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Gestational Exposure to Selective Serotonin Reuptake Inhibitors and Offspring Psychiatric Disorders: A National Register-Based Study

https://doi.org/10.1016/j.jaac.2016.02.013Get rights and content

Objective

To investigate the impact of gestational exposure to selective serotonin reuptake inhibitors (SSRIs) on offspring neurodevelopment.

Method

This is a cohort study using national register data in Finland between the years 1996 and 2010. Pregnant women and their offspring were categorized into 4 groups: SSRI exposed (n = 15,729); exposed to psychiatric disorder, no antidepressants (n = 9,651); exposed to SSRIs only before pregnancy (n = 7,980); and unexposed to antidepressants and psychiatric disorders (n = 31,394). We investigated the cumulative incidence of offspring diagnoses of depression, anxiety, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) for the 4 groups from birth to 14 years, adjusting for confounders.

Results

The cumulative incidence of depression among offspring exposed prenatally to SSRIs was 8.2% (95% CI = 3.1–13.3%) by age 14.9 years, compared with 1.9% (95% CI = 0.9–2.9%) in the psychiatric disorder, no medication group (adjusted hazard ratio [HR] = 1.78; 95% CI = 1.12–2.82; p = .02) and to 2.8% (95% CI = 1.4–4.3%) in the SSRI discontinued group (HR = 1.84; 95% CI = 1.14–2.97; p = .01). Rates of anxiety, ASD, and ADHD diagnoses were comparable to rates in offspring of mothers with a psychiatric disorder but no medication during pregnancy. Comparing SSRI exposed to unexposed individuals, the HRs were significantly elevated for each outcome.

Conclusion

Prenatal SSRI exposure was associated with increased rates of depression diagnoses in early adolescence but not with ASD or ADHD. Until confirmed, these findings must be balanced against the substantial adverse consequences of untreated maternal depression.

Section snippets

Data Sources and Study Population

We used a population-based, prospective cohort study design. All data were collected from national registers linked by the unique personal identification number assigned to all citizens and permanent residents of Finland. In Finland, all children regularly attend child welfare clinics where trained public health nurses or physicians perform medical examinations; this is offered to all and is free of charge. These services are particularly designed to identify psychiatric and neurodevelopmental

Results

Maternal and family characteristics tested as covariates by exposure status are shown in Table 1, tested by offspring outcome diagnosis in Table S1 (available online), and specifically for offspring depression in Table S2 (available online). The distribution of offspring by birth year demonstrates that in the SSRI exposed group, fewer offspring were in the oldest age cohort (1.6%) compared to offspring in the psychiatric disorder, no medication group (2.3%), or the SSRI discontinued group

Principal Findings

Using national register data, we observed increased rates of depression emerging at 12 to 14 years in offspring exposed prenatally to SSRIs. Taking into account maternal underlying psychiatric disorder, SSRI exposure was not associated with an increased risk of ASDs, ADHD, or anxiety. This study, like all studies attempting to answer questions about the long-term effects of in utero exposure to SSRIs, was observational, as it would not be possible to carry out a clinical trial of different

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      Citation Excerpt :

      Similarly, Kieviet and colleagues reported that, while severe symptoms such as convulsions are rare, 20–77% of infants exposed to SSRIs in utero have sleeping difficulties, tremors, agitation/irritability, and frequent crying [58]. An increased rate of depression diagnoses in early adolescence was also associated with prenatal SSRI exposure [64]. However, unquestionable correlations and causal links between these symptoms and SSRI exposure during development remain to be established [121].

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    This article is discussed in an editorial by Drs. Tim F. Oberlander and Simone N. Vigod on page 351.

    Clinical guidance is available at the end of this article.

    An interview with the author is available by podcast at www.jaacap.org or by scanning the QR code to the right.

    This research was supported by National Institutes of Health grant P50MH090966 (all authors), the Sackler Institute for Developmental Psychobiology of Columbia University (M.W., J.G.), grants from the Sigrid Juselius Foundation, the Foundation for Pediatric Research in Finland, and the Finnish Medical Foundation (D.G.).

    Ms. Hinkka-Yli-Salomäki and Drs. McKeague and Wickramaratne served as the statistical experts for this research.

    The authors thank Juha-Pekka Virtanen, BSc, for data management, and Jukka Huttunen, Project Coordinator, both of the Department of Child Psychiatry, University of Turku, Turku, Finland, for administrative support.

    Disclosure: Dr. Weissman has received funding from the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), the National Alliance for Research on Schizophrenia and Depression (NARSAD), the Sackler Foundation, and the Templeton Foundation; and has received royalties from Oxford University Press, Perseus Press, the American Psychiatric Association Press, and MultiHealth Systems, in the past 3 years. None of these disclosures pose conflicts of interest. Drs. Malm, Brown, Gissler, Gyllenberg, McKeague, Wickramaratne, Artama, Gingrich, Sourander, and Ms. Hinkka-Yli-Salomäki report no biomedical financial interests or potential conflicts of interest.

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