Sex-specific differences in birth outcomes in relation to maternal blood lead levels: ALSPAC prospective cohort study

Abstract

BackgroundThe results of previous studies of the associations between prenatal blood lead levels (BLL) and pregnancy outcomes such as birthweight and preterm delivery have been inconsistent. Such effects are important because poor birth outcomes are associated with poor developmental trajectories in infancy and have long-term implications for adult health. Male fetuses are thought to be more prone to the effects of environmental stressors on adverse pregnancy outcomes than are female fetuses, but there has been no attempt to ascertain whether there is a difference in the susceptibility to the adverse effects of maternal BLL. Our aim was to study these associations by sex in a large cohort of mother–child pairs. MethodsPregnant women resident in the Avon area of the UK were enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective cohort study, with an expected delivery date between April, 1991, and December, 1992. Whole blood samples were collected at a median of 11 weeks' gestation (IQR 9–13) and analysed by inductively coupled plasma dynamic reaction cell mass spectrometry (n=4285, resulting in n=4267 livebirths). Self-completion postal questionnaires were used to collect data for lifestyle, diet, and environmental factors during pregnancy. Data collected for the infants included anthropometric variables and gestational age at delivery. Statistical analysis was done with SPSS (version 18). Regression models stratified by sex of the infant were adjusted for maternal height and pre-pregnancy weight, smoking, gestational age, and parity (n=1345–1525 for girls and n=1392–1626 for boys). For logistic regression, maternal BLL was categorised as less than 5 or at least 5 μg/dL. FindingsMean maternal BLL was 3·67 μg/dL (SD 1·47; median 3·41, range 0·41–19·14). The risk of low birthweight was 5·4% for girls and 4·6% for boys (p=0·234). The risk of preterm delivery was 4·9% for girls and 6·5% for boys (p=0·024). In boys, the risk of low birthweight was significantly increased for maternal BLL at least 5 μg/dL (odds ratio [OR] 2·17, 95% CI 1·22–3·86; p=0·008) in adjusted logistic regression models, but this association was not apparent in girls (1·54, 0·81–2·90; p=0·186). There was an increased risk of preterm delivery in both boys (OR 1·86, 95% CI 1·11–3·12; p=0·018) and girls (2·14, 1·10–2·94; p=0·015). Associations of maternal BLL with reductions in birthweight, head circumference, and crown–heel length in adjusted linear regression models showed weak evidence of significance in boys (p=0·030, p=0·067, and p=0·056, respectively), but were not significant in girls (p=0·196, p=0·133, and p=0·225, respectively). InterpretationEven though the mean maternal BLL was below the level generally judged to be of any consequence, there was evidence of an adverse effect of maternal BLL on pregnancy outcomes for boys, with reductions in birthweight, head circumference, and crown–heel length, and an increased risk of preterm delivery and low birthweight, in adjusted regression models. These associations were not apparent for girls, except for the risk of preterm delivery. These adverse effects could have important long-term effects on the physical and neurological development of boys. The reasons for boys being more susceptible to the effect of maternal BLL in utero are unclear but might be related to the increased demand for oxygen and nutrients to fuel a faster rate of growth, differences in the hormonal milieu, the anti-oestrogenic effect of lead, sex-specific methylation differences, or a combination thereof. There is a need to develop public health policies to minimise exposure to lead before and during pregnancy, especially for the mothers of boys, and to provide postnatal support for boys. FundingThe UK MRC and the Wellcome Trust (grant ref 092731) and the University of Bristol provide core support for ALSPAC. CMT was supported by a Daphne Jackson Trust Fellowship sponsored by the University of Bristol.