Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn

Meyers Primary Care Institute, University of Massachusetts Medical School, Fallon Foundation, and Fallon Community Health Plan, Worcester, MA 01605, USA.
Pharmacoepidemiology and Drug Safety (Impact Factor: 2.94). 03/2009; 18(3):246-52. DOI: 10.1002/pds.1710
Source: PubMed


To determine the prevalence of persistent pulmonary hypertension of the newborn (PPHN) among infants whose mothers were exposed to antidepressants in the third trimester of pregnancy compared to the prevalence among infants whose mothers were not exposed to antidepressants in the third trimester.
A retrospective study was conducted using the automated databases of four health plans participating in the HMO Research Network Center for Education and Research on Therapeutics. Women who delivered an infant in a hospital from 1 January 1996 through 31 December 2000 were identified. The administrative databases were used to identify full-term infants whose mothers received an antidepressant during the third trimester of pregnancy and unexposed infants whose mothers did not receive an antidepressant during the third trimester. Hospitalization data were used to identify diagnoses or procedure codes potentially indicative of PPHN.
Among 1104 infants exposed to antidepressants in the third trimester and a matched sample of 1104 unexposed infants, five infants were classified by the expert reviewers as having PPHN. Among those infants whose mothers were exposed to selective serotonin reuptake inhibitors (SSRIs) in the third trimester, the prevalence of PPHN was 2.14 per 1000 (95% confidence interval (CI) 0.26, 7.74), while the prevalence among infants whose mothers were not exposed was 2.72 per 1000 (95%CI 0.56, 7.93).
We did not find an association between SSRI use in late pregnancy and PPHN. Limitations of the present study, including the small number of confirmed cases, suggest further research in this area may be warranted.

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    • "The FDA responded to the initial positive report by issuing a public health advisory in 2006 about an increased risk of PPHN associated with maternal SSRI use after the 20th gestational week.134 However, subsequent results of a retrospective cohort study of 1,104 infants exposed to antidepressants during the third trimester135 and a retrospective chart review of 24,214 deliveries (808 of which involved antepartum SSRI exposure)96 did not find an association between antenatal SSRI exposure and PPHN. In a large case-control study of 11,923 births (20 with primary PPHN), cesarean delivery prior to the onset of labor, but not in utero SSRI exposure after 20 weeks’ gestation, was significantly associated with PPHN.136 "
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    ABSTRACT: In pregnant women with major depression, the overarching goal of treatment is to achieve or maintain maternal euthymia, thus limiting both maternal and fetal exposure to the harmful effects of untreated or incompletely treated depression. However, the absence of uniformly effective therapies with guaranteed obstetric and fetal safety makes the treatment of major depression during pregnancy among the most formidable of clinical challenges. Clinicians and patients are still faced with conflicting data and expert opinion regarding the reproductive safety of antidepressants in pregnancy, as well as large gaps in our understanding of the effectiveness of most antidepressants and nonpharmacological alternatives for treating antenatal depression. In this paper, we provide a clinically focused review of the available information on potential maternal and fetal risks of untreated maternal depression during pregnancy, the effectiveness of interventions for maternal depression during pregnancy, and potential obstetric, fetal, and neonatal risks associated with antenatal antidepressant use.
    Full-text · Article · Sep 2014 · Drug, Healthcare and Patient Safety
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    • "This study included 1,618,255 infants born after 33 weeks gestational age, and reported that SRI exposure doubled the risk of neonatal PPHN [104]. Several other smaller studies, however, reported no association between SRI use and PPHN [105]. Most recently, a large case-control study of infants delivered at Madigan Army Medical Center between 2003 and 2009 reported that mode of delivery was the only factor found to be associated with PPHN with caesarean delivery before the onset of labour, increasing the risk of PPHN nearly five-fold (OR ¼ 4.9 95% CI 1.7 to 14.0) [7]. "
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    ABSTRACT: Depression, anxiety, or both, during pregnancy are common complications during the perinatal period, with 15-20% of women experiencing depression at some point during their pregnancy. Considerable evidence suggests that untreated or undertreated maternal Axis I mood disorders can increase the risk for preterm birth, low birth weight, and alter neurobehavioral development in utero. Serotonin reuptake inhibitor antidepressants are often considered for antenatal therapy, with the goal of improving maternal mental health during pregnancy. Treatment with a serotonin-reuptake inhibitor, however, does not guarantee remission of depression, and in-utero serotonin reuptake inhibitor exposure has also been linked to increased risks for adverse infant outcomes. In this chapter, evidence linking serotonin reuptake inhibitor use with an increased risk for postnatal adaptation syndrome, congenital heart defects, and neonatal persistent pulmonary hypertension is reviewed. Management decisions should include attention to the continuum of depression symptoms, from subclinical to severe major depressive disorder and the long-term developmental risks that might also be associated with pre- and postnatal exposure.
    Full-text · Article · Sep 2013 · Best practice & research. Clinical obstetrics & gynaecology
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    • "For SSRIs, studies have been published where paroxetine and maybe bupropion, sertraline and citalopram are at risk for cardiac congenital anomalies [9–15]. Paroxetine and also venlafaxin and fluoxetine, are at risk of pulmonary hypertension [16–19]. Further, SSRIs are possibly associated with an increased risk of omphalocele, anencephaly, and craniosynostosis [20]. "
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    ABSTRACT: Purpose The use of antidepressants during pregnancy is common. Some studies suggest an association between in utero exposure to antidepressants and the occurrence of pulmonary diseases like asthma later in life. Serotonin reuptake inhibitors (SSRIs) as well tricyclic antidepressants (TCAs) are thought to be involved in the development of the respiratory rhythm generator (RRG) and the maturation of the formation of surfactant. In this study the use of drugs for pulmonary diseases in children who were exposed to antidepressants in utero were compared with non-exposed children. Methods The pharmacy prescription database was used for a cohort study in which the use of drugs for pulmonary disease in children after in utero exposure to antidepressants (TCAs, SSRIs) was compared with children with no antidepressant exposure in utero. Drugs for pulmonary diseases were applied as a proxy for disturbed development of the respiratory tract. Results A small though significant increase in the incidence risk ratio (IRR) of the use of drugs for pulmonary disease was found after any-time in utero exposure to SSRIs, adjusted for maternal use of antibiotics, of 1.17 (95 % CI 1.16–1.18). An increase was also seen when we looked specifically for the use of SSRIs in at least the first trimester (IRR = 1.18, 95 % CI 1.17–1.20). An increased IRR in the use of drugs for pulmonary disease was also seen when children were exposed to TCAs, but this was not statistically significant. However, in both groups our sample size was rather small. The effect size is modest and may also be confounded by maternal smoking. Conclusions In utero exposure to SSRIs leads to a statistically significant increase in the use of drugs for pulmonary diseases, especially when exposure occurred during the first trimester of pregnancy. The increase in the use of drugs for pulmonary disease may also be related to other factors. Therefore, further study is recommended.
    Full-text · Article · Jul 2012 · European Journal of Clinical Pharmacology
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