Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

The association of maternal hypertensive disorders with neonatal congenital heart disease: analysis of a United States cohort

Journal of Perinatology volume 40, pages 1617–1624 (2020)Cite this article

Subjects

Abstract

Objective

To examine the association of any type of maternal hypertensive disorders of pregnancy (HDP) and neonatal congenital heart diseases (CHD).

Study design

We compared the prevalence of CHD between neonates born to mothers with HDP to those delivered to mothers without HDP among 24,525,889 hospital records of living infants, from a national database. We controlled for multiple confounding factors by using multiple logistic regression analysis.

Results

Infants delivered to mothers with HDP had higher prevalence of CHD compared to infants born to mothers without HDP [5.20% vs. 1.47%; aOR: 2.51(2.38–2.64), p < 0.001]. Maternal diabetes was more frequent among infants born to mothers with HDP and was independently associated with CHD [aOR 5.14 (5.04–5.23), p < 0.001].

Conclusion

Infants born to mothers with hypertension had almost a threefold increase in CHD compared with those born to mothers without hypertension. Further studies are needed to investigate the underlying mechanism and direction of this association.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. ACOG Practice Bulletin No. 202: Gestational hypertension and preeclampsia. Obstet Gynecol. 2019;133:e1–25.

  2. Lo JO, Mission JF, Caughey AB. Hypertensive disease of pregnancy and maternal mortality. Curr Opin Obstet Gynecol. 2013;25:124–32.

    Article  Google Scholar 

  3. Donofrio MT, Moon-Grady AJ, Hornberger LK, Copel JA, Sklansky MS, Abuhamad A, et al. American Heart Association Adults With Congenital Heart Disease Joint Committee of the Council on cardiovascular disease in the young and council on clinical cardiology, council on cardiovascular surgery and anesthesia, and council on cardiovascular and stroke nursing. Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association. Circulation. 2014;129:2183–242.

    Article  Google Scholar 

  4. Boyd HA, Basit S, Behrens I, Leirgul E, Bundgaard H, Wohlfahrt J, et al. Association between fetal congenital heart defects and maternal risk of hypertensive disorders of pregnancy in the same pregnancy and across pregnancies. Circulation. 2017;136:39–48.

    Article  CAS  Google Scholar 

  5. Auger N, Fraser WD, Healy-Profitós J, Arbour L. Association between preeclampsia and congenital heart defects. JAMA. 2015;314:1588–98.

    Article  CAS  Google Scholar 

  6. Brodwall K, Leirgul E, Greve G, Vollset SE, Holmstrøm H, Tell GS, et al. Possible common aetiology behind maternal preeclampsia and congenital heart defects in the child: a cardiovascular diseases in Norway project study. Paediatr Perinat Epidemiol. 2016;30:76–85.

    Article  Google Scholar 

  7. Leslie K, Whitley GS, Herse F, Dechend R, Ashton SV, Laing K, et al. Increased apoptosis, altered oxygen signaling, and antioxidant defenses in first-trimester pregnancies with high-resistance uterine artery blood flow. Am J Pathol. 2015;185:2731–41.

    Article  CAS  Google Scholar 

  8. Hayes Ryan D, McCarthy FP, O’Donoghue K, Kenny LC. Placental growth factor: a review of literature and future applications. Pregnancy Hypertens. 2018;14:260–4.

    Article  CAS  Google Scholar 

  9. Llurba Olive E, Xiao E, Natale DR, Fisher SA. Oxygen and lack of oxygen in fetal and placental development, feto-placental coupling, and congenital heart defects. Birth Defects Res. 2018;110:1517–30.

    Article  CAS  Google Scholar 

  10. Shi H, O’Reilly VC, Moreau JL, Bewes TR, Yam MX, Chapman BE, et al. Gestational stress induces the unfolded protein response, resulting in heart defects. Development. 2016;143:2561–72.

    Article  CAS  Google Scholar 

  11. Llurba E, Sánchez O, Ferrer Q, Nicolaides KH, Ruíz A, Domínguez C, et al. Maternal and foetal angiogenic imbalance in congenital heart defects. Eur Heart J. 2014;35:701–7.

    Article  CAS  Google Scholar 

  12. Ruiz A, Cruz-Lemini M, Masoller N, Sanz-Cortés M, Ferrer Q, Ribera I, et al. Longitudinal changes in fetal biometry and cerebroplacental hemodynamics in fetuses with congenital heart disease. Ultrasound Obstet Gynecol. 2017;49:379–86.

