Prenatal environmental chemical exposures and child IQ: sex-specific effects in the MIREC cohort

Prenatal exposure to environmental chemicals may pose significant risks to neurodevelopment, with growing evidence linking maternal exposure to several metals, fluoride, pesticides, PFAS, and phthalates in pregnancy with reductions in children's intelligence quotient (IQ). Male children may be particularly susceptible, potentially due to a combination of sex-specific differences in neurodevelopment, placental physiology, thyroid regulation, as well as toxicokinetic and epigenetic factors. We synthesized findings from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, a comprehensively phenotyped Canadian pregnancy and birth cohort, focusing on eight studies that examined sex-specific associations between prenatal chemical exposures and child IQ at age 3-4 years. Across these studies, more than 25 chemical biomarkers were measured in maternal blood or urine, and in cord blood. Child IQ was assessed using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Sex-effects were interpreted as meaningful if either the interaction p -value was <.10 or a sex-stratified association was statistically significant (p <.05). There was a consistent trend of male susceptibility observed across studies. Higher prenatal concentrations of lead, mercury, fluoride, PBDEs (i.e., BDE-47), PFAS (i.e., PFOS, PFOA, PFHxS), phthalates (i.e., ΣDiDPm), and pesticides (i.e., DEAP) were associated with lower IQ scores in male children, especially in Performance IQ. Associations in females were largely null. These sex-specific associations likely reflect a combination of biological, developmental, and cohort-specific factors. Given the population-level implications of even modest IQ reductions, these findings highlight the importance of systematically evaluating the sex-specific susceptibility of intelligence to environmental chemicals.

Pregnant women and their fetuses are routinely exposed to complex mixtures of chemicals: from metals in water, to flame retardants in furniture, pesticides in food, and plasticizers in cosmetics. Mounting evidence has associated higher exposure to many of these environmental chemicals with poorer neurodevelopmental outcomes, including lower Intelligence Quotient (IQ) scores in children (1–7). Epidemiological studies report that prenatal exposure to metals (4, 8), pesticides (5, 9), fluoride (1, 10), polybrominated diphenyl ethers (PBDEs) (2, 11), poly- and perfluoroalkyl substances (PFAS) (6, 12), and phthalates (7, 13) is linked with reductions in children's IQ scores. Emerging findings from several studies also suggest that males may be especially vulnerable to these effects (14, 15), potentially due to sex-specific differences in maternal and fetal thyroid regulation, placental physiology, and other biological mechanisms. A 2023 systematic review reported sex-related differences in the neurodevelopmental effects of environmental chemicals in multiple pregnancy cohorts (14). While this approach allows for examination of the generalizability of study findings, differences in population characteristics, study design, and exposure and outcome assessment methods can hinder identification of consistent patterns in results.

In this narrative synthesis, we summarized findings from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, a well-characterized pan-Canadian pregnancy and birth cohort. We provide a brief overview of eight publications (1–7, 16) that quantified associations between prenatal concentrations of environmental chemicals and child IQ, with consideration of sex-specific differences in the MIREC study population (17, 18). We then 1) discuss possible biological mechanisms underlying these associations and 2) interpret the findings within the context of the MIREC birth cohort. This within-cohort approach allows for more direct comparison across previously published MIREC findings, reduces heterogeneity in study design and exposure measurement, and enables us to assess the consistency of sex-specific associations across multiple environmental contaminants under similar methodological conditions. The added value of this work is being able to identify consistent trends that may not be apparent when findings are considered in isolation or across multiple cohorts.

Sex-specific associations in MIREC

Eligible studies were restricted to those from the MIREC cohort and included analyses that quantified prenatal chemical concentrations (in any trimester or exposure matrix) and assessed child IQ (n = 245–606; sample sizes presented in Supplementary Table S2). Of those, we identified eight studies (Supplementary Table S1) that investigated sex-specific associations between prenatal chemical concentrations and child IQ in the MIREC cohort (1–7, 16). These studies analyzed more than 25 biomarkers in first-trimester maternal urine or blood samples using gold-standard methods (Supplementary Table S2). Some biomarkers were also measured in second-trimester, third-trimester or cord blood. Daily fluoride intake from water, tea, and coffee was estimated across pregnancy for all women. As the timing of exposure assessment and type of biological matrix varied across studies, we were unable to evaluate critical windows of susceptibility across chemicals.

