Prevention of retinoic acid-induced early craniofacial abnormalities by vitamin B12 in mice.

OBJECTIVE: The purpose of the present study was to identify the potential effect of prenatal vitamin B12 administration on retinoic acid (RA)-induced early craniofacial abnormalities in mice and to investigate the possible mechanisms by which vitamin B12 reduces malformations. DESIGN: In our study, whole embryo culture was used to explore the effect of vitamin B12 on mouse embryos during the critical period of organogenesis. All embryos were exposed to 0.4 µM RA and different concentrations of vitamin B12 and scored for their growth in the branchial region at the end of a 48-hour culture period. The endothelin-1 (ET-1)/dHAND protein expression levels in the first branchial arch were investigated using an immunohistochemical method. RESULTS: In the whole embryo culture, 100 and 10 µM vitamin B12 dose-dependently prevented branchial region malformations and decreased craniofacial defects by 90.5% and 77.3%, respectively. ET-1 and dHAND protein levels were significantly increased in vitamin B12-supplemented embryos compared to the RA-exposed group in embryonic branchial region. CONCLUSIONS: These results suggest that vitamin B12 may prevent RA-induced craniofacial abnormalities via prevention of an RA-induced decrease of ET-1 and dHAND protein levels in the branchial region during the organogenic period. This study may shed new light on preventing craniofacial abnormalities.

Effect of folic acid on prenatal alcohol-induced modification of brain proteome in mice.

Maternal alcohol consumption during pregnancy can induce central nervous system abnormalities in the fetus, and folic acid supplementation can reverse some of the effects. The objective of the present study was to investigate prenatal alcohol exposure-induced fetal brain proteome alteration and the protective effect of folic acid using proteomic techniques. Alcohol (5.0 g/kg) was given intragastrically from gestational day (GD) 6 to 15, with or without 60.0 mg folic acid/kg given intragastrically during GD 1-16 to pregnant Balb/c mice. The control group received distilled water only. Results of litter evaluation on GD 18 showed that supplementation of folic acid reversed the prevalence of microcephaly induced by alcohol. Proteomic analysis indicated that, under the dosage of the present investigation, folic acid mainly reversed the alcohol-altered proteins involved in energy production, signal pathways and protein translation, which are all important for central nervous system development.

Methadone-exposed newborn infants: outcome after alterations to a service for mothers and infants.

OBJECTIVE: To evaluate the impact of a shared care approach in clinical management with a drug liaison midwife (DLM) service for mothers and infants established in 1995-1996 in an inner city area and to address the problem of congenital abnormality and microcephaly with fetal drug exposure. METHODS: Descriptive analysis of data in live births of women enrolled in a methadone maintenance programme in 1991-1994 (n = 78) and 1997-2001 (n = 98), including time spent in hospital, treatment for neonatal abstinence syndrome (NAS), admission to the neonatal medical unit (NMU) and follow-up for child health checks. RESULTS: In 1997-2001 compared with 1991-1994, the mothers used more methadone in the last week of pregnancy (median 40.0 mg/day vs. 21.5 mg/day, P = 0.0006) and there were more preterm deliveries (36% vs. 21%, P = 0.03). The infants spent less time in hospital (median 5 days vs. 28 days, P < 0.0001), a smaller proportion had treatment for NAS (14% vs. 79%, P < 0.0001), and NMU admission was reduced (median 14 days vs. 26 days, P < 0.0003). Neonatal convulsions (P = 0.0001) and jaundice (P < 0.001) occurred less frequently, and more infants were breastfed (P = 0.001). One infant in each study group had a cleft palate and none had microcephaly. Child health checks for 18-24 months showed a favourable outcome in 1997-2001. CONCLUSIONS: We altered antenatal care and modified neonatal management, subsequently infants spent less time in hospital and NMU admissions were reduced with less NAS treatment. Congenital abnormalities and microcephaly were not common and as regular child health checks were possible, the impact of the DLM service in shared management merits further investigation, for mother-infant bonding and developmental outcome.

The distribution of serotonergic nerves in microencephalic rats treated prenatally with methylazoxymethanol.

Prenatal exposure of pregnant rats to methylazoxymethanol acetate (MAM) induces microencephaly in the offspring. In the present study of these microencephalic rats (MAM rats) we used quantitative autoradiography to investigate [3H] paroxetine binding sites, which are a selective marker of serotonin (5-HT) transporters (5-HTT). The binding in the accumbens, cortex, hippocampus, and dorsolateral thalamus was significantly increased in MAM rats, compared to the control rats, while there was a significant decrease in the dorsal raphe nucleus of the MAM rats. The levels of 5-HTT mRNA in the dorsal raphe nuclei were analyzed by in situ hybridization, which revealed a significant decrease in 5-HTT mRNA-positive neurons in the MAM rats compared to the control rats. The results imply serotonergic hyperinnervation in the cerebral hemispheres of MAM rats, while a target-dependent secondary degeneration of 5-HT neurons might be induced in the dorsal raphe nuclei of MAM rats.