Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2018 Aug 1;75(8):809-819.
doi: 10.1001/jamapsychiatry.2018.0854.

Association of Hypertensive Disorders of Pregnancy With Risk of Neurodevelopmental Disorders in Offspring: A Systematic Review and Meta-analysis

Gillian M Maher  1   2 , Gerard W O'Keeffe  1   3 , Patricia M Kearney  2 , Louise C Kenny  4 , Timothy G Dinan  5   6 , Molly Mattsson  1   7 , Ali S Khashan  1   2
Affiliations
Meta-Analysis

Association of Hypertensive Disorders of Pregnancy With Risk of Neurodevelopmental Disorders in Offspring: A Systematic Review and Meta-analysis

Gillian M Maher et al. JAMA Psychiatry. .

Abstract

Importance: Although research suggests an association between hypertensive disorders of pregnancy (HDP) and autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and other neurodevelopmental disorders in offspring, consensus is lacking. Given the increasing prevalence of hypertension in pregnancy, it is important to examine the association of HDP with neurodevelopmental outcome.

Objective: To synthesize the published literature on the association between HDP and risk of neurodevelopmental disorders in offspring in a systematic review and meta-analysis.

Data sources: On the basis of a preprepared protocol, a systematic search of PubMed, CINAHL, Embase, PsycINFO, and Web of Science was performed from inception through June 7, 2017, supplemented by hand searching of reference lists.

Study selection: Two investigators independently reviewed titles, abstracts, and full-text articles. English-language cohort and case-control studies were included in which HDP and neurodevelopmental disorders were reported.

Data extraction and synthesis: Data extraction and quality appraisal were performed independently by 2 reviewers. Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed throughout.

Main outcomes and measures: Random-effects meta-analyses of estimated pooled odds ratios (ORs) for HDP and ASD and for HDP and ADHD. Stand-alone estimates were reported for all other neurodevelopmental disorders.

Results: Of 1166 studies identified, 61 unique articles met inclusion criteria. Twenty studies reported estimates for ASD. Eleven of these (including 777 518 participants) reported adjusted estimates, with a pooled adjusted OR of 1.35 (95% CI, 1.11-1.64). Ten studies reported estimates for ADHD. Six of these (including 1 395 605 participants) reported adjusted estimates, with a pooled adjusted OR of 1.29 (95% CI, 1.22-1.36). Subgroup analyses according to type of exposure (ie, preeclampsia or other HDP) showed no statistically significant differences for ASD or ADHD. Thirty-one studies met inclusion criteria for all other neurodevelopmental disorders. Individual estimates reported for these were largely inconsistent, with few patterns of association observed.

Conclusions and relevance: Exposure to HDP may be associated with an increase in the risk of ASD and ADHD. These findings highlight the need for greater pediatric surveillance of infants exposed to HDP to allow early intervention that may improve neurodevelopmental outcome.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Flow Diagram of Studies Selected for Inclusion in the Systematic Review
ADHD indicates attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder. aAn additional 6 studies are also included for ASD and 1 for ADHD.
Figure 2.
Figure 2.. Forest Plot for Studies of the Association of Hypertensive Disorders of Pregnancy (HDP) With Autism Spectrum Disorder (ASD)
Odds ratios (ORs) are calculated using random-effects analysis. The generic inverse variance method was used to include studies that do not report raw data. Diamonds indicate effect size; size of markers, 95% CI. HBP indicates high blood pressure.
Figure 3.
Figure 3.. Forest Plot for Studies of the Association of Hypertensive Disorders of Pregnancy (HDP) With Attention-Deficit/Hyperactivity Disorder (ADHD)
Odds ratios (ORs) are calculated using random-effects analysis. The generic inverse variance method was used to include studies that do not report raw data. Diamonds indicate effect size; size of markers, 95% CI.
See this image and copyright information in PMC

References

    1. Brown MA, Magee LA, Kenny L, et al. ; International Society for the Study of Hypertension in Pregnancy (ISSHP) . The hypertensive disorders of pregnancy: ISSHP classification, diagnosis and management recommendations for international practice 2018 [published online May 22, 2018]. Preg Hypertens. doi:10.1016/j.preghy.2018.01.005 - DOI - PubMed
    1. Olson-Chen C, Seligman NS. Hypertensive emergencies in pregnancy. Crit Care Clin. 2016;32(1):29-41. - PubMed
    1. Gillon TER, Pels A, von Dadelszen P, MacDonell K, Magee LA. Hypertensive disorders of pregnancy: a systematic review of international clinical practice guidelines. PLoS One. 2014;9(12):e113715. - PMC - PubMed
    1. Hakim J, Senterman MK, Hakim AM. Preeclampsia is a biomarker for vascular disease in both mother and child: the need for a medical alert system. Int J Pediatr. 2013;2013:953150. - PMC - PubMed
    1. Davis EF, Lazdam M, Lewandowski AJ, et al. . Cardiovascular risk factors in children and young adults born to preeclamptic pregnancies: a systematic review. Pediatrics. 2012;129(6):e1552-e1561. - PubMed

Publication types