Antidepressant Use In Pregnancy Research Articles

Timing of Antidepressant Use in Pregnancy and Preterm Birth

OBJECTIVE: To evaluate the implication of timing of antidepressant exposure on preterm birth to better guide clinical counseling. DATA SOURCES: A systematic review and meta-analysis was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, using PubMed, MEDLINE Complete, EBSCO, CINAHL Plus, and ClinicalTrials.gov along with a manual search of references in relevant publications. The databases were searched between January 2000 and December 2022 with the following keywords: antidepressants, antidepressant medication, SSRI, selective serotonin reuptake inhibitors, TCA, or SNRI AND pregnancy, pregnant, prenatal, antenatal, perinatal, maternal AND trimester or timing AND preterm or premature. METHODS OF STUDY SELECTION: The database search resulted in 162 studies. The 13 studies that met inclusion criteria compared preterm birth rates in pregnant patients exposed to antidepressants at a specified time in pregnancy (early, late, or throughout pregnancy) and a control group. Covidence was used for screening and data extraction. Excel and R were used for tabulation and statistical analysis, respectively. TABULATION, INTEGRATION, AND RESULTS: Of the 13 studies, nine measured preterm birth rates with antidepressant use in early pregnancy, 10 in late pregnancy, and four throughout pregnancy. Separate random effects models were used to synthesize the effect sizes from studies that did not adjust for presence of maternal depression in the study sample and those that did. In each model, subgroup analysis was conducted to assess the effect of timing of antidepressant exposure on the odds of preterm birth. In the model unadjusted for depression, pooled odds ratios (ORs) for the association between use of antidepressants and preterm birth were 1.41 (95% CI, 1.10–1.81) in early pregnancy, 1.51 (95% CI, 1.26–1.82) in late pregnancy, and 2.79 (95% CI, 1.27–6.12) throughout pregnancy. After adjusting for depression, the pooled ORs were 1.04 (95% CI, 0.83–1.31) in early pregnancy, 1.26 (95% CI, 0.95–1.66) in late pregnancy, and 1.79 (95% CI, 0.54–5.91) throughout pregnancy. No significant effect of timing was found in either model. CONCLUSION: Antidepressant use in pregnancy was not associated with preterm birth, regardless of timing of use. Pregnant patients with an established diagnosis of depression should receive individualized counseling regarding antidepressant use while taking into consideration their risk factors for preterm birth and the implications of untreated depression. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023390136.

Assessing decisional conflict and challenges in decision-making among perinatal women using or considering using antidepressants during pregnancy—a mixed-methods study

This study aims to investigate decisional conflict and elucidate challenges in decision-making among perinatal women using or considering using antidepressant (AD) during pregnancy. A sequential, mixed-methods study was employed among pregnant and postnatal women in Norway who had been offered ADs in the last 5 years. Quantitative data were obtained through an electronic questionnaire. Decisional conflict in pregnancy was assessed using the Decisional Conflict Scale (DCS) defined as either low (< 25) or moderate-high ( ≥ 25) (evaluated retrospectively for postnatal women). Logistic regression was used to identify factors associated with moderate–high decisional conflict. Qualitative data were collected through focus groups with pregnant and postnatal women, and an inductive approach was used for data analysis. Among 174 pregnant and 102 postnatal women, 67.8% and 69.6%, respectively, reported moderate–high decisional conflict during pregnancy. Unsatisfactory doctor-patient relationship was associated with greater likelihood of having moderate–high decisional conflict in pregnancy, both in pregnant (aOR = 1.20, 95% CI: 1.00–1.44) and postnatal women (aOR = 1.40, 95% CI: 1.08–1.82). Reported barriers to decision-making regarding AD use in pregnancy encompassed five DCS subscales: uninformed knowledge following contradictory research and unfamiliarity with authorised resources, unclear values due to emotional blunting and fear associated with AD use, inadequate support, uncertainty in decisions and ineffective decisions due to difficulty in finding personalised treatment, and diverging recommendations by the healthcare providers (HCPs). The quality of the interaction with the HCP plays a crucial role in managing decisional conflict and supporting informed decisions in the management of perinatal mental illness. This study highlights the need for increased provision of clear, evidence-based information by HCPs to facilitate shared decision-making and create personalised treatments for perinatal women considering AD use during pregnancy.

