Background: Early life exposure to lead, mercury, polychlorinated biphenyls (PCBs), polybromide diphenyl ethers (PBDEs), organophosphate pesticides (OPPs), and phthalates have been associated with lowered IQ in children. In some studies, these neurotoxicants impact males and females differently. We aimed to examine the sex-specific effects of exposure to developmental neurotoxicants on intelligence (IQ) in a systematic review and meta-analysis. Method: We screened abstracts published in PsychINFO and PubMed before December 31st, 2021, for empirical studies of six neurotoxicants (lead, mercury, PCBs, PBDEs, OPPs, and phthalates) that (1) used an individualized biomarker; (2) measured exposure during the prenatal period or before age six; and (3) provided effect estimates on general, nonverbal, and/or verbal IQ by sex. We assessed each study for risk of bias and evaluated the certainty of the evidence using Navigation Guide. We performed separate random effect meta-analyses by sex and timing of exposure with subgroup analyses by neurotoxicant. Results: Fifty-one studies were included in the systematic review and 20 in the meta-analysis. Prenatal exposure to developmental neurotoxicants was associated with decreased general and nonverbal IQ in males, especially for lead. No significant effects were found for verbal IQ, or postnatal lead exposure and general IQ. Due to the limited number of studies, we were unable to analyze postnatal effects of any of the other neurotoxicants. Conclusion: During fetal development, males may be more vulnerable than females to general and nonverbal intellectual deficits from neurotoxic exposures, especially from lead. More research is needed to examine the nuanced sex-specific effects found for postnatal exposure to toxic chemicals.

Fluoride exposure >1.5 mg/L from water has been associated with adverse pregnancy and birth outcomes. Little is known, however, about the effect of fluoride at levels consistent with water fluoridation (i.e., 0.7 mg/L) on pregnancy and birth outcomes. We examined the relationship between maternal fluoride exposure, fertility, and birth outcomes in a Canadian pregnancy cohort living in areas where municipal drinking water fluoride concentrations ranged from 0.04 to 0.87 mg/L. Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, we estimated fluoride exposure during pregnancy using three different metrics: (1) maternal urinary fluoride concentrations standardized for specific gravity (MUF_SG) and averaged across all three trimesters (N = 1566), (2) water fluoride concentration (N = 1370), and (3) fluoride intake based on self-reported consumption of water, coffee, and tea, adjusted for body weight (N = 1192). Data on fertility, birth weight, gestational age, preterm birth, and small-for-gestational age (SGA) were assessed. We used multiple linear regression to examine associations between fluoride exposure, birth weight and gestational age, and logistic regression to examine associations with fertility, preterm birth, and SGA, adjusted for relevant covariates. Median (IQR) MUF_SG was 0.50 (0.33-0.76) mg/L, median water fluoride was 0.52 (0.17-0.64) mg/L, and median fluoride intake was 0.008 (0.003-0.013) mg/kg/day. MUF_SG, water fluoride concentrations, and fluoride intake were not significantly associated with fertility, birth weight, gestational age, preterm birth, or SGA. Fetal sex did not modify any of the associations. Fluoride exposure during pregnancy was not associated with fertility or birth outcomes in this Canadian cohort.

In animal studies, the combination of in utero fluoride exposure and low iodine has greater negative effects on offspring learning and memory than either alone, but this has not been studied in children. We evaluated whether the maternal urinary iodine concentration (MUIC) modifies the association between maternal urinary fluoride (MUF) and boys’ and girls’ intelligence. We used data from 366 mother–child dyads in the Maternal–Infant Research on Environmental Chemicals Study. We corrected trimester-specific MUF and MUIC for creatinine, and averaged them to yield our exposure variables (MUF_CRE, mg/g; MUIC_CRE, µg/g). We assessed children’s full-scale intelligence (FSIQ) at 3 to 4 years. Using multiple linear regression, we estimated a three-way interaction between MUF_CRE, MUIC_CRE, and child sex on FSIQ, controlling for covariates. The MUIC_CRE by MUF_CRE interaction was significant for boys (p = 0.042), but not girls (p = 0.190). For boys whose mothers had low iodine, a 0.5 mg/g increase in MUF_CRE was associated with a 4.65-point lower FSIQ score (95% CI: −7.67, −1.62). For boys whose mothers had adequate iodine, a 0.5 mg/g increase in MUF_CRE was associated with a 2.95-point lower FSIQ score (95% CI: −4.77, −1.13). These results suggest adequate iodine intake during pregnancy may minimize fluoride’s neurotoxicity in boys.