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Long-term prenatal effects of antidepressant use on the risk of affective disorders in the offspring: a register-based cohort study.

ABSTRACT: To investigate the association between intrauterine antidepressant exposure and offspring affective disorders over an 18-year follow-up period using Danish national registers. We included 42,988 singletons born during 1998-2011 and followed-up until 2016, death, emigration, or date of first affective disorder diagnosis. Children were categorised into two groups according to maternal antidepressant use within 2 years before and during pregnancy: continuation (use before and during pregnancy) or discontinuation (use before but not during pregnancy). The outcome was an affective disorders diagnosis in the offspring based on secondary/tertiary care records and primary care prescription data. Hazard ratios (HR) of affective disorders were estimated using Cox regression models. To consider confounding by shared environmental or genetic factors, we investigated the effect of paternal antidepressant use on the risk for affective disorders. Affective disorders were diagnosed in 1538 children. Children whose mothers continued antidepressants during pregnancy had an increased risk of affective disorders (HR = 1.20, 95% CI = 1.08-1.34), compared with children whose mothers discontinued before pregnancy. Similarly, continued paternal antidepressant use during pregnancy was associated with higher risk for offspring affective disorders (HR = 1.29, 95% CI = 1.12-1.49), compared to discontinuation. Based on data from primary and secondary/tertiary care, maternal antidepressant use during pregnancy was associated with an increased risk of affective disorders in the offspring. As similar associations were observed in children whose fathers continued antidepressant use across the pregnancy period, the observed association may be attributable to the underlying parental psychopathology, rather than the direct intrauterine exposure to antidepressants.

SUBMITTER: Rommel AS

PROVIDER: S-EPMC8209173 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objective To investigate the association between in utero exposure to antidepressants and risk of psychiatric disorders.Design Population based cohort study.Setting Danish national registers.Participants 905?383 liveborn singletons born during 1998-2012 in Denmark and followed from birth until July 2014, death, emigration, or date of first psychiatric diagnosis, whichever came first. The children were followed for a maximum of 16.5 years and contributed 8.1×106 person years at risk.Exposures for observational studies Children were categorised into four groups according to maternal antidepressant use within two years before and during pregnancy: unexposed, antidepressant discontinuation (use before but not during pregnancy), antidepressant continuation (use both before and during pregnancy), and new user (use only during pregnancy).Main outcome measure First psychiatric diagnosis in children, defined as first day of inpatient or outpatient treatment for psychiatric disorders. Hazard ratios of psychiatric disorders were estimated using Cox regression models.Results Overall, psychiatric disorders were diagnosed in 32?400 children. The adjusted 15 year cumulative incidence of psychiatric disorders was 8.0% (95% confidence interval 7.9% to 8.2%) in the unexposed group, 11.5% (10.3% to 12.9%) in the antidepressant discontinuation group, 13.6% (11.3% to 16.3%) in the continuation group, and 14.5% (10.5% to 19.8%) in the new user group. The antidepressant continuation group had an increased risk of psychiatric disorders (hazard ratio 1.27, 1.17 to 1.38), compared with the discontinuation group.Conclusions In utero exposure to antidepressants was associated with increased risk of psychiatric disorders. The association may be attributable to the severity of underlying maternal disorders in combination with antidepressant exposure in utero. The findings suggest that focusing solely on a single psychiatric disorder among offspring in studies of in utero antidepressant exposure may be too restrictive.

Project description: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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Long-term prenatal effects of antidepressant use on the risk of affective disorders in the offspring: a register-based cohort study.

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