Quantifying the impact of unmeasured confounding in observational studies with the E value

The E value method deals with unmeasured confounding, a key source of bias in observational studies. The E value method is described and its use is shown in a worked...

Use of psychotropic medications during pregnancy and the postpartum period: Review on Recent Works and Clinical Scenarios

IntroductionThe effects of antidepressant and antipsychotic medications in the perinatal period in both mothers and children have been a subject of interest for many decades. Risks and benefits should be considered according to the illness stage, trimester of pregnancy/ postpartum period, and neonatal outcomes.ObjectivesOur goal was to summarize the knowledge about the use of antidepressants and antipsychotics in the perinatal period. To illustrate the complexity of treatment decisions with clinical reports.MethodsReview: A narrative review was carried out using the PubMed database including papers published in 2022. Evidence about the risks and benefits of using antidepressants and antipsychotics in the perinatal period is presented. Search terms: antidepressants OR antipsychotics AND (perinatal OR pregnancy OR postpartum).Case reports (5 clinical scenarios): (1) pre-pregnancy counselling, (2-4) first-, second- and third-trimester of pregnancy, and (5)postpartum/breastfeeding.ResultsReview: (1)Depression/antidepressants. Treating maternal depressive symptoms is associated with a lower risk of pregnancy complications. Although placental passage of sertraline is low, drug monitoring is recommended. Antidepressant use in pregnancy is associated with preterm delivery and low weight at birth. (2)Psychosis/Antipsychotics. Antipsychotic intrauterine exposure is not significantly associated with increased risk of major congenital malformations. Minimum effective doses are recommended.Case reports. (1)Pre-pregnancy counselling. Schizoaffective disorder receiving perphenazine, quetiapine and lithium. (2)First-trimester pregnancy. Discontinuation of treatment in major depressive disorder. (3-4)Second/third trimester. Occurrence of anxiety symptoms in posttraumatic stress disorder. (5)Postpartum/Breastfeeding. Discontinuation of antidepressants.ConclusionsShared decision-making models for antidepressants and antipsychotics prescription represent patient-centered approaches to be recommended in perinatal period.Disclosure of InterestNone Declared

Psychiatric visits during the postpartum year in women with eating disorders who continue or discontinue antidepressant treatment in pregnancy.

To determine the association between continued antidepressant use in pregnancy and postpartum psychiatric visits for eating (ED) or mood/anxiety disorders in women with preexisting ED. Using Danish health registry data (1998-2015), we identified 3529 pregnancies in women with ED prepregnancy: (i) 564 with continued antidepressant use before and during pregnancy; (ii) 778 with discontinued antidepressants before pregnancy; (iii) 2137 unexposed. Outpatient and inpatient postpartum visits for an ED or a mood/anxiety disorder constituted the outcome measures. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) using Cox regression with inverse probability of treatment weighting, and performed stratified analyses by antidepressant prescription filling in the first 3 months postpartum. The weighted cumulative incidence for an ED visit at end of follow-up was 4.5% (continued) and 4.8% (discontinued). We found no association between continued antidepressant and postpartum ED visit, relative to discontinued (HR: 0.89, 95% CI: 0.52-1.52). The HR for postpartum mood/anxiety disorder visit was 1.27 (95% CI: 0.68-2.36) with continued antidepressants versus discontinued but decreased if more than two antidepressant prescriptions were refilled. Continued antidepressant use was associated with a 57% reduced likelihood of a postpartum ED visit versus discontinued use in pregnancies with antidepressant prescription refills in the early postpartum. Among women with preexisting ED, there was no association between continued antidepressant use during pregnancy and the likelihood of postpartum psychiatric visits, relative to discontinued antidepressants before pregnancy. Continuation of treatment into the early postpartum is associated with reduced likelihood of postpartum ED visit. Based on data from the Danish registries, we identified 3529 pregnancies among women with preexisting eating disorders before pregnancy. Women with continued antidepressant treatment both before and during pregnancy did not have a lower probability of having postpartum psychiatric visits for an eating disorder or for mood/anxiety disorders (often coexisting with eating disorders), relative to those who discontinued antidepressants before pregnancy. Further continuation of antidepressant treatment into the early postpartum is associated with improved maternal postpartum outcomes. However, residual confounding by disease severity limits confidence in this conclusion.

