INTRODUCTION — Depressive disorders and anxiety disorders occur in approximately 10 to 15 percent of pregnant women and can have short- and long-term deleterious effects upon the mother, child, and family [1-4]. Although patients with mild to moderate illness may respond to psychotherapy, patients with severe (eg, suicidality or psychosis), chronic, or recurrent syndromes often require pharmacotherapy.
The decision to prescribe antidepressants for pregnant patients requires clinicians to weigh the negative impact of untreated mood and anxiety disorders against the adverse effects of antidepressants. Although the risks to the offspring from antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) appear to be small to nonexistent, the potential risks are uncertain due to the lack of high quality data on the impact of these drugs. The complexity of managing pregnant women with mood and anxiety disorders requires coordinated efforts among psychiatrists, primary care clinicians, obstetricians, and pediatricians.
Maternal use of SSRIs and SNRIs during pregnancy is estimated at roughly 8 percent [5]. SSRIs and SNRIs are first- and second-line medications for depressive and anxiety disorders, as well as other disorders such as obsessive-compulsive disorder and posttraumatic stress disorder. In addition, these antidepressants are often combined with second-generation antipsychotics for treating bipolar major depression in pregnant women.
When studying the long-term effects of antenatal antidepressants, it is difficult to disentangle medication effects from other factors, such as pre-existing and ongoing maternal psychiatric illness. Women with psychiatric symptoms in pregnancy are at high risk for postpartum depression and anxiety, and thus for impaired mother-infant interactions that are associated with emotional and behavioral dysfunction in the offspring [4]. Maternal depression and anxiety can be chronic and recurrent [6], so the impact upon children can extend beyond the immediate postnatal phase. In addition, the evidence suggests that children of depressed mothers are more likely to exhibit psychiatric symptoms and disorders (eg, anxiety disorders, depressive disorders, attention deficit hyperactivity disorder, oppositional defiant disorder, and other behavioral disturbances) compared with children of mothers with remitted depression [7-10].
This topic reviews the association between antenatal exposure to SSRIs and SNRIs and the risk of psychopathology in the offspring. Antenatal exposure to SSRIs and SNRIs and neonatal outcomes, as well as the risk of abnormalities in growth, motor skills, and cognition, are discussed separately. The antenatal use of antidepressants and risk of teratogenicity and adverse pregnancy outcomes are also discussed separately, as are the clinical features and choice of treatment for antenatal depression, and the risks of exposure to antenatal depression:
●(See "Mild to moderate episodes of antenatal unipolar major depression: Choosing treatment".)
●(See "Severe antenatal unipolar major depression: Choosing treatment".)
●(See "Antenatal depression: Pregnancy and neonatal outcomes".)
●(See "Antenatal depression: Risks of abnormal infant and child development".)
●(See "Antenatal depression: Risks of cognitive impairment and psychopathology in the offspring".)
INTERPRETING THE EVIDENCE — The evidence regarding the potential risk of antenatal exposure to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors is limited due to several factors. (See "Antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs): Neonatal outcomes", section on 'Interpreting the evidence'.)
TERATOGENICITY — The teratogenicity of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors is discussed separately. (See "Antenatal use of antidepressants and the potential risk of teratogenicity and adverse pregnancy outcomes: Selective serotonin reuptake inhibitors".)
PREGNANCY OUTCOMES — The effects of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors on pregnancy outcomes, including spontaneous abortion, stillbirth, length of gestation, fetal growth, and neonatal mortality are discussed separately. (See "Antenatal use of antidepressants and the potential risk of teratogenicity and adverse pregnancy outcomes: Selective serotonin reuptake inhibitors".)
NEONATAL EFFECTS — The neonatal effects of antenatal exposure to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are discussed separately. (See "Antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs): Neonatal outcomes".)
ABNORMALITIES IN GROWTH, MOTOR SKILLS, AND COGNITION — Antenatal exposure to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors and the risk of abnormalities in growth, motor skills, and cognition are discussed separately. (See "Infants and children with antenatal exposure to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors: Risk of abnormalities in growth, motor skills, and cognition".)
PSYCHOPATHOLOGY — It is not known whether antenatal antidepressant exposure is associated with psychiatric symptoms and disorders in the offspring. In studying the association, it is difficult to distinguish medication effects from other factors such as antenatal and especially postnatal maternal psychiatric illness. Multiple studies suggest that children of depressed mothers are more likely to exhibit psychiatric disorders; this association is due to genetic factors, environmental effects, or both. (See "Antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs): Neonatal outcomes", section on 'Interpreting the evidence'.)
