Plasma Folate Levels Could Attenuate the Association between Serum Lead Levels During Pregnancy and Autistic Behavior in Children

by | Dec 12, 2024 | 2024, Autism, Brain Health, Folic Acid & Folate, Heavy Metals, Infant and Children's Health, Pregnancy and Lactation, Recent Articles

Written by Chrystal Moulton, Staff Writer. Researchers  saw a significant interaction between plasma total folate concentrations below 49.3 nmol/L and the association between gestational blood lead levels and SRS-2 scores.

young smiling boyAutism is a neurodevelopmental disease that has been linked to environmental factors1. Lead exposure is detrimental to neurodevelopment in children1-3.  Meta-analyses and systemic reviews suggest a possible link between lead exposure and autism1,4. Epidemiological studies suggest that prenatal folic acid supplementation could counteract the effects of pesticides5, phthalate metabolites6, and air pollutants7 and the risk of autism. In the current analysis, researchers investigated whether gestational folic acid supplementation affected the relationship between gestational blood lead levels and childhood autistic like behaviors. Researchers further investigated any association specific to the maternal MTHFR 677C > T genotype8.

Researchers used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, which was conducted in 10 Canadian cities between 2008 in 2011. Individuals 18 years and older who were <14 weeks pregnant and planning on delivering at a local hospital were recruited for the MIREC study. A total of 1,983 women were eligible for the MIREC study and 1,861 gave birth to a single infant. Demographic and nutritional information was recorded upon enrollment and again at the 16th week of pregnancy. Dietary recall was done to assess folate supplementation 30 days prior to enrollment and 24-hour dietary recall questionnaire was also used. Participants were characterized into one of three groups based on folic acid intake from supplements: < 400 mcg/d, 400-1000 mcg/d, and >1000 mcg/d. Autistic like behaviors were measured via the Social Responsiveness Scale-2 (SRS-2). High scores on the SRS-2 indicated significant communication problems and repetitive/ non-reciprocal behaviors characteristic of autism. Whole blood samples were collected at the 1st and 3rd trimesters of pregnancy. These samples were used to measure serum lead levels and MTHFR677 C>T genotype expression. Linear regression models was used to assess any association between gestational blood lead levels and SRS-2 scores. Additional three-way linear regression models were applied to assess the relationship between plasma folate concentration, MTHFR 677 C>T genotype, and the association between gestational blood lead levels and SRS-2 scores.

The average age of participants was 33 ±4.6 years old. 2% of the children exhibited mild autistic like behaviors. Children with higher SRS-2 scores were generally boys from single parent homes with lower household income who grew up in a less stimulating environment. 70% of participants supplemented with folate within the recommended values (400- 1000 mcg/d). With regards to the MTHFR 677 C> T allele, 10% of mothers had the double recessive gene, while 44% at either the dominant heterozygous or dominant homozygous gene. Researchers found for every twofold difference in blood lead levels within the first trimester there was a 0.4-point increase in the SRS-2 scores after controlling for confounding variables. Researchers also saw a significant interaction between plasma total folate concentrations below 49.3 nmol/L and the association between gestational blood lead levels and SRS-2 scores. Essentially, women in the third trimester with plasma total folate concentration <49.3 nmol/L had an increased risk of bearing a child with higher scores on the SRS-2 (beta= 3.3, P < 0.001). Researchers also observed that in women with the dominant homozygous MTHFR genotype who had total plasma folate concentration ≥69.0 nmol/L, the association between serum lead levels and SRS-2 scores was significant (beta= 1.6, P= 0.02). A significant association between serum lead levels and SRS-2 scores was also observed in women with the recessive MTHFR genotype who had total plasma folate concentration <69.0 nmol/L (beta= 2.2, P= 0.003). No additional statistically significant findings were observed.

Results from this evaluation showed that low total plasma folate levels within the third trimester increases the risk of autistic like behaviors in children. Further studies will be needed to verify these findings and establish clear causal link between gestational diet, heavy metal exposure, and the risk of autism.

Source: Alampi, Joshua D., Bruce P. Lanphear, Amanda J. MacFarlane, Youssef Oulhote, Joseph M. Braun, Gina Muckle, Tye E. Arbuckle et al. “Combined exposure to folate and lead during pregnancy and autistic-like behaviors among Canadian children from the MIREC pregnancy and birth cohort.” Environmental Health Perspectives 132, no. 10 (2024): 107003.

Click here to read the full text study.

Posted December 11, 2024.

Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.

References:

  1. Saghazadeh A, Rezaei N. Systematic review and meta-analysis links autism and toxic metals and highlights the impact of country development status: Higher blood and erythrocyte levels for mercury and lead, and higher hair antimony, cadmium, lead, and mercury. Progress in neuro-psychopharmacology & biological psychiatry. Oct 3 2017;79(Pt B):340-368. doi:10.1016/j.pnpbp.2017.07.011
  2. Oulhote Y, Bellinger DC. Neurodevelopment and neurobehavioral disorders in relation to developmental exposures. Health Impacts of Developmental Exposure to Environmental Chemicals. 2020:153-174.
  3. Landrigan PJ, Fuller R, Acosta NJ, et al. The Lancet Commission on pollution and health. The lancet. 2018;391(10119):462-512.
  4. Roberts AL, Lyall K, Hart JE, et al. Perinatal air pollutant exposures and autism spectrum disorder in the children of Nurses’ Health Study II participants. Environ Health Perspect. Aug 2013;121(8):978-84. doi:10.1289/ehp.1206187
  5. Schmidt RJ, Kogan V, Shelton JF, et al. Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder. Environ Health Perspect. Sep 8 2017;125(9):097007. doi:10.1289/ehp604
  6. Oulhote Y, Lanphear B, Braun JM, et al. Gestational Exposures to Phthalates and Folic Acid, and Autistic Traits in Canadian Children. Environ Health Perspect. Feb 2020;128(2):27004. doi:10.1289/ehp5621
  7. Goodrich AJ, Volk HE, Tancredi DJ, et al. Joint effects of prenatal air pollutant exposure and maternal folic acid supplementation on risk of autism spectrum disorder. Autism Res. Jan 2018;11(1):69-80. doi:10.1002/aur.1885
  8. Alampi JD, Lanphear BP, MacFarlane AJ, et al. Combined Exposure to Folate and Lead during Pregnancy and Autistic-Like Behaviors among Canadian Children from the MIREC Pregnancy and Birth Cohort. Environ Health Perspect. Oct 2024;132(10):107003. doi:10.1289/ehp14479

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