PDF herunterladen
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 › Institutsangaben 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.
› Weitere Informationen
Auch verfügbar auf
    Lizenzen und Reprints

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



Publikationsverlauf

Eingereicht: 29. Juni 2021

Angenommen: 01. November 2021

Accepted Manuscript online:
09. November 2021

Artikel online veröffentlicht:
29. Dezember 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Abalos E, Cuesta C, Grosso AL, Chou D, Say L. Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol 2013; 170 (01) 1-7
    CrossrefPubMedSuche in Google Scholar
  • 2 Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol 2009; 33 (03) 130-137
    CrossrefPubMedSuche in Google Scholar
  • 3 Pauli JM, Repke JT. Preeclampsia: short-term and long-term implications. Obstet Gynecol Clin North Am 2015; 42 (02) 299-313
    CrossrefPubMedSuche in Google Scholar
  • 4 Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet 2010; 376 (9741): 631-644
    Suche in Google Scholar
  • 5 Goffin SM, Derraik JGB, Groom KM, Cutfield WS. Maternal pre-eclampsia and long-term offspring health: is there a shadow cast?. Pregnancy Hypertens 2018; 12: 11-15
    CrossrefPubMedSuche in Google Scholar
  • 6 Seely EW, Rich-Edwards J, Lui J. et al. Risk of future cardiovascular disease in women with prior preeclampsia: a focus group study. BMC Pregnancy Childbirth 2013; 13: 240
    CrossrefPubMedSuche in Google Scholar
  • 7 Wilkins-Haug L, Celi A, Thomas A, Frolkis J, Seely EW. Recognition by women's health care providers of long-term cardiovascular disease risk after preeclampsia. Obstet Gynecol 2015; 125 (06) 1287-1292
    CrossrefPubMedSuche in Google Scholar
  • 8 McDonald SD, Malinowski A, Zhou Q, Yusuf S, Devereaux PJ. Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses. Am Heart J 2008; 156 (05) 918-930
    CrossrefPubMedSuche in Google Scholar
  • 9 Ananth CV, Friedman AM. Ischemic placental disease and risks of perinatal mortality and morbidity and neurodevelopmental outcomes. Semin Perinatol 2014; 38 (03) 151-158
    CrossrefPubMedSuche in Google Scholar
  • 10 Cheng SW, Chou HC, Tsou KI, Fang LJ, Tsao PN. Delivery before 32 weeks of gestation for maternal pre-eclampsia: neonatal outcome and 2-year developmental outcome. Early Hum Dev 2004; 76 (01) 39-46
    CrossrefPubMedSuche in Google Scholar
  • 11 Maher GM, McCarthy FP, McCarthy CM. et al. A perspective on pre-eclampsia and neurodevelopmental outcomes in the offspring: does maternal inflammation play a role?. Int J Dev Neurosci 2019; 77: 69-76
    CrossrefPubMedSuche in Google Scholar
  • 12 Many A, Fattal A, Leitner Y, Kupferminc MJ, Harel S, Jaffa A. Neurodevelopmental and cognitive assessment of children born growth restricted to mothers with and without preeclampsia. Hypertens Pregnancy 2003; 22 (01) 25-29
    CrossrefPubMedSuche in Google Scholar
  • 13 Spinillo A, Iasci A, Capuzzo E, Egbe TO, Colonna L, Fazzi E. Two-year infant neurodevelopmental outcome after expectant management and indicated preterm delivery in hypertensive pregnancies. Acta Obstet Gynecol Scand 1994; 73 (08) 625-629
    CrossrefPubMedSuche in Google Scholar
  • 14 Ehrenstein V, Rothman KJ, Pedersen L, Hatch EE, Sørensen HT. Pregnancy-associated hypertensive disorders and adult cognitive function among Danish conscripts. Am J Epidemiol 2009; 170 (08) 1025-1031
    CrossrefPubMedSuche in Google Scholar
  • 15 Heikura U, Hartikainen AL, Nordström T, Pouta A, Taanila A, Järvelin MR. Maternal hypertensive disorders during pregnancy and mild cognitive limitations in the offspring. Paediatr Perinat Epidemiol 2013; 27 (02) 188-198
    CrossrefPubMedSuche in Google Scholar
  • 16 Whitehouse AJ, Robinson M, Newnham JP, Pennell CE. Do hypertensive diseases of pregnancy disrupt neurocognitive development in offspring?. Paediatr Perinat Epidemiol 2012; 26 (02) 101-108
    CrossrefPubMedSuche in Google Scholar
  • 17 Seidman DS, Laor A, Gale R, Stevenson DK, Mashiach S, Danon YL. Pre-eclampsia and offspring's blood pressure, cognitive ability and physical development at 17-years-of-age. Br J Obstet Gynaecol 1991; 98 (10) 1009-1014
