Maternal depression, antidepressant prescriptions, and congenital anomaly risk in offspring: a population-based cohort study

BJOG. 2014 Nov;121(12):1471-81. doi: 10.1111/1471-0528.12682. Epub 2014 Mar 11.

Abstract

Objective: To estimate risks of major congenital anomaly (MCA) among children of mothers prescribed antidepressants during early pregnancy or diagnosed with depression but without antidepressant prescriptions.

Design: Population-based cohort study.

Setting: Linked UK maternal-child primary care records.

Population: A total of 349,127 singletons liveborn between 1990 and 2009.

Methods: Odds ratios adjusted for maternal sociodemographics and comorbidities (aORs) were calculated for MCAs, comparing women with first-trimester selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) and women with diagnosed but unmedicated depression, or women without diagnosed depression.

Main outcome measures: Fourteen system-specific MCA groups classified according to the European Surveillance of Congenital Anomalies and five specific heart anomaly groups.

Results: Absolute risks of MCA were 2.7% (95% confidence interval, 95% CI, 2.6-2.8%) in children of mothers without diagnosed depression, 2.8% (95% CI 2.5-3.2%) in children of mothers with unmedicated depression, and 2.7% (95% CI 2.2-3.2%) and 3.1% (95% CI 2.2-4.1%) in children of mothers with SSRIs or TCAs, respectively. Compared with women without depression, MCA overall was not associated with unmedicated depression (aOR 1.07, 95% CI 0.96-1.18), SSRIs (aOR 1.01, 95% CI 0.88-1.17), or TCAs (aOR 1.09, 95% CI 0.87-1.38). Paroxetine was associated with increased heart anomalies (absolute risk 1.4% in the exposed group compared with 0.8% in women without depression; aOR 1.78, 95% CI 1.09-2.88), which decreased marginally when compared with women with diagnosed but unmedicated depression (aOR 1.67, 95% CI 1.00-2.80).

Conclusions: Overall MCA risk did not increase with maternal depression or with antidepressant prescriptions. Paroxetine was associated with increases of heart anomalies, although this could represent a chance finding from a large number of comparisons undertaken.

Keywords: Antidepressants; SSRIs; TCAs; congenital anomaly; depression.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced / etiology*
  • Adult
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Cohort Studies
  • Depression / drug therapy*
  • Female
  • Humans
  • Logistic Models
  • Odds Ratio
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Prospective Studies
  • Risk Factors
  • Serotonin Uptake Inhibitors / adverse effects
  • Serotonin Uptake Inhibitors / therapeutic use

Substances

  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors