Birth outcomes after prenatal exposure to antidepressant medication

doi:10.1067/mob.2003.172

American Journal of Obstetrics and Gynecology

Volume 188, Issue 3, March 2003, Pages 812-815

https://doi.org/10.1067/mob.2003.172 Get rights and content

Abstract

Objective: The purpose of this study was to examine prospectively the incidence of congenital anomalies and neonatal complications after prenatal exposure to antidepressant medication. Study Design: Birth outcomes were obtained from a review of obstetric and neonatal records of 138 women who were treated with selective serotonin reuptake inhibitor antidepressant medications (SSRIs) during pregnancy. Results: The incidence of congenital anomalies in this study was 1.4%, comparable to general population rates. Rates of low birth weight and preterm births were low, occurring in 2.9% and 6.5% of births, respectively. The low birth weight infants had been exposed to relatively high doses of fluoxetine (40-80 mg/d) throughout pregnancy. Average maternal weight gain in pregnancy was comparable across the three major medication categories (fluoxetine, paroxetine, sertraline). Conclusion: After prenatal use of selective serotonin reuptake inhibitor antidepressant medications, neonatal complications and congenital anomalies appear to occur within general population rates. However, maternal use of high doses of fluoxetine throughout pregnancy may be associated with a risk for low birth weight. (Am J Obstet Gynecol 2003;188:812-5.)

Section snippets

Methods

Pregnant women who were at any stage of pregnancy and who were receiving SSRI antidepressant medication were included in the study and were followed prospectively between June 1997 and May 2002. Subjects were nonsmokers, in good health, on no known teratogenic substances during the pregnancy, and had no history of drug or alcohol abuse. Subjects signed written informed consent for study participation and for release of records.

Obstetric and neonatal outcomes were obtained from review of

Results

A total of 147 pregnant women were enrolled in this study. Nine of the women were lost to follow-up; therefore, the study group consisted of 138 subjects. Subjects were between the ages of 24 to 44 years and were predominantly white and Hispanic. All women began prenatal care early in pregnancy. Seventy-three women received fluoxetine therapy, 36 women received sertraline therapy, 19 women received paroxetine therapy, 7 women received citalopram therapy, and 3 women received fluvoxamine

Comment

The incidence of congenital anomalies in this study was 1.4%, which is comparable to general population rates⁹ and which confirms previous reports that SSRIs do not appear to increase the risk of congenital anomalies. The two anomalies consisted of Hirschsprung disease, which has a general population incidence of 1 in 5000 infants,¹⁰ and cavum septi pellucidi, with a general population incidence of approximately 17%.¹¹

Common neonatal findings similarly occurred within expected rates9, 12 and

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Low maternal weight gain in the second or third trimester increases the risk for intrauterine growth retardation
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JAMA
(1998)

There are more references available in the full text version of this article.

Cited by (185)

