Selective Serotonin-Reuptake Inhibitors and Risk of Persistent Pulmonary Hypertension of the Newborn

Chambers, Christina D.; Hernández–Dı́az, Sonia; Marter, Linda J. Van; Werler, Martha M.; Louik, Carol; Jones, Kenneth Lyons; Mitchell, Allen A.

doi:10.1056/nejmoa052744

Cited by 778 publications

(408 citation statements)

References 30 publications

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“…A higher rate of respiratory distress has been described among infants of mothers treated with SRI medications [4,5,9,10] as well as persistent pulmonary hypertension of the newborn [17]. The current study agrees with the observation of a higher incidence of respiratory distress, though in most cases the respiratory distress lasted only several hours, the need for oxygen >6 h of life was similar between study and control groups and no infants were admitted to the NICU due to a respiratory condition.…”

Section: Discussionmentioning

confidence: 99%

Short-Term Neonatal Outcome among Term Infants after in utero Exposure to Serotonin Reuptake Inhibitors

Leibovitch¹,

Rymer-Haskel²,

Schushan-Eisen³

et al. 2013

Neonatology

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Background: Serotonin reuptake inhibitor (SRI) medications are commonly in use during pregnancy. Objectives: To evaluate short-term neonatal clinical signs among infants exposed to intrauterine SRI medications, in order to estimate the need for postnatal monitoring and observation. Methods: Retrospective review of clinical data in medical files of term infants born to mothers who reported treatment with SRIs during pregnancy. Results: Out of 401 infants in the study group, 165 (41%) were reported to have at least 1 clinical symptom, including respiratory distress, jitteriness, restlessness, feeding difficulties, regurgitations, fever ≥38°C, a short cyanotic event and convulsions. In the symptomatic group, 70% exhibited mild symptoms, among them restlessness, jitteriness or feeding difficulties, while around 30% exhibited significant symptoms. Overall, 12% of the total cohort, mostly males (70%), presented significant clinical symptoms, but none had an urgent or life-threatening condition. Infants in the study group were shorter in length and had a higher rate of Apgar score <7 at 1 min, meconium-stained amniotic fluid and respiratory distress. Conclusions: Despite the high incidence of clinical signs among infants born to SRI-treated mothers, most of their symptoms were mild and self-limited. These infants should be observed while they are close to their mothers on the maternity ward for 48 h after birth.

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Section: Discussionmentioning

confidence: 99%

Short-Term Neonatal Outcome among Term Infants after in utero Exposure to Serotonin Reuptake Inhibitors

Leibovitch¹,

Rymer-Haskel²,

Schushan-Eisen³

et al. 2013

Neonatology

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“…To date, clinical reports on prenatal SSRI exposure have documented an increased risk of altered newborn behavior [18], congenital anomalies [19] and persistent pulmonary hypertension [20] in neonates. In addition, prenatal exposure to SSRI medications has been associated with reduced serotonin and serotonin metabolite (5-hydroxyindoleacetic acid) serum levels in human neonates at birth [21].…”

Section: Serotonin and Developmentmentioning

confidence: 99%

Perinatal Selective Serotonin Reuptake Inhibitor Exposure: Impact on Brain Development and Neural Plasticity

Pawluski¹

2011

Neuroendocrinology

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Selective serotonin reuptake inhibitor (SSRI) medications are the most common antidepressant treatment used during pregnancy and the postpartum period. Up to 10% of pregnant women are prescribed SSRIs. Serotonin plays an integral part in neurodevelopment, and questions have been raised about the placental transfer of SSRIs and the effects of preventing reuptake of presynaptic serotonin on fetal neurodevelopment. Preclinical data is beginning to document a role of early exposure to SSRIs in long-term developmental outcomes related to a number of brain regions, such as the hippocampus, cortex and cerebellum. To date, the majority of preclinical work has investigated the developmental effects of SSRIs in the offspring of healthy mothers; however, more research is needed on the effects of these medications in the face of maternal adversity. This minireview will highlight emerging evidence from clinical and preclinical studies investigating the impact of perinatal SSRI exposure on brain development and neural plasticity.

