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Antidepressants during pregnancy and autism in offspring: population based cohort study.

Abstract Objectives To study the association between maternal use of antidepressants during pregnancy and autism spectrum disorder (ASD) in offspring.Design Observational prospective cohort study with regression methods, propensity score matching, sibling controls, and negative control comparison.Setting Stockholm County, Sweden.Participants 254 610 individuals aged 4-17, including 5378 with autism, living in Stockholm County in 2001-11 who were born to mothers who did not take antidepressants and did not have any psychiatric disorder, mothers who took antidepressants during pregnancy, or mothers with psychiatric disorders who did not take antidepressants during pregnancy. Maternal antidepressant use was recorded during first antenatal interview or determined from prescription records.Main outcome measure Offspring diagnosis of autism spectrum disorder, with and without intellectual disability.Results Of the 3342 children exposed to antidepressants during pregnancy, 4.1% (n=136) had a diagnosis of autism compared with a 2.9% prevalence (n=353) in 12 325 children not exposed to antidepressants whose mothers had a history of a psychiatric disorder (adjusted odds ratio 1.45, 95% confidence interval 1.13 to 1.85). Propensity score analysis led to similar results. The results of a sibling control analysis were in the same direction, although with wider confidence intervals. In a negative control comparison, there was no evidence of any increased risk of autism in children whose fathers were prescribed antidepressants during the mothers' pregnancy (1.13, 0.68 to 1.88). In all analyses, the risk increase concerned only autism without intellectual disability.Conclusions The association between antidepressant use during pregnancy and autism, particularly autism without intellectual disability, might not solely be a byproduct of confounding. Study of the potential underlying biological mechanisms could help the understanding of modifiable mechanisms in the aetiology of autism. Importantly, the absolute risk of autism was small, and, hypothetically, if no pregnant women took antidepressants, the number of cases that could potentially be prevented would be small.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title bmj (clinical research ed.)
Publication Year Start




PMID- 28724519
OWN - NLM
STAT- MEDLINE
DA  - 20170720
DCOM- 20170724
LR  - 20170724
IS  - 1756-1833 (Electronic)
IS  - 0959-535X (Linking)
VI  - 358
DP  - 2017 Jul 19
TI  - Antidepressants during pregnancy and autism in offspring: population based cohort
      study.
PG  - j2811
LID - 10.1136/bmj.j2811 [doi]
AB  - Objectives To study the association between maternal use of antidepressants
      during pregnancy and autism spectrum disorder (ASD) in offspring.Design
      Observational prospective cohort study with regression methods, propensity score 
      matching, sibling controls, and negative control comparison.Setting Stockholm
      County, Sweden.Participants 254 610 individuals aged 4-17, including 5378 with
      autism, living in Stockholm County in 2001-11 who were born to mothers who did
      not take antidepressants and did not have any psychiatric disorder, mothers who
      took antidepressants during pregnancy, or mothers with psychiatric disorders who 
      did not take antidepressants during pregnancy. Maternal antidepressant use was
      recorded during first antenatal interview or determined from prescription
      records.Main outcome measure Offspring diagnosis of autism spectrum disorder,
      with and without intellectual disability.Results Of the 3342 children exposed to 
      antidepressants during pregnancy, 4.1% (n=136) had a diagnosis of autism compared
      with a 2.9% prevalence (n=353) in 12 325 children not exposed to antidepressants 
      whose mothers had a history of a psychiatric disorder (adjusted odds ratio 1.45, 
      95% confidence interval 1.13 to 1.85). Propensity score analysis led to similar
      results. The results of a sibling control analysis were in the same direction,
      although with wider confidence intervals. In a negative control comparison, there
      was no evidence of any increased risk of autism in children whose fathers were
      prescribed antidepressants during the mothers' pregnancy (1.13, 0.68 to 1.88). In
      all analyses, the risk increase concerned only autism without intellectual
      disability.Conclusions The association between antidepressant use during
      pregnancy and autism, particularly autism without intellectual disability, might 
      not solely be a byproduct of confounding. Study of the potential underlying
      biological mechanisms could help the understanding of modifiable mechanisms in
      the aetiology of autism. Importantly, the absolute risk of autism was small, and,
      hypothetically, if no pregnant women took antidepressants, the number of cases
      that could potentially be prevented would be small.
CI  - Published by the BMJ Publishing Group Limited. For permission to use (where not
      already granted under a licence) please go to
      http://group.bmj.com/group/rights-licensing/permissions.
FAU - Rai, Dheeraj
AU  - Rai D
AD  - Centre for Academic Mental Health, School of Social and Community Medicine,
      University of Bristol, Bristol, UK [email protected]
AD  - Avon and Wiltshire Partnership NHS Mental Health Trust, Bristol, UK.
AD  - Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
AD  - NIHR Biomedical Research Centre, University of Bristol, Bristol, UK.
FAU - Lee, Brian K
AU  - Lee BK
AD  - Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
AD  - Drexel University School of Public Health, Philadelphia, PA, USA.
AD  - AJ Drexel Autism Institute, Philadelphia, PA, USA.
FAU - Dalman, Christina
AU  - Dalman C
AD  - Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
AD  - Centre for Epidemiology and Community Medicine, Stockholm Health Care Services,
      Stockholm, Sweden.
FAU - Newschaffer, Craig
AU  - Newschaffer C
AD  - Drexel University School of Public Health, Philadelphia, PA, USA.
AD  - AJ Drexel Autism Institute, Philadelphia, PA, USA.
FAU - Lewis, Glyn
AU  - Lewis G
AD  - Division of Psychiatry, University College London, London, UK.
FAU - Magnusson, Cecilia
AU  - Magnusson C
AD  - Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
AD  - Centre for Epidemiology and Community Medicine, Stockholm Health Care Services,
      Stockholm, Sweden.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20170719
PL  - England
TA  - BMJ
JT  - BMJ (Clinical research ed.)
JID - 8900488
RN  - 0 (Antidepressive Agents)
SB  - AIM
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antidepressive Agents/*administration & dosage
MH  - Autistic Disorder/*chemically induced/epidemiology
MH  - Child
MH  - Child, Preschool
MH  - Depressive Disorder/*drug therapy/epidemiology
MH  - Female
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Pregnancy
MH  - Pregnancy Complications/*drug therapy/epidemiology
MH  - Prenatal Exposure Delayed Effects/chemically induced/epidemiology
MH  - Prospective Studies
MH  - Risk Factors
MH  - Sweden/epidemiology
COI - Competing interests: All authors have completed the ICMJE uniform disclosure form
      atwww.icmje.org/coi_disclosure.pdf and declare: no support from any organisation 
      for the submitted work; no financial relationships with any organisations that
      might have an interest in the submitted work in the previous three years; no
      other relationships or activities that could appear to have influenced the
      submitted work.
EDAT- 2017/07/21 06:00
MHDA- 2017/07/25 06:00
CRDT- 2017/07/21 06:00
PST - epublish
SO  - BMJ. 2017 Jul 19;358:j2811. doi: 10.1136/bmj.j2811.