Intrauterine and lactational exposure to fluoxetine enhances endothelial modulation of aortic contractile response in adult female rats
2018, Vascular Pharmacology
The study aimed to evaluate if maternal exposure to fluoxetine (FLX) during pregnancy and lactation would result in altered aortic reactivity in adult offspring. We also sought to understand the role of endothelium derived relaxing factors in aortic response. Wistar rats (75–80 days old), whose progenitors had received FLX (5 mg/kg, FLX offspring) or tap water (control offspring) during pregnancy and lactation were anesthetized, after which the aorta was removed and cut into two rings, one with (Endo+) and the other without (Endo-) endothelium. Concentration-effect curves for acetylcholine (ACh), sodium nitroprusside (SNP), and phenylephrine (Phe) were performed. The vasodilation to ACh and SNP was similar between control and FLX groups in both male and female offspring. In male rats, the response to Phe was similar between the FLX and control groups on Endo+ and Endo- rings. The response to Phe was reduced on Endo+ rings from female FLX when compared with the control group. The endothelium removal, as well as L-NAME, indomethacin, and tranylcypromine incubation corrected the reduced Phe-induced contraction in the aorta from the female FLX group. On the other hand, catalase, NS-398, and L-NIL did not interfere with the vasoconstriction. The aortic level of nitric oxide (NO) was higher in the female FLX than the control group. Although endothelial NO synthase isoform and cyclooxygenase (COX)-1 expressions were similar between the groups, there was a notable increment in neuronal NO synthase expression in the aorta of FLX-exposed female rats, suggesting an important role of this enzyme in the higher levels of NO. Our results show that developmental exposure to FLX causes sex-specific alteration in aortic function through a mechanism involving endothelial factors, probably NO and COX-1 products.
The effects of maternal antidepressant use on offspring behaviour and brain development: Implications for risk of neurodevelopmental disorders
2017, Neuroscience and Biobehavioral Reviews
Approximately 10% of pregnant women are prescribed antidepressant drugs (ADDs), with selective serotonin reuptake inhibitors (SSRIs) the most widely prescribed. SSRIs bind to the serotonin transporter (SERT), blocking the reabsorption of serotonin by the presynaptic neuron and increasing serotonin levels in the synaptic cleft. The serotonergic system regulates a range of brain development processes including neuronal proliferation, migration, differentiation and synaptogenesis. Given the presence of SERT in early brain development, coupled with the ability of SSRIs to cross the placenta and also enter breast milk, concerns have been raised regarding the effects of SSRI exposure on the developing foetus and newborns. In this review, we evaluate preclinical and clinical studies that have examined the effects of maternal SSRI exposure and the risk for altered neurodevelopment and associated behaviours in offspring. While the current body of evidence suggests that maternal SSRI treatment may cause perturbations to the neurobiology, behaviour and ultimately risk for neurodevelopmental disorders in exposed offspring, conflicting findings do exist and the evidence is not conclusive. However, given the increasing incidence of depression and number of women prescribed ADDs during pregnancy, further investigation into this area is warranted.
Behavioural outcomes of adult female offspring following maternal stress and perinatal fluoxetine exposure
2017, Behavioural Brain Research
Depression, anxiety, and stress are common in pregnant women. One of the primary pharmacological treatments for anxiety and depression is the antidepressant fluoxetine (Flx). Maternal stress, depression, and Flx exposure are known to effect neurodevelopment of the offspring, however, their combined effects have been scarcely studied, especially in female offspring. The present study investigated the combined effects of maternal stress during pregnancy and perinatal exposure to Flx on the behaviour of female mice as adults.
Mouse dams were exposed to either chronic unpredictable stress (embryonic (E) day 7 to E18), or FLX (E15- postnatal day 12), or a combination of stress and FLX or left untreated. At two months of age, the female offspring went through a comprehensive behavioural test battery.
Maternal stress led to increased activity and alterations of prepulse inhibition in the adult female offspring. Maternal treatment with Flx had a potentially beneficial effect on spatial memory. The combination of prenatal stress and perinatal Flx exposure did not interact in their effects. These results suggest that gestational Flx exposure may have a limited negative impact on female offspring.
Does fish oil or folic acid prevent vascular changes in female progeny caused by maternal exposure to fluoxetine?
2016, Life Sciences
Fluoxetine (FLX) is an antidepressant worldwide prescribed throughout life stages, including pregnancy and breastfeeding. Out of pregnancy, the combination of FLX with fish oil (FO) and folic acid (FA) is carried to enhance the therapeutic activity and reduce the side effects of the antidepressant. During pregnancy, FO and FA have been used to promote fetal development, and reduce, in mother, the risk of gestational and post-pregnancy depression. To evaluate if maternal exposure during pregnancy and lactation to FLX associated with FO or FA would prevent the antidepressant side effects in aorta reactivity and nitric oxide metabolites (NOx) plasmatic levels. We also sought to understand, in female offspring, the vascular effects of intrauterine and lactation exposure to FO and FA monotherapy.
Wistar rats were treated with water (control group), FLX (5 mg/kg/day), FO (1.3 g/kg/day), FA (3 mg/kg/day), FLX + FO and FLX + FA, throughout pregnancy and lactation. On adulthood, in female offspring were evaluated the vascular reactivity to phenylephrine (Phe), the NOx and homocysteine (HCY) plasmatic levels.
The developmental exposure to the associations of FO or FA with FLX did not correct the aortic hyporreactivity and increased NOx levels induced by intrauterine and lactation exposure to FLX. Also, isolated exposure to FO and FA did not interfere with Phe-induced aortic contraction and neither interferes with NOx and HCY plasmatic levels.
The developmental exposure to FO and FA was safe for vascular function of female offspring but did not prevent the vascular effects of FLX-exposure.
Drugs and Environmental Agents in Pregnancy and Lactation: Teratology, Epidemiology
2016, Obstetrics: Normal and Problem Pregnancies
MOTHERISK ROUNDS: The Use of Antidepressants in Pregnancy: Focus on Maternal Risks
2015, Journal of Obstetrics and Gynaecology Canada
Studies have consistently reported a decrease in the use of antidepressants during pregnancy compared with the pre-pregnancy period. Multiple recent studies have focused on the potential fetal risks of selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), with very little attention paid to maternal risks. The maternal risks of these medications are the focus of this review.
Untreated depression is associated with increased risks of maternal morbidity, both somatic and psychiatric. In contrast, use of antidepressants has been associated with increased risks of hypertension, preeclampsia, and bleeding. In this review we present the evidence for maternal risks in an attempt to develop a risk-benefit ratio.
Les études indiquent uniformément une baisse du recours aux antidépresseurs pendant la grossesse, par comparaison avec la période prégrossesse. De multiples études récentes se sont centrées sur les risques fœtaux potentiellement liés aux inhibiteur sélectif du recaptage de la sérotonine (ISRS) et aux inhibiteur sélectif du recaptage de la norépinéphrine (ISRN), tout en ne portant que très peu attention aux risques maternels. La présente analyse est axée sur les risques maternels qui sont liés à ces médicaments.
La dépression ne faisant pas l’objet d’un traitement est associée à des risques accrus de morbidité maternelle, tant somatique que psychiatrique. Par contre, l’utilisation d’antidépresseurs a été associée à des risques accrus d’hypertension, de prééclampsie et de saignement. Dans le cadre de la présente analyse, nous présentons les données dont nous disposons au sujet des risques maternels afin de tenter d’établir un rapport risques-avantages.

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^☆: Supported by grant No. MH01451-01 from the National Institute of Mental Health, grant No. MO1 RR00425 from the National Centers for Research Resources at the National Institutes of Health, and grant No. HD 01304-01A1 from the National Institute of Child Health and Development.

^☆☆: Reprint requests: Victoria Hendrick, MD, UCLA Medical Plaza, Building 300, Suite 2345, Los Angeles, CA 90095. E-mail: [email protected]

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General Obstetrics and Gynecology ObstetricsBirth outcomes after prenatal exposure to antidepressant medication☆,☆☆

Abstract

Section snippets

Methods

Results

Comment

Obstet Gynecol

Reprod Toxicol

Biol Psychiatr

J Nutr

Neurodevelopment of children exposed in utero to antidepressant drugs

N Engl J Med

Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors

JAMA

General Obstetrics and Gynecology Obstetrics
Birth outcomes after prenatal exposure to antidepressant medication☆,☆☆