Exposure to selective serotonin reuptake inhibitors and the risk of congenital malformations: a nationwide cohort study

Abstract

ObjectivesTo analyse the relation between selective serotonin reuptake inhibitor (SSRI) use and major congenital malformations, with focus on malformations of the heart.DesignRegister-based retrospective nationwide cohort study, using the Danish Medical Birth Registry.SettingDenmark.ParticipantsPregnant women in Denmark between 1997 and 2009 and their offspring.Primary outcome measuresFor each SSRI, ORs for major congenital malformations were estimated using multivariable logistic regression models for women exposed to an SSRI during the first trimester and for women with paused exposure during pregnancy.ResultsThe authors identified 848 786 pregnancies; 4183 were exposed to an SSRI throughout the first trimester and 806 pregnancies paused exposure during pregnancy. Risks of congenital malformations of the heart were similar for pregnancies exposed to an SSRI throughout the first trimester, adjusted OR 2.01 (95% CI 1.60 to 2.53), and for pregnancies with paused SSRI treatment during pregnancy, adjusted OR 1.85 (95% CI 1.07 to 3.20), p value for difference: 0.94. The authors found similar increased risks of specific congenital malformations of the heart for the individual SSRIs. Furthermore, the authors found no association with dosage.ConclusionsThe apparent association between SSRI use and congenital malformations of the heart may be confounded by indications. The moderate absolute risk increase combined with uncertainty for causality still requires the risk versus benefit to be evaluated in each individual case.

Links between serotonin reuptake inhibition during pregnancy and neurodevelopmental delay/spectrum disorders: A systematic review of epidemiological and physiological evidence

“…A study by Malm and colleagues has found that women taking SSRIs show a 10 fold greater incidence of Fetal Alcohol Spectrum Disorders (FASD) compared with women not on SSRIs [43]. These findings are supported by adverse event reports of FASD and behavioral effects consistent with FASD to FDA for all SSRIs and reports of SSRIs causing compulsive alcohol intake [84].…”

“…Nothing better illustrates this than the evidence from Malm et al study [43], which is consistent with known effects of SSRIs in triggering alcohol intake in a sub-population of subjects and a recent RCT showing poorer drinking outcomes with citalopram treatment for alcohol dependence disorder [118].…”

“…The study by Malm et al [43] suggests it does. Fourth, a noted feature of SSRIs is that they produce the experience of blunted emotion [90].…”

A Rough Obscurity: Using Antidepressants in Pregnancy

“…Contrary to positive associations, there are many reviews pretending no relationship between antidepressant use and congenital malformations (3). In a study by JimenezSolem et al, authors submitted that women using antidepressant treatment tend to visit health care providers for screening their children and this tendency might be accepted as a confounding factor (4). In addition to vast literature about results of antidepressant use in pregnancy suggesting no significant increase in malformations in the offspring, no concrete evidence about their teratogenicity has been emerged (5).…”

Treatment of Depression During Pregnancy and the Postpartum Period

“…49, 60, 64, 70, 86, 90, 103, 104, 114-116, 120, 125, 147, 150 Two of the studies were methodologically strong, with low risk of bias, 104,125 and two were methodologically weak, high risk of bias, due primarily to potentially biased selection of patients, lack of assessment of comparability of subjects at baseline, and lack of appropriate statistical analysis, including controlling for potential confounding. 103,115 Because major malformations are a fairly rare and serious adverse event, a signal from indirect evidence may be important.…”