Folic acid reduces the effect of prenatal lead exposure on autistic-like behaviors in children

Folate may reduce the link between lead exposure during pregnancy and autistic-like behaviors in offspring, according to research funded by NIEHS. Previous studies show that folate, an essential B vitamin, supports neurodevelopment and may prevent the toxic effects of chemical exposures in the womb. This study is the first to examine whether folate reduces the adverse effects of prenatal lead exposure on child behavior.

The study included 601 mother-child pairs enrolled in a Canadian pregnancy and birth study between 2008 and 2011. The researchers measured blood lead levels and folate concentrations during the first and third trimesters of pregnancy. Using participant surveys, they also estimated the mother’s intake of folic acid from supplements. The team relied on parent survey responses to assess autistic-like behaviors, such as communication difficulties and repetitive behaviors, in children ages 3-4 years old. In addition, they examined how variation in the MTHFR gene, which processes folate in the body, modified the relationship among lead, folate, and behavior.

The association between maternal lead exposure and autistic-like behaviors in children was weaker among women with adequate folate or folic acid concentrations compared to those with lower concentrations. Specifically, taking at least 400 micrograms of folic acid per day was enough to lessen the neurotoxic effects of lead; there were no added benefits from taking higher doses of 1,000 micrograms per day. Folate’s protective effect was stronger in the third trimester compared to the first trimester. The effect of lead exposure in the third trimester on autistic-like behaviors was slightly stronger among mothers with MTHFR gene variations, although this relationship was not significant.

According to the authors, results suggest that folic acid supplementation during pregnancy may mitigate the neurotoxic effects of lead exposure.

Citation: Alampi JD, Lanphear BP, MacFarlane AJ, Oulhote Y, Braun JM, Muckle G, Arbuckle TE, Ashley-Martin J, Hu JMY, Chen A, McCandless LC. 2024. 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 132(10):107003.

Dust from a drying lake may worsen children’s respiratory health

Windblown dust from a drying lake in the Southwestern U.S. may worsen the respiratory health of children who live nearby, according to NIEHS-funded researchers.

Extreme heat, drought, and competing water demands are drying up the Salton Sea, a lake located in California’s Imperial Valley. Windswept dust from the desiccated lakebed contributes to coarse particulate matter air pollution in the region, which can harm the health of nearby residents. The authors previously reported that child asthma rates in the Imperial Valley are nearly three times higher than the national average.

The study included 722 children, ages 5-11 years old, from largely Latino and Hispanic communities in the Imperial Valley. The researchers used hourly particulate matter data from a network of regulatory air monitors to estimate the number of dust storm events children were exposed to between 2017 and 2019. They assessed child respiratory symptoms using caregiver survey responses about their child’s health in the previous 12 months.

During the study period, children were exposed to between 98 and 395 dust event hours per year, defined as hours when ambient coarse particulate matter concentrations were more than 150 micrograms per cubic meter. For children living within 11 kilometers of the lake, exposure to an additional 100 dust storm hours annually resulted in a 9.5% increase in wheeze, a 6.7% increase in sleep disturbance due to wheeze, and a 4.6% rise in bronchitic symptoms. There was no relationship between dust storm events with wheeze or bronchitic symptoms among children living more than 11 kilometers away from Salton Sea.

According to the authors, study results suggest that children living closer to the Salton Sea may experience worse respiratory health impacts from dust events compared to those further away.

Citation: Johnston JE, Kamai E, Duenas Barahona D, Olmedo L, Bejarano E, Torres C, Zuidema C, Seto E, Eckel SP, Farzan SF. 2024. Air quality and wheeze symptoms in a rural children's cohort near a drying saline lake. Environ Res 263(Pt 2):120070.

PFAS mixtures more harmful to health than exposure to a single compound

Exposure to mixtures of PFAS chemicals may pose a greater health risk than exposure to a single PFAS alone, found NIEHS-funded researchers. Results suggest that different PFAS compounds interact in ways that make a mixture more toxic.

The scientists tested four PFAS mixtures: one made up of 12 PFAS commonly found in surface water; one containing the four most frequently detected PFAS in the blood of the average American; and two mixtures mimicking the chemical makeup of samples collected from a wastewater treatment plant. They predicted the toxicity of each individual PFAS using a chemical-specific baseline toxicity model, which determines the minimum toxicity of a chemical due to their accumulation in cell membranes. To assess how each mixture may affect health, they used two cell-based assays. The first, called the neurotoxicity assay, assessed the effects of exposure on the growth of nervous system cells. The second, known as the cytotoxicity assay, measured cell damage.

In mixtures, individual PFAS chemicals acted together in an additive manner. In the surface water mixture, perfluorooctanoic acid (PFOA) was the most toxic of all 12 chemicals — accounting for nearly one-half of the mixture’s cytotoxicity despite its low concentration. In the neurotoxicity assay, PFOA and perfluorooctane sulfonic acid (PFOS) were each responsible for roughly one-quarter of the observed neurotoxic effects, although they only accounted for 10% and 15% of the mixture, respectively. In the blood mixture, PFOA was the most toxic chemical in both assays. Exposure to the wastewater treatment plant samples resulted in high toxicity in both assays, although both mixtures contained low levels of PFOA.

According to the authors, study results have important implications for risk assessment and suggest that PFAS should be regulated as mixtures.

Citation: Ríos-Bonilla KM, Aga DS, Lee J, König M, Qin W, Cristobal JR, Atilla-Gokcumen GE, Escher BI. 2024. Neurotoxic effects of mixtures of perfluoroalkyl substances (PFAS) at environmental and human blood concentrations. Environ Sci Technol 58(38):16774-84.

Extreme heat exposure during pregnancy may increase the risk of neural tube defects

Exposure to extreme heat in early pregnancy may increase the risk of neural tube defects (NTDs), according to research funded by NIEHS.

NTDs are severe birth defects that affect brain and spine development in the first month of pregnancy. The most common types of NTDs are spina bifida and anencephaly. Previous research supports an association between NTDs and exposures that increase a mother’s core body temperature, such as fever and hot tub use. However, less is known about the impacts of extreme heat in early pregnancy.

The study included data from roughly 825 NTD cases and 3,300 controls born in Georgia between 1994 and 2017. To estimate heat exposure during pregnancy, the researchers linked daily temperature data from each mother’s county of residence to birth and fetal death records. The team defined extreme heat exposure as the number of consecutive days in which a mother experienced unusually high temperatures for her county of residence. They assessed this exposure during the four weeks before and after conception.

Exposure to extreme heat in early pregnancy increased the odds of NTDs. Specifically, mothers exposed to 1-2, 3-5, or 6 or more consecutive days of extreme heat in very early pregnancy had a 9%, 18%, and 29% increased risk, respectively, of having a child with an NTD, compared to mothers experiencing no extreme heat. Across all weeks in the eight-week periconception period, extreme heat exposure consistently elevated NTD risk. This association was largely driven by spina bifida cases and was generally stronger in the four weeks after conception.

According to the authors, study results highlight the potential for rising global temperatures to increase rates of serious birth defects like NTDs.

Citation: LaPointe S, Beagle LE, Zheng X, Kancherla V, Mutic A, Chang HH, Gaskins AJ. 2024. Associations between exposure to extreme ambient heat and neural tube defects in Georgia, USA: a population-based case-control study. Environ Res 261:119756.