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Cited by 333Infant Development and Preterm CareMaternal Mental Health During Pregnancy and PostpartumNeonatal Respiratory Health Research

Associations Between Maternal Antenatal Corticosteroid Treatment and Mental and Behavioral Disorders in Children

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Räikkönen, Katri, Gissler, Mika, Kajantie, Eero·2020·JAMA
DOI 10.1001/jama.2020.3937PMC PMC7237984
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Abstract

Importance: Maternal antenatal corticosteroid treatment is standard care to accelerate fetal maturation when birth before 34 weeks is imminent. Recently, expansion of the indications beyond 34 gestational weeks has been debated. However, data about long-term outcomes remain limited, especially among infants who after treatment exposure are born at term. Objective: To study if antenatal corticosteroid treatment is associated with mental and behavioral disorders in children born at term (≥37 weeks 0 days' gestation) and preterm (<37 weeks 0 days' gestation) and if unmeasured familial confounding explains these associations. Design, Setting, and Participants: Population-based retrospective cohort study using nationwide registries of all singleton live births in Finland surviving until 1 year and a within-sibpair comparison among term siblings. Children were born between January 1, 2006, and December 31, 2017, and followed up until December 31, 2017. Exposures: Maternal antenatal corticosteroid treatment. Main Outcomes and Measures: Primary outcome was any childhood mental and behavioral disorder diagnosed in public specialized medical care settings. Results: Of the 674 877 singleton children born in Finland during the study period, 670 097 were eligible for analysis. The median length of follow-up was 5.8 (interquartile-range, 3.1-8.7) years. Of the 14 868 (2.22%; 46.1% female) corticosteroid treatment-exposed children, 6730 (45.27%) were born at term and 8138 (54.74%) were born preterm; of the 655 229 (97.78%; 48.9% female) nonexposed children, 634 757 (96.88%) were born at term and 20 472 (3.12%) were born preterm. Among the 241 621 eligible term-born maternal sibpairs nested within this population, 4128 (1.71%) pairs were discordant for treatment exposure. Treatment exposure, compared with nonexposure, was significantly associated with higher risk of any mental and behavioral disorder in the entire cohort of children (12.01% vs 6.45%; absolute difference, 5.56% [95% CI, 5.04%-6.19%]; adjusted hazard ratio [HR], 1.33 [95% CI, 1.26-1.41]), in term-born children (8.89% vs 6.31%; absolute difference, 2.58% [95% CI, 1.92%-3.29%]; HR, 1.47 [95% CI, 1.36-1.69]), and when sibpairs discordant for treatment exposure were compared with sibpairs concordant for nonexposure (6.56% vs 4.17% for within-sibpair differences; absolute difference, 2.40% [95% CI, 1.67%-3.21%]; HR, 1.38 [95% CI, 1.21-1.58]). In preterm-born children, the cumulative incidence rate of any mental and behavioral disorder was also significantly higher for the treatment-exposed compared with the nonexposed children, but the HR was not significant (14.59% vs 10.71%; absolute difference, 3.38% [95% CI, 2.95%-4.87%]; HR, 1.00 [95% CI, 0.92-1.09]). Conclusions and Relevance: In this population-based cohort study, exposure to maternal antenatal corticosteroid treatment was significantly associated with mental and behavioral disorders in children. These findings may help inform decisions about maternal antenatal corticosteroid treatment.

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  • Recent literature suggests a need for a more judicious approach to antenatal corticosteroid administration due to concerns about long-term neurodevelopmental effects of in-utero corticosteroid exposure.

    “Recent literature has suggested the need for a more judicious approach to administration of antenatal corticosteroids due to growing concerns about potential long-term neurodevelopmental effects of in-utero corticosteroid exposure.”

    From Artificial intelligence in obstetric ultrasound: A scoping review. (2023) · cites this paper as [141]

  • First trimester Dex exposure of non-CAH fetuses is associated with differences in brain morphology.

    “Moreover, first trimester Dex exposure of non-CAH fetuses is associated with differences in brain morphology (489).”

    From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [489]

    The Maternal Antenatal Corticosteroid Treatment section (page unavailable) describes recommended betamethasone treatment and says the register did not record treatment timing. The Results and Discussion (pages unavailable) address mental and behavioral disorders, not brain morphology. Searches for first-trimester dexamethasone exposure, non-CAH fetuses, and brain morphology found no passage addressing the claim. (LLM, conf=0.78)

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Authors
Räikkönen, K., Gissler, M., & Kajantie, E.
Affiliations
  • University of Helsinki (FI)
  • University of Turku (FI)
Corresponding author
Räikkönen, Katri
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2020-05-19
Volume
323
Issue
19
Pages
1924
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2020.3937
PMC
PMC7237984
OpenAlex
W3027678838
Cited by
327
References
31
Citations by year
2026: 33 · 2025: 58 · 2024: 44 · 2023: 59 · 2022: 68 · 2021: 45 · 2020: 20
FWCI
47.80
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • European Commission
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (462-16-040)
  • Lastentautien Tutkimussäätiö
  • Novo Nordisk Fonden (NNF19OC0057393)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
Keywords
antenatal corticosteroids, child psychopathology, behavioral disorders, term birth, preterm birth, long-term outcomes, familial confounding, fetal maturity, singleton live births, birth cohort
MeSH terms
Adrenal Cortex Hormones, Mental Disorders, Child, Child Behavior Disorders, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Newborn, Infant, Premature, Male, Pregnancy, Prenatal Care, Prenatal Exposure Delayed Effects, Retrospective Studies

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