://www.foxnews.com/health/public-health-crisis-in-mexico-as-breastfeeding-rates-drop-experts-claim
88) Steliarova-Foucher et al., editors (2017). International Incidence of Childhood Cancer, Volume III (electronic version). Lyon, France: International Agency for Research on Cancer. Available from: http://iicc.iarc.fr/results/, specific page at http://iicc.iarc.fr/includes/results/comparative/00_All-neoplasms.pdf, accessed 1/20/2020
89) International Incidence of Childhood Cancer 3, International Agency for Research on Cancer (IARC/ WHO), at http://iicc.iarc.fr/results/comparative.php Click on "Main diagnostic groups," then click on "All neoplasms," then scroll down to (Europe)
89a) Steliarova-Foucher et al., editors (2017). International Incidence of Childhood Cancer, Volume III (electronic version). Lyon, France: International Agency for Research on Cancer. Available from: http://iicc.iarc.fr/results/, specific page at http://iicc.iarc.fr/includes/results/comparative/00_All-neoplasms.pdf, accessed 1/20/2020
89b) van Larebeke et al., The Belgian PCB and Dioxin Incident of January–June 1999: Exposure Data and Potential Impact on Health, Environ Health Perspec, 2001, at https://www.webpages.uidaho.edu/etox/lectures/lecture11/Belgian_Dioxin_Paper.pdf
89c) International Incidence of Childhood Cancer 3, International Agency for Research on Cancer (IARC/ WHO), at http://iicc.iarc.fr/results/comparative.php Click on "Main diagnostic groups," then click on "All neoplasms," then scroll down to (Europe)
89d) p. 257 of Waldherr (doctoral dissertation): The role of contextual factors for breastfeeding outcomes and their potential integration into related guidelines: case studies of Germany, the United Kingdom and Ghana, 2017, Technischen Universität Berlin, at https://depositonce.tu-berlin.de/bitstream/11303/7959/5/waldherr_ruth.pdf See also Dulon et al., Duration of breastfeeding and associated factors in Western and Eastern Germany, Acta Pediatr, 2001 Also the SuSe study of 1997/98
89e) International Incidence of Childhood Cancer 3, International Agency for Research on Cancer (IARC/ WHO), at http://iicc.iarc.fr/results/comparative.php Click on "Main diagnostic groups," then click on "All neoplasms," then scroll down to (Europe). The data shows 5 Western German registries (1994-2012) at 157.5 per million and 6 Eastern German registries (2001-2007) at 141.2 per million.
89f) Table 2 of Bosi et al., Breastfeeding practices and policies in WHO European Region Member States, Public Health Nutr, 2016, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754616/
89g) Steliarova-Foucher et al., editors (2017). International Incidence of Childhood Cancer, Volume III (electronic version). Lyon, France: International Agency for Research on Cancer. Available from: http://iicc.iarc.fr/results/, specific page at http://iicc.iarc.fr/includes/results/comparative/00_All-neoplasms.pdff, accessed 1/20/2020
89h) Parkin et al., Eds., International Incidence of Childhood Cancer, WHO/ International Agency for Research on Cancer, 1988, p. 275
89j) Bosi et al., Breastfeeding practices and policies in WHO European Region Member States, Public Health Nutr, 2016, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754616/
89k) International Incidence of Childhood Cancer 3, International Agency for Research on Cancer (IARC/ WHO), at http://iicc.iarc.fr/results/comparative.php Click on "Main diagnostic groups," then click on "All neoplasms," then scroll down to Europe
89l) Steliarova-Foucher et al., editors (2017). International Incidence of Childhood Cancer, Volume III (electronic version). Lyon, France: International Agency for Research on Cancer. Available from: http://iicc.iarc.fr/results/, specific page at http://iicc.iarc.fr/includes/results/comparative/00_All-neoplasms.pdf, accessed 1/20/2020
89m) Kodylkova et al., Trends in incidence of childhood cancers in the Czech Republic: population- based analysis of national registries (1994-2014). Neoplasma, 2018, at https://www.ncbi.nlm.nih.gov/pubmed/30064234
89n) WHO/European Commission: Nutrition, Physical Activity and Obesity: Croatia, at http://www.euro.who.int/__data/assets/pdf_file/0003/243291/Croatia-WHO-Country-Profile.pdf?ua=1
89o) Steliarova-Foucher et al., editors (2017). International Incidence of Childhood Cancer, Volume III (electronic version). Lyon, France: International Agency for Research on Cancer. Available from: http://iicc.iarc.fr/results/, specific page at http://iicc.iarc.fr/includes/results/comparative/00_All-neoplasms.pdff, accessed 1/20/2020
