Effects of Exposure to Selective Serotonin Reuptake Inhibitors During Pregnancy on Serotonergic Symptoms in Newborns and Cord Blood Monoamine and Prolactin Concentrations

Laine, Kari; Heikkinen, Terho; Ekblad, Ulla; Kero, Pentti

doi:10.1001/archpsyc.60.7.720

Cited by 290 publications

(264 citation statements)

References 32 publications

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“…A large fraction of children exposed in utero to SSRIs have been reported to display signs of antidepressant withdrawal in the first week or two of life (Nordeng et al, 2001;Laine et al, 2003;Zeskind and Stephens, 2004;Sanz et al, 2005), indicating that the fetus can be exposed to neurobiologically relevant doses of these drugs. In fact, significant SSRI and metabolite concentrations have been detected in both umbilical cord blood and amniotic fluid in women taking these medications during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Maciąg

Simpson

Coppinger

et al. 2005

Neuropsychopharmacol

273

275

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A significant fraction of infants born to mothers taking selective serotonin reuptake inhibitors (SSRIs) during late pregnancy display clear signs of antidepressant withdrawal indicating that these drugs can penetrate fetal brain in utero at biologically significant levels. Previous studies in rodents have demonstrated that early exposure to some antidepressants can result in persistent abnormalities in adult behavior and indices of monoaminergic activity. Here, we show that chronic neonatal (postnatal days 8-21) exposure to citalopram (5 mg/kg, twice daily, s.c.), a potent and highly selective SSRI, results in profound reductions in both the rate-limiting serotonin synthetic enzyme (tryptophan hydroxylase) in dorsal raphe and in serotonin transporter expression in cortex that persist into adulthood. Furthermore, neonatal exposure to citalopram produces selective changes in behavior in adult rats including increased locomotor activity and decreased sexual behavior similar to that previously reported for antidepressants that are nonselective monoamine transport inhibitors. These data indicate that the previously reported neurobehavioral effects of antidepressants are a consequence of their effects on the serotonin transporter. Moreover, these data argue that exposure to SSRIs at an early age can disrupt the normal maturation of the serotonin system and alter serotonin-dependent neuronal processes. It is not known whether this effect of SSRIs is paralleled in humans; however, these data suggest that in utero, exposure to SSRIs may have unforeseen long-term neurobehavioral consequences.

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Section: Introductionmentioning

confidence: 99%

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Maciąg

Simpson

Coppinger

et al. 2005

Neuropsychopharmacol

273

275

View full text Add to dashboard Cite

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“…Most studies [3][4][5][6][7][8][9] have reported relatively consistent findings on the adverse effects of SSRI use during pregnancy, which include neonatal withdrawal syndrome, low birth weight, and preterm birth. Many studies [10][11][12] have indicated no major fetal malformations higher than the baseline population risk of 1% to 3% with use of SSRIs during pregnancy.…”

mentioning

confidence: 99%

Congenital Heart Disease Associated With Selective Serotonin Reuptake Inhibitor Use During Pregnancy

Wichman

Moore

Lang

et al. 2009

Mayo Clinic Proceedings

144

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OBJECTIVE:To determine the risk of congenital cardiac abnormalities associated with use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. PATIENTS AND METHODS:We conducted a retrospective review of the medical records of all pregnant women presenting at Mayo Clinic's site in Rochester, MN, from January 1, 1993, to July 15, 2005, and identified 25,214 deliveries. A total of 808 mothers were treated with SSRIs at some point during their pregnancy. We reviewed the medical records of the newborns exposed to SSRIs during pregnancy to analyze their outcomes, specifically for congenital heart disease and persistent pulmonary hypertension of the newborn. RESULTS:Of the study patients, 808 (3.2%) took an SSRI at some point during the antenatal period. Of the 25,214 deliveries, 208 newborns (0.8%) were diagnosed as having congenital heart disease. Of the 808 women exposed to SSRI during pregnancy, 3 (0.4%) had congenital heart disease compared with 205 (0.8%) of the 24,406 women not exposed to an SSRI (P=.23). Of the total number of deliveries, 16 newborns were diagnosed as having persistent pulmonary hypertension of the newborn, none of whom had exposure to SSRIs (P>.99). © 2009 Mayo Foundation for Medical Education and ResearchR ecent data indicate that approximately 10% to 15% of women will have depression at some point during pregnancy or the postpartum period. 1,2 Untreated depression during pregnancy may lead to poor outcomes, including low birth weight, preterm delivery, or lower Apgar scores; poor prenatal care; failure to recognize or report signs of labor; and an increased risk of fetal abuse, neonaticide, or suicide. 1,2 Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacotherapy for depression, and SSRI use during pregnancy has been well documented.Overall, data regarding the use of SSRIs during pregnancy have been reassuring. Most studies 3-9 have reported relatively consistent findings on the adverse effects of SSRI use during pregnancy, which include neonatal withdrawal syndrome, low birth weight, and preterm birth. Many studies 10-12 have indicated no major fetal malformations higher than the baseline population risk of 1% to 3% with use of SSRIs during pregnancy. One study 13 has indicated increased risks for specific defects, whereas another study 14 noted an association between overall SSRI use during pregnancy and 3 distinct types of birth defects.Congenital heart disease (CHD) is recognized in approximately 0.4% to 1% of all live births, 15-17 and several studies have suggested that use of an SSRI, particularly paroxetine, may be associated with an increased risk of CHD. In particular, ventricular septal defects (VSDs) have been associated with use of paroxetine during the first trimester, 18-22 although a recent meta-analysis 23 that reviewed both previously published and unpublished data did not confirm this association. One report 20 showed a dose response in neonates exposed to paroxetine during the first trimester; infants exposed to paroxetine at dosag...