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“…Although these disorders are generally associated to genetic abnormalities, they can also be induced by prenatal exposure to teratogens. SSRIs represent a class of commonly used antidepressants in pregnant and lactating women and several epidemiological investigations report long-lasting molecular, physiological and behavioral changes in offspring prenatally exposed B C A Serotonin 2B receptor developmental role 713 2005 and 2006, stating that the use of SSRIs in pregnancy was associated with increased birth defects (Chambers et al, 2006, Wogelius et al, 2006. Prenatal exposure to SSRIs also impacts fetal brain development that may have long-term mental health implications (Hanley et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Unraveling new roles for serotonin receptor 2B in development: key findings from Xenopus

Ori¹,

Lucchini²,

Marras³

et al. 2013

Int. J. Dev. Biol.

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The serotonin receptor 5-HT2B has been shown to be critically important during embryogenesis as the knockout of this gene in mice causes heart defects and embryonic lethality that impairs further analyses on other embryonic cell and tissue types. In the present review, we highlight how the use of Xenopus laevis, an alternative vertebrate model suitable for gene loss and gain of function analyses, has contributed to our understanding of the role of 5-HT2B signaling during development. In vivo studies showed that 5-HT2B signaling is not only required for heart development, but that it also has a crucial role in ocular and craniofacial morphogenesis, being involved in shaping the first branchial arch and the jaw joint, in retinogenesis and possibly in periocular mesenchyme development. These findings may be relevant for our understanding of congenital defects including human birth malformations. In addition, 5-HT2B appears to be required for the therapeutic actions of selective serotonin reuptake inhibitors commonly prescribed as antidepressant drugs to pregnant and lactating women. We discuss how the understanding of the molecular basis of serotonin signaling in a suitable animal embryogenesis model may open new lines of investigations and therapies in humans. KEY WORDS: 5-HT2B, neural crest cell, eye, craniofacial morphogenesis, SSRISerotonin, an ancient molecule with unsuspected and still unveiled functions Serotonin (5-hydroxytryptamine, 5-HT) is a phylogenetically ancient monoamine that fulfills a broad role in the control of many vital functions including the control of gastrointestinal motility and secretion, cardiovascular regulation, hemostatic processes, the regulation of circadian rhythms, the control of the sleep-wake cycle, memory and learning, perception of pain, appetite and sexual behavior (reviewed by Berger et al., 2009). The broad action of the serotonin signaling system has attracted the interest of researchers in various fields of biology and molecular medicine, spanning from developmental biology, neurobiology to molecular psychiatry. 5-HT is best known for its role in the nervous system where it is one of the neurotransmitters mainly involved in the etiology of various human psychiatric disorders, including anxiety, depression, obsessive-compulsive disorders, schizophrenia, pain and migraine. Accordingly, many substances that interfere with the serotonergic system are commonly used as therapeutic agents. Selective serotonin reuptake inhibitors (SSRIs) are, in fact, the most frequently prescribed drugs for the treatment of depression Int. J. Dev. Biol. 57: 707-714 (2013) Abbreviations used in this paper: 5-HT, serotonin; 5-HTT, serotonin transporter; CNS, central nervous system; CMZ, ciliary marginal zone; Edn1, endothelin 1; GCL, gaglion cell layer; INL, inner nuclear layer; NCCs, neural crest cells; POM, periocular mesenchyme; SSRI, selective serotonin reuptake inhibitors; Tph2, tryptophan hydroxylase 2.and anxiety-related disorders (Berton and Nestler, 2006). These drugs inhibit...

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Selective Serotonin-Reuptake Inhibitors and Risk of Persistent Pulmonary Hypertension of the Newborn

Abstract: These data support an association between the maternal use of SSRIs in late pregnancy and PPHN in the offspring; further study of this association is warranted. These findings should be taken into account in decisions as to whether to continue the use of SSRIs during pregnancy.

Cited by 778 publications

References 30 publications

Short-Term Neonatal Outcome among Term Infants after in utero Exposure to Serotonin Reuptake Inhibitors

Short-Term Neonatal Outcome among Term Infants after in utero Exposure to Serotonin Reuptake Inhibitors

Perinatal Selective Serotonin Reuptake Inhibitor Exposure: Impact on Brain Development and Neural Plasticity

Unraveling new roles for serotonin receptor 2B in development: key findings from Xenopus

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