89p) Table 2 of Paapsi et al., Childhood cancer incidence and survival trends in Estonia (1970–2016): a nationwide population-based study, BMC Cancer, 2020, at https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-6510-7
89q) Lang et al., [Incidence of pediatric brain tumors in Hungary between 1989 and 1999], Orv.Hetil, 2002, at https://www.ncbi.nlm.nih.gov/pubmed/12013686
89r) Torok: Changes of the incidence and survival in pediatric malignant tumors between 1988-1997, according to the data of the Hungarian Pediatric Cancer Registry], Orv Hetil, 2001, at https://www.ncbi.nlm.nih.gov/pubmed/11433919
89s) Karim-Kos et al., Trends in incidence, survival and mortality of childhood and adolescent cancer in Austria, 1994-2011, Cancer Epidemiology, 2016, at https://www.sciencedirect.com/science/article/abs/pii/S1877782116300406?via%3Dihub Table 2a included.
89t) National cancer registry of Ukraine: Bulletin of the national cancer registry of Ukraine (English), 2013-2018, at http://www.ncru.inf.ua/publications/index.htm. Scroll down to "Cancer in Ukraine" (various years), click as appropriate; then, under Sites of tumor, scroll down to Annex A - Cancer incidence rates by site, age and gender in Ukraine, (year) and click on Link to file. Add up the eight entries for the four different age groups that comprise the 0-14 age range, for both males and females. For the years 2013-2017, respectively, the totals were 126.1, 133.6, 142.0, 135.8, and 131.4, with a five-year mean of 133.7
89u) Steliarova-Foucher et al., editors (2017). International Incidence of Childhood Cancer, Volume III (electronic version). Lyon, France: International Agency for Research on Cancer. Available from: http://iicc.iarc.fr/results/, specific page at http://iicc.iarc.fr/includes/results/comparative/00_All-neoplasms.pdf, accessed 1/20/2020
89v) Lu et al., Childhood cancer: an emerging public health issue in China, Ann Transl Med, 2015, at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620100/
89w) World Bank Country and Lending Groups, The World Bank, at https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups
89x) Blondel et al., Trends in perinatal health in metropolitan France from 1995 to 2016: Results from the French National Perinatal Surveys, Journal of Gynecology Obstetrics and Human Reproduction, 2017, at https://www.researchgate.net/publication/320382734_Trends_in_perinatal_health_in_metropolitan_France_from_1995_to_2016_Results_from_the_French_National_Perinatal_Surveys
90) Hjalgtrim et al., Age- and Sex-Specific Incidence of Childhood Leukemia by Immunophenotype in the Nordic Countries, Journal of the National Cancer Institute, 2003, at https://cceg.ki.se/documents/pubs/58.pdf
90a) Report on the Chernobyl Nuclear Power Station, NUREG-1250, U.S. Nuclear Regulatory .Commission, Washington, DC, Jan. 1987, at https://www.nrc.gov/docs/ML0716/ML071690245.pdf, p. 15 of Section 8
90b) Miller and Zanzonico: Radioiodine Fallout and Breast-Feeding, Radiation Research 164 (2005)
90c) P. 57 of OECD Nuclear Protection Agency, Chernobyl: Assessment of Radiological and Health Impacts, 2002 Update,
90d) Snihs, Contamination and Radiation Exposure, Evaluation and Measures in the Nordic Countries after the Chernobyl Accident, ISSN 0282-4434,
90e) Jaworowski, The Chernobyl Disaster and How It Has Been Understood, International Dose-Response Society 2010, ISSN 1559-3258, at http://vandyke.mynetgear.com/Chernobyl-Articles/jaworowski_chernobyl.pdf
90g) Hubbard et al., Trends in International Incidence of Pediatric Cancers in Children Under 5 Years of Age: 1988–2012, JNCI Cancer Spectrum, 2019, at https://academic.oup.com/jncics/article/3/1/pkz007/5435642
91) Smoking and Health, Report of the Advisory Committee to the Surgeon General of the Public Health Service, U.S. Dept. of Health, Education and Welfare, Public Health Service Publication No. 1103, 1964, especially pp. 146 and 165, at https://www.govinfo.gov/content/pkg/GPO-SMOKINGANDHEALTH/pdf/GPO-SMOKINGANDHEALTH.pdf
93) Scientific statement on the health-based guidance values for dioxins and dioxin-like PCBs, European Food Safety Authority, EFSA Journal, 2015, at https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2015.4124 -- Also European Food Safety Authority Panel on Contaminants in the Food Chain (CONTAM), Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food, Nov. 2018, at https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2018.5333
94) European Food Safety Authority: Dioxins and related PCBs: tolerable intake level updated, Nov. 2018, at https://www.efsa.europa.eu/en/press/news/181120.)
