2 Sex difference of Developmental Neurotoxicants on Intellectual Abilities: A Systematic Review and Meta-Analysis

Abstract

Objective:Early life exposures to lead, mercury, polychlorinated biphenyls (PCBs), polybromide diphenyl ethers (PBDEs), organophosphate pesticides (OPPs), and phthalates have been associated with diminished IQ scores in children. Some studies suggest that these neurotoxicants impact boys and girls differently. We conducted a systematic review and meta-analysis to identify and quantify sex differences in IQ deficits from pre- and post-natal exposures to these developmental neurotoxicants.Participants and Methods:We used PubMed and PsychINFO to screen abstracts of articles published between January 1, 1950 and December 31, 2021 for empirical studies of six neurotoxicants [lead, mercury, PCBs, PBDEs, OPPs, and/or phthalates] that (1) used an individualized biomarker; (2) measured exposure during the prenatal period or within the first six years of life; and (3) provided different effect estimates on children's intellectual abilities by sex. We assessed each study for risk of bias using Navigation Guide (Woodruff & Sutton, 2014). For studies with combinable data, we performed separate random effects meta-analyses for boys and girls with subgroup analyses by neurotoxicant. To homogenize the magnitude of effect observed in each study, we recalculated results to be expressed as the absolute change in intellectual abilities for a relative change of 1.5 times (i.e., 50% increase) in the exposure variable.Results:Of 3205 studies screened, 53 met inclusion criteria: 34 evaluated prenatal exposure, 11 postnatal exposure, and 8 both pre- and post-natal exposure. We generally rated these studies as "low" to "probably low" risk of bias. Among the studies examining prenatal exposure, 27 reported no significant differences between the sexes, 7 found negative associations in boys, 4 found negative associations in girls, 5 found negative nonsignificant associations in boys and positive nonsignificant associations in girls, and 3 found no clear pattern, where differences by sex depended on the specific phthalate compound or outcome measurement. Among the studies examining postnatal exposure, 14 reported no significant differences between the sexes, 1 found a negative association in boys, 2 found negative associations in girls, and 2 found positive associations for either boys or girls. In our meta-analysis of 16 studies (4 lead, 4 mercury, 2 PBDEs, 2 OPPs, 4 phthalates), we found that prenatal exposure to developmental neurotoxicants was associated with decreased full-scale intelligence in boys (B = -0.26; 95% CI: -0.45, -0.08), but not girls (B = 0.09; 95% CI: -0.14, 0.31). In subgroup analyses by neurotoxicant, prenatal exposure to lead (B = -1.07; 95% CI: -1.63, -0.52), and ZPBDEs (B = -0.57; 95% CI: -1.14, -0.01) were associated with decreased full-scale intelligence in boys, whereas the girls' effect sizes were consistently near zero.Conclusions:During fetal development, boys appear to be more vulnerable than girls to IQ deficits from neurotoxic exposures, and especially from lead and PBDEs. More research is needed to examine the nuanced sex-specific effects found for postnatal exposures to toxic chemicals.