Associations between prenatal lead exposure and birth outcomes: Modification by sex and GSTM1/GSTT1 polymorphism

Maternal lead exposure is associated with poor birth outcomes. However, modifying effects of polymorphism in glutathione S-transferases (GST) gene and infant sex remain unexplored. Our aim was to evaluate whether associations between prenatal lead and birth outcomes differed by maternal GST genes and infant sex. Prospective data of 782 mother-child pairs from Mothers and Children's Environmental Health (MOCEH) study were used. The genotyping of GST-mu 1 (GSTM1) and theta-1 (GSTT1) polymorphisms was carried out using polymerase chain reaction. Multivariable linear regression was used to examine whether the association between blood lead (BPb) level and birth outcomes (birthweight, length, and head circumference) varied by maternal GST genes and sex. We did not find a statistically significant association between prenatal BPb levels and birth outcomes; in stratified analyses, the association between higher BPb level during early pregnancy and lower birthweight (β=-224 per square root increase in BPb; 95% confidence interval (CI): -426, -21; false discovery rate p=0.036) was significant in males of mothers with GSTM1 null. Results were similar for head circumference model (β=-0.78 per square root increase in BPb; 95% CI: -1.69, 0.14, p=0.095), but the level of significance was borderline. Head circumference model showed a significant three-way interaction among BPb during early pregnancy, GSTM1, and sex (p=0.046). For combined analysis with GSTM1 and GSTT1, GSTM1 null and GSTT1 present group showed a significant inverse association of BPb with birthweight and head circumference in males. Our findings of the most evident effects of BPb on the reduced birthweight and head circumference in male born to the mother with GSTM1 null may suggest a biological interaction among lead, GST genes and sex in detoxification process during fetal development.