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

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.

• Authors: Erin A S Clark, Steven J Weiner, Dwight J Rouse, Brian M Mercer, Uma M Reddy, Jay D Iams, Ronald J Wapner, Yoram Sorokin, Fergal D Malone, Mary J O'Sullivan, Alan M Peaceman, Gary D V Hankins, Donald J Dudley, Steve N Caritis, Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units (MFMU) Network
• Journal: American journal of perinatology (Am J Perinatol) Vol. 35 Issue 10 Pg. 1012-1022 (08 2018) ISSN: 1098-8785 [Electronic] United States
• PMID: 29510423 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Chemical References

• IL6R protein, human
• Neuroprotective Agents
• Receptors, Interleukin-6
• Magnesium Sulfate

Topics

• Case-Control Studies
• Cerebral Palsy (genetics, prevention & control)
• Child, Preschool
• Female
• Genetic Variation
• Gestational Age
• Humans
• Infant
• Infant Mortality
• Infant, Newborn
• Infant, Premature, Diseases (etiology)
• Logistic Models
• Magnesium Sulfate (therapeutic use)
• Male
• Neurodevelopmental Disorders (genetics, prevention & control)
• Neuroprotective Agents (therapeutic use)
• Polymorphism, Single Nucleotide
• Pregnancy
• Premature Birth
• Prenatal Care (methods)
• Prenatal Exposure Delayed Effects
• Psychomotor Disorders (genetics, prevention & control)
• Receptors, Interleukin-6 (genetics)
• Stillbirth