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Association Between Hypertensive Disorders of Pregnancy and Neurodevelopmental Outcomes Among Offspring
Örebro University, School of Medical Sciences. Örebro University Hospital. Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, Bristol, United Kingdom. (Clinical Epidemiology and Biostatistics)ORCID iD: 0000-0002-3720-1274
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, Bristol, United Kingdom.
Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID iD: 0000-0002-6851-3297
Örebro University, School of Medical Sciences. Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.ORCID iD: 0000-0001-6328-5494
2021 (English)In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 175, no 6, p. 577-585Article in journal (Refereed) Published
Abstract [en]

Importance: Hypertensive disorders of pregnancy (HDP) have been associated with poorer neurodevelopmental outcomes in offspring, but the role of familial confounding in these associations is unclear.

Objective: To investigate associations of maternal HDP with risks in offspring of autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID), as well as variation in overall cognitive performance in offspring.

Design, Setting, and Participants: This Swedish register-based study used data from a birth cohort divided into 1 085 024 individuals born between 1987 and 1996 and followed up until December 31, 2014, and 285 901 men born between 1982 and 1992 who attended assessments for military conscription, including a cognitive function test. Statistical analysis was performed from April 1, 2019, to June 1, 2020.

Exposures: Diagnoses of HDP, which were provided by the Medical Birth Register.

Main Outcomes and Measures: Diagnoses of ASDs, ADHD, and ID were extracted from the National Patient Register. Cognitive function was assessed using written tests and summarized as a single 9-point score. Whole-cohort and within-sibship analyses were performed; the latter accounted for unmeasured familial confounding factors shared by siblings.

Results: The study included 1 085 024 individuals (556 912 male participants [51.3%]) born between 1987 and 1996 and 285 901 men born between 1982 and 1992 who attended assessments for military conscription. The prevalence of maternal HDP was 4.0% in the 1987-1996 birth cohort (n = 42 980) and 5.1% in the military conscription cohort (n = 14 515). A total of 15 858 participants received a diagnosis of ASD, 36 852 received a diagnosis of ADHD, and 8454 received a diagnosis of ID. The mean (SD) cognitive score among the men in the conscription cohort was 5.1 (1.9). In whole-cohort analyses with multivariable adjustment, HDP were associated with offspring ASDs (hazard ratio [HR], 1.22; 95% CI, 1.13-1.31), ADHD (HR, 1.10; 95% CI, 1.05-1.16), and ID (HR, 1.39; 95% CI, 1.27-1.53). Analyses comparing siblings discordant for HDP were less statistically powered but indicated estimates of similar magnitude for ASDs (HR, 1.19; 95% CI, 1.00-1.42) and possibly ADHD (HR, 1.09; 95% CI, 0.95-1.24), but not for ID (HR, 1.04; 95% CI, 0.83-1.29). Hypertensive disorders of pregnancy were associated with somewhat lower cognitive scores in whole-cohort analysis (mean difference comparing offspring exposed with those unexposed, -0.10; 95% CI, -0.13 to -0.07), but in within-sibship analysis, the association was null (mean difference, 0.00; 95% CI, -0.09 to 0.08).

Conclusions and Relevance: The study results suggest that HDP are associated with small increased risks of ASDs and possibly ADHD in offspring, whereas associations with ID and cognitive performance are likely confounded by shared familial (environmental or genetic) factors.

Place, publisher, year, edition, pages
American Medical Association , 2021. Vol. 175, no 6, p. 577-585
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:oru:diva-90666DOI: 10.1001/jamapediatrics.2020.6856ISI: 000635709400004PubMedID: 33749704Scopus ID: 2-s2.0-85102900823OAI: oai:DiVA.org:oru-90666DiVA, id: diva2:1539173
Note

Funding Agencies:

UK Research & Innovation (UKRI)

Economic & Social Research Council (ESRC) ES/R008930/1

Nyckelfonden OLL-695391

European Research Council (ERC) European Commission 669545

United States Department of Health & Human Services

National Institutes of Health (NIH) - USA R01 DK10324

University of Bristol MC_UU_00011/3 MC_UU_00011/6

UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MC_UU_00011/3 MC_UU_00011/6

National Institute for Health Research (NIHR) NF-0616-10102

Available from: 2021-03-23 Created: 2021-03-23 Last updated: 2023-12-08Bibliographically approved

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Brand, JudithLarsson, HenrikMontgomery, Scott

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