In each of the eight studies, child IQ was assessed between 36 and 47 months using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-III). The WPPSI-III is a standardized test for assessing cognitive ability in young children (19). Full-Scale (FSIQ), Verbal (VIQ), and Performance IQ (PIQ) scores were the main outcomes of interest. Associations between prenatal chemical concentrations and children's IQ scores were estimated using linear regression models (1–3, 6, 7, 16), generalized estimating equations (5), or general linear mixed models (4), with adjustment for relevant covariates and potential confounders (e.g., maternal age, race, level of education, pre-pregnancy body mass index, smoking status, alcohol intake, parity, city of residence, child sex, quality of the home environment); for a list of study-specific covariates and confounders, see Supplementary Table S1. Effect modification by child sex was explored either by including an exposure by sex interaction term (1–3, 6, 7, 16) or stratifying analyses for male and female children separately (4, 5). Given differences in modeling and reporting practices across studies, our narrative synthesis adopts a liberal and inclusive approach to identifying sex-specific effects to minimize the chance of overlooking possible sex differences. Specifically, we interpreted results as meaningful if either the interaction p -value was <.10 or a sex-stratified association was statistically significant (p <.05). We identified 19 statistically meaningful sex differences (Figure 1) among 72 chemical biomarkers across the three IQ domains. Detailed information on how results were reported and interpreted in the original studies is provided in Supplementary Table S2 and visualized in Supplementary Figure S1 for FSIQ.

Sex-specific associations were observed in analyses of metals (i.e., lead and mercury), fluoride, PBDEs, PFAS, phthalates, organophosphate pesticides (OPPs), and broad-spectrum herbicides (i.e., glyphosate) (Figure 1; Supplementary Table S2). Results for prenatal mercury exposure are described separately due to additional stratification by level of maternal fish consumption in pregnancy, to account for its dual role as both a source of mercury and potential neuroprotective nutrients (see Packull-McCormick et al., 2023 for more information). For nine chemicals, higher prenatal concentrations were associated with lower IQ in male children, but not in female children. Higher maternal or cord-blood concentrations of lead (3), fluoride (1), BDE-47 (2), PFOS, PFOA, and PFHxS (6), DEAP (5), and ΣDiDPm (7), were associated with lower IQ scores in males, with reductions up to 4.5 points in FSIQ, 4.6 points in PIQ, and 6.3 points in VIQ. In contrast, each doubling in maternal urinary MEP and MMP concentration (averaged across pregnancy) was associated with a 0.7-point decrease and 3.2-point increase in females VIQ and PIQ scores, respectively. According to the criteria employed in this review, we observed a sex-specific difference in the association between glyphosate and VIQ (p -int = 0.05); however, neither association in males nor females was statistically significant (n = 499). Across the studies reviewed, the non-null associations consistently showed an inverse relationship between prenatal chemical concentrations and IQ in male children, with largely null associations in females (Figure 1). These male-specific effects were more commonly observed with PIQ than with VIQ.

The relationship between prenatal mercury exposure and child IQ varied by child sex, IQ domain, and level of maternal fish consumption (4). For mothers with low fish consumption in pregnancy (i.e., 0-2 times/month), a two-fold increase in cord blood mercury was associated with a 3.3-point decrease in PIQ in male children. In contrast, moderate and high mercury levels were linked with higher FSIQ in females. These findings suggest that, in the absence of co-occurring exposure to the neuroprotective benefits of fish consumption, male children are susceptible to potential IQ-related effects of in utero mercury exposure (4).

Overall, greater male susceptibility was observed across multiple chemical classes, exposure sources, matrices, and time points, demonstrating preliminary evidence of a consistent sex-based susceptibility to developmental neurotoxicants within this cohort.

Why may males be more susceptible?

Neurotoxicants may operate through overlapping mechanisms that converge on the same neurodevelopmental outcome; yet the question remains: why do males appear to display greater reductions in IQ following exposure to various common environmental chemicals? Here we consider the biological, developmental and cohort-specific factors that may increase male susceptibility.

Is it biological?

Males are at heightened risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intellectual disability (ID) (20). Innate sex-specific differences in physiology as well as chemical toxicokinetics may contribute to the enhanced male susceptibility to early life neurotoxicant exposures (21–23). Potential mechanistic explanations include sex-specific differences in neurodevelopmental trajectories (i.e., brain maturation), placental physiology, sex hormone profiles, metabolism, epigenetic markers, and maternal thyroid function.

