Women who are depressed during pregnancy and who take selective serotonin inhibitors (SSRIs) may be more likely to have a pre-term birth than those who do not take SSRIs. Pre-term birth occurred in 6.8% of women with depression during pregnancy treated with SSRIs compared to 5.8% of depressed women who were treated with talking therapies alone.
However, because this is a review of observational (cohort) studies rather than randomised controlled trials it is not possible to say that SSRIs cause pre-term birth. For example, it is possible that women who had worse depression were more likely to be prescribed SSRIs, and it may have been the greater severity of depression rather than the SSRIs that caused pre-term birth.
The benefits of drugs for depression during pregnancy need to be weighed against potential harms. This information does not suggest a change in practice, but may help the discussion between doctor and patient.
Why was this study needed?
About one in ten women will experience depression during pregnancy. Maternal depression during pregnancy has been associated with an increase in pre-term births, low birth-weight and complications after birth.
Depression during pregnancy can be treated by talking therapies and drug treatments. SSRIs are a class of antidepressant considered to be the safest for use in pregnancy. The class of drugs includes citalopram, sertraline, paroxetine and fluoxetine. Though safe, they are still associated with an increased risk of rare complications including raised blood pressure in the mother, congenital heart defects in the child and miscarriage.
Whether SSRIs are also associated with preterm births independent of the link to depression is unclear. This review was designed to evaluate whether taking SSRIs during pregnancy is associated with an increased risk of pre-term birth.
What did this study do?
This was a systematic review and meta-analysis of eight cohort studies including 1,237,669 pregnant women that measured the incidence of pre-term birth in those with depression who took SSRIs compared to those who didn’t take SSRIs. The control group in five studies were pregnant women without depression; the remaining three studies had control groups of pregnant women with depression but treated with talking therapies alone.
Three studies were from the USA, two from Sweden, two from Canada and one from Denmark. The type of SSRI received varied, and depression was defined differently across studies.
Studies were assessed to be at low risk of bias. However, just three studies adjusted for other influences that may impact on outcomes (confounders), such as maternal age, smoking, and number of previous births. Observational studies can show an association between SSRI exposure and pre-term birth but they cannot prove a direct cause and effect.
What did it find?
- Pre-term birth was more common in the SSRI group (11.6%) than the control group (5.2%); this remained the case when taking into account confounders (adjusted odds ratio [aOR] 1.24, 95% confidence interval [CI] 1.09 to 1.41).
- When looking at the three studies in which controls were pregnant women with depression, pre-term birth remained more common in the SSRI group compared to controls. However, the difference between the two groups was reduced (6.8% versus 5.8%; OR 1.17, 95% CI 1.10 to 1.25).
- There was little difference in risk for women on paroxetine compared to fluoxetine (OR 1.42, 95% CI 0.88 to 2.31).
- There were no results comparing other SSRIs with each other.
What does current guidance say on this issue?
The 2014 NICE guideline on antenatal and postnatal mental health recommends that SSRIs can be considered for woman with moderate or severe depression in pregnancy. To be considered, the woman must understand the risks associated with antidepressants. She must also have expressed either a preference for drug therapy or declined the option of (or not responded to) talking therapies.
What are the implications?
The results show an association between taking SSRIs in pregnancy and pre-term birth. However, they cannot show that SSRIs cause pre-term birth.
Interpretation is complicated by the fact that depression in pregnancy is itself associated with pre-term birth. It is likely that women who were prescribed SSRIs had more severe depression than those in the control groups, and so it is possible that it was the more severe depression that contributed to pre-term birth rather than the SSRIs.
Other confounders, such as maternal age and smoking, may also have contributed to pre-term birth. Only three of the eight studies accounted for any confounders.
This moderate level evidence from observational studies, is probably sufficient to warrant a caution in the use of SSRIs in pregnancy, something that can be discussed with women. There are likely to be situations when the risk of untreated depression is greater than the small risk of a premature birth and a clinical judgment will be required, one that ideally takes this research into account.
Citation and Funding
Eke AC, Saccone G, Berghella V. Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and risk of preterm birth: a systematic review and meta-analysis. BJOG. 2016. [Epub ahead of print].
No funding information was provided for this study.
NICE. Antenatal and postnatal mental health: clinical management and service guidance. CG192. National Institute for Health and Care Excellence: London; 2014.
Wadhwa PD, Entringer S, Buss C, Lu MC. The contribution of maternal stress to preterm birth: issues and considerations. Clin Perinatol. 2011;38(3):351-84.
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