May 16, 2014

 

 

Prenatal vs. Postnatal Damage to the Brain:

 Comments on the 2014 study by Stoner et al., “Patches of Disorganization

in the Neocortex of Children with Autism”(1)

 

This study’s authors indicated some uncertainty about the time of origin of the abnormalities observed in postmortem examinations of children with ASD, saying “Our data support a probable dysregulation… at prenatal stages.”  They did not appear to explain why they suspected prenatal origin.  There are good reasons to see a probable postnatal origin.

 

The authors said that migration defects could have led to the disorganization of brain cells that they detected.  It appears to be well accepted that migration of brain cells continues postnatally.(2)  The authors found disorganization of neurons “in prefrontal and temporal cortical tissue.”  Note that both of those specific brain sections are known either to develop extensively postnatally (in the case of the dorsolateral prefrontal cortex, where most of the disorganization was found(3)) or at least to include a section that is known to develop well into postnatal life.(4)

 

There is a specific toxin that could well be a postnatal cause of the migration defects, a toxin (methylmercury) to which most contemporary infants are exposed in doses that far exceed established safe guideline levels. (details to follow)  The U.S. Agency for Toxic Substances and Disease Registry (ATSDR) refers to “deranged neuronal cell migration” that may result from the developing nervous system’s exposure to methylmercury.  And they say that “particularly sensitive” periods of children’s neurological development to effects of developmental toxins include “the early months after birth.”(5)  An EPA report to Congress stated that “neuronal migration, a process specifically affected by methylmercury …continues until five months after birth.”(6) (emphasis added)

 

(Considering the significance of methylmercury in this discussion, be sure to distinguish this form of mercury from the ethyl form, which some studies have found to be unrelated to autism risk.  Also note that methylmercury is usually a very major part of the total mercury in the human body.(7))

 

Developing fetuses and infants are both exposed to methylmercury, but in very different concentrations. According to an EPA publication, "a wealth of information" indicates that lactational transfer of maternal mercury during the first 15 days of lactation is equal to about a third of the total transfer of mercury that takes place during gestation.(8)  A 1999 Swedish study estimated, “About 10% of the Hg present in (a mother’s) circulating blood would be transferred to the milk every day.”(9)  The U.S. ATSDR reports that typical human milk has been determined to have a mean of 8 ppb of mercury, which compares with the maximum of 2 ppb that is allowed in U.S. bottled water;(10) breast milk levels would often be significantly higher than the mean, depending on the mother’s occupational, dietary or regional exposures, and also depending on how early in the lactational period the measurement is taken. Other studies have provided additional verification of the rapid transfer of a mother’s mercury to breastfed infants.(11)

 

When answering parents’ questions such as the one in an Autism Speaks web page, “If autism has to do with prenatal development, how come our child seemed fine until age two?”, if an expert refers to autism’s being “difficult to detect” in young children, that response will probably seem insufficient to many parents who had been watching their children closely.  Many parents would be interested to know that, through a voluntary process, infants are widely exposed to a toxin about which it can be said,

(a) it is known to cause derangement of brain cells,

(b) most infants ingest it in doses far exceeding established safe guidelines (see above),

(c) it has been observed to have effects in humans that closely resemble traits of ASD (see below); and finally

(d) it is known to the U.S. ATSDR to have latent periods after exposure ranging from months to years, before the effects become apparent.(12)

 

Methylmercury’s latency of effect, in addition to its other characteristics that help it fit well as a possible cause of ASD, is apparently unusual and may even be unique among neurodevelopmental toxins.  This is evidenced by the statement by the expert on neurological toxicology, D.C. Rice, who said, “Methylmercury may represent the only environmental toxicant for which there is good evidence for delayed neurotoxicity that may be manifested many years after cessation of exposure.”(13)

 

Some other ways in which mercury’s effects are compatible with characteristics of ASD:  

1) A scientist and M.D. (D.T. Wigle), writing in a publication of the Oxford University Press, points out that relatively low developmental exposures to mercury cause “abnormal social behavior.(14)  

2) The ATSDR points out that major effects of methylmercury exposure include sensory dysfunction (specifically visual) and ataxia(15) (lack of muscular coordination, including poor control of eye movement);(16) these effects, also, sound similar to traits that are typical of ASD:  clumsiness and lack of eye contact.  

3) There are many other close similarities between observed effects of mercury exposure and traits of ASD, itemized in section 5.e at www.autism-correlations.info .

 

Unfortunately that toxin is ingested in especially high doses by means of a type of infant feeding (breastfeeding) that is heavily favored by current prevailing opinion, including in the medical community.  The fact that autism was extremely rare for the generation born in the mid-20th century, for whom that type of feeding was also rare, is of only minor significance.  Of greater significance are the findings of three studies, as follows:

- In a study by a highly-published scientist of data for all 50 states and 51 U.S. counties, it was 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."(17)

- Another U.S. study found that 37% of children with autism had been breastfed for at least 6 months, as compared with 13% in the comparison group.(18)

- A U.K. study of 1189 children with ASD found an unusually high percentage of ASD cases had been exclusively breastfed for more than four weeks (65%, compared with about 28% in the general population).(19)

 

Apparently only four developmental toxins are known to be widely ingested by developing fetuses or infants in concentrations well above established safe guideline levels.  The ones other than mercury (dioxins, PBDEs, and PCBs) are also known to be far higher in human milk than in infant formula.(20)   The author of this article has asked Alycia Halladay (Autism Speaks senior director of environmental and clinical sciences) and seven other scientists at that organization if they were aware of any other toxins (besides the above-mentioned few) to which developing brains are widely exposed in concentrations that greatly exceed established safe guidelines; none of the replies received as of several months later have included mention of any other toxins to which developing brains are known to be widely exposed at levels exceeding established safe guidelines.

 

So mercury is apparently unusual in the following respects:

--  it is ingested by developing infants in doses well beyond established safe guidelines;

--  it is known to cause derangement of brain cells;

--  it is known to do that during the period in which it is ingested in especially high doses by infants;

--  it is known to have latency of effect that is compatible with the frequent emergence of ASD after development was apparently going well;

--  exposure to it is known to produce symptoms similar to those of ASD;   

--  the feeding method by which infants ingest it in doses far above safe guidelines has been found in three studies to correlate with autism prevalence.

 

It may be especially significant that developing brains are exposed to mercury (as well as the other neurodevelopmental toxins mentioned above) in doses far above established safe guidelines by means of a type of infant feeding that could be easily and rapidly replaced with an alternative, satisfactory type of infant feeding.  Infant formula is not only many times lower in all of the toxins mentioned(20) but it was also the predominant feeding type in the mid-20th century,(21) leading to health outcomes that were apparently better than the outcomes that followed after breastfeeding later increased greatly.  Four decades of historical child health data (mainly from the CDC) have shown that the huge increases in breastfeeding rates that took place after 1971(22) have been followed by epidemics and increases in major childhood disorders:  diabetes, asthma, allergies, obesity, ADHD and apparently mental retardation and autism.(23)

 

Good reasons to see a reversion to mainly bottle-feeding as a reasonable alternative, compared with the type of infant feeding that is high in known neuro-developmental toxins, can be found in

-- the historical record (see above),

-- the 50+ studies that have found adverse effects of breastfeeding;(24) (this is stated not because it is conclusive evidence of anything but to cast a skeptical light on the widespread belief, based on what other “studies have found,” that breastfeeding is beneficial); and

-- the increasingly wide acceptance of the “hygiene hypothesis” as an explanation for the increases in immunity-related diseases (including asthma, allergies and type 1 diabetes) among children;(25) according to this hypothesis, recent microbial exposure in contemporary developed countries has already been too low to provide the needed stimulus for proper development of children’s immune systems; the additional shielding of infants from microbes as provided by the immune cells in breast milk should be seen in that light.

 

Considerable additional information on the subject of neurodevelopmental effects of postnatal versus prenatal exposures can be found at www.breastfeeding-research.info/postnatal-effects.htm

 

In closing:  The strong possibility that the abnormalities observed in the Stoner study arose postnatally, and the likely effect of methylmercury in causing those abnormalities, should be taken into account in future research and in infant feeding recommendations.