Neurodevelopmental trajectories

Male and female fetuses differ in the rate of neural maturation, with slower functional maturation reported in males (14, 24). Evidence for faster functional maturation in females includes earlier behavioural responsiveness (by approximately two weeks) to vibratory stimulation applied to the maternal abdomen (25). In neonates, females also show signs of more advanced cortical electroencephalogram activity during both sleep and wakeful periods (26), along with faster neural conduction in auditory (27) and visual response pathways (28). While few corresponding anatomical sex-related differences in the fetal brain have been identified, one study reported slightly earlier formation of the corpus callosum in female fetuses (29). This slower maturation of the male nervous system potentially extends the developmental window during which the brain is vulnerable to disruption from prenatal neurotoxicant exposure. This extended window of vulnerability may also lower the threshold of sensitivity to toxicants in males, making them more susceptible to adverse effects at lower levels of exposure than females; a pattern that has been reported in the context of lead exposure (24). This issue is relevant to the MIREC study, as exposure levels in this Canadian cohort are relatively low compared with other countries (30, 31).

Placental physiology

The sexually dimorphic nature of the human placenta is another potential explanation for male susceptibility to neurotoxicant exposures. Prior studies suggest that the female placenta exhibits a more adaptive and protective response to maternal stressors, whereas the male placenta is less flexible under similar conditions (14). Compared with males, the female placenta shows greater expression of genes (e.g., K1, IL2RB, Clusterin) (32) and proteins involved in transport, immune regulation, growth, and development, which allows the female fetus to better adjust to changes in the maternal environment, providing a certain level of protection from prenatal insults (33). In contrast, the male placenta tends to invest resources primarily in growth (34) which may result in a reduced capacity to adapt to adversity and a greater risk of morbidity, mortality, and neurodevelopmental disruption (33).

Developmental toxicants can accumulate differently in the placenta depending on sex. Concentrations of flame retardants and PFAS have been reported to be higher in the male placenta (34, 35). Placental transporter voltage-dependent anion-selective channel protein 1, a major calcium transport channel critical for fetal development, is also preferentially enhanced in male placentas (36). This increased channel activity could predispose male fetuses to toxicants that can exploit this receptor during the prenatal period. Differences in placental inflammation and oxidative stress may also contribute to male susceptibility. Intrauterine inflammation has been shown to trigger a neuroinflammatory response including up-regulation of pro-inflammatory cytokines and greater macrophage activation in males specifically (37). Male infants also exhibit higher levels of placental oxidative stress at birth relative to females (38). As many environmental chemicals have been shown to induce oxidative stress in the placenta (39, 40), higher baseline levels of oxidative stress in males may increase their risk of surpassing a pathological threshold. Stronger neuroinflammatory responses and oxidative stress in males could, in turn, contribute to greater neurodevelopmental vulnerability.

Differences in placental physiology between males and females, including the male placenta's limited adaptability (14), greater accumulation of toxicants (34, 35), and excess inflammation and oxidative stress (38), may contribute to increased susceptibility of male offspring to neurodevelopmental effects associated with prenatal chemical exposures.

Sex hormones

Estrogen is widely recognized as neuroprotective (41–43), activating molecular pathways that reduce oxidative stress and neuroinflammation while enhancing synaptic plasticity, axonal growth, neurogenesis, remyelination and other repair processes. These protective effects are further supported by evidence that the female brain demonstrates greater resilience to neurotoxic injury (14). Male fetuses have fewer estrogen receptors than females and may, therefore be more susceptible to the neurotoxic effects of chemicals, as has been found for metals (41).

Toxicokinetics

Differences in metabolism and clearance of environmental chemicals may also contribute to male susceptibility. Animal studies indicate that certain chemicals, like PFAS, persist longer in males than females due to slower clearance and extended half-lives (6, 44). Additional animal evidence suggests that male fetuses exhibit a faster metabolic rate and more rapid growth than females in early gestation (45). These traits could promote greater accumulation and transfer of chemicals from the mother to the male fetus, as higher nutrient uptake through the placenta may also facilitate increased toxicant transfer. Findings from a Chinese epidemiologic study (46) supports this hypothesis, reporting that male fetuses accumulated higher levels of metals (e.g., silver and titanium) than female fetuses. Specifically, they found that the placenta-to-maternal ratio of silver was significantly higher for males, providing further evidence that placentas of male fetuses may accumulate and transfer toxicants more readily than those of females. The greater accumulation and prolonged retention of toxic chemicals in male fetuses may result in elevated cumulative exposure during critical periods of brain development, increasing the potential for adverse neurodevelopmental outcomes, including lowered IQ.

