Intra-uterine exposure to selective serotonin reuptake inhibitors (SSRIs), maternal psychopathology, and neurodevelopment at age 2.5years-Results from the prospective cohort SMOK study

Background: Selective serotonin reuptake inhibitors (SSRIs) are prescribed in 2-8% during pregnancy. Whether prenatal exposure to SSRIs has long-term effects on the children's development is unknown. Aim: The aim of this study was to determine the effect of prenatal exposure to SSRIs on children's cognitive, motor, and behavioral outcomes at 2.5 years, adjusted for maternal depression and anxiety. Methods: In a prospective, longitudinal cohort-study we included 111 pregnant women treated either or not with an SSRI. We examined cognitive and motor development of their children at 2.5 years, using the Bayley Scale of Infant and Toddler Development, 3rd Edition, and measured emotional and behavioral problems using the parent-rated Child Behavior Checklist (CBCL). Maternal depression and anxiety was determined during pregnancy and at the children's assessment. Differences of normed cognitive, motor, and behavioral scores between SSRI-exposed and non-SSRI-exposed children were tested using multiple linear regression analyses. Results: We examined 102 children. SSRI-exposed children had lower scaled scores on cognition and gross motor development than non-SSRI-exposed children: 9.0 +/- 1.4 (mean +/- SD) versus 9.9 +/- 1.7 [P = 0.004], and 7.9 +/- 2.2 versus 9.0 +/- 2.5 [P = 0.01], respectively. Differences remained significant after adjusting for maternal depression and anxiety and other confounders in various models (mean difference for cognition 0.8 to 0.9 points, for gross motor 1.1 to 1.2 points). Only after adjusting for severity of maternal anxiety, differences in gross motor scores lost significance. Conclusions: Prenatal exposure to SSRIs is associated with poorer cognitive and gross motor development of the children at 2.5 years. Effects on gross motor development disappeared after correction for severity of maternal anxiety

Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: Study protocol of a pragmatic multicentre non-inferiority randomized controlled trial

Background: Approximately 6.2% of women in the USA and 3.7% of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2%. Nonetheless, SSRI use during pregnancy is still controversial. On the one hand SSRIs may be toxic to the intrauterine developing child, while on the other hand relapse or recurrence of depression during pregnancy poses risks for both mother and child. Among patients and professionals there is an urgent need for evidence from randomized studies to make rational decisions regarding continuation or tapering of SSRIs during pregnancy. At present, no such studies exist. Methods/Design: 'Stop or Go' is a pragmatic multicentre randomized non-inferiority trial among 200 pregnant women with a gestational age of less than 16weeks who use SSRIs without clinically relevant depressive symptoms. Women allocated to the intervention group will receive preventive cognitive therapy with gradual, guided discontinuation of SSRIs under medical management (STOP). Women in the control group will continue the use of SSRIs (GO). Primary outcome will be the (cumulative) incidence of relapse or recurrence of maternal depressive disorder (as assessed by the Structured Clinical Inter

Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy:study protocol of a pragmatic multicentre non-inferiority randomized controlled trial

Background: Approximately 6.2 % of women in the USA and 3.7 % of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2 %. Nonetheless, SSRI use during pregnancy is still controversial. On the one hand SSRIs may be toxic to the intrauterine developing child, while on the other hand relapse or recurrence of depression during pregnancy poses risks for both mother and child. Among patients and professionals there is an urgent need for evidence from randomized studies to make rational decisions regarding continuation or tapering of SSRIs during pregnancy. At present, no such studies exist.Methods/Design: 'Stop or Go' is a pragmatic multicentre randomized non-inferiority trial among 200 pregnant women with a gestational age of less than 16 weeks who use SSRIs without clinically relevant depressive symptoms. Women allocated to the intervention group will receive preventive cognitive therapy with gradual, guided discontinuation of SSRIs under medical management (STOP). Women in the control group will continue the use of SSRIs (GO). Primary outcome will be the (cumulative) incidence of relapse or recurrence of maternal depressive disorder (as assessed by the Structured Clinical Interview for DSM disorders) during pregnancy and up to three months postpartum. Secondary outcomes will be child outcome (neonatal outcomes and psychomotor and behavioural outcomes up to 24 months postpartum), and health-care costs. Total study duration for participants will be therefore be 30 months. We specified a non-inferiority margin of 15 % difference in relapse risk.Discussion: This study is the first to investigate the effect of guided tapering of SSRIs with preventive cognitive therapy from early pregnancy onwards as compared to continuation of SSRIs during pregnancy. We will study the effects on both mother and child with a pragmatic approach. Additionally, the study examines cost effectiveness. If non-inferiority of preventive cognitive therapy with guided tapering of SSRIs compared to intended continuation of SSRIs is demonstrated for the primary outcome, this may be the preferential strategy during pregnancy.</p

Early Neurological Outcome of Young Infants Exposed to Selective Serotonin Reuptake Inhibitors during Pregnancy:Results from the Observational SMOK Study

<p>Background: Use of selective serotonin reuptake inhibitors (SSRI) during pregnancy is common while the effect on the infant's neurological outcome is unknown. Our objective was to determine the effects of prenatal SSRI-exposure on the infants' neurological functioning, adjusted for maternal mental health.</p><p>Methods: A prospective observational study from May 2007 to April 2010. The study groups comprised 63 SSRI-exposed infants (SSRI group) and 44 non-exposed infants (non-SSRI group). Maternal depression and anxiety were measured using questionnaires. The main outcome measures during the first week after birth and at three to four months were the quality of the infants' general movements (GMs) according to Prechtl and a detailed motor optimality score. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for abnormal GM quality in the SSRI and non-SSRI groups, and adjusted for maternal depression, anxiety, and other confounders. The study was registered under 53506435 in the ISRCTN.</p><p>Findings: All infants were born around term. During the first week, abnormal GMs occurred more frequently in the SSRI group than in the non-SSRI group (59% versus 33%) and the median MOS was lower (13 versus 18). The OR for abnormal GMs in the SSRI versus the non-SSRI group was 3.0 (95% CI, 1.3 to 6.9) and increased after adjustment for confounders. At three to four months, more SSRI-exposed infants had monotonous movements (48% versus 20%) with lower median MOSs (26 versus 28). The OR for monotonous movements was 3? 5 (95% CI, 1.5 to 8.6) and increased after adjusting for confounders.</p><p>Interpretation: Prenatal exposure to SSRI had an adverse effect on early neurological functioning as reflected by GM quality, irrespective of maternal depression and anxiety, and other confounders. Physicians should take this into account in consultation with parents.</p>