Emotional and behavioral dysfunction — Emotional and behavioral dysfunction is a composite outcome variable that includes symptoms of psychiatric disorders, such as anxiety disorders, attention deficit hyperactivity disorder, conduct disorder, depressive disorders, and oppositional defiant disorder. Due to conflicting results from different observational studies, it is not clear whether antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) is associated with overall emotional and behavioral dysfunction in children and adolescents. This literature is difficult to interpret when emotional and behavioral disorders are considered as a composite outcome because etiological mechanisms underlying the development of each type of dysfunction differ; disaggregated evidence for specific disorders is presented in the subsequent section.
Evidence that suggests antenatal exposure to SSRIs is not associated with emotional and behavioral dysfunction includes the following:
●A prospective study evaluated 45 sibling pairs, one of whom was exposed to SSRIs and/or SNRIs during gestation and one of whom was not; this approach accounted for shared genetic and environmental factors [11]. The antidepressants were prescribed for maternal depressive disorders during pregnancy. Maternal report questionnaires were used to assess the children between the ages of three to six years for emotional/internalizing problems (eg, depressed affect and social withdrawal), and for behavioral/externalizing problems (eg, aggressive and delinquent behaviors). After controlling for potential confounding factors (eg, child’s age, birth order, and severity of maternal depressive episodes during pregnancy and after delivery), the analyses found that emotional and behavioral problems in the exposed and unexposed siblings were comparable. However, severity of maternal depression during pregnancy and at the time of assessment was associated with greater levels of emotional and behavioral problems in the children.
●A prospective nationwide study included three groups: pregnant women (n = 210) treated for depression with antidepressants (primarily SSRIs), pregnant women who were depressed but not treated with antidepressants (n = 231), and pregnant women who were not depressed and did not take antidepressants (n >48,000) [12]. The children of these women were assessed at age seven years for behavioral problems with a questionnaire completed by their parents. The analyses were adjusted for potential confounding maternal factors (eg, age, antenatal mood, and smoking status) and compared each group of children with the other two groups. The analyses found that neither antenatal antidepressant exposure nor untreated depression was associated with emotional problems, peer problems, conduct problems, and hyperactivity/inattention problems in the children.
●A prospective study recruited pregnant women treated for depression with antidepressants (n = 415, treated primarily with SSRIs) and pregnant women with untreated depression (n = 489) [13]. The offspring were assessed at an average age of six months. After adjusting for potential confounding factors (eg, maternal age, birth outcomes, and postnatal depression), the analyses found that social behavior in exposed and unexposed infants was comparable.
A subsequent study from the same sample included children of mothers with antenatal depression that was treated with antidepressants (n = 127) and children of mothers with antenatal depression that was not treated with antidepressants (n = 98); the children were assessed at age four or five years [14]. Emotional symptoms, conduct problems, peer and social relationships, hyperactivity, and inattention were each comparable in the two groups.
However, other studies suggest that antenatal exposure to SSRIs may perhaps be associated with an increased risk of emotional and behavioral dysfunction:
●A prospective study included discordant sibling pairs (n = 141), one of whom was exposed to an antidepressant during gestation and one of whom was not; this approach accounted for shared genetic and environmental factors [15]. Most of the antidepressants were SSRIs, and the sibling pairs were assessed at age 18 months and again 36 months. After adjusting for potential confounding factors (eg, maternal lifetime depression and antenatal use of other medications, alcohol, or tobacco), the analyses found that at age 18 months, fetal antidepressant exposure was not associated with anxiety, emotional reactivity, somatic symptoms, sleep problems, attention problems, or aggression. At age 36 months, fetal antidepressant exposure was associated with anxiety, but no other psychiatric symptoms.
●A prospective study enrolled pregnant women during the second trimester, including women who used SSRIs and venlafaxine during pregnancy for treatment of maternal depressive and anxiety disorders (n = 44) and women who did not use antidepressants (n = 66) [16]. Maternal mood was periodically assessed beginning at the time of study entry during the second trimester and the offspring were assessed at age three years and again at age six years. After controlling for potential confounding factors (eg, pre- and postnatal maternal depression, and antenatal use of alcohol and other psychotropic drugs), the analyses found that emotional/internalizing problems were greater in exposed children than unexposed children at ages three and six years. However, behavioral/externalizing problems were comparable for the two groups at both ages. In addition, concurrent maternal depression when the children were ages three and six years was associated with emotional and behavioral problems.
