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Am J Perinatol 2022; 39(09): 0921-0929
DOI: 10.1055/a-1692-0659
SMFM Fellowship Series Article

Association between Hypertensive Disorders of Pregnancy and Long-Term Neurodevelopmental Outcomes in the Offspring

Anna Palatnik 
1   Department of Obstetrics and Gynecology of Northwestern University, Chicago, Illinois
,
Lisa Mele
2   George Washington University Biostatistics Center, Washington, District of Columbia
,
Brian M. Casey
3   Department of Obstetrics and Gynecology, University of Texas, Southwestern, Dallas, Texas
,
Michael W. Varner 
4   Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah
,
Yoram Sorokin
5   Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan
,
Uma M. Reddy
6   Department of Obstetrics and Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
,
Ronald J. Wapner
7   Department of Obstetrics and Gynecology, Columbia University, New York, New York
,
John M. Thorp Jr.
8   Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, North Carolina
,
George R. Saade
9   Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas
,
Alan T. N. Tita
10   Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama
,
Dwight J. Rouse
11   Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island
,
Baha Sibai
12   Department of Obstetrics and Gynecology, University of Texas—Houston, Houston, Texas
,
Maged M. Costantine 
13   Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio
,
Brian M. Mercer
14   Department of Obstetrics and Gynecology, Case Western Reserve University, Cleveland, Ohio
,
Jorge E. Tolosa
15   Department of Obstetrics and Gynecology, Oregon Health Sciences University, Portland, Oregon
,
Steve N. Caritis
16   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 Network, Bethesda, MD, USA› Author Affiliations
Funding This study was supported by grants (HD34116, HD40512, HD27917, HD34208, HD40485, HD40560, HD53097, HD27869, HD40500, HD40545, HD27915, HD40544, HD53118, HD21410, and U10HD36801) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Neurological Disorders and Stroke. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Abstract

Objective The long-term impact of hypertensive disorders of pregnancy (HDP) exposure on offspring health is an emerging research area. The objective of this study was to evaluate the association between a maternal diagnosis of HDP (gestational hypertension and preeclampsia) and adverse neurodevelopmental outcomes in the offspring.

Study Design This was a secondary analysis of two parallel multicenter clinical trials of thyroxine therapy for subclinical hypothyroid disorders in pregnancy. Women with singleton nonanomalous gestations diagnosed with subclinical hypothyroidism or hypothyroxinemia were randomized to thyroxine therapy or placebo. The primary outcome was child intelligence quotient (IQ) at 5 years of age. Secondary outcomes included several neurodevelopmental measures, including the Bayley-III cognitive, motor, and language scores at 12 and 24 months, Differential Ability Scales-II (DAS-II) scores at 36 months, the Conners' rating scales-revised at 48 months, and scores from the Child Behavior Checklist at 36 and 60 months. Thyroxine therapy did not influence neurodevelopment in either of the primary studies. Associations between neurodevelopment outcomes and maternal HDP were examined using univariable and multivariable analyses.

Results A total of 112 woman–child dyads with HDP were compared with 1,067 woman–child dyads without HDP. In univariable analysis, mean maternal age (26.7 ± 5.9 vs. 27.8 ± 5.7 years, p = 0.032) and the frequency of nulliparity (45.5 vs. 31.0%, p = 0.002) differed significantly between the two groups. Maternal socioeconomic characteristics did not differ between the groups. After adjusting for potential confounders, there were no significant differences in any primary or secondary neurodevelopment outcome between offspring exposed to HDP and those unexposed. However, when dichotomized as low or high scores, we found higher rates of language delay (language scores <85: −1 standard deviation) at 2 years of age among offspring exposed to HDP compared with those unexposed (46.5 vs. 30.5%, adjusted odds ratio = 2.22, 95% confidence interval [CI]: 1.44–3.42).

Conclusion In this cohort of pregnant women, HDP diagnosis was associated with language delay at 2 years of age. However, other long-term neurodevelopmental outcomes in offspring were not associated with HDP.

Key Points

  • No differences were found in neurodevelopment between offspring exposed to HDP and controls.

  • Higher rates of language delay at 2 years of age were found in offspring exposed to HDP.

  • The results did not differ when analysis was stratified by preterm birth.

Keywords

hypertensive disorders of pregnancy - neurodevelopmental outcomes - intelligence quotient - language delay - in utero exposure

Note

This study was presented in poster format at the 40th annual meeting of the Society for Maternal-Fetal Medicine, Grapevine, Texas, February 3–8, 2020.


* Other members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network are listed in [Supplementary Appendix A1].


Supplementary Material



Publication History

Received: 29 June 2021

Accepted: 01 November 2021

Accepted Manuscript online:
09 November 2021

Article published online:
29 December 2021

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