 

Any comments on the above would be welcome.  Especially eagerly requested are mentions of any other developmental toxins (other than the ones mentioned earlier) to which developing brains are known to be widely exposed in doses exceeding established safe guidelines.  Please send comments to dm@pollutionaction.org  or to the address below:

Don Meulenberg, Director

Pollution Action

33 McWhirt Loop, Ste. 115

Fredericksburg, VA  22406

 

________________________

(1) Stoner et al., Patches of Disorganization in the Neocortex of Children with Autism, New England Journal of Medicine, 2014 online at http://medicine6.com/download/8599

 

(1a) “Autism and Prenatal Development”, on Autism Speaks website March 28, 2014, at http://www.autismspeaks.org/science/science-news/autism-and-prenatal-development?utm_source=email&utm_medium=text-link&utm_campaign=sciencedigest

 

(2) Stiles et al.,The Basics of Brain Development,  Neuropsychol Rev. Dec 2010; 20(4): 327–348. Published online Nov 3, 2010  at http://www.ncbi.nlm.nih.gov/pmc/articles/pmc298900;   also Tau et al., Normal Development of Brain Circuits, Neuropsychopharmacology. Jan 2010; 35(1): 147–168. Published online Sep 30, 2009.   at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055433;  also Rodier, Developing Brain as a Target of Toxicity, presentation at Symposium on Preventing Child Exposures to Environmental Hazards: accessed at www.ncbi.nlm.nih.gov/pmc/articles/PMC1518932/pdf/envhper00365-0077.pdf

  

(3)  Gao et al., The Unique Properties of the Prefrontal Cortex and Mental Illness, InTech, 2012,  at http://neurobio.drexelmed.edu/GaoWeb/papers/Gao_etal_The_unique_properties_of_the_prefrontal_cortex_and_mental_illness_2012.pdf 

Also: Luciana, ed. by Charles A. Nelson; Monica (2001). Handbook of developmental cognitive neuroscience. Cambridge, Mass. [u.a.]: MIT Press. ISBN 0-262-14073-X

 

(4) The dentate gyrus is the section in the temporal cortex that is specifically known to continue to develop into adulthood.  Eriksson et al., Neurogenesis in the adult human hippocampus,  Nature Medicine 4, 1313 - 1317 (1998) at http://www.nature.com/nm/journal/v4/n11/full/nm1198_1313.html

 

(5) U.S. ATSDR, Public Health Service, Toxicological Profile for Mercury  at www.atsdr.cdc.gov/toxprofiles/tp46.pdf,  p. 214 re “deranged” neuronal migration.  Also Section 1.6 re particularly sensitive periods of neurological development.

 

(6)  EPA-452/R-97-009 December 1997  p. 5-29 (Section 5.6.1) at http://www.epa.gov/ttn/oarpg/t3/reports/volume7.pdf

 

(7) Mahaffey et al., Blood Organic Mercury and Dietary Mercury Intake: National Health and Nutrition Examination Survey, 1999 and 2000, top lines of Tables 2 and 4, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241922/pdf/ehp0112-000562.pdf

Mercury levels in studies of humans are normally not speciated, but they are mainly methylmercury;  among U.S. women with mercury concentrations in the highest 10% of those tested in the 1999-2000 NHANES survey, 92% of the mercury in their blood was methylmercury, as indicated in above source.

                  

(8)  Exploration of Perinatal Pharmacokinetic Issues, EPA/630/R-01/004, Section 4.7.4.3,  at www.epa.gov/raf/publications/pdfs/PPKFINAL.PDF  

 

(9) Vahter et al., Longitudinal Study of Methylmercury and Inorganic Mercury in Blood and Urine of Pregnant and Lactating Women, as Well as in Umbilical Cord Blood, Environmental Research, Section A 84,

186}194 (2000) at http://www.detoxmetals.com/content/FISH/FISH/Hg%20in%20pregnant%20urine%20and%20cord.pdf

 

(10)  P. 443 of U.S. ATSDR, Public Health Service, Toxicological Profile for Mercury  at http://www.atsdr.cdc.gov/toxprofiles/tp46.pdf, and Code of Federal Regulations, Title 21, Chapter 1, Subchapter B, Part 165, Subpart B, Sec. 165.110 Bottled water, fourth table in section, at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=165.110

 

