Antidepressant Studies

SSRI Antidepressants More than Double the Risk of Lung Complication in Newborns

 Each of the studies chosen by the investigators was selected for the high quality of its study design.In this meta-analysis, researchers pooled data from seven previous studies that had investigated the relationship between maternal use of SSRI antidepressants and a serious condition in newborn babies known as persistent pulmonary hypertension of the newborn (PPHN). Each of the studies chosen by the investigators was selected for the high quality of its study design. The study was published online on January 14, 2014 in the British Medical Journal.

The time of exposure to SSRIs was divided into four categories: exposure in early pregnancy; at any time in pregnancy; during most or all of the pregnancy; and during late pregnancy. Studies varied in their definitions of early and late pregnancy, but early pregnancy generally meant from ninety days before pregnancy up to fifty-five days into the pregnancy, or before week twenty. Late pregnancy meant during or after week twenty, or during the third trimester.

The investigators reported an increased risk for newborns exposed to SSRIs late in pregnancy that was two and a half times greater than non-exposed babies. However, after adjusting their results for potential publication bias (the selective publishing of only studies with positive results) the authors estimated that late exposure to SSRIs increased the risk of PPHN 2.84 times, nearly triple the risk of babies not exposed. The risk for babies who were exposed “most or all of pregnancy” was estimated to be even higher: 3.3 times the risk.

Exposure was primarily determined by prescription registries, but such registries can only tell investigators if a drug was prescribed, not if it was taken. According to the investigators, “the pool effects were dominated by the registry studies, and yet we cannot be confident that the mothers used the drugs as prescribed.” Scientists in one study found that estimates of exposure based on prescription registries tended to overestimate exposure, particularly early in pregnancy. This would have the effect of underestimating risk in all categories, but particularly early in pregnancy, leaving open the possibility that early exposure might also increase risk significantly.

The authors noted that one of the studies included in the meta-analysis had found a slight increased risk of PPHN associated with a history of admission to hospital for a psychiatric condition (30% increased risk), but the risk for women with this history who used SSRIs in late pregnancy was over three times that of women who did not use the drugs. Results of another study included in the meta-analysis suggested that there was no independent association between maternal depression and PPHN. Risk in the Canadian study appears to increase with increased exposure, another sign that the drug itself, not depression, is causing PPHN.

The authors explained that the blood vessels in the lungs of infants with PPHN do not relax after birth, leading to poor oxygenation. “Symptoms can range in severity from mild respiratory distress to the most severe form, with hypoxia necessitating intensive medical care.” The condition is typically estimated to be fatal in 10-20% of cases, though a 2011 study in the journal Pulmonary Medicine reported a mortality rate over 30%.

Even among survivors there are long-term consequences. A September 2, 2013 review article in the journal Frontiers in Pediatrics stated that neurodevelopmental disabilities including cognitive delays and hearing deficit can be seen in 6.4% of PPHN survivors. A long-term follow-up study found that children treated for PPHN “are at high risk for sensorineural hearing loss” and added, “The incidence of chronic health problems and use of remedial education was high.”

Summary Information


Prenatal exposure to antidepressants and persistent pulmonary hypertension of the newborn: systematic review and meta-analysis


Sophie Grigoriadis1,2; Emily H. VonderPorten1; Lana Mamisashvili1; George Tomlinson3; Cindy-Lee Dennis4; Gideon Koren4; Meir Steiner6; Patricia Mousmanis7; Amy Cheung1,2; Lori E. Ross8

  1. Department of Psychiatry, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada, M4N 3M5
  2. Department of Psychiatry, Faculty of Medicine, University of Toronto and Sunnybrook Research Institute, Toronto, Ontario, Canada
  3. Department of Medicine, University Health Network/Mount Sinai Hospital, Toronto, Ontario, Canada
  4. Faculties of Nursing and Medicine, University of Toronto and Women’s College Research Institute, Toronto, Ontario, Canada
  5. Motherisk Program, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
  6. Women’s Health Concerns Clinic, St Joseph’s Healthcare, Hamilton, Ontario, Canada
  7. Healthy Child Development Program, Ontario College of Family Physicians, Toronto, Ontario, Canada
  8. Health Systems and Health Equity Research Group, Centre for Addiction and Mental Health, Toronto, Ontario, Canada


British Medical Journal, 2014; 348:f6932. Published online January 14, 2014.


This study was funded by a research syntheses grant from the Canadian Institutes of Health Research (KRS-83127) and the Ontario Ministry of Health and Long-Term Care through the Drug Innovation Fund (grant No 2008-005). Sophie Grigoriadis held a new investigator award in women’s health research from Canadian Institutes of Health Research in partnership with the Ontario Women’s Health Council (award NOW-88207). Lori E. Ross held a new investigator award from the Canadian Institutes of Health Research and the Ontario Women’s Health Council (award NOW-84656). The funding sources had no role in the study design; collection, analysis, or interpretation of results; writing of the manuscript; or submission of the manuscript for publication. The researchers were independent from the funders.