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“…It and other SSRIs have become increasingly used for the treatment of depression in pregnancy because of their effectiveness and lower incidence of maternal side effects and wider safety margin compared with tricyclic antidepressants and monoamine oxidase inhibitors (4,5). However, there have been several reports that use of these drugs during pregnancy can increase the incidence of adverse pregnancy outcomes, including preterm delivery, fetal growth restriction, and poor neonatal adaptation (5)(6)(7)(8). There is also evidence for postnatal consequences of prenatal SSRI exposure, including reduced weight gain, slight delays in psychomotor development and motor movement control, and our own findings of reduced facial and heart rate responses to painful stimuli (9 -11).…”

mentioning

confidence: 99%

“…FX and other SSRIs increase extracellular serotonin (5-HT) levels acutely and serotonergic neurotransmission chronically, and these actions could underlie the reported adverse effects of these agents on pregnancy outcome and postnatal development (7,10,12). Serotonin plays a major role in the regulation of the HPA axis and adrenocortical secretion of cortisol (13).…”

mentioning

confidence: 99%

Chronic Maternal Fluoxetine Infusion in Pregnant Sheep: Effects on the Maternal and Fetal Hypothalamic-Pituitary-Adrenal Axes

Morrison¹,

Riggs

Chien

et al. 2004

Pediatr Res

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Depression during pregnancy is frequently treated with the selective serotonin reuptake inhibitor, fluoxetine (FX). FX increases serotonergic neurotransmission and serotonin plays a role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. We have therefore investigated the effect of chronic administration of FX to the pregnant ewe on the maternal and fetal HPA axes. Nineteen late-gestation sheep were surgically prepared for chronic study of the fetus. FX (n ϭ 7, 98.5 g/kg/d) or sterile water (control, n ϭ 8) was administered to the ewe for 8 d by constant rate i.v. infusion with an initial FX bolus dose of 70 mg. Maternal and fetal plasma ACTH and cortisol concentrations were determined at 0700 h each day. Maternal plasma ACTH concentrations fell on infusion d 2, but no changes were observed in maternal plasma cortisol concentrations. Fetal plasma ACTH concentrations increased on infusion d 7, and fetal plasma cortisol concentrations increased on infusion d 6, 7, and 8 in the FX group. In addition, the regression coefficient for the relationship between fetal ACTH and cortisol levels was significantly greater in the FX group compared with the control group. Thus, maternal FX treatment increased fetal plasma cortisol concentration. These results are of particular interest in the context that exposure of the fetus to excess glucocorticoids at critical windows during development has been shown to increase the risk of poor health outcomes in later life. Clinical depression occurs in 5-15% of pregnant women (1). Treatment of depression during pregnancy is important to fetal outcome by preventing poor maternal self-care and nutrition, disturbed sleep, lack of prenatal care, increased exposure to alcohol and drugs, and a higher risk of suicide by the mother (1). Depression at 28 wk gestation is related to an increase in negative pregnancy outcome, including an increased risk of low-birth-weight newborns, preterm delivery, and small-forgestational-age newborns (2). FX is a SSRI that increases serotonergic neurotransmission and is prescribed clinically for the treatment of depression, obsessive-compulsive disorder, and bulimia (3). It and other SSRIs have become increasingly used for the treatment of depression in pregnancy because of their effectiveness and lower incidence of maternal side effects and wider safety margin compared with tricyclic antidepressants and monoamine oxidase inhibitors (4, 5). However, there have been several reports that use of these drugs during pregnancy can increase the incidence of adverse pregnancy outcomes, including preterm delivery, fetal growth restriction, and poor neonatal adaptation (5-8). There is also evidence for postnatal consequences of prenatal SSRI exposure, including reduced weight gain, slight delays in psychomotor development and motor movement control, and our own findings of reduced facial and heart rate responses to painful stimuli (9 -11). ABSTRACT40

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Effects of Exposure to Selective Serotonin Reuptake Inhibitors During Pregnancy on Serotonergic Symptoms in Newborns and Cord Blood Monoamine and Prolactin Concentrations

Abstract: Infants exposed to SSRIs during late pregnancy are at increased risk for serotonergic central nervous system adverse effects, and the severity of these symptoms is significantly related to cord blood 5-HIAA levels.

Cited by 290 publications

References 32 publications

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Congenital Heart Disease Associated With Selective Serotonin Reuptake Inhibitor Use During Pregnancy

Chronic Maternal Fluoxetine Infusion in Pregnant Sheep: Effects on the Maternal and Fetal Hypothalamic-Pituitary-Adrenal Axes

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