(11)  Drexler et al., The mercury concentration in breast milk resulting from amalgam fillings and dietary habits,  Environ Res. 1998 May;77(2):124-9. at   http://www.ncbi.nlm.nih.gov/pubmed/9600805. This study found that concentrations of mercury in breast milk of 85 lactating women at two months after birth had declined by an average of over 70% from their levels at time of birth;   

    Also Marques et al., Hair mercury in breast-fed infants exposed to thimerosal-preserved vaccines,  Eur J Pediatr. 2007 Sep;166(9):935-41. Epub 2007 Jan 20.  at http://www.ncbi.nlm.nih.gov/pubmed/17237965.  This study of 82 mother-infant pairs found that mercury levels in mothers’ hair decreased 57% during six months of lactation;15e

 

(12) Section 2.6, p. 302 of U.S. ATSDR, Public Health Service, Toxicological Profile for Mercury  at http://www.atsdr.cdc.gov/toxprofiles/tp46.pdf

 

(13) Rice DC, .Evidence for delayed neurotoxicity produced by methylmercury,  Neurotoxicology. 1996 Fall-Winter;17(3-4):583-96, at at http://www.ncbi.nlm.nih.gov/pubmed/9086479www.ncbi.nlm.nih.gov/pubmed/9086479

 

(14)  D.T. Wigle, MD, PhD, MPH:  Child Health and the Environment, Oxford University Press, 2003, Ch. 5. p. 103,106, typically available through Ebsco Host at local libraries)  Note that the studies referred to by the author normally based their observations of effects of “prenatal” exposures on umbilical cord blood levels of mercury, or on both cord blood and maternal hair mercury levels; those would be good indicators of levels in breast milk, at least levels in milk that is ingested in the early, most critical period of postnatal neurological development.

 

(15) Next-to-last paragraph of Section 2.2.2.4 of U.S. ATSDR, Public Health Service, Toxicological Profile for Mercury  at http://www.atsdr.cdc.gov/toxprofiles/tp46.pdf

 

(16) From a web page of Medical News Today, at www.medicalnewstoday.com/articles/162368.php

 

(17) Autism rates associated with nutrition and the WIC program. Shamberger R.J., Phd, FACN, King James Medical Laboratory, Cleveland, OH   J Am Coll Nutr. 2011 Oct;30(5):348-53. Abstract at www.ncbi.nlm.nih.gov/pubmed/22081621

 

(18) Breastfeeding and Autism  P. G. Williams, MD, Pediatrics, University of Louisville, and L. L. Sears, MD, presented at International Meeting for Autism Research, May 22, 2010, Philadelphia Marriot, found at https://imfar.confex.com/imfar/2010/webprogram/Paper6362.html

 

(19)  Trends in Developmental, Behavioral and Somatic Factors by Diagnostic Sub-group in Pervasive Developmental Disorders: A Follow-up Analysis, pp. 10, 14   Paul Whiteley (Faculty of Applied Sciences, University of Sunderland, UK), et al.  Autism Insights 2009:1 3-17  at www.la-press.com/trends-in-developmental-behavioral-and-somatic-factors-by-diagnostic-s-article-a1725)   This study found that 65% of children with autism had been breastfed exclusively for at least four weeks.  The authors looked at a comparison figure of 54%, 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.   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 at just after four weeks.  The 2010 edition of the U.K.’s Infant Feeding publication showed an almost identical percentage for the general U.K. population, about 28%.

 

(20) For details and authoritative sources indicating hazardous levels of dioxins, PBDEs and PCBs (as well as mercury) in human milk, go to www.autism-research.net/postnatal-effects.htm#f29 and subsequent references at that location.

 Re: dioxins in formula less than 1% of dioxins in breast milk:

- Re dioxins in breast milk, at 242 pg TEQ at initiation of breastfeeding, see Infant Exposure to Dioxin-like Compounds in Breast Milk  Lorber (Senior Scientist at EPA) and Phillips  Volume 110 | Number 6 | June 2002 • Environmental Health Perspectives at  http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=54708#Download.