Analysis: antidepressant use in pregnancy not linked to child neurodevelopmental disorders

Results of a cohort study based on records from both public and private insurance databases suggest that antidepressant use in pregnancy does not increase risk of neurodevelopmental disorders in children. The most fully adjusted analyses showed no difference in adverse neurodevelopmental outcomes between antidepressant‐exposed and ‐unexposed children.

Antidepressant Fill and Dose Trajectories in Pregnant Women with Depression and/or Anxiety: A Norwegian Registry Linkage Study.

Few studies investigated longitudinal antidepressant exposure during pregnancy and included dosage in the assessment. We conducted a nationwide, registry-linkage study in Norway using data on antidepressant prescription fills in pregnancies lasting ≥32 weeks in women with a delivery between 2009 and 2018 who had a depression/anxiety diagnosis and antidepressant fills prior to pregnancy. Information on antidepressant exposure by week (measured by filled prescriptions) and prescribed average daily dose was used in longitudinal k-means trajectory modelling for a 108-week time window from six months prior to pregnancy to one year after delivery. Factors associated with trajectory group membership were examined using multinomial logistic regression models. We included 8,460 pregnancies in 8,092 women. Four antidepressant fill trajectories were identified based on filled antidepressant prescriptions: two distinct discontinuing patterns, one at around the start of pregnancy (30.4%) and one around the end of pregnancy (33.8%); one continuing pattern (20.6%); and one interrupting pattern (15.2%). Using average usual daily dose, we identified low dose discontinuing (60.3%), medium dose reducing (20.6%) and high dose continuing (15.2%) patterns. The multinomial logistic regressions showed that the fill trajectory group membership was strongly associated with: antidepressant type and dose prior to pregnancy and co-medication prior to pregnancy, maternal age, marital status, parity, previous pregnancy loss, and pregnancy planning. Longitudinal trajectory modelling revealed distinct antidepressant fill and dosage patterns in the period around pregnancy. Knowledge about factors associated with utilization trajectories might be useful for health-care personnel counselling women about antidepressant use in pregnancy.

Association of Antidepressant Use During Pregnancy With Risk of Neurodevelopmental Disorders in Children