Epigenetics

While epigenetic modifications occur throughout life, the prenatal period is considered a period of particular epigenetic malleability and remodeling (47). Mechanisms such as DNA methylation play a central role in regulating neurodevelopment, and mounting evidence suggests that environmental toxicants can induce sex-specific changes in these processes (6).

Prenatal PFOS exposure has been linked to DNA methylome alterations in cord blood from males but not females, with predicted downstream effects on genes involved in embryonic and nervous system development (48). Similarly, perinatal lead exposure produced hypomethylation in hippocampal genes related to learning and memory exclusively in male rats (49), while prenatal mercury exposure in humans was associated with altered methylation at the Paraoxonase 1 (PON1) gene in males but not females (50). Notably, PON1 methylation changes were predictive of lower receptive vocabulary in early childhood. Together, these findings point to sex-specific epigenetic programming as a possible mechanism linking prenatal toxicant exposure to greater neurodevelopmental risk in males.

Maternal thyroid function

Environmental chemicals may exert their neurotoxic effects on the developing brain by interfering with maternal thyroid functioning. Thyroid disruption is of particular concern in pregnancy because the developing fetus relies exclusively on maternal thyroid hormones during the first 10 to 12 weeks of gestation and to a lesser extent throughout the second and third trimesters (51). Thyroid hormones are essential for regulating early stages of brain development, such as neurogenesis, myelination, dendrite proliferation, and synapse formation (52). As such, gestational hypothyroidism has been associated with various adverse neurodevelopmental outcomes in children including preterm birth, increased risk of neurological (e.g., seizure disorders) and neurodevelopmental disorders (e.g., ASD and ADHD), and lower IQ (53–55). Some evidence suggests that maternal thyroid hormone levels in pregnancy may differ by fetal sex. Specifically, Belgian and Chinese women pregnant with male fetuses were more likely to exhibit elevated thyroid-stimulating hormone levels (56, 57), indicating a potential sex-specific susceptibility in maternal thyroid regulation.

While endocrine disrupting chemicals (EDCs) like fluoride (58), certain phthalates (59), PFAS (60, 61), and phenols (62) have been shown to disrupt maternal thyroid function in pregnancy, less is known about potential sex-specific differences in the associations between maternal exposure to environmental chemicals and thyroid dysfunction. Among some populations of pregnant women and children, associations between fluoride (63, 64), PFOA (65), dichlorodiphenyldichloroethylene (66), and PBDE (67) exposure and thyroid hormone levels in the fetus or offspring differed by sex. There is also evidence that environmental chemicals induce sex-specific changes in the expression of thyroid related genes in the placenta (67, 68). Specifically, prenatal exposure to persistent organic pollutants was found to influence the methylation of thyroid transporter genes (e.g., deiodinase type 3 and monocarboxylate transporter 8) in the placenta in a sexually dimorphic manner (68). Thus, it is possible that EDCs exert sex-specific changes in the quantity and frequency of thyroid hormone transport from mother to fetus. In summary, maternal thyroid dysfunction in pregnancy is a plausible mechanism underlying the sex-specific effects of environmental chemicals on neurodevelopment.

Are these patterns specific to the MIREC cohort?

The unique characteristics of the MIREC study population are unlikely to determine the observed sex-specific associations between prenatal environmental chemical exposures and child IQ.

Compared with the general Canadian pregnant population, the MIREC cohort primarily consists of women who are older (mean age = 32.2 years; SD = 5.1), White, highly educated (>62% with a university degree), with adequate nutrient status (e.g., iodine, folate) and relatively few lifestyle and health risk factors (e.g., largely nonsmokers, widespread prenatal supplement use) (17). Although the demographic composition of the MIREC cohort limits its generalizability to the broader Canadian population, the sociodemographic homogeneity helps minimize the potential for residual confounding by socioeconomic status and related factors. Moreover, the MIREC cohort has undergone extensive and detailed phenotypic characterization, and researchers have adjusted for most key covariates (apart from maternal IQ, which was not assessed in MIREC). Many of the studies included in this narrative synthesis conducted extensive sensitivity analyses to adjust for additional precision variables including parental depression, stress, and co-exposures to environmental chemicals. Therefore, it is unlikely that the observed sex-specific associations in MIREC are driven by confounding bias or are unique to this population.

Biomarker concentrations of prenatal environmental chemical exposures in MIREC participants are relatively low compared with levels reported in other parts of the world (30, 31, 69). As such, the sex-specific associations observed in this cohort are notable because they occur at relatively low exposure levels; in more diverse populations with higher exposure burdens, the associations may be even stronger and more pervasive.

