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. 2017 May 31:357:j2350.
doi: 10.1136/bmj.j2350.

Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: population based cohort study

Kenneth K C Man  1   2   3   4 , Esther W Chan  1 , Patrick Ip  2 , David Coghill  5   6 , Emily Simonoff  7 , Phyllis K L Chan  8 , Wallis C Y Lau  1 , Martijn J Schuemie  9 , Miriam C J M Sturkenboom  4 , Ian C K Wong  10   2   3
Affiliations

Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: population based cohort study

Kenneth K C Man et al. BMJ. .

Abstract

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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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: EWC reports grants from Janssen (a division of Johnson & Johnson), BMS, Pfizer, the Research Grants Council (RGC, Hong Kong), received for other work. DC reports grants from the European Union FP7 programme and Shire and honorariums from Shire, Eli Lilly, Novartis, and Janssen-Cilag; acted as an advisor to Shire and Lundbeck; and received royalties from Oxford University press. DC was a member of the British Association for Psychopharmacology ADHD, Depression and Bipolar Disorder guideline groups. ES reports grants from Innovative Medicines Initiative (IMI), National Institute for Health Research programme grant for applied research, and the National Institute for Health Research Biomedical Research Centre for Mental Health. PI reports grants from RGC and the Health and Medical Research Fund (Food and Health Bureau, Hong Kong). ICKW reports grants from RGC, IMI, Shire, Janssen-Cilag, Eli-Lily, Pfizer, and the European Union FP7 programme, outside the submitted work. ICKW is a member of the National Institute for Health and Clinical Excellence ADHD Guideline Group and was a member of the British Association for Psychopharmacology ADHD guideline group and acted as an advisor to Shire. PKLC acted as an advisor to Eli Lilly. MCJMS is leading a research group that received grants for specific post-authorisation safety projects from Novartis, Boehringer, GSK, and Servier, none related to this topic. MJS is a full time employee and shareholder of Johnson & Johnson.

Figures

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Fig 1 Flowchart of mother-child pairs identification
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Fig 2 Fully adjusted results from analysis for gestational users of antidepressants compared with non-gestational users. SSRI=selective serotonin reuptake inhibitor; ADHD=attention-deficit/hyperactivity disorder
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Fig 3 Fully adjusted results from analyses of different comparisons. SSRI=selective serotonin reuptake inhibitor; ADHD=attention-deficit/hyperactivity disorder
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Fig 4 Fully adjusted results from analyses of comparisons with active comparator. SSRI=selective serotonin reuptake inhibitor; ADHD=attention-deficit/hyperactivity disorder
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