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

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

doi:10.1055/s-0038-1635109

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

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

^*Corresponding author for this work

Obstetrics and Gynecology

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1012-1022
Number of pages	11
Journal	American journal of perinatology
Volume	35
Issue number	10
DOIs	https://doi.org/10.1055/s-0038-1635109
State	Published - Aug 1 2018

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.

Keywords

candidate genes
magnesium sulfate
mental developmental delay
neurodevelopmental delay
polymorphisms
preterm birth
psychomotor delay
single-nucleotide polymorphisms

ASJC Scopus subject areas

Obstetrics and Gynecology
Pediatrics, Perinatology, and Child Health

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Clark, E. A. S., Weiner, S. J., Rouse, D. J., Mercer, B. M., Reddy, U. M., Iams, J. D., Wapner, R. J., Sorokin, Y., Malone, F. D., O'Sullivan, M. J., Peaceman, A. M., Hankins, G. D. V., Dudley, D. J., & Caritis, S. N. (2018). Genetic Variation, Magnesium Sulfate Exposure, and Adverse Neurodevelopmental Outcomes Following Preterm Birth. American journal of perinatology, 35(10), 1012-1022. https://doi.org/10.1055/s-0038-1635109

@article{635555451c634722824456509a9054de,

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

abstract = "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.",

keywords = "candidate genes, magnesium sulfate, mental developmental delay, neurodevelopmental delay, polymorphisms, preterm birth, psychomotor delay, single-nucleotide polymorphisms",

author = "Clark, {Erin A.S.} and Weiner, {Steven J.} and Rouse, {Dwight J.} and Mercer, {Brian M.} and Reddy, {Uma M.} and Iams, {Jay D.} and Wapner, {Ronald J.} and Yoram Sorokin and Malone, {Fergal D.} and O'Sullivan, {Mary J.} and Peaceman, {Alan M.} and Hankins, {Gary D.V.} and Dudley, {Donald J.} and Caritis, {Steve N.}",

year = "2018",

month = aug,

day = "1",

doi = "10.1055/s-0038-1635109",

language = "English (US)",

volume = "35",

pages = "1012--1022",

journal = "American journal of perinatology",

issn = "0735-1631",

publisher = "Thieme Medical Publishers",

number = "10",

}

Clark, EAS, Weiner, SJ, Rouse, DJ, Mercer, BM, Reddy, UM, Iams, JD, Wapner, RJ, Sorokin, Y, Malone, FD, O'Sullivan, MJ, Peaceman, AM, Hankins, GDV, Dudley, DJ & Caritis, SN 2018, 'Genetic Variation, Magnesium Sulfate Exposure, and Adverse Neurodevelopmental Outcomes Following Preterm Birth', American journal of perinatology, vol. 35, no. 10, pp. 1012-1022. https://doi.org/10.1055/s-0038-1635109

TY - JOUR

T1 - Genetic Variation, Magnesium Sulfate Exposure, and Adverse Neurodevelopmental Outcomes Following Preterm Birth

AU - Clark, Erin A.S.

AU - Weiner, Steven J.

AU - Rouse, Dwight J.

AU - Mercer, Brian M.

AU - Reddy, Uma M.

AU - Iams, Jay D.

AU - Wapner, Ronald J.

AU - Sorokin, Yoram

AU - Malone, Fergal D.

AU - O'Sullivan, Mary J.

AU - Peaceman, Alan M.

AU - Hankins, Gary D.V.

AU - Dudley, Donald J.

AU - Caritis, Steve N.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

KW - candidate genes

KW - magnesium sulfate

KW - mental developmental delay

KW - neurodevelopmental delay

KW - polymorphisms

KW - preterm birth

KW - psychomotor delay

KW - single-nucleotide polymorphisms

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U2 - 10.1055/s-0038-1635109

DO - 10.1055/s-0038-1635109

M3 - Article

C2 - 29510423

AN - SCOPUS:85044097010

SN - 0735-1631

VL - 35

SP - 1012

EP - 1022

JO - American journal of perinatology

JF - American journal of perinatology

IS - 10

ER -

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

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