●A prospective study included infants who were exposed in utero to SSRIs or venlafaxine (n = 31) for treatment of maternal depressive disorders, and infants who were not exposed (n = 52) [17]. Maternal mood was periodically assessed beginning at the time of study entry during the second trimester and the infants were assessed at 10 months of age. After controlling for potential confounding factors (pre- and postnatal maternal depression, and antenatal smoking and alcohol use), the analyses found that social/emotional development and adaptive behavior were each worse in the exposed infants.
The association between maternal antenatal depression and emotional and behavioral dysfunction in the offspring is discussed separately. (See "Antenatal depression: Risks of cognitive impairment and psychopathology in the offspring", section on 'Emotional and behavioral dysfunction'.)
Anxiety disorders — Use of SSRIs and SNRIs during pregnancy does not appear to be associated with anxiety disorders in the offspring. A national registry study identified three groups: pregnant women who used SSRIs (n >15,000), pregnant women with psychiatric disorders who did not use SSRIs during pregnancy (n >9000), and pregnant women who used SSRIs in the year prior to pregnancy but not during pregnancy (n >7000) [18]. The offspring were followed for up to 14 years after birth. After controlling for potential confounding factors (eg, maternal smoking, maternal history of psychiatric disorders, and family socioeconomic status), the analyses found that the cumulative incidence of anxiety disorders was comparable for the three groups (approximately 2 to 3 percent).
The association between maternal antenatal depression and anxiety disorders in the offspring is discussed separately. (See "Antenatal depression: Risks of cognitive impairment and psychopathology in the offspring", section on 'Anxiety'.)
Attention deficit hyperactivity disorder — It appears that use of SSRIs and SNRIs during pregnancy is not associated with attention deficit hyperactivity disorder (ADHD) in the offspring, based upon several studies [19-22]:
●A study using an electronic medical record database included children of mothers who received SSRI monotherapy during pregnancy (n = 425) and children of mothers who did not use SSRIs during pregnancy (n >189,000); the age of the children ranged from 6 to 14 years [23]. After controlling for potential confounding factors (eg, maternal age, psychiatric and general medical disorders, and antenatal use of other psychotropic drugs), the analyses found that the incidence of ADHD was comparable in the exposed and unexposed children (hazard ratio 1.1, 95% CI 0.8-1.6).
In addition, the study identified sibling pairs, one of whom was exposed to antidepressants during gestation and one of whom was not; this approach accounted for shared genetic and environmental factors. The sibling analysis found that the risk of ADHD was comparable for exposed and unexposed siblings (hazard ratio 0.5, 95% CI 0.2-1.7).
In a third analysis, which compared children of mothers with psychiatric disorders who did not use antidepressants with children of mothers who did not have psychiatric disorders and did not use antidepressants, the risk of ADHD was greater in the children of mothers with psychiatric disorders (hazard ratio 1.8, 95% CI 1.5-2.2).
●A national registry study identified differentially exposed siblings, who were either exposed to SSRIs in utero during the first trimester or were not [24]. The sample included more than 24,000 individuals who were followed for 15 years. After adjusting for potential confounding factors (eg, parental age at childbearing, education, and history of psychiatric illness), the analyses found that the risk of ADHD was comparable for the exposed and unexposed siblings (hazard ratio 0.9, 95% CI 0.7-1.2).
In addition, other analyses compared children of fathers who received SSRIs during the first trimester with children of fathers who did not receive SSRIs before, during, or after pregnancy. The risk of ADHD was greater in offspring of fathers who received SSRIs. This suggests that genetic or environmental factors may at least partially account for results in other studies, which found maternal use of SSRIs during pregnancy was associated with an increased risk of ADHD.
●A national registry study identified three groups: pregnant women who used SSRIs (n >15,000), pregnant women with psychiatric disorders who did not use SSRIs during pregnancy (n >9000), and pregnant women who used SSRIs in the year prior to pregnancy but not during pregnancy (n >7000) [18]. The offspring were followed for up to 14 years after birth. After controlling for potential confounding factors (eg, maternal smoking and maternal and paternal history of psychiatric disorders and socioeconomic status), the analyses found that the cumulative incidence of ADHD was comparable for the three groups (approximately 4 to 5 percent).
