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

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, 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 language	English
Article number	j2350
Pages (from-to)	1-9
Number of pages	9
Journal	BMJ
Volume	357
DOIs	https://doi.org/10.1136/bmj.j2350
Publication status	Published - 31 May 2017

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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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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

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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

M3 - Article

C2 - 28566274

SN - 0959-8146

VL - 357

SP - 1

EP - 9

JO - BMJ

JF - BMJ

M1 - j2350

ER -

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

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