Neurobehavioral follow-up of children exposed to selective serotonin reuptake inhibitors in utero.

BACKGROUND: Systematic data regarding long-term neurobehavioral effects of maternal antidepressant use during pregnancy are sparse. The aim of this study was to evaluate the impact of gestational exposure to antidepressants on later neurodevelopmental function. METHODS: This study describes a cohort of mother-child dyads (44 mothers, 54 children) in which maternal depressive symptoms and medication exposures were prospectively collected across pregnancy and the postpartum period. Children age 6 to 17 were assessed using validated instruments across domains of childhood behavior and executive memory and functioning. RESULTS: No associations were found between maternal use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and atypical neurodevelopment of children. Borderline clinical or clinical ranges of internalizing symptoms were associated with exposure to a higher maternal depressive symptom burden during pregnancy compared with those in the normal range. Compared with age- and sex-matched controls, the SSRI-exposed group showed superior performance on executive function tasks; findings did not demonstrate elevated risk for abnormal neurodevelopment in children age 6 to 17 exposed to SSRIs in utero. Deviations from the norm were instead associated with higher in utero exposure to maternal depression burden. CONCLUSIONS: This study highlights the need for rigorous studies of long-term outcomes after fetal antidepressant exposure.

Course of major depressive disorder after pregnancy and the postpartum period.

BACKGROUND: Maternal major depressive disorder (MDD) has an adverse effect on child development and increases risk for child psychopathology. It is paramount to understand the course of maternal depression during the childhood years particularly before, during, and after pregnancy. OBJECTIVE: To follow the course of MDD in women with prior histories of depression followed during an index pregnancy. METHODS: Subjects were women with histories of MDD who had participated in prior prospective, observational studies during pregnancy. In the follow-up, participants completed a structured interview that addressed (1) the course of MDD since their index pregnancy, (2) new psychiatric diagnoses, and (3) the course of MDD and treatment across subsequent pregnancies. RESULTS: Out of 129 eligible women, 48.8% participated (N = 63) with an average/mean time of 12.9 years (SD = 1.9, 8.8-16.7) elapsed since participation in the prior pregnancy studies. Although approximately one third reported sustained remission from MDD since the pregnancy during which they had been originally followed, of the remaining two thirds of women who reported subsequent depressive episodes, almost one fifth (∼12% of the total sample) endorsed depression more than 50% of the time following their index pregnancy. A total of 6.3% of the women with previous validated diagnoses of MDD reported new diagnoses of bipolar disorder. Women reported similar treatment choices regarding the use of antidepressants during pregnancies subsequent to the one followed in the previous study. CONCLUSION: Women with MDD experienced high rates of recurrent depression across the childbearing years. This represents a critical variable for clinical care and research.

Vortioxetine for major depressive disorder, vasomotor, and cognitive symptoms associated with the menopausal transition.

BACKGROUND: In a preliminary trial, we assessed the efficacy of vortioxetine for major depressive disorder (MDD) during the menopausal transition. Secondary outcomes included hot flashes (HFs), anxiety, and cognitive complaints. METHODS: Perimenopausal and early postmenopausal women with MDD (N = 27) received 8 weeks of open-label, flexible-dose treatment with vortioxetine. The Montgomery-Åsberg Depression Rating Scale (MADRS) was the primary outcome measure. Secondary measures included: HF frequency, the Greene Climacteric Scale (GCS), Menopause-Specific Quality of Life Questionnaire (MEN-QOL), Beck Anxiety Inventory (BAI), Cognitive and Physical Functioning Questionnaire (CPFQ), Digit Symbol Substitution Test (DSST), and Cogstate testing. RESULTS: Of the 27 women, 24 (88.8%) were evaluated (≥1 follow-up), and 21 (77.8%) completed the study; 1 discontinued because of adverse effects. The mean MADRS score decreased significantly (P = .0001) from 31.3 (standard deviation [SD] = 5.5) at pretreatment to 8.1 (SD = 7.8) at posttreatment. The depression response rate (≥50% reduction in MADRS) and remission rate (final MADRS ≤10) were 75% and 70.8%, respectively. GCS, MEN-QOL, BAI, CPFQ, and DSST scores improved significantly (P = .0030, P = .0001, P = .0001, P = .0001, and P = .0133, respectively); Cogstate test scores did not. Frequency and severity of HFs improved significantly (P = .0291 and P = .0299, respectively). CONCLUSIONS: These data support further study of vortioxetine for treating menopausal depression and associated symptoms.