    Article  CAS  Google Scholar 

  13. Ruiz A, Ferrer Q, Sánchez O, Ribera I, Arévalo S, Alomar O, et al. Placenta-related complications in women carrying a foetus with congenital heart disease. J Matern Fetal Neonatal Med. 2016;29:3271–5.

    PubMed  Google Scholar 

  14. Ye Z, Su Q, Li L, Letter by Ye. et al. Regarding article, “association between fetal congenital heart defects and maternal risk of hypertensive disorders of pregnancy in the same pregnancy and across pregnancies”. Circulation. 2018;137:95–6.

    Article  Google Scholar 

  15. HCUP Databases. Healthcare Cost and Utilization Project (HCUP). September 2019. Agency for Healthcare Research and Quality, Rockville, MD. https://www.hcup-us.ahrq.gov/kidoverview.jsp. Accessed 18 Dec 2019.

  16. American Institute of Ultrasound in Medicine. AIUM practice guideline for the performance of fetal echocardiography. J Ultrasound Med. 2013;32:1067–82.

    Article  Google Scholar 

  17. Van Gelder MM, Van Bennekom CM, Louik C, Werler MM, Roeleveld N, Mitchell AA. Maternal hypertensive disorders, antihypertensive medication use, and the risk of birth defects: a case-control study. BJOG. 2015;122:1002–9.

    Article  Google Scholar 

  18. Grossfeld P, Nie S, Lin L, Wang L, Anderson RH. Hypoplastic Left Heart Syndrome: A New Paradigm for an Old Disease? J Cardiovasc Dev Dis. 2019;6:E10.

    Article  Google Scholar 

  19. Crucean A, Alqahtani A, Barron DJ, Brawn WJ, Richardson RV, O’Sullivan J, et al. Re-evaluation of hypoplastic left heart syndrome from a developmental and morphological perspective. Orphanet J Rare Dis. 2017;12:138.

    Article  CAS  Google Scholar 

  20. Arcelli D, Farina A, Cappuzzello C, Bresin A, De Sanctis P, Perolo A, et al. Identification of circulating placental mRNA in maternal blood of pregnancies affected with fetal congenital heart diseases at the second trimester of pregnancy: implications for early molecular screening. Prenat Diagn. 2010;30:229–34.

    Article  CAS  Google Scholar 

  21. Dobierzewska A, Palominos M, Irarrazabal CE, Sanchez M, Lozano M, Perez-Sepulveda A, et al. NFAT5 is up-regulated by hypoxia: possible implications in preeclampsia and intrauterine growth restriction. Biol Reprod. 2015;93:14.

    Article  Google Scholar 

  22. Lisowski LA, Verheijen PM, Copel JA, Kleinman CS, Wassink S, Visser GH, et al. Congenital heart disease in pregnancies complicated by maternal diabetes mellitus. An international clinical collaboration, literature review, and meta-analysis. Herz. 2010;35:19–26.

    Article  Google Scholar 

  23. Balsells M, García-Patterson A, Gich I, Corcoy R. Major congenital malformations in women with gestational diabetes mellitus: a systematic review and meta-analysis. Diabetes Metab Res Rev. 2012;28:252–7.

    Article  Google Scholar 

  24. Inversetti A, Fesslova V, Deprest J, Candiani M, Giorgione V, Cavoretto P. Prenatal growth in fetuses with isolated cyanotic and non-cyanotic congenital heart defects. Fetal Diagn Ther. 2018. https://doi.org/10.1159/000493938.

  25. Hutcheon JA, Lisonkova S, Joseph KS. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol. 2011;25:391–403.

    Article  Google Scholar 

  26. MacDorman MF, Kirmeyer S. Fetal and perinatal mortality, United States, 2005. Natl Vital Stat Rep. 2009;57:1–19.

    PubMed  Google Scholar 

  27. Divanovic A, Bowers K, Michelfelder E, Jaekle R, Newman T, Marcotte M, et al. Intrauterine fetal demise after prenatal diagnosis of congenital heart disease: assessment of risk. Prenat Diagn. 2016;36:142–7.

    Article  Google Scholar 

  28. Lytzen R, Vejlstrup N, Bjerre J, Petersen OB, Leenskjold S, Dodd JK, et al. Live-born major congenital heart disease in Denmark: incidence, detection rate, and termination of pregnancy rate from 1996 to 2013. JAMA Cardiol. 2018;3:829–37.

