Prenatal exposure to selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors and risk for persistent pulmonary hypertension of the newborn: a systematic review, meta-analysis, and network meta-analysis

Masarwa, Reem; Bar‐Oz, Benjamin; Gorelik, Einat; Reif, Shimon; Perlman, Amichai; Matok, Ilan

doi:10.1016/j.ajog.2018.08.030

Cited by 59 publications

(51 citation statements)

References 48 publications

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“…SSRIs have been linked to an increased risk of a severe respiratory neonatal con‐dition (persistent pulmonary hypertension of the unborn), but with a small ab‐solute risk of around 3 in 1,000 reported in a recent systematic review 126 .…”

Section: Interventionsmentioning

confidence: 99%

Perinatal mental health: a review of progress and challenges

2020

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Perinatal mental health has become a significant focus of interest in recent years, with investment in new specialist mental health services in some high‐income countries, and inpatient psychiatric mother and baby units in diverse settings. In this paper, we summarize and critically examine the epidemiology and impact of perinatal mental disorders, including emerging evidence of an increase of their prevalence in young pregnant women. Perinatal mental disorders are among the commonest morbidities of pregnancy, and make an important contribution to maternal mortality, as well as to adverse neonatal, infant and child outcomes. We then review the current evidence base on interventions, including individual level and public health ones, as well as service delivery models. Randomized controlled trials provide evidence on the effectiveness of psychological and psychosocial interventions at the individual level, though it is not yet clear which women with perinatal mental disorders also need additional support for parenting. The evidence base on psychotropic use in pregnancy is almost exclusively observational. There is little research on the full range of perinatal mental disorders, on how to improve access to treatment for women with psychosocial difficulties, and on the effectiveness of different service delivery models. We conclude with research and clinical implications, which, we argue, highlight the need for an extension of generic psychiatric services to include preconception care, and further investment into public health interventions, in addition to perinatal mental health services, potentially for women and men, to reduce maternal and child morbidity and mortality.

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Section: Interventionsmentioning

confidence: 99%

Perinatal mental health: a review of progress and challenges

2020

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“…The possible effect of non‐SSRIs was assessed in 3 studies. In addition, 1 meta‐analysis by Masarwa et al 14 reported data about effects of the use of SSRIs or SNRIs. None of the meta‐analyses included data on TCAs.…”

Section: Resultsmentioning

confidence: 99%

“…None of the meta‐analyses included data on TCAs. The number of meta‐analyses evaluating individual neonatal outcomes was as follows: autism spectrum disorders, 10 15‐24 ; ADHD, 4 21,23,31,32 ; preterm birth, 4 25‐28 ; persistent pulmonary hypertension, 3 14,33,34 ; low birth weight, 2 25,29 ; and spontaneous abortion, 2 28,30 …”

Section: Resultsmentioning

confidence: 99%

Neonatal and Childhood Outcomes in Offspring of Pregnant Women Using Antidepressant Medications: A Critical Review of Current Meta‐Analyses

Uğuz

2020

The Journal of Clinical Pharma

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This article reviewed the results of 21 recent meta‐analyses examining the relationship between maternal use of antidepressants during pregnancy and negative outcomes in newborns and children. PubMed was searched for meta‐analyses published in English between January 1, 2011, and November 30, 2019, by using combinations of the keywords pregnancy, antidepressants, review, meta‐analysis, selective serotonin reuptake inhibitors, selective serotonin‐norepinephrine reuptake inhibitors, tricyclic antidepressants, neonatal outcomes, autism spectrum disorders, attention deficit hyperactivity disorder (ADHD), preterm birth, low birth weight, spontaneous abortion, persistent pulmonary hypertension, infant, newborn, children, and offspring. The present review included a total of 21 relevant meta‐analyses that met the inclusion criteria. Most of the meta‐analyses reported that compared to non‐users, the risks of preterm birth, low birth weight, spontaneous abortion, persistent pulmonary hypertension, autism spectrum disorders, and ADHD in offspring of antidepressant users were significantly higher. Some meta‐analyses also noted that the elevated risks were no longer statistically significant when pregnant women with psychiatric diagnoses treated with an antidepressant were compared with control patients who remained untreated. Although this review of current meta‐analyses suggests a moderately increased risk of neonatal and childhood outcomes assessed with maternal use of antidepressants, it is difficult to ascertain whether these outcomes are independent of underlying maternal psychiatric disorders.

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“…In a recent meta-analysis of 11 studies reporting on a total of 156,978 women and their offspring exposed to SRI [73] the risk of PPHN was increased by 82% (OR 1.82, 95% confidence interval 1.31–2.54). Similar figures emerged when restricting the analysis to exposure after 20 weeks of gestation.…”

Section: Neonatal Effectsmentioning

confidence: 99%

SSRIs and SNRIs (SRI) in Pregnancy: Effects on the Course of Pregnancy and the Offspring: How Far Are We from Having All the Answers?

Ornoy¹,

Koren

2019

IJMS

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Serotonin has important roles in the development of the brain and other organs. Manipulations of synaptic serotonin by drugs such as serotonin reuptake inhibitors (SRI) or serotonin norepinephrine reuptake inhibitors (SNRI) might alter their development and function. Of interest, most studies on the outcome of prenatal exposure to SRI in human have not found significant embryonic or fetal damage, except for a possible, slight increase in cardiac malformations. In up to a third of newborns exposed to SRI, exposure may induce transient neonatal behavioral changes (poor neonatal adaptation) and increased rate of persistent pulmonary hypertension. Prenatal SRI may also cause slight motor delay and language impairment but these are transient. The data on the possible association of prenatal SRIs with autism spectrum disorder (ASD) are inconsistent, and seem to be related to pre-pregnancy treatment or to maternal depression. Prenatal SRIs also appear to affect the hypothalamic hypophyseal adrenal (HPA) axis inducing epigenetic changes, but the long-term consequences of these effects on humans are as yet unknown. SRIs are metabolized in the liver by several cytochrome P450 (CYP) enzymes. Faster metabolism of most SRIs in late pregnancy leads to lower maternal concentrations, and thus potentially to decreased efficacy which is more prominent in women that are rapid metabolizers. Studies suggest that the serotonin transporter SLC6A4 promoter is associated with adverse neonatal outcomes after SRI exposure. Since maternal depression may adversely affect the child’s development, one has to consider the risk of SRI discontinuation on the fetus and the child. As with any drug treatment in pregnancy, the benefits to the mother should be considered versus the possible hazards to the developing embryo/fetus.

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Prenatal exposure to selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors and risk for persistent pulmonary hypertension of the newborn: a systematic review, meta-analysis, and network meta-analysis

Cited by 59 publications

References 48 publications

Perinatal mental health: a review of progress and challenges

Perinatal mental health: a review of progress and challenges

Neonatal and Childhood Outcomes in Offspring of Pregnant Women Using Antidepressant Medications: A Critical Review of Current Meta‐Analyses

SSRIs and SNRIs (SRI) in Pregnancy: Effects on the Course of Pregnancy and the Offspring: How Far Are We from Having All the Answers?

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