Antidepressant use during pregnancy has been associated with neurodevelopmental disorders in children in some studies. However, results may be explained by uncontrolled confounding by parental mental health status, genetics, and environmental factors. To evaluate the association between antidepressant use in pregnancy and neurodevelopmental outcomes in children. This cohort study of health care utilization data was separated into cohorts of publicly and privately insured pregnant individuals and their children nested in the Medicaid Analytic eXtract (MAX; 2000-2014) and the IBM MarketScan Research Database (MarketScan; 2003-2015). A total of 1.93 million pregnancies in MAX and 1.25 million pregnancies in MarketScan were recorded. Children were followed from birth until outcome diagnosis, disenrollment, death, or end of study (maximum 14 years). Analyses were conducted between August 2020 and July 2021. Dispensing of antidepressant medication from gestational week 19 until delivery, the period of synaptogenesis. Neurodevelopmental disorders in children defined using validated algorithms. Early pregnancy exposure was considered in sensitivity analyses, and approaches to confounding adjustment included propensity score fine stratification, discontinuers comparison, and sibling analyses. Among the individuals included in the analysis, there were 145 702 antidepressant-exposed and 3 032 745 unexposed pregnancies; the mean (SD) age among the antidepressant exposed and unexposed was 26.2 (5.7) and 24.3 (5.8) years in MAX and 32.7 (4.6) and 31.9 (4.6) years in MarketScan, respectively; and in MAX, which collected information on race and ethnicity, 72.4% of the antidepressant-exposed and 37.1% of the unexposed individuals were White. Crude results suggested up to a doubling in risk of neurodevelopmental outcomes associated with antidepressant exposure; however, no association was observed in the most fully adjusted analyses. When comparing antidepressant-exposed and unexposed siblings, hazard ratios were 0.97 (95% CI, 0.88-1.06) for any neurodevelopmental disorder, 0.86 (95% CI, 0.60-1.23) for autism spectrum disorder, 0.94 (95% CI, 0.81-1.08) for attention-deficit/hyperactivity disorder, 0.77 (95% CI, 0.42-1.39) for specific learning disorders, 1.01 (95% CI, 0.88-1.16) for developmental speech/language disorder, 0.79 (95% CI, 0.54-1.17) for developmental coordination disorder, 1.00 (95% CI, 0.45-2.22) for intellectual disability, and 0.95 (95% CI, 0.80-1.12) for behavioral disorders. Results were generally consistent for antidepressant classes and drugs and across exposure windows. The results of this cohort study suggest that antidepressant use in pregnancy itself does not increase the risk of neurodevelopmental disorders in children. However, given strong crude associations, antidepressant exposure in pregnancy may be an important marker for the need of early screening and intervention.

Depression and antidepressant treatment in the development of hypertensive disorders of pregnancy: Results from a prospective cohort study.

Hypertensive disorders of pregnancy are associated with longer term cardiovascular risk. Understanding if depression or antidepressant use in pregnancy is associated with HDP is important in identifying those potentially vulnerable to poorer health in later life. This study examines if depression and antidepressants are associated with HDP. In all, 815 pregnant women were recruited within an Australian pregnancy cohort study at less than 20 weeks of pregnancy, all undertook the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and were assigned to four groups for this paper: those with unmedicated depression meeting criteria for current depression (n = 97), those taking selective serotonin reuptake inhibitors in early pregnancy (n = 101), those taking serotonin and noradrenaline reuptake inhibitors in early pregnancy (n = 31), and those without depression or taking antidepressant medication (control; n = 586). Women were then assessed again following birth. Hypertensive disorders of pregnancy were diagnosed according to the Society of Obstetric Medicine in Australia and New Zealand Guidelines. Use of serotonin and noradrenaline reuptake inhibitors (SNRIs) (adjusted risk ratio = 9.10, 95% confidence interval = [3.82, 21.67]) and unmedicated depression (adjusted risk ratio = 3.11, 95% confidence interval = [1.32, 7.35]) were independently associated with significantly higher risk for developing hypertensive disorders of pregnancy compared to controls. Selective serotonin reuptake inhibitors (SSRIs) use did not confer any increased risk. Higher doses of SNRIs, but not selective serotonin reuptake inhibitors, were associated with significantly higher risk for developing HDP (adjusted risk ratio = 4.83, 95% confidence interval = [1.50, 15.58]). Our findings suggest that those with depression in pregnancy and/or on an serotonin and noradrenaline reuptake inhibitor should have closer surveillance for the development of hypertensive disorders of pregnancy. These findings support treatment of depression in pregnancy, however, also the consideration of class of antidepressant.