    Article  Google Scholar 

  29. Mai CT, Isenburg JL, Canfield MA, Meyer RE, Correa A, Alverson CJ, et al. National birth defects prevention network. National population-based estimates for major birth defects, 2010–4. Birth Defects Res. 2019;111:1420–35.

    Article  CAS  Google Scholar 

  30. Urquia ML, Glazier RH, Gagnon AJ, Mortensen LH, Nybo Andersen AM, Janevic T, et al. ROAM Collaboration. Disparities in pre-eclampsia and eclampsia among immigrant women giving birth in six industrialised countries. BJOG. 2014;121:1492–500.

    Article  CAS  Google Scholar 

  31. Iacobelli S, Bonsante F, Robillard PY. Pre-eclampsia and preterm birth in Reunion Island: a 13 years cohort-based study. Comparison with international data. J Matern Fetal Neonatal Med. 2016;29:3035–40.

    Article  Google Scholar 

  32. Thilaganathan B. Preeclampsia and fetal congenital heart defects: spurious association or maternal confounding? Circulation. 2017;136:49–51.

    Article  Google Scholar 

  33. Courtney JA, Cnota JF, Jones HN. The role of abnormal placentation in congenital heart disease; cause, correlate, or consequence? Front Physiol. 2018;9:1045.

    Article  Google Scholar 

  34. Llurba E, Syngelaki A, Sánchez O, Carreras E, Cabero L, Nicolaides KH. Maternal serum placental growth factor at 11–13 weeks’ gestation and fetal cardiac defects. Ultrasound Obstet Gynecol. 2013;42:169–74.

    Article  CAS  Google Scholar 

  35. Perez-Garcia V, Fineberg E, Wilson R, Murray A, Mazzeo CI, Tudor C, et al. Placentation defects are highly prevalent in embryonic lethal mouse mutants. Nature. 2018;555:463–8.

    Article  CAS  Google Scholar 

  36. Watson ED, Cross JC. Development of structures and transport functions in the mouse placenta. Physiology. 2005;20:180–93.

    Article  CAS  Google Scholar 

  37. Mayer-Pickel K, Kolovetsiou-Kreiner V, Stern C, Münzker J, Eberhard K, Trajanoski S, et al. Effect of low-dose aspirin on soluble FMS-like tyrosine kinase 1/placental growth factor (sFlt-1/PlGF ratio) in pregnancies at high risk for the development of preeclampsia. J Clin Med. 2019;8:E1429.

    Article  Google Scholar 

  38. Panagodage S, Yong HE, Da Silva Costa F, Borg AJ, Kalionis B, Brennecke SP, et al. Low-dose acetylsalicylic acid treatment modulates the production of cytokines and improves trophoblast function in an in vitro model of early-onset preeclampsia. Am J Pathol. 2016;186:3217–24.

    Article  CAS  Google Scholar 

  39. Su MT, Wang CY, Tsai PY, Chen TY, Tsai HL, Kuo PL. Aspirin enhances trophoblast invasion and represses soluble fms-like tyrosine kinase 1 production: a putative mechanism for preventing preeclampsia. J Hypertens. 2019;37:2461–9.

    Article  CAS  Google Scholar 

  40. Psoter KJ, Rosenfeld M. Opportunities and pitfalls of registry data for clinical research. Paediatr Respir Rev. 2013;14:141–5.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Women’s Medicine Collaborative-Division of Research, The Miriam Hospital, Providence, RI, USA

    Laura Sanapo

  2. Division of Fetal and Translational Medicine, Children’s National Hospital, Washington, DC, USA

    Mary T. Donofrio

  3. Division of Cardiology, Children’s National Hospital, Washington, DC, USA

    Mary T. Donofrio

  4. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

    Homa K. Ahmadzia

  5. Women & Infants Hospital, Brown University, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Providence, RI, USA

    Alexis C. Gimovsky

  6. Division of Newborn Services, The George Washington University Hospital, Washington, DC, USA

    Mohamed A. Mohamed

Authors
  1. Laura Sanapo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mary T. Donofrio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Homa K. Ahmadzia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexis C. Gimovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohamed A. Mohamed
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laura Sanapo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sanapo, L., Donofrio, M.T., Ahmadzia, H.K. et al. The association of maternal hypertensive disorders with neonatal congenital heart disease: analysis of a United States cohort. J Perinatol 40, 1617–1624 (2020). https://doi.org/10.1038/s41372-020-00795-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-020-00795-9

This article is cited by

Search

Advanced search

Quick links