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Am J Perinatol 2018; 35(10): 1012-1022
DOI: 10.1055/s-0038-1635109
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

Erin A. S. Clark
1   Department of Obstetrics and Gynecology at the University of Utah Health Sciences Center, Salt Lake City, Utah
,
Steven J. Weiner
2   The George Washington University Biostatistics Center, Washington, District of Columbia
,
Dwight J. Rouse
3   Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama
,
Brian M. Mercer
4   Department of Obstetrics and Gynecology, MetroHealth Medical Center-Case Western Reserve University, Cleveland, Ohio
5   Department of Obstetrics and Gynecology, University of Tennessee, Memphis, Tennessee
,
Uma M. Reddy
6   Department of Obstetrics and Gynecology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
,
Jay D. Iams
7   Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio
,
Ronald J. Wapner
8   Department of Obstetrics and Gynecology, Thomas Jefferson University and Drexel University, Philadelphia, Pennsylvania
,
Yoram Sorokin
9   Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan
,
Fergal D. Malone
10   Department of Obstetrics and Gynecology, Columbia University, New York, New York
,
Mary J. O'Sullivan
11   Department of Obstetrics and Gynecology, University of Miami, Miami, Florida
,
Alan M. Peaceman
12   Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois
,
Gary D. V. Hankins
13   Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas
,
Donald J. Dudley
14   Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, Texas
,
Steve N. Caritis
15   Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania
,
for the Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units (MFMU) Network› Author Affiliations
Funding 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.
Further Information

Publication History

21 January 2018

23 January 2018

Publication Date:
06 March 2018 (online)

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Abstract

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.

Keywords

candidate 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.