Persistent pulmonary hypertension of the newborn and selective serotonin reuptake inhibitors: lessons from clinical and translational studies.
ABSTRACT Two recent studies linking in utero exposure to selective serotonin reuptake inhibitors (SSRIs) with persistent pulmonary hypertension of the newborn (PPHN), a potentially serious but rare respiratory illness, have made clinicians and patients more reluctant to use SSRIs during pregnancy. However, additional clinical studies have associated maternal depression rather than SSRI exposure as a risk factor for PPHN. This review summarizes the current knowledge regarding PPHN pathophysiology, including the role of serotonin and genetic risk factors; the effects of SSRIs on pulmonary vasculature; the possible link between SSRIs and PPHN; and the diagnosis, clinical management, and prognosis of PPHN.
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ABSTRACT: To study the association between parental depression and maternal antidepressant use during pregnancy with autism spectrum disorders in offspring. Population based nested case-control study. Stockholm County, Sweden, 2001-07. 4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43 277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16 845 controls with data on maternal antidepressant use nested within a cohort (n=589 114) of young people aged 0-17 years. A diagnosis of autism spectrum disorder, with or without intellectual disability. EXPOSURES: Parental depression and other characteristics prospectively recorded in administrative registers before the birth of the child. Maternal antidepressant use, recorded at the first antenatal interview, was available for children born from 1995 onwards. A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. All associations were higher in cases of autism without intellectual disability, there being no evidence of an increased risk of autism with intellectual disability. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder. In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. However, assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly towards the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases.BMJ (Clinical research ed.). 01/2013; 346:f2059.
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ABSTRACT: Persistent pulmonary hypertension of the newborn (PPHN) is a rare but potentially life-threatening neonatal condition. Several authors have suggested that late pregnancy exposure to selective serotonin reuptake inhibitors (SSRIs) may increase the risk of PPHN. This association has been investigated in seven published studies that have shown mixed findings based on diverse methods. Several methodological limitations may account for the diversity of findings, which include, in some studies, a lack of control for well established risk factors for PPHN. The methodological improvement in the most recent study tentatively suggests that infants prenatally exposed to SSRIs are approximately twice as likely to suffer PPHN. Further research on the biological mechanisms involved is required. Clinicians should consider late pregnancy exposure to SSRIs as one of several possible risks for PPHN, which has implications for both prescribing SSRIs to pregnant women and for neonatal care of SSRI-exposed infants.CNS Drugs 10/2012; 26(10):813-22. · 4.83 Impact Factor
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ABSTRACT: OBJECTIVE: Conflicting data have led to controversy regarding antidepressant use during pregnancy. The objectives of this study are to i) review the risks of untreated depression and anxiety, ii) review the literature on risks of exposure to antidepressants during pregnancy, iii) discuss the strengths and weaknesses of the different study designs used to evaluate those risks, and iv) provide clinical recommendations. METHOD: MEDLINE/PubMed was searched for reports and studies on the risk of first-trimester teratogenicity, postnatal adaptation syndrome (PNAS), and persistent pulmonary hypertension (PPHN) with in utero antidepressant exposure. RESULTS: While some individual studies suggest associations between some specific major malformations, the findings are inconsistent. Therefore, the absolute risks appear small. PNAS occurs in up to 30% of neonates exposed to antidepressants. In some studies, PPHN has been weakly associated with in utero antidepressant exposure, while in other studies, there has been no association. CONCLUSION: Exposures of concern include that of untreated maternal illness as well as medication exposure. It is vital to have a careful discussion, tailored to each patient, which incorporates the evidence to date and considers methodological and statistical limitations. Past medication trials, previous success with symptom remission, and women's preference should guide treatment decisions.Acta Psychiatrica Scandinavica 12/2012; · 4.86 Impact Factor