Serotonergic Antidepressant Use in Pregnancy Is Not Associated with Increased Risk for Seizures in Children

Serotonergic Antidepressant Use in Pregnancy Is Not Associated with Increased Risk for Seizures in Children

The development of a patient decision aid to reduce decisional conflict about antidepressant use in pregnancy

BackgroundPeople with moderate to severe depression in pregnancy must weigh potential risks of untreated or incompletely treated depression against the small, but uncertain risks of fetal antidepressant drug exposure. Clinical support alone appears insufficient for helping individuals with this complex decision. A patient decision aid (PDA) has the potential to be a useful tool for this population. The objective of our work was to use internationally recognized guidelines from the International Patient Decision Aids Standards Collaboration to develop an evidence-based PDA for antidepressant use in pregnancy.MethodsA three-phased development process was used whereby, informed by patient and physician perspectives and evidence synthesis, a steering committee commissioned a web-based PDA for those deciding whether or not to start or continue antidepressant treatment for depression in pregnancy (Phase 1). A prototype was developed (Phase 2) and iteratively revised based on feedback during field testing based on a user-centred process (Phase 3).ResultsWe developed a web-based PDA for people deciding whether to start or continue antidepressant use for depression in pregnancy. It has five interactive sections: (1) information on depression and treatment; (2) reasons to start/continue an antidepressant and to start/stop antidepressant medication; (3) user assessment of values regarding each issue; (4) opportunity to reflect on factors that contribute to decision making; and (5) a printable PDF that summarizes the user’s journey through the PDA.ConclusionsThis tool, which exclusively focuses on depression treatment with Selective Serotonin Reuptake Inhibitors and Serotonin–Norepinephrine Reuptake Inhibitors, can be used by individuals making decisions about antidepressant use to treat depression during pregnancy. Limitations of the PDA are that it is not for other conditions, nor other medications that can be used for depression, and in its pilot form cannot be used by women who do not speak English or who have a visual impairment. Pending further study, it has the potential to enhance quality of care and patient experience.

Maternal Serotonergic Antidepressant Use in Pregnancy and Risk of Seizures in Children.

Background and ObjectivesTo evaluate whether children born to women who use serotonergic antidepressants during pregnancy have higher risk of neonatal seizures and epilepsy.MethodsWe used Swedish register-based data to examine associations between maternal reported use of selective serotonin reuptake inhibitors (SSRIs) or serotonin–norepinephrine reuptake inhibitors (SNRIs) in pregnancy and diagnosis of neonatal seizures or epilepsy in >1.2 million children. To account for systematic differences between exposed and unexposed children, we adjusted for a wide range of measured confounders. After first evaluating the role of maternal indication for SSRI/SNRI use (i.e., depression or anxiety) and parental epilepsy, we adjusted for remaining parental background factors (e.g., age, comorbidities, education, and family socioeconomic indices) and pregnancy-specific characteristics (e.g., maternal use of other psychotropic medications and tobacco smoking in early pregnancy).ResultsCompared with all other children, children of women who reported use of SSRI/SNRI in pregnancy had an elevated risk of neonatal seizures and epilepsy (risk ratio [RR] 1.41, 95% CI 1.03–1.94; hazard ratio [HR] 1.21, 95% CI 1.03–1.43, respectively). The estimates of association were attenuated by adjustment for maternal indications for SSRI/SNRI use (RR 1.30, 95% CI 0.94–1.80; HR 1.13, 95% CI 0.95–1.33), but not by additional adjustment for parental history of epilepsy. Full adjustment for all measured parental and pregnancy-specific factors resulted in substantial attenuation of the remaining associations (RR 1.10, 95% CI 0.79–1.53; HR 0.96, 95% CI 0.81–1.14).DiscussionWe found no support for the concern that maternal SSRI/SNRI use in pregnancy increases children's risk for neonatal seizures or epilepsy.Classification of EvidenceThis study provides Class II evidence that exposure to SSRIs/SNRIs in the first trimester of pregnancy is not associated with an increased incidence of neonatal seizures/epilepsy.

Examining differences in placental efficiency following exposure to antidepressants and current depression: Findings from an Australian pregnancy cohort study.