97) Cell Research advance online publication 24 April 2012; doi: 10.1038/cr.2012.65 Early exposure to germs and the Hygiene Hypothesis Dale T Umetsu Division of Immunology, Karp Laboratories, Children's Hospital Boston, Harvard Medical School, Boston, MA http://www.nature.com/cr/journal/vaop/ncurrent/full/cr201265a.html
98) Clin Exp Allergy. 2006 April; 36(4): 402-425. Blackwell Publishing Ltd Too clean, or not too clean: the Hygiene Hypothesis and home hygiene SF Bloomfield et al. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1448690/
104) DellaValle et al., Environmental determinants of polychlorinated biphenyl concentrations in residential carpet dust, Environ Sci Technol. 2013 Sep 17; 47(18): 10405-10414. at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076890 the p-value for this finding was <.01, indicating a high level of statistical significance.
105) Corts et al., PCDD/PCDF and dl-PCB in the ambient air of a tropical Andean city: passive and active sampling measurements near industrial and vehicular pollution sources, Sci Total Environ. <#> 2014 Sep 1 at https://www.ncbi.nlm.nih.gov/pubmed/24555963 Note that PCDD/F is a designation for what is more commonly referred to as dioxins
106) Ishaq et al., PCBs, PCNs, PCDD/Fs, PAHs and Cl-PAHs in air and water particulate samples--patterns and variations, in Chemosphere March 2003 at https://www.researchgate.net/publication/10934371_PCBs_PCNs_PCDDFs_PAHs_and_Cl-PAHs_in_air_and_water_particulate_samples--patterns_and_variations
106a) For details and sources, see http://www.pollutionaction.org/case-deaton-comment.htm.
107) Sidlova et al., Dioxin-Like and Endocrine Disruptive Activity of Traffic-Contaminated Soil Samples, Arch Environ Contam Toxicol (2009), at https://www.researchgate.net/publication/26259547_Dioxin-Like_and_Endocrine_Disruptive_Activity_of_Traffic-Contaminated_Soil_Samples; specifically, Table 3, 1st column re dioxins.
108) Re presence of PBDEs in vehicular emissions, citing two other studies as well as its own findings about PBDEs in vehicular emissions, see Lien-Te Hsieh et al., Reduction of Toxic Pollutants Emitted from Heavy-duty Diesel Vehicles by Deploying Diesel Particulate Filters, Aerosol and Air Quality Research, at http://aaqr.org/VOL11_No6_November2011/8_AAQR-11-05-OA-0058_709-715.pdf ;
Re PBDEs being produced in vehicle emissions in larger amounts than PCBs, see Table 3, Total PCBs and Table 4, Total (PBDEs), ("before" in both cases), noting that PBDEs are shown in nanograms, which must be multiplied by 1000 to be equivalent to the picograms by which the PCBs are quantified.
109) Wang et al., Emission estimation and congener-specific characterization of polybrominated diphenyl ethers from various stationary and mobile sources, Environmental Pollution, Vol. 158, Issue 10, Oct. 2010, at http://www.sciencedirect.com/science/article/pii/S0269749110002769
110) State of Oregon web page on PBDEs at http://public.health.oregon.gov/HealthyEnvironments/HealthyNeighborhoods/ToxicSubstances/Pages/pbde.aspx)
111) Project TENDR: Targeting Environmental Neuro-Developmental Risks: The TENDR Consensus Statement, Environ Health Perspect. 2016 Jul; 124(7): A118-A122. at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937840