Maternal Use of Selective Serotonin Reuptake Inhibitors and Risk of Congenital Malformations

Wogelius, Pia; Nørgaard, Mette; Gislum, Mette; Pedersen, Lars; Munk, Estrid Muff; Mortensen, Preben Bo; Lipworth, Loren; Sørensen, Henrik Toft

doi:10.1097/01.ede.0000239581.76793.ae

Cited by 182 publications

(135 citation statements)

References 14 publications

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“…4 In 2005, based on early results of two epidemiologic studies, the US Food and Drug Administration (FDA) warned healthcare professionals that early prenatal exposure to paroxetine may increase the risk of congenital cardiac malformations and reclassified it to pregnancy category D. 5 Most malformations in the early reports leading to the FDA warning were septal defects. Since then, several studies have evaluated the teratogenicity of SSRIs and other antidepressants [6][7][8][9][10][11][12][13][14][15][16][17][18][19] , but considerable controversy remains as to whether this is a "serious concern or much ado about little" as noted in an editorial published with two of the reports. 13,1420 Existing studies have reported different associations, often in the context of multiple comparisons.…”

Section: Conclusion-resultsmentioning

confidence: 99%

Antidepressant Use in Pregnancy and the Risk for Cardiac Defects

Huybrechts

Palmsten

Avorn

et al. 2014

Obstetrical &Amp; Gynecological Survey

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Background-There is controversy regarding whether the use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants in pregnancy is associated with increased risks for congenital cardiac defects. In particular, concerns exist about a possible association between paroxetine and right ventricular outflow tract obstruction (RVOTO), and between sertraline and ventricular septal defects (VSD).

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Section: Conclusion-resultsmentioning

confidence: 99%

Antidepressant Use in Pregnancy and the Risk for Cardiac Defects

Huybrechts

Palmsten

Avorn

et al. 2014

Obstetrical &Amp; Gynecological Survey

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“…At present, a much used methodology is based on linkage between national or regional registers of prescriptions with registers of delivery outcomes. Such studies of antidepressants have been made for instance in Canada [5,6], Finland [7], and Denmark [8,9]. Timing of drug use during pregnancy is then made from the date of filling the prescription related to the week of pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Antidepressant use during pregnancy: comparison of data obtained from a prescription register and from antenatal care records

Källén

Nilsson

Olausson

2011

Eur J Clin Pharmacol

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Purpose: To compare interview data on drug use during pregnancy with data identifed from a register of prescriptions.Materials: We compared information from the Swedish Prescribed Drug Register with the Swedish Medical Birth Register on antidepressant use. In order to evaluate the clinical significance of difference in ascertainment with the two methods, the rate of preterm births among singletons and of neonatal symptoms were studied.Results: During the year before the last menstrual period, 1.5% of the women filled prescriptions for antidepressants each month. Already before the pregnancy was known, the rate of filled prescriptions decreased and reached 0.5% towards end of pregnancy. Twentytwo per cent of first trimester use of antidepressant was unidentified using interview data and prescriptions during 2 nd and 3 rd pregnancy months covered only 55% of actual use. When women who filled prescriptions one or three months before the last menstrual period were included, 17 and 43%, respectively, of women were included who probably did not use the drugs in the first trimester. Prescriptions gave a more complete ascertainment of drug use after the first trimester than data from antenatal care which seemed to over-estimate drug use.Conclusions: Interview data seem to give the most valid results on early use. When interview data are not available, prescription data could be used but should not include prescriptions given earlier than one month before the last menstrual period. Studies of drug use later in pregnancy are best based on prescription data in absence of interview data.

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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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Maternal Use of Selective Serotonin Reuptake Inhibitors and Risk of Congenital Malformations

Abstract: We found an increased risk of congenital malformations after exposure to SSRIs in early pregnancy. It is unclear whether the effects were causal or due to factors related to the underlying disease. There was no evidence that the association was specific to particular malformations.

Cited by 182 publications

References 14 publications

Antidepressant Use in Pregnancy and the Risk for Cardiac Defects

Antidepressant Use in Pregnancy and the Risk for Cardiac Defects

Antidepressant use during pregnancy: comparison of data obtained from a prescription register and from antenatal care records

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

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