Although some studies have found that antidepressant exposure during gestation is associated with an increased risk of ADHD [25], several studies support the hypothesis that maternal mental illness confounds the observed association between in utero exposure to antidepressants and increased risk of ADHD in the children [21]. If women with depressive disorders or other indications for SSRIs are more likely to have children with ADHD, a false association between SSRI use and ADHD may be observed (confounding by indication). Genetic factors are apparently involved in the pathogenesis of ADHD, and studies have found that genes putatively involved in the pathogenesis of unipolar major depression may also confer risk for ADHD [26].
The association between maternal antenatal depression and hyperactivity in the offspring is discussed separately. (See "Antenatal depression: Risks of cognitive impairment and psychopathology in the offspring", section on 'Hyperactivity'.)
Autism — It is not known whether use of SSRIs and SNRIs by pregnant women is associated with a small increased risk of autism spectrum disorder in the children [27]. Nevertheless, observational studies suggest that the risk of autism spectrum disorder due to antenatal exposure to SSRIs is small to nonexistent, and many experts view the study results as reassuring for both parents and clinicians [27-29]. As an example, multiple studies found that use of SSRIs during pregnancy was not associated with autism in the offspring [18,24,28,30-32]. Although smaller studies found that antenatal exposure to SSRIs was associated with a small increase in autism spectrum disorders, the studies concluded that antenatal SSRI exposure was highly unlikely to be a major risk factor for autism [33-35].
It is plausible that any observed association between antenatal SSRI exposure and autism is due to confounding by indication [30]. If women with depressive disorders, anxiety disorders, or other indications for SSRIs are more likely to have children with autism spectrum disorder, a false association between SSRI use and autism may be found in observational studies [36]. This hypothesis is supported by the following:
●Multiple observational studies have found that in their initial analytic models, antenatal exposure was associated with autism spectrum disorder, but that after controlling for maternal mental illness in the subsequent and more rigorous models, exposure was no longer associated with the disorder [18,24,25,30-32,36,37].
●Multiple observational studies have found that after controlling for potential confounding factors, antenatal antidepressant exposure was not associated with an increased risk of autism spectrum disorder in the offspring. However, use of antidepressants prior to pregnancy was associated with an elevated risk of autism spectrum disorder, suggesting that maternal psychopathology may be related to risk of autism spectrum disorder. Specifically, the risk of autism spectrum disorder was greater in children of women who received antidepressants prior to but not during pregnancy, compared with children of women who did not receive antidepressants prior to or during pregnancy. This elevated risk was comparable across studies:
•Odds ratio 1.6, 95% CI 1.2-2.2 [25]
•Relative risk 1.5, 95% CI 1.2-1.8 [36]
•Hazard ratio 1.9, 95% CI 1.4-2.5 [30]
In addition, preconception use of antidepressants was associated with an increased risk of autism spectrum disorder in a meta-analysis of four studies (odds ratio 1.8, 95% CI 1.5-2.1) [28], as well as a meta-analysis of three studies (odds ratio 1.8, 95% CI 1.5-2.3) [38].
●Multiple studies have found higher rates of depression in mothers of autistic children than mothers of controls [39,40].
Another aspect of confounding by indication is severity of the depressive syndrome. Most women discontinue antidepressants during pregnancy, which suggests that continued use of antidepressants in pregnancy may be a marker of the severity of the underlying depressive illness and of other characteristics associated with depression (eg, chronicity) [27,41,42]. Increased severity of depression may reflect increased dysregulation of maternal hypothalamic-pituitary-adrenal axis hormones and increased fetal exposure to cortisol.
Genetic factors are apparently involved in the pathogenesis of autism spectrum disorder, and studies have found that genes putatively involved in the pathogenesis of unipolar major depression may also confer risk for autism [26]. In multiple observational studies that have controlled for genetic vulnerability to autism, antenatal exposure to antidepressants was not associated with autism. Specifically, the studies compared the risk of autism spectrum disorder between siblings, one of whom was exposed to SSRIs in utero and one of whom was not [24,30,37,43].
Additional information about the association between maternal antenatal depression and autism in the offspring is discussed separately, as is information about the pathogenesis of autism. (See "Antenatal depression: Risks of cognitive impairment and psychopathology in the offspring", section on 'Autism' and "Autism spectrum disorder: Terminology, epidemiology, and pathogenesis", section on 'Pathogenesis'.)