Placental dysfunction and inefficiency, is important in understanding fetal growth restriction and low birth weight. Two recent studies have examined the relationship between antidepressant use in pregnancy and placental weight ratios; one found lower placental weight ratio associated with antidepressant use and the other found a higher ratio. This study examined 342 women recruited in early pregnancy, including 75 taking antidepressants, 29 with current depression and 238 controls. Antidepressant use was measured through self-report in early and late pregnancy, hospital records at delivery and drug concentrations in umbilical cord and maternal blood obtained at delivery. Maternal depression was measured using the Structured Clinical Interview for the DSM IV (SCID) at recruitment. Placentas were collected at delivery and weighed, and infant birth weight recorded. Placental efficiency was measured using standardised placental weight residuals and included as the outcome in general linear models (ANOVA/ANCOVA) to test hypotheses. While placental weight was higher for those on antidepressants compared to controls (z=.30 c.f. Z=-0.08, p=.012), there were no significant differences between the three groups after adjusting for maternal body mass index at recruitment. When comparing antidepressant groups separately there were small-to-moderate positive associations between (SSRI) concentrations and placental weight (rho's>0.20, p's>0.05), which did not reach significance. Antidepressant use in pregnancy was not associated with significant changes in placental efficiency after adjustment for confounding variables. Future research should expand on this to examine other aspects of placental function and include a wide range of potential confounding variables to draw clinically meaningful conclusions.

Antidepressants in pregnancy: Challenges in decision‐making despite low risks

When looking at the effects of antidepressants taken during pregnancy on outcomes in children, the most serious confounder is the effects of the condition itself on the children. This is a major challenge of studies, and in those of the highest quality — with well‐defined exposures and outcomes, as well as a reasonable methods of controlling by indication — there have been only small, uncertain, or no significant associations between antidepressant use in pregnancy and adverse outcomes. There are also risks in not treating depression at any time, including during pregnancy, and that includes risks to the child.

Association between antidepressant use in pregnancy and gestational diabetes mellitus: Results from the Norwegian Mother, Father and Child Cohort Study.

This study sought to determine the association between gestational diabetes mellitus (GDM) and antidepressant exposure during early-mid pregnancy, overall and according to antidepressant affinity to the histamine-1 (H1 ) receptor. Data originate from the nation-wide, Norwegian Mother, Father and Child Cohort Study conducted in 1999-2008, linked to the national Medical Birth Registry. The study included 6647 pregnancies within women with depressive/anxiety disorders during and/or 6 months prior to pregnancy. Pregnancies exposed in early-mid gestation to antidepressants having low (group 1, n=814) or high (group 2, n=77) affinity to the H1 receptor were compared to non-medicated (n=5756). We fit crude and weighted modified Poisson regression models using inverse probability of treatment weighting (IPTW). Overall, 84 (1.3%) of the pregnancies developed GDM. Relative to non-medicated pregnancies, the risk of GDM was slightly lower in antidepressant group 1 exposed (1.3% vs 1.1%), but more elevated in those exposed to group 2 antidepressants (3.9%). In the weighted analysis, there was no evidence for an association between antidepressant group 1 exposure in early-mid pregnancy and risk of GDM [relative risk (RR): 0.69, 95% confidence interval: 0.31-1.51]. Gestational use of antidepressants with low H1 receptor affinity, mainly SSRIs and SNRIs, does not pose a substantial risk of GDM in women with depressive/anxiety disorders in pregnancy, compared to no use.

Effect of Selected Antidepressants on Placental Homeostasis of Serotonin: Maternal and Fetal Perspectives.