As the analytic sample investigated in each study was a subset of the complete MIREC study population, it is also important to consider the potential for selection bias. However, based on comparisons between the analytic samples and the overall cohort in each original paper, there is no evidence to suggest that the observed associations were driven by selection bias. In the study of prenatal mercury exposure (4), for example, the authors found consistent results between the inverse probability weighted and unweighted models, suggesting that selection bias is not a primary explanatory factor.

Are the sex-specific results explained by differences in exposure levels?

Biomarker and intake levels did not significantly differ between women carrying male and female fetuses among 26 of the 28 (93%) exposures examined (Table 1). As reported by Goodman et al. (2025) (7), two biomarkers of maternal phthalate exposure (i.e., ΣDiBPm and MCPP) were significantly higher in women pregnant with males, than those pregnant with females (p <.05); however, these exposures were not significantly associated with child IQ (Supplementary Table S1). This finding indicates that the significant effects of prenatal chemical exposures on male IQ are unlikely to be driven by differences in observed exposure levels in pregnant women.

Do lower IQ scores make males in the MIREC cohort more vulnerable?

Independent of the effects of neurotoxicant exposures, female children in the MIREC cohort have higher IQ scores than males (70). The differences are most pronounced for VIQ, but also reach significance for FSIQ and PIQ. This female advantage aligns with some developmental literature indicating that preschool aged females, on average, out-perform preschool aged males on verbal (71) and speeded tasks (72). However, the pattern observed in the MIREC cohort contrasts with other studies reporting that preschool aged males tend to show greater accuracy than females on spatial tasks (73, 74). Of note, we have ruled out any significant sex-based differences in critical social or environmental predictors of intelligence among MIREC children, including parental education levels and household income, that could potentially explain the observed female advantage in the MIREC cohort. It is also worth noting that there is a lack of consensus regarding sex differences in intelligence, particularly when more current studies are examined and developmental changes are factored in, underscoring the need for caution when generalizing sex differences in cognitive domains (74, 75).

Importantly, the differences in intelligence scores between males and females in the MIREC cohort do not explain the observed sex-specific associations between prenatal chemical exposures and child IQ. Rather, the observed exposure-outcome associations observed predominantly in males, compared with females, may reflect a male susceptibility to prenatal chemical exposures. More specifically, males have an increased risk of neurodevelopmental disorders, including intellectual disability, which could make them more susceptible than females to the impacts of prenatal chemical exposures. Genetic risk factors influencing general intelligence (which may explain the disproportionate numbers of males with intellectual disability) (76), could therefore reduce an individual's “reserve capacity” for responding adaptively to later brain insults, such as early-life exposures to neurotoxicants.

Thus, even if underlying sex differences in IQ scores do exist, they would not determine whether associations between prenatal chemical exposures and child IQ differ by sex. In other words, baseline sex differences in IQ do not explain why higher prenatal neurotoxicant exposures appear to affect males more than females in the MIREC cohort.

Why is performance IQ more sensitive?

The observed pattern of predominantly lower non-verbal IQ (i.e., PIQ) in males may be explained by differential effects of neurotoxicants on brain regions that develop earlier in gestation (14). The hippocampus, for example, is highly sensitive to chemical exposures (e.g., PFAS, fluoride) (77) during development, and in addition to its role in learning and memory, contributes directly to higher-order spatial processing (78). The visual system also matures early, with the human fetus demonstrating the capacity to process perceptual information by the third trimester (79). This early development suggests that visual-spatial skills, which are central to PIQ, may be especially susceptible to disruptions during early prenatal life. Importantly, this aligns with the timing of exposure assessment in the MIREC studies, as most (86%) biomarkers showing significant associations with PIQ capture first-trimester exposure, when these brain structures would be undergoing critical stages of development. In contrast, brain regions that support language development and verbal intelligence mature later, and verbal skills are largely shaped by enriched early home environments (80), which may buffer against potential adverse effects of prenatal exposures in the MIREC cohort. Taken together, these developmental and environmental considerations may explain why non-verbal intelligence may be more affected by prenatal neurotoxicant exposures in males.

It is also important to consider that IQ was assessed at a single time point, between 36 and 47 months of age. As such, it is possible that the observed sex-specific associations may not reflect stable differences in IQ that persist into later childhood, and the magnitude of these effects could also change over time (81). Although intelligence has been shown to be relatively stable across development (82), both the prenatal period and early childhood remain critical periods of neurodevelopment during which the impacts of neurotoxicants on the brain may vary over time (81, 83). Moreover, associations observed in early childhood may still be modifiable and could attenuate, strengthen, or otherwise change depending on the child's developmental context (84, 85). Similarly, patterns that appear male-specific at this age may emerge in females at later developmental stages. Longitudinal follow-up is needed to determine the stability and long-term implications of these sex-specific associations.