- Re dioxins in formula:  U.K. Food Standards Agency Food Survey Information Sheet 49/04 MARCH 2004, Dioxins and Dioxin-Like PCBs in Infant Formulae,  found at http://www.food.gov.uk/multimedia/pdfs/fsis4904dioxinsinfantformula.pdf   According to their “upper bound” determinations (which they said were probably higher than actual concentrations) for 2003, almost all samples provided doses of 1.1 pg TEQ/kg body weight per day or less.  Very compatible figures were found in the following:  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

 

Re:  PBDEs in formula less than 3% of concentration in breast milk:

- Re PBDEs in breast milk, 1,056 pg/g wet weight:  Schecter et al., Polybrominated Diphenyl Ether (PBDE) Levels in an Expanded Market Basket Survey of U.S. Food and Estimated PBDE Dietary Intake by Age and Sex, Environ Health Perspect. Oct 2006; 114(10): 1515–1520, 4th paragraph from end, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626425  This study was cited in the EPA document below, Section 5.6.2, 2nd paragraph.

- PBDEs in formula:  Section 4.7 , p. 4-77, 2nd paragraph of U.S. EPA  (2010) An exposure assessment of polybrominated diphenyl ethers.  http:/cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=210404  (citing Schechter et al., finding of 25 and 32 pg/g wwt, )

 

Re:  Mercury in formula less than 1% as high as in human milk:

- See footnote 10 above re mercury in breast milk, at 8 ppb.

- Re mercury in infant formula at .03 ppb, see Food Additives & Contaminants: Part B: Surveillance Vol 5, Issue1,  2012  Robert W. Dabeka et al., Survey of total mercury in infant formulae and oral electrolytes sold in Canada  DOI: 10.1080/19393210.2012.658087  at

http://academic.research.microsoft.com/Publication/57536306/survey-of-total-mercury-in-infant-formulae-and-oral-electrolytes-sold-in-canada

 

Re:  PCBs in infant formula typically less than 1% but up to about 4% as high as in human milk:

-  In breast milk:  About 250 ng/g lipid weight.  In soy-based formula:  about 10 ng/g lipid weight.  U.S. Agency for Toxic Substances and Disease Registry, Toxicological Profile for Polychlorinated Biphenyls (PCBs), 2000, pp. 560, 573, at http://www.atsdr.cdc.gov/toxprofiles/tp17.pdf  Data does not appear to be available for PCBs in cow’s-milk-based infant formula, but data for whole milk could give an approximation, as follows:  adding together the figures for the two kinds of PCBs in this study provides a range of  52 to 2455 ng/kg fat, which equals .05 to 2.45 ng/g fat (lipid)  (Krokos et al., Levels of selected ortho and non-ortho polychlorinated biphenyls in UK retail milk, Chemosphere. 1996 Feb;32(4):667-73.  at www.ncbi.nlm.nih.gov/pubmed/8867147)

 

(21)  American Academy of Family Physicians website at www.aafp.org/about/policies/all/breastfeeding-support.html

 

(22) Surgeon General’s Call to Action to Support Breastfeeding, Fig. 1, at http://www.surgeongeneral.gov/library/calls/breastfeeding/calltoactiontosupportbreastfeeding.pdf

 

(23)  CDC’s MMWR National Surveillance for  Asthma -- United States, 1980-2004, Table 29, at www.cdc.gov/mmwr/preview/mmwrhtml/ss5608a1.htm

Re allergies: CDC’s Health United States 2011, Table 46, p. 3, at  www.cdc.gov/nchs/data/hus/hus11.pdf  

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 

Re ADHD:  see www.breastfeeding-and-ADHD.info for substantial evidence about the time trend of ADHD in the U.S.

Re mental retardation trend: National Center for Health Statistics, Healthy People 2000 Review, 1997.  Public Health Service. Lib. of Congress Cat. No. 76-641496, Figure R, found at www.cdc.gov/nchs/data/hp2000/2k97.pdf

Also see www.breastfeeding-health-effects.info, where numerous peer-reviewed studies are cited in support of this statement .

 

(24)  See www.breastfeeding-studies.info, where over 50 peer-reviewed studies are cited in support of this statement.

(25) http://www.fda.gov/biologicsbloodvaccines/resourcesforyou/consumers/ucm167471.htm  Also 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/   Also 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

Also, "About Allergies/ Why Are Allergies Increasing?" at http://fooddrugallergy.ucla.edu/body.cfm?id=40