Depression is a prevalent condition affecting up to 20% of pregnant women. Hence, more than 10% are prescribed antidepressant drugs, mainly serotonin reuptake inhibitors (SSRIs) and selective serotonin and noradrenaline reuptake inhibitors (SNRIs). We hypothesize that antidepressants disturb serotonin homeostasis in the fetoplacental unit by inhibiting serotonin transporter (SERT) and organic cation transporter 3 (OCT3) in the maternal- and fetal-facing placental membranes, respectively. Paroxetine, citalopram, fluoxetine, fluvoxamine, sertraline, and venlafaxine were tested in situ (rat term placenta perfusion) and ex vivo (uptake studies in membrane vesicles isolated from healthy human term placenta). All tested antidepressants significantly inhibited SERT- and OCT3-mediated serotonin uptake in a dose-dependent manner. Calculated half-maximal inhibitory concentrations (IC50) were in the range of therapeutic plasma concentrations. Using in vitro and in situ models, we further showed that the placental efflux transporters did not compromise mother-to-fetus transport of antidepressants. Collectively, we suggest that antidepressants have the potential to affect serotonin levels in the placenta or fetus when administered at therapeutic doses. Interestingly, the effect of antidepressants on serotonin homeostasis in rat placenta was sex dependent. As accurate fetal programming requires optimal serotonin levels in the fetoplacental unit throughout gestation, inhibition of SERT-/OCT3-mediated serotonin uptake may help explain the poor outcomes of antidepressant use in pregnancy.

Antidepressant use in pregnancy and severe cardiac malformations: Danish register-based study.

Studies restricted to live births may underestimate severe teratogenic effects. We address the limitation by including data from both prenatal and postnatal diagnoses of cardiac malformations. Register-based study. Denmark. 364012 singleton pregnancies from 2007 to 2014. We used data from five nationwide registries. Exposure to antidepressants was measured using redeemed prescriptions. Pregnancies with cardiac malformations that end in miscarriage, termination, stillbirth, postnatal death or cardiac surgery <1year of birth were classified as severe cardiac malformations (SCM). Propensity scores with adjusted prevalence ratios (PRs) were calculated. SCM were reported in 972 of 364012 pregnancies overall and in 16 of 4105 exposed. For venlafaxine, the PR for SCM was 2.13 (95% confidence interval [CI] 0.89-5.13), 1.73 (95% CI 1.08-2.77) for other cardiac malformations, and there was a cluster of hypoplastic left heart syndromes (HLHS) (crude PR 17.4 [95% CI 6.41-47.2]), none of which ended in a live birth. For HLHS, the absolute risk increase was 4.4/1000 and the number needed to harm was 225. For selective serotonin reuptake inhibitors, the PRs were 1.09 (95% CI 0.52-2.30) and 1.38 (95% CI 1.00-1.92) for SCM and other cardiac malformations, respectively. Pregnancy exposure to venlafaxine is associated with an increased risk of severe cardiac malformations but with a low absolute risk. Potential mechanisms include direct effects or confounding by indication. Venlafaxine exposure is a marker for risk pregnancies for which fetal echocardiography may be considered. Exposure to venlafaxine is associated with an increased risk of cardiac malformations but with a low absolute risk.

Association between Antidepressant Treatment during Pregnancy and Postpartum Self-Harm Ideation in Women with Psychiatric Disorders: A Cross-Sectional, Multinational Study.

This study sought to estimate whether there is a preventative association between antidepressants during pregnancy and postpartum self-harm ideation (SHI), as this knowledge is to date unknown. Using the Multinational Medication Use in Pregnancy Study, we included a sample of mothers who were in the five weeks to one year postpartum period at the time of questionnaire completion, and reported preexisting or new onset depression and/or anxiety during pregnancy (n = 187). Frequency of postpartum SHI (‘often/sometimes’ = frequent, ‘hardly ever’ = sporadic, ‘never’) was measured via the Edinburgh Postnatal Depression Scale (EPDS) item 10, which reads “The thought of harming myself has occurred to me”. Mothers reported their antidepressant use in pregnancy retrospectively. Overall, 52.9% of women took an antidepressant during pregnancy. Frequent SHI postpartum was reported by 15.2% of non-medicated women and 22.0% of women on past antidepressant treatment in pregnancy; this proportion was higher following a single trimester treatment compared to three trimesters (36.3% versus 18.0%). There was no preventative association of antidepressant treatment in pregnancy on reporting frequent SHI postpartum (weighted RR: 1.90, 95% CI: 0.79, 4.56), relative to never/hardly ever SHI. In a population of women with antenatal depression/anxiety, there was no preventative association between past antidepressant treatment in pregnancy and reporting frequent SHI in the postpartum year. This analysis is only a first step in providing evidence to inform psychiatric disorder treatment decisions for pregnant women.

