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Teratogenicity risk small with SSRIs

Obstetrics and gynaecology

Obstetrics and gynaecology

Depressive disorders are common and in women cluster around the menopause, during and especially after pregnancy, and the premenstrual period.

Selective serotonin re-uptake inhibitors (SSRIs) are prescribed for depression following, and increasingly during, pregnancy. The risk of teratogenesis is always a worry, but withdrawal of treatment during pregnancy is not without risk as well.

Two large, case-controlled studies of SSRI use in pregnancy provide reassurance to prescribers and patients alike.

The studies were conducted among women in the USA and Canada. Both collected a cohort of women whose pregnancy had been complicated by a birth defect. Combining the data, nearly 20,000 affected pregnancies were identified and compared with randomly selected pregnancies, from the same localities, where no birth defect had been identified. The studies excluded genetic disorders.

The studies compared SSRI use (pre-conceptually and in the first trimester) in the birth defect and control groups. In the Alwan et al study, SSRIs were used by 2.3% of women within the study time frame.

The studies controlled for demographic variables including ethnicity, affluence, BMI, alcohol and tobacco use.

The analyses focussed on the role of SSRIs where a sufficient number of particular birth defects had occurred.

Neither study was able to identify any significant association between overall SSRI use and the majority of birth defects.

Alwan et al found that the odds ratios for anencephaly, craniosynostosis and omphalocele were 2.4, 2.5 and 2.8 respectively in women who had taken an SSRI compared with women who had not. However, the low background incidence of the disorders and the wide confidence intervals suggest that absolute risks were small.

Louik et al found no overall increase in risk with SSRI use, but some association between specific SSRIs and birth defects. In particular, sertraline exposure was associated with omphalocele and septal defects (odds ratios 5.7 and 2.0 respectively).

The study also found that paroxetine exposure was associated with right ventricular outflow tract obstruction (odds ratio 3.3). However, for both drugs and all three defects the absolute numbers of affected infants were very small.

Previous research has suggested that SSRI use might be associated with birth defects. These two large studies suggest that there might be some risk associated with use of SSRIs (in particular sertraline and paroxetine) in early pregnancy but the absolute risks, if they exist at all, are extremely small.

I find these data reassuring and feel supported in recommending the initiation or continuation of SSRIs during pregnancy in situations that warrant their use.

Louik C, Lin AE, Werler MM et al. First-trimester Use of Selective Seratonin-Reuptake Inhibitors and the Risk of Birth Defects. N Engl J Med 2007; 356:2675-83

Alwan S, Reefhuis J, Rasmussen SA et al. Use of Selective Seratonin-Reuptake Inhibitors in Pregnancy and the Risk of Birth Defects. N Engl J Med 2007;356:2684-92

Reviewer

Dr Chris Barclay
GP, Sheffield

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