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Increased Risk of Autism in Children of Older Mothers

 

In the largest study of its kind (as of its publication in 2008), looking at more than 300,000 U.S. births, the researchers found a 20% increase in the risk of autism with each 10-year increase in the parents' ages.(a)   Seven other studies have found a direct positive association between older parental age and at least one form of autism.(b)

 

Consideration of risk for a child of an older mother should take into account the mother’s increasing levels, through the years, of “persistent bioaccumulative toxins” (PBTs).  “Bioaccumulation” means the increase in concentration of a chemical in an organism (such as a mother) over time.(1)   Several PBTs are recognized by major health authorities to be developmental toxins.  One of those is PCBs, about which the U.S. Agency for Toxic Substances and Disease Registry (ATSDR) says, “it is age rather than the number of deliveries that seems to affect the concentration of PCBs, with older women having higher concentrations.”(1a)

 

Quoting from the report of a workshop attended by experts contracted by the EPA, “PBT chemicals have the potential to accumulate within a woman’s lipids over the course of many years prior to pregnancy and child birth (Arcus-Arth et al., 2005).  PBT chemicals partition from body lipids into breast milk because of its high lipid content;… because of the relatively small size of a nursing infant, this high exposure may lead to PBT chemical levels in blood and tissues that far exceed those in the mother.”(1b)

 

According to a study by a team headed by a highly-published EPA researcher, “Neurotoxic effects of a number of environmental agents have been demonstrated in various studies, with critical windows of vulnerability to these agents occurring both pre- and postnatally; (1c)  Adverse effects of postnatal exposures of infants to developmental toxins are verified in statements by the NIH, WHO, the American Congress of Obstetricians and Gynecologists, the U.S. Agency for Toxic Substances and Disease Registry, the EPA in a report to Congress, and dozens of other studies.(1d)

 

Mercury, bioaccumulating in mothers, transferred in high doses to infants during a developmentally-vulnerable period, and with latency of effect:

There are several reasons to focus on mercury as a likely cause of neurodevelopmental harm to infants. Breastfed infants are exposed to this chemical in doses that are typically eight times the WHO guideline value for safe levels of mercury in drinking water,(2) and very often substantially higher than that (including from occupational exposures or high-seafood diets).  The U.S. Agency for Toxic Substances and Disease Registry refers to the “particularly sensitive” periods of children’s neurological development to effects of mercury, which include “the early months after birth.”(3)  Many studies have found high mercury levels in those diagnosed with autism.(4)  (The studies that have failed to find this association have (a) focused on thimerosal, which contains ethylmercury, only one of many species of mercury, (b) measured mercury levels in children far past the vulnerable early-postnatal period, or (c) assessed effects at too young an age to observe the long-term results of this slow-acting toxin.)

In relation to the known phenomena of “regression” or “late emergence” in autism, it is very significant that mercury is known to have latencies ranging from months to years after exposure before effects become apparent.(5a)

There are numerous close similarities between known specific effects of mercury exposure and traits of ASD:  impaired social interaction, repetitive activity, easily startled, hyperkinesia, and many others that can be read about in section 5.e in www.autism-correlations.info.  The compatibility of mercury’s known latency of effect, on the one hand, with regression in autism on the other hand, is also quite noteworthy. (Mercury is very unusual in having latent effects.(5b))

The bioaccumulative nature of mercury (as well as of dioxins, PCBs and PBDEs) also probably relates to why autism risk is higher among children of older mothers.  The greater the age, the greater the build-up of these neuro-developmental toxins in mothers’ bodies, on average.  Then that accumulation passes rapidly to a breastfed newborn:  a 1998 German 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.(6)  According to a 1999 Swedish study, about 10% of the Hg present in circulating blood (5 L]0.3 lg/L) would be transferred to the milk every day.”(7)  Transfer of a mother’s dioxins to an infant is less rapid than that of mercury, but still substantial:  different studies have estimated that concentrations of dioxins in breast milk decline in the range of 48% to 70% during 6 months of breastfeeding.(8)

The hazardous nature of breast milk concentrations of PBTs other than mercury is also significant:  Dioxins have been found to be present in breast milk in average concentrations exceeding the EPA’s RfD (Reference Dose, or estimated relatively safe dose) by scores to hundreds of times.(9)   PBDEs have been found in human milk in concentrations normally three times but up to 40 times the EPA’s RfD for that toxin.(10) 

 

Note that the above numbers are averages, for women of average childbearing age.  Since these toxins are bioaccumulative, milk from older mothers would have higher concentrations than those averages.  Also, there is good evidence indicating that older mothers are more likely to breastfeed than younger mothers,(11) and that older mothers continue breastfeeding for longer periods than younger mothers.(12). 

 

So the exposures of breastfed infants of older mothers to bioaccumulative toxins is more concentrated and also apparently more frequent and of longer duration than exposures of children of younger mothers. Since one or more of those toxins is known (a) to be neurodevelopmentally toxic, (b) to produce effects very similar to those of ASD, and (c) to have latencies of effect compatible with late appearance of ASD symptoms, those toxins in breast milk should be considered as likely causes of autism in children of older mothers.

 

The above-discussed toxins are recognized to be developmentally toxic in general, not merely with children of older mothers.  A study that investigated data from all 50 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.”(13)  Additional support for this correlation was provided by two additional studies, carried out in the U.S. and the U.K.(14)

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References:

(a)   Maureen S. Durkin et al., Advanced Parental Age and the Risk of Autism Spectrum Disorder,  Am J Epidemiol. 2008 December 1; 168(11): 1268–1276. Published online 2008 October 21. doi: 10.1093/aje/kwn250  American Journal of Epidemiology at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2638544/

 

(b) Lisa A. Croen,et al., Maternal and Paternal Age and Risk of Autism Spectrum Disorders ANRV305-PU28-21 ARI 22 December 2006 7:53     Craig J. Newschaffer et al., The Epidemiology of Autism Spectrum Disorders, Annu. Rev. Public Health 2007. 28:21.1–21.24  at https://idea.library.drexel.edu/bitstream/handle/1860/2632/2006175339.pdf;jsessionid=1770039FF47550724E3AAC08B1774404?sequence=1

 

(1) Extoxnet:  “Bioaccumulation,” rev. 1993.  Extension Toxicology Network is a Pesticide Information Project of offices of Cornell University, Oregon State University, the University of Idaho, and the University of California at Davis and the Institute for Environmental Toxicology, Michigan State University.  at http://extoxnet.orst.edu/tibs/bioaccum.htm

 

(1a) U.S. ATSDR:  Toxicological Profile for Polychlorinated Biphenyls (PCBs), 2000 at http://www.atsdr.cdc.gov/toxprofiles/tp17.pdf, p. 569

 

(1b) ICF International, Workshop Summary Report, "Improving the Risk Assessment of Persistent, Bioaccumulative, and Toxic Chemicals in Breast Milk,”  2013, prepared for U.S. EPA, at http://cfpub.epa.gov/ncea/risk/recordisplay.cfm?deid=262210. p. 4

 

(1c) Mendola P et al., Environmental factors associated with a spectrum of neurodevelopmental deficits, Ment Retard Dev Disabil Res Rev. 2002;8(3):188-97  at www.ncbi.nlm.nih.gov/pubmed/12216063

 

(1d) See www.autism-research.net/postnatal-effects.htm, which has links to peer-reviewed sources. 

(2) Typical 8 parts per billion in breast milk, according to U.S. ATSDR document on mercury at http://www.atsdr.cdc.gov/toxprofiles/tp46-c5.pdf, p. 443,  which compares with1 microgram per liter (1 microgram per billion micrograms), or 1 part per billion, the WHO guideline value for drinking water:  (WHO, Mercury in Drinking-water Background document for development of WHO Guidelines for Drinking-water Quality  WHO/SDE/WSH/03.04/10  at http://www.who.int/water_sanitation_health/dwq/chemicals/en/mercury.pdf  p. 8)

(3) U.S. ATSDR, Public Health Service, Toxicological Profile for Mercury  at http://www.atsdr.cdc.gov/toxprofiles/tp46.pdf, Section 1.6 

 

(4) See footnotes 6, 15, 16, and 29 in D. Austin, An epidemiological analysis of the ‘autism as mercury poisoning’ hypothesis’, International Journal of Risk and Safety in Medicine, 20 (2008) 135-142 at http://researchbank.swinburne.edu.au/vital/access/manager/Repository/swin:9302 Also see Geier DA et al., Blood mercury levels in autism spectrum disorder: Is there a threshold level? Acta Neurobiol Exp (Wars). 2010;70(2):177-86, www.ncbi.nlm.nih.gov/pubmed/20628441.

