Risk of congenital malformations and perinatal events among infants exposed to antidepressant medications during pregnancy

ArticleinPharmacoepidemiology and Drug Safety 16(10):1086-94 · October 2007with19 Reads
DOI: 10.1002/pds.1462 · Source: PubMed
Abstract
To evaluate risks for perinatal complications and congenital defects among infants exposed in utero to antidepressants. We identified 2201 women who were prescribed an antidepressant during pregnancy and who delivered an infant within one of five large managed care organizations (HMO). Prescription drug dispensings and inpatient and outpatient diagnoses were obtained from automated databases at each HMO. Antidepressants were categorized into tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs), and medication timing was assessed by trimester. Rates of congenital anomalies or perinatal complications were compared to infants whose mothers were not prescribed antidepressants during pregnancy. Infants exposed to SSRIs or TCAs during pregnancy had a significant increase in preterm delivery risk. Fullterm infants exposed to SSRIs during the third trimester had an increased risk for respiratory distress syndrome, endocrine and metabolic disturbances, hypoglycemia, temperature regulation disorders, and convulsions. Third-trimester exposure to TCAs was also associated with an increased risk for respiratory distress syndrome, endocrine and metabolic disturbances, and temperature regulation disorders. There were 182 infants exposed to Paroxetine, and these infants did not have an increased risk of cardiac septal defects. SSRIs and TCAs did not show a consistent link with congenital anomalies. Paroxetine exposure was not linked with an increased risk for cardiovascular anomalies, although our study power to detect a moderate increase in risk was limited. Infants exposed to antidepressants were at increased risk for preterm delivery. Both SSRIs and TCAs used during the third trimester appeared to increase the risk for perinatal complications and their use should be managed carefully among pregnant women with depression.
    • "Most studies are population-based, linking drug exposure data from prescription databases with foetal outcome data from hospitals or birth defect registries. This approach has many limitations because these cohorts were not designed to investigate the foetal outcome following exposure to specific drugs [8,17,18,21,[23][24][25]29,31]. Consequently, many confounding factors cannot be addressed, and biases in exposure and outcome definitions have always been major considerations [38]. "
    [Show abstract] [Hide abstract] ABSTRACT: Serotonin reuptake inhibitors (SRIs) are often prescribed during pregnancy. Previous studies that found an increased risk of congenital anomalies, particularly congenital heart anomalies (CHA), with SRI use during pregnancy have created concern among pregnant women and healthcare professionals about the safety of these drugs. However, subsequent studies have reported conflicting results on the association between CHA and SRI use during pregnancy. These discrepancies in the risk estimates can potentially be explained by genetic differences among exposed individuals. In this review, we explore the potential pharmacogenetic predictors involved in the pharmacokinetics and mechanism of action of SRIs, and their relation to the risk of CHA. In general, the risk is dependent on the maternal concentration of SRIs and the foetal serotonin level/effect, which can be modulated by the alteration in the expression and/or function of the metabolic enzymes, transporter proteins and serotonin receptors involved in the serotonin signalling of the foetal heart development. Pharmacogenetics might be the key to understanding why some children exposed to SRIs develop a congenital heart anomaly and others do not.
    Full-text · Article · Aug 2016
    • "Late in utero exposure to SSRIs has been identified as a risk factor for impaired neonatal adaptation. Reported findings among newborn infants whose mothers had been treated with SSRIs prior to delivery include respiratory distress, temperature instability, feeding difficulties, jitteriness, restlessness , convulsions, rigidity, hypoglycemia, jaundice, and other symptoms of abnormal neonatal adaptation [17, 23,[66][67][68][69][70][71]. These symptoms appear to be especially common with high-dose maternal treatment late in pregnancy, particularly with paroxetine [72] . "
    [Show abstract] [Hide abstract] ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant medications worldwide. However, over the past decade, their use during pregnancy, a period of extreme vulnerability to the onset of depression, has become highly concerning to patients and their healthcare providers in terms of safety to the developing fetus. Exposure to SSRIs in pregnancy has been associated with miscarriage, premature delivery, neonatal complications, birth defects-specifically cardiac defects-and, more recently, neurodevelopmental disorders in childhood, specifically autism spectrum disorders. Studies addressing the effect of individual SSRIs indicate a small but higher risk for birth defects with maternal fluoxetine and paroxetine use. Though the excess in absolute risk is small, it may still be of concern to some patients. Meanwhile, antenatal depression itself is associated with adverse perinatal outcomes, and discontinuing antidepressant treatment during pregnancy is associated with a high risk of relapse of depression. Whether the observed adverse fetal effects are related to the mother's medication use or her underlying maternal illness remains difficult to determine. It is important that every pregnant woman being treated with an SSRI (or considering such treatment) carefully weighs the risks of treatment against the risk of untreated depression for both herself and her child. The importance of recognizing a higher risk for the development of adverse outcomes lies in the potential for surveillance and possibly a timely intervention. Therefore, we recommend that pregnant women exposed to any SSRI in early pregnancy be offered options for prenatal diagnosis through ultrasound examinations and fetal echocardiography to detect the presence of birth defects. Tapering off or switching to other therapy in early pregnancy, if appropriate for the individual, may also be considered on a case-by-case basis.
    Full-text · Article · May 2016
    • "Recent epidemiological studies have proposed a possible association between maternal use of SSRIs during early pregnancy and risk of CHD in the offspring. However , results for specific types of SSRIs are conflicting121314151617181920212223, and some studies have not been able to detect an association24252627282930. The majority of the studies have based their information about congenital anomalies on administrative register data, for which the validity of these conditions is questionable and often limited to live born children [31]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Previous studies suggest a possible association between maternal use of selective serotonin-reuptake inhibitors (SSRIs) during early pregnancy and congenital heart defects (CHD). The purpose of this study was to verify this association by using validated data from the Danish EUROCAT Register, and secondary, to investigate whether the risk differs between various socioeconomic groups. Methods We conducted a cohort study based on Danish administrative register data linked with the Danish EUROCAT Register, which includes all CHD diagnosed in live births, fetal deaths and in pregnancies terminated due to congenital anomalies. The study population consisted of all registered pregnancies (n = 72,280) in Funen, Denmark in the period 1995–2008. SSRI-use was assessed using The Danish National Prescription Registry, information on marital status, maternal educational level, income, and country of origin from Statistics Denmark was used as indicators of socioeconomic situation, and the CHD were studied in subgroups defined by EUROCAT. Logistic Regression was used to investigate the association between redeemed prescriptions for SSRIs and CHD. Results The risk of severe CHD in the offspring of the 845 pregnant women who used SSRIs during first trimester increased four times (AOR 4.03 (95% CI 1.75-9.26)). We found no increased risk of septal defects. Socioeconomic position did not modify the association between maternal SSRI-use during pregnancy and severe CHD. Conclusion This study, which is based on data with high case ascertainment, suggests that maternal use of SSRIs during first trimester increases the risk of severe CHD, but does not support findings from previous studies, based on administrative register data, regarding an increased risk of septal defects. The study was unable to document an interaction between socioeconomic status and maternal SSRI-use on the risk of severe CHD.
    Full-text · Article · Sep 2014
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