Timing of Circumcision and Breastfeeding Frequency: A Multicenter, Randomized Clinical Trial.

OBJECTIVE: To date, there is little in the literature that describes any relationship between newborn circumcision, its timing, and breastfeeding outcomes. We sought to determine if the timing of circumcision in term, healthy newborns affects exclusive breastfeeding rates during the first 6 months of life. METHODS: One hundred and forty-eight maternal-infant dyads were enrolled in a randomized, multicenter, clinical trial between June 2016 and July 2019. Study participants included parent-infant dyads who desired both circumcision and breastfeeding. Newborns were randomized into 3 groups for circumcision: "early," circumcised within 24 hours of delivery; "intermediate," circumcised between 24 to 72 hours of age; and "late," circumcised between 1 and 3 weeks of age. The primary outcome was exclusive breastfeeding duration, assessed at discharge, 2 weeks, and 2, 4, and 6 months. RESULTS: Baseline characteristics between groups were similar. Exclusive breastfeeding decreased more rapidly over 6 months in the intermediate group (by 74%, 89% to 23%), as compared to the early (by 34%, 81% to 53%) or late (by 50%, 88% to 44%) groups (P = .04). Exclusive breastfeeding was less common in the intermediate group (circumcision between 24 and 72 hours), as compared to the early and late circumcision groups, at each measured time point beyond 2 weeks of age. CONCLUSIONS: Circumcision before 24 hours of age may be advantageous with respect to increased exclusive breastfeeding throughout the first 6 months of life. Deferral of circumcision beyond the immediate newborn period was not superior to performing the procedure within the first 24 hours.

Enhanced phosphoserine insertion during Escherichia coli protein synthesis via partial UAG codon reassignment and release factor 1 deletion.

Genetically encoded phosphoserine incorporation programmed by the UAG codon was achieved by addition of engineered elongation factor and an archaeal aminoacyl-tRNA synthetase to the normal Escherichia coli translation machinery (Park et al., 2011) Science 333, 1151). However, protein yield suffers from expression of the orthogonal phosphoserine translation system and competition with release factor 1 (RF-1). In a strain lacking RF-1, phosphoserine phosphatase, and where seven UAG codons residing in essential genes were converted to UAA, phosphoserine incorporation into GFP and WNK4 was significantly elevated, but with an accompanying loss in cellular fitness and viability.

Relationship between antiepileptic drugs and biological markers affecting long-term cardiovascular function in children and adolescents.

BACKGROUND: Epilepsy is a neurological disorder, relatively common in the paediatric population. These children are often treated with antiepileptic drugs (AEDs) for several years. The consequence of such long-term exposure may lead to variations in plasma homocysteine and serum lipoprotein concentrations. OBJECTIVE(S): To review the cardiovascular effects of anticonvulsant therapy and their use in childhood epilepsy with special reference to homocysteine and lipoprotein. METHODS: A literature search was conducted on PubMed (1966-May 2009) and MEDLINE (1966-May 2009). Key terms included antiepileptic drugs, epilepsy, homocysteine, cardiovascular events, and children. RESULTS: Certain AEDs including carbamazepine, phenobarbital, phenytoin and valproic acid, as well as the presence of a homozygous 5-methylenetetrahydrofolate reductase polymorphism in the genotype, are potential causes of elevation in plasma homocysteine and serum lipoprotein concentrations. CONCLUSIONS: Persistent elevation in these biochemical markers has shown to be associated with the development of long-term sequelae such as cardiovascular diseases, prompting concerns about the long-term implications of chronic AED use in children and cardiovascular risk. Further research is needed to assess the relationship between specific chronic AED use, homocysteine and lipoprotein concentrations, the influence of genotype, as well as the risk of long-term sequelae in the paediatric population.