Evidence that suggests antenatal SSRI exposure is not associated with autism includes the following meta-analyses of observational studies:
●A meta-analysis was performed using three case-control studies; the studies identified cases with autism (total n >3000) and controls (total n >22,000) without autism, and then compared exposure during pregnancy in the two groups [31]. Each study controlled for some potential confounding factors, including maternal mental illness. Antenatal use of SSRIs was comparable for the cases and controls (odds ratio 1.4, 95% CI 0.9-2.2). Other analyses further controlled for maternal mental illness by restricting the samples to mothers with a psychiatric diagnosis (ie, both the cases with autism and the controls without autism were the offspring of women with a mental illness); again, exposure to SSRIs was not associated with an increased risk of autism.
●A meta-analysis pooled two retrospective cohort studies; the studies identified individuals exposed in utero to SSRIs (total n >7000) and controls who were not exposed (n >700,000), and then compared the rate of autism in the two groups [31]. Each study controlled for some potential confounding factors, including maternal mental illness. The rate of autism was comparable among individuals who were exposed to SSRIs and individuals not exposed (odds ratio 1.5, 95% CI 0.9-2.7). In a different study, a meta-analysis that pooled the same two cohort studies also found that antenatal SSRI exposure was not associated with autism (hazard ratio 1.3, 95% CI 0.9-1.7) [28].
In addition, studies published after the meta-analyses were conducted also found that gestational exposure to antidepressants was not associated with an elevated risk of autism spectrum disorders [18]:
●A study used national registries to identify sibling pairs, one of whom was exposed to SSRIs in utero during the first trimester and one of whom was not; this approach accounted for shared genetic and environmental factors [24]. The sample included more than 24,000 individuals who were followed for 15 years. After adjusting for potential confounding factors (eg, parental age at childbearing; parental education; and parental history of severe psychiatric illness such as schizophrenia, bipolar disorder, or suicide attempt), the analyses found that the risk of autism spectrum disorder was comparable for the exposed and unexposed siblings (hazard ratio 0.8, 95% CI 0.6-1.1).
●Another study used an administrative health claims database to examine the incidence of autism spectrum disorder in children who were followed for an average of five years following birth (n >35,000); the sample included children exposed in utero to SSRIs or SNRIs (n >2800) [30]. After adjusting for the probability (propensity) to receive an antidepressant, based upon 500 potential confounding factors such as maternal age, general medical and psychiatric diagnoses, and use of concomitant medications, the analyses found that antenatal exposure was not associated with autism spectrum disorder (hazard ratio 1.61, 95% CI 0.997-2.59). In addition, a sibling analysis found that the risk of autism spectrum disorder was comparable for the exposed and unexposed siblings (hazard ratio 1.6, 95% CI 0.7-3.7).
●A third study used national registries to identify a cohort of children who were born to mothers with a lifetime diagnosis of a depressive or anxiety disorder and were followed from birth until age seven or eight years; the cohort consisted of children who were either exposed to antidepressants during pregnancy (n >2600) or were not exposed (n >14,000) [32]. The antidepressants were largely SSRIs. After adjusting for potential confounding factors (eg, parental age, maternal use of other psychotropic medications during pregnancy, and paternal lifetime diagnosis of mental illness), the incidence of autism spectrum disorder in the exposed and nonexposed offspring was comparable (2.4 and 1.9 percent; relative risk 1.1, 95% CI 0.8-1.4).
Other analyses in the study support the hypothesis that maternal mental illness confounds any observed association between in utero exposure to antidepressants and increased risk of autism in the children:
•The risk of autism spectrum disorder was lower in children of mothers who used antidepressants during pregnancy, compared with children of mothers who did not use antidepressants during pregnancy, but had a lifetime diagnosis of at least three different mental disorders (relative risk 0.70, 95% CI 0.50-0.98).
•Analyses that separately examined in utero exposure to SSRIs, non-SSRI antidepressants, or non-antidepressant psychotropic medications found similar results: for each drug class, the risk of autism spectrum disorder was comparable for exposed and unexposed children.
Studies that found antidepressant use during pregnancy was associated with a small increase in autism spectrum disorders include the following observational studies [44,45]:
●A meta-analysis pooled odds ratios, which were adjusted for a variety of potential confounding factors, from five studies (total n >100,000); each study compared in utero exposure to antidepressants (primarily SSRIs) in cases with autism and controls without autism [28]. Antenatal use of antidepressants was greater in the cases than controls (odds ratio 1.5, 95% CI 1.1-2.1). However, heterogeneity across studies was moderate to large.
