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Association of Hypertensive Disorders of Pregnancy With Risk of Neurodevelopmental Disorders in Offspring: A Systematic Review and Meta-analysis
Open accessAbstract
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.
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“A meta-analysis of six studies combining 1.4 million people found that children whose mothers had hypertensive disorders during pregnancy had a 25% increase in the rate of ADHD (Maher et al., 2018).”
From The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder (2021) · cites this paper as Maher et al., 2018
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“The offspring of women with HDP are reported to be at a greater risk of developing cognitive and psychiatric disorders, such as autism spectrum disorder (ASD), attention-deficit–hyperactivity disorder (ADHD)217–219 or epilepsy during their later life220.”
From A global view of hypertensive disorders and diabetes mellitus during pregnancy (2022) · cites this paper as [217]
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“with a pooled OR of 1.35 for ASD risk (95% CI 1.11–1.64) [93].”
From The contribution of environmental exposure to the etiology of autism spectrum disorder (2019) · cites this paper as [93]
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Metadata
- Authors
- Maher, G. M., O’Keeffe, G. W., Kearney, P. M., Kenny, L. C., Dinan, T. G., Mattsson, M., & Khashan, A. S.
- Affiliations
- University College Cork (IE)
- University of Liverpool (GB)
- Royal College of Surgeons in Ireland (IE)
- Corresponding author
- Khashan, Ali S.
- ORCID
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2018-08-01
- Volume
- 75
- Issue
- 8
- Pages
- 809
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC6143097
- OpenAlex
- W2807447863
- Semantic Scholar
- ba3650aa55b2b292f27ad45f2a1a91216af80bb4
- Cited by
- 271
- References
- 106
- Citations by year
- 2026: 20 · 2025: 31 · 2024: 29 · 2023: 51 · 2022: 44 · 2021: 40 · 2020: 36 · 2019: 15 · 2018: 5
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Psychiatry (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Health Research Board (SPHeRE/2013/1)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- hypertensive disorders of pregnancy, preeclampsia, autism spectrum disorder, attention deficit hyperactivity disorder, neurodevelopmental disorders, offspring, maternal hypertension, prenatal exposure
- MeSH terms
- Correlation of Data, Female, Humans, Pregnancy, Prenatal Exposure Delayed Effects, Risk Factors, Hypertension, Pregnancy-Induced, Neurodevelopmental Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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