A population pharmacokinetic model for sertraline in women during the perinatal period-A contribution from the ConcePTION project.

AIMS: Sertraline is frequently prescribed for mental health conditions in both pregnant and breastfeeding women. According to the limited available data, only small amounts of sertraline are transferred into human milk, yet with a large amount of unexplained interindividual variability. This study aimed to develop a population pharmacokinetic (popPK) model to describe the pharmacokinetics of sertraline during the perinatal period and explain interindividual variability. METHODS: Pregnant women treated with sertraline were enrolled in the multicenter prospective cohort SSRI-Breast Milk study. A popPK model for sertraline maternal plasma and breast milk concentrations was developed and allowed estimating the milk-to-plasma ratio (MPR). An additional fetal compartment allowed cord blood concentrations to be described. Several covariates were tested for significance. Ultimately, model-based simulations allowed infant drug exposure through placenta and breast milk under various conditions to be predicted. RESULTS: Thirty-eight women treated with sertraline were included in the study and provided 89 maternal plasma, 29 cord blood and 107 breast milk samples. Sertraline clearance was reduced by 42% in CYP2C19 poor metabolizers compared to other phenotypes. Doubling milk fat content increased the MPR by 95%. Simulations suggested a median daily infant dosage of 6.9 µg kg-1 after a 50 mg maternal daily dose, representing 0.95% of the weight-adjusted maternal dose. Median cord blood concentrations could range from 3.29 to 33.23 ng mL-1 after maternal daily doses between 25 and 150 mg. CONCLUSIONS: Infant exposure to sertraline, influenced by CYP2C19 phenotype and breast milk fat content, remains low, providing reassurance regarding the use of sertraline during pregnancy and breastfeeding.

Joint observation in NICU (JOIN): A randomized controlled trial testing an early, one-session intervention during preterm care to improve perceived maternal self-efficacy and other mental health outcomes.

BACKGROUND: Parents of preterm infants in the Neonatal Intensive Care Unit (NICU) environment may experience psychological distress, decreased perceived self-efficacy, and/or difficulties in establishing an adaptive parent-infant relationship. Early developmental care interventions to support the parental role and infant development are essential and their impact can be assessed by an improvement of parental self-efficacy perception. The aims were to assess the effects of an early intervention provided in the NICU (the Joint Observation) on maternal perceived self-efficacy compared to controls (primary outcome) and to compare maternal mental health measures (perceived stress, anxiety, and depression), perception of the parent-infant relationship, and maternal responsiveness (secondary outcomes). METHODS: This study was a monocentric randomized controlled trial registered in clinicatrials.gov (NCT02736136), which aimed at testing a behavioural intervention compared with treatment-as-usual. Mothers of preterm neonates born 28 to 32 6/7 weeks gestation were randomly allocated to either the intervention or the control groups. Outcome measures consisted of self-report questionnaires completed by the mothers at 1 and 6 months after enrollment and assessing perceived self-efficacy, mental health, perception of the parent-infant relationship and responsiveness, as well as satisfaction with the intervention. RESULTS: No statistically significant group effects were observed for perceived maternal self-efficacy or the secondary outcomes. Over time, perceived maternal self-efficacy increased for mothers in both groups, while anxiety and depression symptoms decreased. High satisfaction with the intervention was reported. CONCLUSIONS: The joint observation was not associated with improved perceived maternal self-efficacy or other mental health outcomes, but may constitute an additional supportive measure offered to parents in a vulnerable situation during the NICU stay.

Reducing intrusive traumatic memories after emergency caesarean section: A proof-of-principle randomized controlled study.

Preventative psychological interventions to aid women after traumatic childbirth are needed. This proof-of-principle randomized controlled study evaluated whether the number of intrusive traumatic memories mothers experience after emergency caesarean section (ECS) could be reduced by a brief cognitive intervention. 56 women after ECS were randomized to one of two parallel groups in a 1:1 ratio: intervention (usual care plus cognitive task procedure) or control (usual care). The intervention group engaged in a visuospatial task (computer-game 'Tetris' via a handheld gaming device) for 15 min within six hours following their ECS. The primary outcome was the number of intrusive traumatic memories related to the ECS recorded in a diary for the week post-ECS. As predicted, compared with controls, the intervention group reported fewer intrusive traumatic memories (M = 4.77, SD = 10.71 vs. M = 9.22, SD = 10.69, d = 0.647 [95% CI: 0.106, 1.182]) over 1 week (intention-to-treat analyses, primary outcome). There was a trend towards reduced acute stress re-experiencing symptoms (d = 0.503 [95% CI: -0.032, 1.033]) after 1 week (intention-to-treat analyses). Times series analysis on daily intrusions data confirmed the predicted difference between groups. 72% of women rated the intervention "rather" to "extremely" acceptable. This represents a first step in the development of an early (and potentially universal) intervention to prevent postnatal posttraumatic stress symptoms that may benefit both mother and child. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT02502513.

Maternal Sensitivity: a Resilience Factor against Internalizing Symptoms in Early Adolescents Born Very Preterm?

Compared with full-terms, preterm individuals are more at risk from infancy to adulthood for developing internalizing symptoms. Early maternal interactive behavior, especially maternal sensitivity, has been found to be a resilience factor in the developmental outcome of preterm children. The present longitudinal study aimed at examining whether early interactive parenting behaviors have a long term impact on the internalizing symptoms of preterm-born young adolescents. A total sample of 36 very preterm and 22 full-term children participated in an 11-year follow-up study. Maternal interactive behavior was assessed during a mother-infant interaction when the infant was 18 months old. At 11 years, internalizing symptoms were assessed with the Child Behavior Checklist (CBCL). Hierarchical regression analyses revealed that the interaction between groups (preterm/full-term) and maternal sensitivity at 18 months significantly explained CBCL internalizing symptoms at 11 years (ß = -0.526; p < 0.05). Specifically, although prematurity was related to internalizing problems, preterm children with higher maternal sensitivity did not differ from their full-term-born peers on the CBCL internalizing problems domain. These results suggest that maternal sensitivity is a long-term resilience factor preventing the development of internalizing problems at early adolescence in very preterm individuals.