Prenatal antidepressant exposure and child development at kindergarten age: a population-based study.

Though prenatal antidepressant exposure has been associated with adverse developmental outcomes, the extent to which the effects are due to prenatal drug exposure or underlying maternal mood disturbances is unclear. This was a population-based retrospective cohort study using administrative data from British Columbia, Canada (n = 94,712). Analyses were designed to remove confounding effects of prenatal antidepressant exposure from maternal mood. First, children prenatally exposed to antidepressants were matched to unexposed children using high-dimensional propensity scores (HDPS). Second, children whose mothers had used antidepressants throughout pregnancy were compared against those whose mothers discontinued treatment. In all, 3.87% (n = 3661) of children in the overall study population were prenatally exposed to antidepressants. In both analyses, we report increased odds for lower levels of physical independence (HDPS: OR, 1.14; 95% CI, 1.00-1.30; continuers/discontinuers: OR, 1.14; 95% CI, 0.99-1.32), and higher levels of anxious behaviors (HDPS: OR, 1.30; 95% CI, 1.01-1.66; continuers/discontinuers: OR, 1.32; 95% CI, 1.01-1.72) associated with antidepressant use in pregnancy. All other relationships were not significant using these methods. Prenatal antidepressant exposure was selectively associated with worse anxious behaviors and physical independence at kindergarten age, with no effects on other developmental domains. Effectsare also likelyattributable to maternal mental illness severity or other unmeasured confoundingfactors. Selective associations between prenatal antidepressant exposure and children's anxiety and physical independence at kindergarten were identified, with no impact on other developmental domains. Contradictory reports have emerged regarding the association of adverse child outcomes with prenatal antidepressant exposure. These inconsistencies may be due to differences in control for confounding. Effects of prenatal antidepressant exposure on anxious behaviors and physical independence are likely also attributable to severity of underlying maternal mood disorders, highlighting the importance of maternal mental health for developmental health.

Antidepressant exposure in pregnancy and child sensorimotor and visuospatial development

Motor development underlies many aspects of education and learning. There has been uncertainty about the impact of exposure of antidepressant medication in pregnancy on child motor outcomes. This paper examines whether exposure to antidepressants in utero increases the risk of poorer motor development in two areas: sensorimotor and visuospatial processing. Data were obtained from 195 women and children across 3 groups: women with untreated depression in pregnancy, women treated with antidepressants and control women. Data were collected across pregnancy, postpartum and until 4 years for mother and child. Maternal depression was established at baseline with the Structured Clinical Interview for DSM-IV. Antidepressant exposure, including type, dose and timing, was measured through repeated self-report across pregnancy and the postpartum, medical records at delivery and in cord blood samples collected at delivery. Child sensorimotor and visuospatial outcomes were assessed at 4 years of age with four subtests from the NEPSY-II. Our study found for sensorimotor development, visuomotor precision completion time was associated with better performance for antidepressant-exposed children compared to those with mothers with untreated depression. Yet another measure of sensorimotor development, motor manual sequences, was poorer in those exposed to antidepressants. One subtest for visuospatial processing, block construction, was associated with poorer performance in antidepressant-exposed children who had poor neonatal adaptation and those exposed to a higher dose of antidepressant. These findings suggest an inconsistent association between sensorimotor development and antidepressant use in pregnancy. However, the findings for visuospatial processing would support further exploration of antidepressant associated poor neonatal adaption and later motor development.