What about the impact of chemical mixtures?

Another key consideration is the role of co-exposure to environmental chemicals. Many of the reviewed MIREC studies controlled for concurrent exposure to other neurotoxicants but did not examine the cumulative or joint impact of multiple chemical exposures on child IQ. Puvvula and colleagues (2025), however, recently published results from a pooled analysis of associations between 29 biomarkers of prenatal chemical exposures and cognitive abilities in children from the MIREC study and the US-based Health Outcomes and Measures of the Environment (HOME) pregnancy cohort study (86). This mixture analysis included most of the chemical classes examined in the present narrative synthesis (i.e., lead, mercury, PBDEs, OPPs, PFAS, and phthalates). Overall, the authors found a negative trend between the chemical biomarker mixture and FSIQ (B = −0.64 per 10-fold increase) and PIQ (B = −1.59) only in males, lending further support for the conclusions made here, in that MIREC males appear more sensitive to the adverse impacts of developmental neurotoxicants.

Further consideration of chemical mixtures within the MIREC cohort focused on chemicals with potential shared mechanisms would provide insight into biologically plausible joint effects. For instance, mixtures analyses comprising chemicals with demonstrated toxicity to maternal thyroid may help elucidate and strengthen evidence regarding joint effects on neurodevelopment (87). Despite the value of exploring chemical mixtures, it is worth noting that mixtures analyses must be constructed thoughtfully and appropriately as poorly specified or overly inclusive mixture models can obscure true associations and introduce bias (88).

Evidence from the MIREC cohort reveals a relatively consistent pattern whereby male children appear more adversely affected by prenatal chemical exposures in relation to IQ than females. This clear pattern of male susceptibility fits within a broader body of research suggesting that the male brain is more sensitive to early-life insults (89). The explanation likely involves a complex interplay of biological, developmental, and sample demographic factors. Biologically, sex-specific differences in the timing of neural maturation, placental physiology, sex hormone profiles, toxicokinetics, epigenetic regulation, and maternal thyroid function may collectively impact susceptibility. Developmentally, the timing of exposure relative to critical windows of brain maturation and organization further influences outcomes.

Cohort-specific factors further help contextualize and strengthen the findings. The MIREC cohort is characterized by relatively low chemical exposures and a highly educated and low-risk demographic profile, which minimizes within-study confounding by socioeconomic factors. In this context, the consistent pattern of male susceptibility observed across multiple chemicals provides evidence of a sex-specific effect in this cohort. As discussed, these results are unlikely to be explained by selection bias, confounding, or chance. Moreover, the measurement of chemical exposure levels in the same maternal urine or blood, and cord blood samples, as well as the consistent use of IQ outcomes from 3-to-4 years of age, enhances confidence in the observed associations. Despite the advantages of these cohort-specific factors, we recognize that the existing data did not permit analysis of how sex-specific effects could differ by windows of exposure. Future research is therefore needed to determine whether the timing of prenatal exposures across critical developmental windows differentially influences neurodevelopmental outcomes in males and females.

Results presented in this review align with a wider understanding of the male fetus as being more vulnerable to a range of adverse prenatal conditions, including maternal stress, malnutrition, and infection (89, 90). Together, this body of evidence underscores the importance of systematically testing for sex-specific differences in environmental epidemiology. Without doing so, we risk overlooking critical vulnerabilities. Considering sex differences in early-life susceptibility to neurotoxicants, and the mechanisms that may underlie them, is not only of scientific interest but also of public health importance. This knowledge is essential for identifying at-risk populations and developing targeted policies and prevention strategies aimed at reducing harm from chemical exposures.

The significance of these findings is emphasized by the fact that even modest decrements in IQ can have profound consequences on the population level. In the MIREC studies, reductions of 4.5 to 6.3 IQ points were observed across domains. While these differences may appear small at the individual level, a population-wide shift of 4–6 IQ points has critical societal implications in increasing the number of very low performers while reducing the number of high performers, contributing to significant economic and social costs (14, 91). Moreover, even mild IQ deficits can have lasting consequences for academic achievement, occupational attainment, and psychological well-being (14).

These findings highlight the urgent need to better understand and address sex-specific susceptibilities to prenatal neurotoxicant exposures.