Antidepressant Studies

New Research Ties Antidepressant Use in Pregnancy to Preterm Birth

A thorough search of medical databases turned up 41 studies published between 1993 and 2012 that compared preterm birth rates in women who took antidepressants during pregnancy, with rates for women who did not take antidepressants.A comprehensive review of the research literature on antidepressants and preterm birth by scientists at Harvard Medical School, Vanderbilt University and Tufts University School of Medicine has provided strong confirming evidence that maternal antidepressant usage during pregnancy significantly increases a mother’s risk of having a preterm birth.

A thorough search of medical databases turned up 41 studies published between 1993 and 2012 that compared preterm birth rates in women who took antidepressants during pregnancy, with rates for women who did not take antidepressants. SSRI and SNRI antidepressants were the primary drugs analyzed in all the studies. Preterm birth was defined as birth before 37 weeks’ gestation. The studies were grouped into those that adjusted their findings for the potential influence of various “confounders” (factors other than antidepressants that have also been associated with preterm birth, including maternal age, smoking, alcohol use, and history of prematurity or miscarriage  and those that did not. A third group comprised studies that adjusted for the possible confounding effect of maternal depression or psychiatric illness.

“…[O]ur study findings … reinforce the notion that antidepressants should not be used by pregnant women in the absence of a clear need that cannot be met through alternative approaches.”

Pooling the data from the studies that did not adjust for confounders yielded a 57% increase in risk of preterm birth following antidepressant use early in pregnancy (typically 1st trimester usage) and a 44% increase in risk tied to use any time during pregnancy.

After pooling data from studies that did adjust for potential confounders, the researchers found that early exposure to antidepressants increased the risk of preterm birth only slightly (the association was not statistically significant), whereas usage any time during pregnancy increased the risk by 53% and late exposure (typically 3rd trimester) nearly doubled the risk (96% increase).

Eleven studies attempted to separate the effects of antidepressants from the possible confounding influence of depression or behaviors that might be associated with depression, such as smoking or alcohol intake. The authors report, “Most of these 11 studies nonetheless found an increased risk of preterm birth associated with antidepressant medication use….” The pooled data from these studies demonstrated a 61% increase in risk of preterm birth for antidepressant users compared to women with psychiatric illness but no antidepressant use.

Additional mathematical testing (called sensitivity analysis) demonstrated that the association between antidepressant use and preterm birth found by the investigators was quite strong. In other words, it was unlikely that the findings were the result of confounding that the scientists had not properly measured.

The authors stressed that even “moderate (32 to 33 gestational weeks) and mild (34 to 36 gestational weeks) preterm birth infants are also at increased risk for neonatal and post-neonatal mortality and morbidity,” including “health problems ranging from neurodevelopmental disabilities such as cerebral palsy and mental retardation to other chronic health problems such as asthma.” They also observed that the evidence linking depression itself to preterm birth is “weak.”

Summary Information


Preterm Birth and Antidepressant Medication Use during Pregnancy: A Systematic Review and Meta-Analysis


Krista F. Huybrechts1; Reesha Shah Sanghani2; Jerry Avorn2; Adam C. Urato3

  1. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
  2. Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, Tennessee, United States of America
  3. MetroWest Medical Center, Tufts University School of Medicine, Framingham, Massachusetts, United States of America


PLoS One, March 2014, Volume 9, Issue 3, e92778


There are no current funding sources for this study. Krista Huybrechts is supported by a career development grant K01MH099141 from the National Institute of Mental Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.