Prenatal Lead Exposure, Genetic Factors, and Cognitive Developmental Delay

Abstract

ImportanceAlthough the effects of lead (Pb) exposure on neurocognition in children have been confirmed, the individual associations of prenatal Pb exposure and its interaction with genetic factors on cognitive developmental delay (CDD) in children remain unclear.ObjectiveTo investigate the association of prenatal Pb exposure and its interaction with genetic factors with CDD risk.Design, Setting, and ParticipantsWomen in Wuhan, China, who had an expected delivery date between March 2014 and December 2017, were recruited for this prospective cohort study. Children were assessed for cognitive development at approximately 2 years of age (March 2016 to December 2019). Maternal venous blood, cord blood, and venous blood from children were collected in a longitudinal follow-up. Data analysis was performed from March 2022 to February 2023.ExposurePrenatal Pb exposure, and genetic risk for cognitive ability evaluated by polygenic risk score constructed with 58 genetic variations.Main Outcomes and MeasuresCognitive developmental delay of children aged approximately 2 years was assessed using the Chinese revision of the Bayley Scale of Infant Development. A series of multivariable logistic regressions was estimated to determine associations between prenatal Pb exposure and CDD among children with various genetic backgrounds, adjusting for confounding variables.ResultsThis analysis included 2361 eligible mother-child pairs (1240 boys [52.5%] and 1121 girls [47.5%]; mean [SD] ages of mothers and children, 28.9 [3.6] years and 24.8 [1.0] months, respectively), with 292 children (12.4%) having CDD. Higher maternal Pb levels were significantly associated with increased risk of CDD (highest vs lowest tertile: odds ratio, 1.55; 95% CI, 1.13-2.13), adjusting for demographic confounders. The association of CDD with maternal Pb levels was more evident among children with higher genetic risk (highest vs lowest tertile: odds ratio, 2.59; 95% CI, 1.48-4.55), adjusting for demographic confounders.Conclusions and RelevanceIn this cohort study, prenatal Pb exposure was associated with an increased risk of CDD in children, especially in those with a high genetic risk. These findings suggest that prenatal Pb exposure and genetic background may jointly contribute to an increased risk of CDD for children and indicate the possibility for an integrated strategy to assess CDD risk and improve children’s cognitive ability.

Lasting Adverse Effects of Low-Level Lead Exposure on Cognition and Heritable Susceptibilities

“…From a methodological perspective, it is instructive to note that in this study, 1 lead levels in maternal plasma (as opposed to maternal whole blood) were found to be associated with lower cognition scores among offspring. In so doing, Li et al 1 have provided further support to earlier research suggesting that maternal plasma lead, which is typically less than 1% to 5% of the level of lead in maternal whole blood, is not in complete equilibrium with the lead bound to red cells. Nevertheless, it is the component of lead in blood that is bioavailable to cross the placenta and therefore has the most influence on fetal lead exposure and resulting neurotoxic effects.…”

“…metal mining and processing, electronic waste, and the use of lead as a food adulterant, primarily in spices. 6 In addition, as the authors mentioned in their introduction, 1 for pregnant women, the mobilization of bone lead stores during pregnancy remains of concern. Left unmentioned is that skeletal stores of lead persist for decades, and in women who have had chronic lead exposure, research has clearly shown that the heightened bone resorption that occurs during pregnancy is accompanied by the increased release of bone lead stores, resulting in elevated circulating lead levels even if women are fastidious in avoiding lead exposure during pregnancy itself.…”

“…As opposed to postnatal (ie, pediatric) lead exposure-which, based on the evidence from hundreds of rigorous investigations around the world, has resulted in a long history of evertightening environmental controls, screening of blood lead levels in children, and ever-lower levels of lead in blood that are considered acceptable-there has been relatively little attention to lead exposure in the womb. By conducting this research with both state-of-the-art methods for measuring prenatal and postnatal lead exposure and the advantage of a large sample size, Li et al 1 have advanced the field, generating results indicating that prenatal lead exposure is adversely associated with cognition, independent of postnatal lead exposure.…”

Sex Dependent Intergenerational Effects of Lead in Mouse Model

“…Although numerous studies (Liu et al, 2014;Jia et al, 2023;Shah-Kulkarni et al, 2016) focused on maternal exposure and consequent neurological defects, there has been an increase in the investigation of paternal inherited neurological diseases. This is critical as occupational Pb exposure mostly occurs in men (Balachandar et al, 2020).…”