●A second meta-analysis pooled adjusted odds ratios from an overlapping but not identical set of five studies; the meta-analysis included cases with autism (n >9000) and controls without autism (n >74,000) [38]. In utero exposure to SSRIs was greater in the cases than controls (odds ratio 1.7, 95% CI 1.2-2.2). Heterogeneity across studies was small to moderate.
●A subsequent registry study identified pregnant women who used antidepressants (n >3000; primarily SSRIs) and pregnant women with psychiatric disorders who did not use antidepressants (n >12,000) [43]. After controlling for potential confounding factors (eg, maternal and paternal age, specific maternal psychiatric diagnoses, and other psychotropic drugs used during pregnancy), the analyses found that autism spectrum disorder occurred in more exposed offspring than unexposed offspring (4 versus 3 percent). In addition, another analysis that used propensity scoring to match the two groups on additional potential confounding factors that influence the probability of exposure also found that autism occurred in more exposed children. However, in a third analysis that identified sibling sets (n >3000) in which at least one sibling had autism and one did not, in utero exposure to antidepressants was comparable for the affected and unaffected siblings (odds ratio 1.4, 95% CI 0.8-2.2).
Depressive disorders — Antenatal use of antidepressants may perhaps be associated with an increased risk of depression in the offspring. A national registry study identified three groups: pregnant women who used SSRIs (n >15,000), pregnant women with psychiatric disorders who did not use SSRIs during pregnancy (n >9000), and pregnant women who used SSRIs in the year prior to pregnancy but not during pregnancy (n >7000) [18]. The offspring were followed for up to 14 years after birth. After controlling for potential confounding factors (eg, maternal smoking and maternal and paternal socioeconomic status and history of psychiatric disorders), the analyses found that the cumulative incidence of depression was greater in offspring exposed to SSRIs during gestation, compared with offspring of women with psychiatric disorders who did not use SSRIs (8 versus 2 percent). In addition, depression occurred in more offspring exposed to SSRIs during gestation, compared with offspring of women who used SSRIs prior to pregnancy but not during pregnancy (8 versus 3 percent).
However, given that most women with mental illness discontinue antidepressants during pregnancy, continued use of antidepressants in pregnancy may be a marker of the severity of the underlying mental illness and of other illness characteristics (eg, chronicity) [27,41,42]. Illness severity may be associated with risk of depression in the offspring and thus confound the observed association between gestational exposure to SSRIs and increased risk of depression in the offspring. The study controlled for illness severity in analyses that restricted exposure to SSRI monotherapy and adjusted for maternal suicidal behavior, but these were indirect, proxy measures of severity. In addition, the observed association between SSRI exposure and offspring depression may have been due to residual confounding by unmeasured prognostic variables such as maternal postpartum depression.
The association between maternal antenatal depression and depression in the offspring is discussed separately. (See "Antenatal depression: Risks of cognitive impairment and psychopathology in the offspring", section on 'Depression'.)
SUMMARY
●For neonatal infants who are exposed in utero to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), the risks of adverse outcomes are not completely clear due to the lack of high quality studies. (See 'Introduction' above and "Antenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs): Neonatal outcomes", section on 'Interpreting the evidence'.)
●Emotional and behavioral dysfunction is a composite outcome variable that includes symptoms of various psychiatric disorders. It is not known whether antenatal exposure to SSRIs and SNRIs is associated with emotional and behavioral dysfunction in children and adolescents. (See 'Emotional and behavioral dysfunction' above.)
●Use of SSRIs and SNRIs during pregnancy does not appear to be associated with anxiety disorders in the offspring. (See 'Anxiety disorders' above.)
●It appears that use of SSRIs and SNRIs during pregnancy is not associated with attention deficit hyperactivity disorder in the offspring. (See 'Attention deficit hyperactivity disorder' above.)
●Observational studies suggest that the risk of autism spectrum disorder due to antenatal exposure to SSRIs and SNRIs is small to nonexistent. It is plausible that women with an indication (eg, severe depression) for antidepressants may be more likely to have children with autism; thus, any observed association between antenatal SSRI exposure and autism may be due to confounding by indication. (See 'Autism' above.)
●Antenatal use of antidepressants may perhaps be associated with an increased risk of depression in the offspring; however, few studies accounted for the possible confounding contribution of genetic risk for depressive disorders. (See 'Depressive disorders' above.)