    CrossrefPubMedSuche in Google Scholar
  • 18 Sverrisson FA, Bateman BT, Aspelund T, Skulason S, Zoega H. Preeclampsia and academic performance in children: a nationwide study from Iceland. PLoS One 2018; 13 (11) e0207884
    CrossrefPubMedSuche in Google Scholar
  • 19 Tuovinen S, Eriksson JG, Kajantie E, Räikkönen K. Maternal hypertensive pregnancy disorders and cognitive functioning of the offspring: a systematic review. J Am Soc Hypertens 2014; 8 (11) 832-47.e1
    CrossrefPubMedSuche in Google Scholar
  • 20 Casey BM, Thom EA, Peaceman AM. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network. Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy. N Engl J Med 2017; 376 (09) 815-825
    CrossrefPubMedSuche in Google Scholar
  • 21 Bayley N. Bayley Scales of Infant and Toddler Development. 3rd ed.. San Antonio, TX: The Psychological Corporation; 2006
    Suche in Google Scholar
  • 22 Jo H, Schieve LA, Sharma AJ, Hinkle SN, Li R, Lind JN. Maternal prepregnancy body mass index and child psychosocial development at 6 years of age. Pediatrics 2015; 135 (05) e1198-e1209
    CrossrefPubMedSuche in Google Scholar
  • 23 Anthopolos R, Edwards SE, Miranda ML. Effects of maternal prenatal smoking and birth outcomes extending into the normal range on academic performance in fourth grade in North Carolina, USA. Paediatr Perinat Epidemiol 2013; 27 (06) 564-574
    CrossrefPubMedSuche in Google Scholar
  • 24 Camprubi Robles M, Campoy C, Garcia Fernandez L, Lopez-Pedrosa JM, Rueda R, Martin MJ. Maternal diabetes and cognitive performance in the offspring: a systematic review and meta-analysis. PLoS One 2015; 10 (11) e0142583
    CrossrefPubMedSuche in Google Scholar
  • 25 Robinson M, Mattes E, Oddy WH. et al. Hypertensive diseases of pregnancy and the development of behavioral problems in childhood and adolescence: the Western Australian Pregnancy Cohort Study. J Pediatr 2009; 154 (02) 218-224
    CrossrefPubMedSuche in Google Scholar
  • 26 Sun BZ, Moster D, Harmon QE, Wilcox AJ. Association of preeclampsia in term births with neurodevelopmental disorders in offspring. JAMA Psychiatry 2020; 77 (08) 823-829
    CrossrefPubMedSuche in Google Scholar
  • 27 Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJ. Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA 2002; 288 (06) 728-737
    CrossrefPubMedSuche in Google Scholar
  • 28 Haddow JE, Palomaki GE, Allan WC. et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 1999; 341 (08) 549-555
    CrossrefPubMedSuche in Google Scholar
  • 29 Korevaar TI, Muetzel R, Medici M. et al. Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study. Lancet Diabetes Endocrinol 2016; 4 (01) 35-43
    CrossrefPubMedSuche in Google Scholar
  • 30 Lazarus JH, Bestwick JP, Channon S. et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med 2012; 366 (06) 493-501
    CrossrefPubMedSuche in Google Scholar
  • 31 Levie D, Korevaar TIM, Bath SC. et al. Thyroid function in early pregnancy, child IQ, and autistic traits: a meta-analysis of individual participant data. J Clin Endocrinol Metab 2018; 103 (08) 2967-2979
    CrossrefPubMedSuche in Google Scholar
  • 32 Nelson SM, Haig C, McConnachie A. et al. Maternal thyroid function and child educational attainment: prospective cohort study. BMJ 2018; 360: k452
    CrossrefPubMedSuche in Google Scholar
  • 33 Noten AM, Loomans EM, Vrijkotte TG. et al. Maternal hypothyroxinaemia in early pregnancy and school performance in 5-year-old offspring. Eur J Endocrinol 2015; 173 (05) 563-571
    CrossrefPubMedSuche in Google Scholar
  • 34 Su PY, Huang K, Hao JH. et al. Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China. J Clin Endocrinol Metab 2011; 96 (10) 3234-3241
    CrossrefPubMedSuche in Google Scholar
  • 35 Hales C, Taylor PN, Channon S. et al. Controlled antenatal thyroid screening II: effect of treating maternal suboptimal thyroid function on child cognition. J Clin Endocrinol Metab 2018; 103 (04) 1583-1591
    CrossrefPubMedSuche in Google Scholar