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Genetic Variation, Magnesium Sulfate Exposure, and Adverse Neurodevelopmental Outcomes Following Preterm BirthFunding The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD27869, HD34208, HD34116, HD40544, HD27915, HD34136, HD21414, HD27917, HD27860, HD40560, HD40545, HD40485, HD40500, HD27905, HD27861, HD34122, HD40512, HD53907, HD34210, HD21410, HD36801, HD19897]; MO1-RR-000080; and by the National Institute of Neurological Disorders and Stroke (NINDS). Dr. Clark was supported by the National Institutes of Health, National Institute of Child Health and Human Development (K23HD061910). Comments and views of the authors do not necessarily represent views of the NIH.
21 January 2018
23 January 2018
06 March 2018 (online)
Objective To evaluate the association of magnesium sulfate (MgSO4) 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 MgSO4 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. MgSO4 may abrogate this genotype association for some loci.
Keywordscandidate genes - magnesium sulfate - mental developmental delay - neurodevelopmental delay - preterm birth - polymorphisms - psychomotor delay - single-nucleotide polymorphisms
* The members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network are listed in the Appendix.
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