Melatonin augments the neuroprotective effects of hypothermia in lambs following perinatal asphyxia.

Therapeutic hypothermia (TH) is standard care in high-resource birth settings for infants with neonatal encephalopathy. TH is partially effective and adjuvant therapies are needed. Here, we examined whether the antioxidant melatonin (MLT) provides additive benefit with TH, compared to TH alone or MLT alone, to improve recovery from acute encephalopathy in newborn lambs. Immediately before cesarean section delivery, we induced asphyxia in fetal sheep via umbilical cord occlusion until mean arterial blood pressure fell from 55 ± 3 mm Hg in sham controls to 18-20 mm Hg (10.1 ± 1.5 minutes). Lambs were delivered and randomized to control, control + MLT (60 mg iv, from 30 minutes to 24 hours), asphyxia, asphyxia + TH (whole-body cooling to 35.1 ± 0.8°C vs. 38.3 ± 0.17°C in sham controls, from 4-28 hours), asphyxia + MLT, and asphyxia + TH + MLT. At 72 hours, magnetic resonance spectroscopy (MRS) was undertaken, and then brains were collected for neuropathology assessment. Asphyxia induced abnormal brain metabolism on MRS with increased Lactate:NAA (P = .003) and reduced NAA:Choline (P = .005), induced apoptotic and necrotic cell death across gray and white matter brain regions (P < .05), and increased neuroinflammation and oxidative stress (P < .05). TH and MLT were independently associated with region-specific reductions in oxidative stress, inflammation, and cell death, compared to asphyxia alone. There was an interaction between TH and MLT such that the NAA:Choline ratio was not significantly different after asphyxia + TH + MLT compared to sham controls but had a greater overall reduction in neuropathology than either treatment alone. This study demonstrates that, in newborn lambs, combined TH + MLT for neonatal encephalopathy provides significantly greater neuroprotection than either alone. These results will guide the development of further trials for neonatal encephalopathy.

What has happened with neural tube defects and womens' understanding of folate in Victoria since 1998?

OBJECTIVE: To describe the prevalence of neural tube defects (NTDs) in Victoria, and to evaluate women's knowledge and awareness of the importance of folate after the introduction of voluntary food fortification. DESIGN AND SETTING: Descriptive study, set in Victoria, Australia, based on routinely collected data from the Victorian Birth Defects Register (VBDR) for 1998-2006, and responses by women aged 18-50 years to five questions relating to folate on the 2005 and 2006 Victorian Population Health Surveys (2314 and 2488 women, respectively). MAIN OUTCOME MEASURES: Prevalence of NTDs, and extent of women's knowledge of the importance of folate in NTD prevention, comparing the period before and since voluntary food fortification and a folate awareness campaign. RESULTS: The total prevalence of pregnancies affected by NTDs declined from approximately 17 to 14 per 10,000 births from 1997 to 1999 (coinciding with the period when voluntary food fortification was introduced, and a 1-year folate awareness campaign was held). It has since remained static. Over the 9-year study period, the termination of pregnancy rate was 79%, resulting in three NTD-affected babies per 10,000 livebirths. Compared with women aged 30-34 years (the reference group), those aged 20-24 years had the greatest likelihood of having a baby with an NTD (adjusted odds ratio, 1.70; 95% CI, 1.33-2.18; P < 0.001). Women aged 18-24 years had the lowest rate of folate supplement use (15.9% in 2006), while women aged 30-34 years had the highest rate (30.3% in 2006). CONCLUSIONS: There has been no further reduction in prevalence of NTDs in Victoria since 1999, and this prevalence remains well above that achievable through adequate folate intake. Accurate knowledge of folate consumption, population-based NTD prevalence data and folate awareness data are essential in monitoring the effectiveness of the mandatory fortification program to be implemented in Australia in the next 2 years.