Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: population based cohort study
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Objective To assess the potential association between prenatal use of antidepressants and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. Design Population based cohort study. Setting Data from the Hong Kong population based electronic medical records on the Clinical Data Analysis and Reporting System. Participants 190 618 children born in Hong Kong public hospitals between January 2001 and December 2009 and followed-up to December 2015. Main outcome measure Hazard ratio of maternal antidepressant use during pregnancy and ADHD in children aged 6 to 14 years, with an average follow-up time of 9.3 years (range 7.4-11.0 years). Results Among 190 618 children, 1252 had a mother who used prenatal antidepressants. 5659 children (3.0%) were given a diagnosis of ADHD or received treatment for ADHD. The crude hazard ratio of maternal antidepressant use during pregnancy was 2.26 (P<0.01) compared with non-use. After adjustment for potential confounding factors, including maternal psychiatric disorders and use of other psychiatric drugs, the adjusted hazard ratio was reduced to 1.39 (95% confidence interval 1.07 to 1.82, P=0.01). Likewise, similar results were observed when comparing children of mothers who had used antidepressants before pregnancy with those who were never users (1.76, 1.36 to 2.30, P<0.01). The risk of ADHD in the children of mothers with psychiatric disorders was higher compared with the children of mothers without psychiatric disorders even if the mothers had never used antidepressants (1.84, 1.54 to 2.18, P<0.01). All sensitivity analyses yielded similar results. Sibling matched analysis identified no significant difference in risk of ADHD in siblings exposed to antidepressants during gestation and those not exposed during gestation (0.54, 0.17 to 1.74, P=0.30). Conclusions The findings suggest that the association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained by confounding by indication of antidepressants. If there is a causal association, the size of the effect is probably smaller than that reported previously.
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The definition of exposure to other medicines during pregnancy focused on other psychotropic drugs, anxiolytics and sedatives, or nicotine products, with only one study accounting for all types of medications used.
“However, the definition of exposure to the use of other medicines during pregnancy focused on the use of other psychotropic drugs [35, 36, 38], use of anxiolytics and sedatives [19, 31, 37] or use of nicotine products [29], with only one study accounting for all types of medications used [25].”
A total of seven observational studies measuring ADHD as an outcome were identified.
“a total of seven observational studies measuring ADHD as an outcome [17, 18, 31, 34, 36–38] were identified”
Three observational studies reported results from sibling analyses for ADHD.
“Three observational studies reported results from sibling analyses [34, 37, 38]”
For ADHD, three case-control studies involving 51,944 patients and 4,375 cases and four cohort studies involving 2,713,779 patients and 51,938 cases were included.
“For ADHD as the outcome, three case–control studies (involving 51,944 patients and 4,375 cases of ADHD) [17, 18, 36] and four cohort studies (involving 2,713,779 patients and 51,938 cases of ADHD) [31, 33, 37, 38] were included.”
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- Authors
- Man, K. K. C., Chan, E. W., Ip, P., Coghill, D., Simonoff, E., Chan, P. K. L., Lau, W. C. Y., Schuemie, M. J., Sturkenboom, M. C. J. M., & Wong, I. C. K.
- Affiliations
- Erasmus MC (NL)
- University of Hong Kong (HK)
- The University of Melbourne (AU)
- King's College London (GB)
- Queen Mary Hospital (CN)
- UCL School of Pharmacy (GB)
- Corresponding author
- Wong, Ian C K
- ORCID
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2017-05-31
- Volume
- 357
- Pages
- j2350
- ISSN
- 1756-1833 (ISSN-L)
- 0959-8138
- PMC
- PMC5450015
- OpenAlex
- W2618699239
- Cited by
- 135
- References
- 27
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 9 · 2023: 12 · 2022: 23 · 2021: 16 · 2020: 23 · 2019: 21 · 2018: 11 · 2017: 8 · 2016: 1
- FWCI
- 14.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- BMJ (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- Discovery Research Portal (University of Dundee) (submittedVersion, cc-by-nc)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion, cc-by-nc-nd)
- Research Portal (King's College London) (submittedVersion, cc-by-nc)
- HighWire Press Open Archive (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
- National Institute for Health and Care Research (NF-SI-0514-10073)
- University of Oxford
- European Commission
- Hospital Authority
- Food and Health Bureau
- Servier
- Cilag
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- prenatal antidepressant exposure, attention deficit hyperactivity disorder, maternal mental illness, confounding by indication, Hong Kong children
- MeSH terms
- Adult, Antidepressive Agents, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Depression, Female, Hong Kong, Humans, Infant, Infant, Newborn, Male, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Risk Factors, Cohort Studies, Proportional Hazards Models, Siblings, Pregnant People
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