Fetal sex-specific epigenetic associations with prenatal maternal depressive symptoms.

Prenatal maternal mental health is a global health challenge with poorly defined biological mechanisms. We used maternal blood samples collected during the second trimester from a Singaporean longitudinal birth cohort study to examine the association between inter-individual genome-wide DNA methylation and prenatal maternal depressive symptoms. We found that (1) the maternal methylome was significantly associated with prenatal maternal depressive symptoms only in mothers with a female fetus; and (2) this sex-dependent association was observed in a comparable, UK-based birth cohort study. Qualitative analyses showed fetal sex-specific differences in genomic features of depression-related CpGs and genes mapped from these CpGs in mothers with female fetuses implicated in a depression-associated WNT/ß-catenin signaling pathway. These same genes also showed enriched expression in brain regions linked to major depressive disorder. We also found similar female-specific associations with fetal-facing placenta methylome. Our fetal sex-specific findings provide evidence for maternal-fetal interactions as a mechanism for intergenerational transmission.

Academy of Medicine-Ministry of Health clinical practice guidelines: attention deficit hyperactivity disorder.

The Academy of Medicine (AMS) and the Ministry of Health (MOH) have developed the clinical practice guidelines on Attention Deficit Hyperactivity Disorder (ADHD) to provide doctors and patients in Singapore with evidence-based treatment for ADHD. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on ADHD, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html.The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Two-year neurodevelopmental outcome in children conceived by intracytoplasmic sperm injection: prospective cohort study.

OBJECTIVE: Primary outcome was to compare neurodevelopmental outcome at two years in intracytoplasmic sperm injection (ICSI) conceived children versus matched controls. Secondary outcome was to determine incidence of major congenital malformations and study perinatal outcome. DESIGN: Prospective cohort study. SETTING: Tertiary care perinatal centre over a period of 13 months. POPULATION: Seventy-six ICSI conceived children and 261 matched controls selected by matching for maternal age, sex, date of delivery, race, plurality and parity. METHODS: Mental Development Index (MDI) and Psychometric Development Index (PDI) of the Bayley's Scale of Development (BSID-II) and Vineland Adaptive Behaviour Scale (VABS) were used to assess the neurodevelopmental and functional outcome. The congenital malformations were classified according to ICD-9 code. MAIN OUTCOME MEASURES: Primary outcome measure--neurodevelopmental and functional outcomes. Secondary outcome measure--congenital malformations and perinatal outcomes. RESULTS: Neurodevelopmental and functional outcome were comparable in both groups. The mean MDI score was 92 [16] versus 90 [14] in the study and control groups respectively. Fourteen (18.4%) in the ICSI group had MDI <85 compared with 87 (33%) controls (P= 0.002). On linear regression the MDI was independently affected by plurality (P= 0.001), maternal education and socio-economic status (P= 0.01). The study group had a lower gestation (36 [3] vs 37.1 [2] weeks; P= 0.005) and a higher incidence of prematurity <34 weeks [19 (25%)] vs [31 (12%)] P= 0.012]. Six (7.9%) of the ICSI babies and seven (2.7%) of the controls had a major congenital malformation (P= 0.05). CONCLUSIONS: Children born by ICSI pregnancies did not have an adverse neurodevelopmental outcome. The incidence of major congenital malformations in ICSI needs further evaluation.