 

(5a) Section 2.6 of U.S. ATSDR, Public Health Service, Toxicological Profile for Mercury, p. 302  at http://www.atsdr.cdc.gov/toxprofiles/tp46.pdf

(5b) 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

(6) 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.  Another study found various forms of mercury in mothers’ blood and urine declined during lactation, and said that was probably attributable to excretion during breastfeeding. (Vahter, 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, Volume 84, Issue 2, October 2000, Pages 186–194

 

(7) 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

(8) Infant Exposure to Dioxin-like Compounds in Breast Milk  Lorber and Phillips  Vol. 110 | No. 6 | June 2002 • Environmental Health Perspectives http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=54708#Download

(9) 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.:

- Infant Exposure to Dioxin-like Compounds in Breast Milk,  Lorber et al., Vol. 110  No. 6  June 02,  Environmental Health Perspectives at http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=54708#Download

(10) RFD for PBDEs:  EPA Technical Fact Sheet on Polybrominitated Diphenyl Eithers (PBDEs) and PBBs, p. 4 re RfD of 1 x 10-4 mg/kg/day (100 ng/kg-d) for BDE-47 and BDE 99  at  www2.epa.gov/sites/production/files/2014-03/documents/ffrrofactsheet_contaminant_perchlorate_january2014_final_0.pdf

-  PBDEs, present in human milk in concentrations normally three times but up to 40 times the EPA’s RfD:

-Table 5-4 of EPA  (2010) An exposure assessment of polybrominated diphenyl ethers. National Center for Environmental Assessment, Washington, DC; EPA/600/R-08/086F.  http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=210404, Schechter study in first page of table, showing  306 ng/kg-d as exposure for breastfed infants. 

- Costa et al., Developmental Neurotoxicity Of Polybrominated Diphenyl Ether (PBDE) Flame Retardants, Neurotoxicology. 2007 November; 28(6): 1047–1067.  at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118052  Last paragraph of “Relevance to Humans” section, re up to 4.1 micrograms (4100 ng)/kg-day exposure of infants

(11)  Infant Feeding Survey 2010: Early Results   A survey carried out on behalf of the NHS Information Centre by IFF Research, University of York, UK, Section 2.2.4  at  http://www.hscic.gov.uk/catalogue/PUB00648/infa-seed-serv-2010-earl-resu-rep.pdf

(12) Research Handbook on the Economics of Family Law, Cohen and Wright, p. 176, citing Scott et al, 1999, and Ynge and Sjostrom, 2001; Maternal and Child Health Journal  Volume 2, Number 3 (1998), 167-179, DOI: 10.1023/A:1021879227044;   Factors Associated with Very Early Weaning Among Primiparas Intending to Breastfeed  Melissa Avery et al (http://link.springer.com/article/10.1023%2FA%3A1021879227044);     Clinician Support and Psychosocial Risk Factors Associated With Breastfeeding Discontinuation  Elsie M. Taveras, et al., Pediatrics, 2003, Vol. 113

(13) 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 

(14) Breastfeeding and Autism, P. G. Williams, MD, 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)

 

Whitely et al., Trends in Developmental, Behavioral and Somatic Factors by Diagnostic Sub-group in Pervasive Developmental Disorders: A Follow-up Analysis, pp. 10, 14  (Faculty of Applied Sciences, University of Sunderland, UK),  Autism Insights 2009:1 3-17  at www.la-press.com/trends-in-developmental-behavioral-and-somatic-factors-by-diagnostic-s-article-a1725)    Whitely et al. 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.

 

*For information about Pollution Action and to see a list of our other publications on the general subject of environmental toxins as related to child development, go to www.pollutionaction.org