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

Kenneth K. C. Man, Esther W. Chan, Patrick Ip, David Coghill, Emily Simonoff, Phyllis K. L. Chan, Wallis C. Y. Lau, Martijn J. Schuemie, Miriam C. J. M. Sturkenboom, Ian C. K. Wong (Lead / Corresponding author)

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    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.

    Original languageEnglish
    Article numberj2350
    Pages (from-to)1-9
    Number of pages9
    JournalBMJ
    Volume357
    DOIs
    Publication statusPublished - 31 May 2017

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    Attention Deficit Disorder with Hyperactivity
    Antidepressive Agents
    Cohort Studies
    Mothers
    Population
    Psychiatry
    Pregnancy
    Hong Kong
    Siblings
    Electronic Health Records
    Public Hospitals
    Research Design
    Outcome Assessment (Health Care)
    Confidence Intervals
    Pharmaceutical Preparations

    Cite this

    Man, K. K. C., Chan, E. W., Ip, P., Coghill, D., Simonoff, E., Chan, P. K. L., ... Wong, I. C. K. (2017). Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: population based cohort study. BMJ, 357, 1-9. [j2350]. https://doi.org/10.1136/bmj.j2350
    Man, Kenneth K. C. ; Chan, Esther W. ; Ip, Patrick ; Coghill, David ; Simonoff, Emily ; Chan, Phyllis K. L. ; Lau, Wallis C. Y. ; Schuemie, Martijn J. ; Sturkenboom, Miriam C. J. M. ; Wong, Ian C. K. / Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring : population based cohort study. In: BMJ. 2017 ; Vol. 357. pp. 1-9.
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    title = "Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: population based cohort study",
    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.",
    author = "Man, {Kenneth K. C.} and Chan, {Esther W.} and Patrick Ip and David Coghill and Emily Simonoff and Chan, {Phyllis K. L.} and Lau, {Wallis C. Y.} and Schuemie, {Martijn J.} and Sturkenboom, {Miriam C. J. M.} and Wong, {Ian C. K.}",
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    Man, KKC, Chan, EW, Ip, P, Coghill, D, Simonoff, E, Chan, PKL, Lau, WCY, Schuemie, MJ, Sturkenboom, MCJM & Wong, ICK 2017, 'Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: population based cohort study', BMJ, vol. 357, j2350, pp. 1-9. https://doi.org/10.1136/bmj.j2350

    Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring : population based cohort study. / Man, Kenneth K. C.; Chan, Esther W.; Ip, Patrick; Coghill, David; Simonoff, Emily; Chan, Phyllis K. L.; Lau, Wallis C. Y.; Schuemie, Martijn J.; Sturkenboom, Miriam C. J. M.; Wong, Ian C. K. (Lead / Corresponding author).

    In: BMJ, Vol. 357, j2350, 31.05.2017, p. 1-9.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring

    T2 - population based cohort study

    AU - Man, Kenneth K. C.

    AU - Chan, Esther W.

    AU - Ip, Patrick

    AU - Coghill, David

    AU - Simonoff, Emily

    AU - Chan, Phyllis K. L.

    AU - Lau, Wallis C. Y.

    AU - Schuemie, Martijn J.

    AU - Sturkenboom, Miriam C. J. M.

    AU - Wong, Ian C. K.

    N1 - No funding

    PY - 2017/5/31

    Y1 - 2017/5/31

    N2 - 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.

    AB - 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.

    U2 - 10.1136/bmj.j2350

    DO - 10.1136/bmj.j2350

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    JO - British Medical Journal

    JF - British Medical Journal

    SN - 0959-8146

    M1 - j2350

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