Genetic Variation, Magnesium Sulfate Exposure, and Adverse Neurodevelopmental Outcomes Following Preterm Birth

Objective To evaluate the association of magnesium sulfate (MgSO ₄) exposure and candidate gene polymorphisms with adverse neurodevelopmental outcomes following preterm birth. Study Design We performed a nested case-control analysis of a randomized trial of maternal MgSO ₄ before anticipated preterm birth for the prevention of cerebral palsy (CP). Cases were children who died within 1 year of life or were survivors with abnormal neurodevelopment at age 2 years. Controls were race- and sex-matched survivors with normal neurodevelopment. We analyzed 45 candidate gene polymorphisms in inflammation, coagulation, and vascular regulation pathways and their association with (1) psychomotor delay, (2) mental delay, (3) CP, and (4) combined outcome of death/CP. Logistic regression analyses, conditional on maternal race and child sex, and adjusted for treatment group, gestational age at birth and maternal education, were performed. Results Four hundred and six subjects, 211 cases and 195 controls, were analyzed. The strongest association was for IL6R (rs 4601580) in which each additional copy of the minor allele was associated with an increased risk of psychomotor delay (adjusted odds ratio 3.3; 95% confidence interval, 1.7-6.5; p < 0.001). Conclusion Candidate gene polymorphisms are associated with death and adverse neurodevelopmental outcomes following preterm birth. MgSO ₄ may abrogate this genotype association for some loci.