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Int J Epidemiol. 2019 Aug 1. pii: dyz170. doi: 10.1093/ije/dyz170. [Epub ahead of print]

Paternal antidepressant use as a negative control for maternal use: assessing familial confounding on gestational length and anxiety traits in offspring.

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Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway.
Pharmacoepidemiology and Drug Safety Research Group, School of Pharmacy & PharmaTox Strategic Research Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
Department of Psychology, University of Oslo, Oslo, Norway.
Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway.



Maternal antidepressant use in pregnancy has been associated with both shorter gestational length and child anxiety. We employed paternal antidepressant use as a negative-control exposure to indirectly assess whether confounding by genetic or shared familial environmental factors associated with depression may explain these associations.


The study sample came from the population-based Norwegian Mother and Child Cohort Study (MoBa) that recruited participants from 1999 to 2008. We included 70 959 families where the father completed a questionnaire about medication use in the 6 months prior to pregnancy. In 42 511 infants who completed the 3-year follow-up, we computed Z-scores for the anxiety domain of the Child Behavior Checklist. We used linear and logistic regression to assess the association between paternal antidepressant use, gestational age at birth and child anxiety.


Antidepressants were used by 1.1% (n = 755) of fathers. Paternal antidepressant use was not associated with gestational age at birth [β = 0.63 days, 95% confidence interval (CI) -1.56, 0.31] whereas it was positively associated with a child anxiety symptom Z-score and high anxiety symptoms (odds ratio 1.33, 95% CI 0.90, 1.97) in unadjusted analyses. This association was attenuated when controlling for maternal and paternal history of depression and other measured factors (odds ratio 1.14, 95% CI 0.76, 1.69).


These results support the suggested effect of maternal use of antidepressants in pregnancy on shorter gestation; however, they suggest familial confounding could explain the association between maternal use of antidepressants and anxiety traits in the offspring.


Antidepressants; MoBa; Norwegian Mother and Child Cohort Study; drug safety; negative controls; paternal exposure; pharmacoepidemiology; pregnancy


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