Summary: Higher gestational concentrations of phthalate metabolites were linked to increased autistic traits in boys but not in girls. Adequate folic acid supplementation during early pregnancy appeared to reduce this risk, researchers report.
Source: University of Massachusetts Amherst
Exposure in the womb to phthalates — a class of endocrine-disrupting chemicals commonly found in cosmetics, personal care products, certain plastics and food packaging — was associated with higher measures of autistic traits in boys aged 3 to 4, but not in girls, according to a new study led by an environmental epidemiologist at the University of Massachusetts Amherst.
The study found that boys whose mothers took the recommended daily folic acid supplement during the first trimester showed fewer autistic-like social and behavioral traits than boys whose mothers did not. These traits, assessed with standardized measures, reflect social behavior differences, repetitive behaviors and restricted interests; they indicate autistic traits but are not the same as a clinical autism diagnosis.
“This is one of the largest cohort studies examining phthalates and neurodevelopment,” said lead author Youssef Oulhote, assistant professor of biostatistics and epidemiology at UMass Amherst’s School of Public Health and Health Sciences. “A key finding is that adequate folic acid supplementation in early pregnancy may offset some potentially harmful effects of prenatal phthalate exposure on autistic traits.”
Published Feb. 19 in the journal Environmental Health Perspectives, this research is the first to identify a protective association of folic acid supplements against the effects of prenatal phthalate exposure on autistic traits. Oulhote noted that prior studies have shown folic acid can also reduce risks associated with other environmental toxins such as certain pesticides and air pollution.
While genetics play a major role in autism spectrum disorder (ASD), these results add to growing evidence that prenatal exposure to environmental chemicals can influence early social development. ASD is diagnosed more frequently in males than females, and this study observed phthalate-related differences at a single point during the preschool years; it does not determine whether these differences persist later in childhood.
“We do not yet know whether the subtle effects linked with prenatal phthalate exposure will continue beyond the preschool period,” noted Gina Muckle, a child development specialist and co-author of the study, who is a professor at Université Laval and affiliated with the Quebec-CHU Research Center.
The study analyzed data from the Maternal-Infant Research on Environmental Chemicals (MIREC) prospective cohort. MIREC enrolled 2,001 women during the first trimester of pregnancy from 10 Canadian cities between 2008 and 2011. Investigators have produced many peer-reviewed papers from MIREC data, and Oulhote previously participated in that work as a postdoctoral researcher and continues to conduct related analyses.
For this analysis, researchers measured 11 phthalate metabolites in first-trimester urine samples from the pregnant participants and recorded reported folic acid supplement intake. Follow-up neuropsychological assessments were conducted when children reached ages 3 to 4. A total of 601 children completed these assessments, which included the Social Responsiveness Scale–Second Edition (SRS-2), a validated parent-report instrument used to quantify autistic traits and social impairment across the general population.
The investigators found that higher maternal urinary concentrations of certain phthalate metabolites were associated with higher SRS-2 scores — indicating greater social impairment — but this association appeared only in children whose mothers had taken less than the recommended 400 micrograms per day of folic acid during the first trimester. In mothers who reported adequate folic acid supplementation (≥400 mcg/day), the phthalate-related increases in SRS-2 scores were smaller or not significant.
Specific metabolites linked to higher SRS-2 scores included mono-n-butyl phthalate (MBP) and mono-3-carboxypropyl phthalate (MCPP). A doubling in MBP or MCPP concentration was associated with small but measurable increases in overall SRS-2 T-scores and in subdomains covering social cognition, social communication, social motivation, and restricted interests or repetitive behaviors. Effects were consistently stronger in boys compared with girls.
Oulhote cautioned that the study population was relatively advantaged: most participants were white, employed, partnered, and well-educated. “These are not the higher phthalate exposures often observed in lower-income communities,” he said, noting that phthalate-free personal care products are often more expensive and less accessible to lower-income families. Phthalates are also present in many plastics, certain food packaging materials, and some medical devices, which can contribute to exposure differences across populations.
Source:
University of Massachusetts Amherst
Media Contacts:
Patty Shillington – University of Massachusetts Amherst
Image Source:
The image is in the public domain.
Original Research: Open access
“Gestational Exposures to Phthalates and Folic Acid, and Autistic Traits in Canadian Children.” Youssef Oulhote, Bruce Lanphear, Joseph M. Braun, Glenys M. Webster, Tye E. Arbuckle, Taylor Etzel, Nadine Forget-Dubois, Jean R. Seguin, Maryse F. Bouchard, Amanda MacFarlane, Emmanuel Ouellet, William Fraser, and Gina Muckle. Environmental Health Perspectives. DOI: 10.1289/EHP5621.
Abstract
Gestational Exposures to Phthalates and Folic Acid, and Autistic Traits in Canadian Children
Background:
The causes of autism spectrum disorder remain incompletely understood. Few studies have examined links between prenatal exposure to endocrine-disrupting chemicals and autistic traits. This study evaluated gestational phthalate exposure and autistic traits in 3- to 4-year-old Canadian children and assessed potential modification by child sex and maternal folic acid supplementation.
Methods:
The cohort enrolled 2,001 women aged over 18 during their first trimester between 2008 and 2011 across 10 Canadian cities. At ages 3–4 years, neuropsychological assessments including the SRS-2 were completed for 610 children. Eleven phthalate metabolites were measured in maternal first-trimester urine, and folic acid intake was recorded. Covariate-adjusted differences in SRS-2 T-scores were estimated for a doubling in phthalate concentrations in 510 children with complete data.
Results:
Mean total SRS-2 T-score was 45.3 (SD = 6.1). Higher gestational concentrations of MBP and MCPP were associated with higher total SRS-2 T-scores and with higher scores across SRS-2 subdomains. A doubling in MBP or MCPP concentrations corresponded to modest increases in total SRS-2 T-scores. Associations were stronger in boys versus girls and were more pronounced among children whose mothers had lower prenatal folic acid supplementation (<400 μg/day) compared with those reporting adequate supplementation (≥400 μg/day).
Conclusions:
Elevated gestational levels of certain phthalate metabolites were associated with higher autistic trait scores measured by the SRS-2 in boys but not girls. First-trimester folic acid supplementation at recommended levels appeared to mitigate these small effects.