Efficacy of vitamin D supplementation in gestational diabetes mellitus: Systematic review and meta-analysis of randomized trials.

BACKGROUND: Trials have examined on the benefits of vitamin D supplementation in pregnant women. OBJECTIVE: This review aimed to evaluate whether oral vitamin D supplements, when given to pregnant women with gestational diabetes mellitus (GDM), would improve maternal and neonatal outcomes, compared with no treatment or placebo. METHOD: We performed a systematic review following Cochrane methodology, and randomized trials were included where pregnant women with GDM received vitamin D supplementation versus placebo/no treatment or vitamin D and calcium versus placebo/no treatment. Primary outcomes were preeclampsia, preterm birth, cesarean delivery, gestational hypertension, and adverse events related to vitamin D supplementation. The search strategies were applied to the following databases: MEDLINE, Embase, LILACS, and CENTRAL. Similar outcomes in at least two trials were plotted using Review Manager 5.3 software. The quality of evidence was generated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: The total of 1224 references were identified, eleven trials were potentially eligible, and six were included in this review (totaling 456 women). The meta-analysis of frequency of cesarean deliveries did not show significant differences between groups, none of the trials evaluated the remaining primary outcomes. For secondary outcomes, our results suggest that vitamin D supplementation in pregnant women with GDM may reduce newborn complications such as hyperbilirubinemia, polyhydramnios (RR: 0.40, 95% CI: 0.23 to 0.68; RR: 0.17, 95% CI: 0.03 to 0.89; respectively), and the need for maternal or infant hospitalization (RR: 0.13; 95% CI: 0.02 to 0.98; RR: 0.40, 95% CI: 0.23 to 0.69). However, the evidence was of low or very low quality. CONCLUSION: We did not find moderate or high quality evidence indicating that vitamin D supplementation, when compared with placebo, improves glucose metabolism, adverse maternal and neonatal outcomes related to GDM in pregnant women.

Azadirachta indica treatment on the congenital malformations of fetuses from rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Azadirachta indica A. Juss, popularly known as neem, presents medicinal and insecticide properties. However, the repercussions of the neem maternal treatment on fetal development should be investigated. Thus, the aim of this study was to evaluated the effects of Azadirachta indica (neem) on the frequency of congenital malformations in fetuses from rats. MATERIALS AND METHODS: Pregnant rats were randomly distributed into three experimental groups: NT=non-treated; TOil=treated with neem seed oil (1.2 mL/day); TAP=treated with active principle of Azadirachta indica (azadirachtin-1.0 mg/mL/day). The neem oil (1.2 mL/day) or azadirachtin (1.0 mg/mL/day) treatments were orally administered throughout pregnancy. Blood samples were collected on days 0, 7, 14 and 20 of pregnancy. Oral glucose test tolerance (OGTT) was performed at day 17 of pregnancy for estimation of total area under the curve (AUC). At term, the fetuses were collected and external and internal (visceral and skeletal) malformations were analyzed. RESULTS: The data showed that the dams treated with neem seed oil and Azadirachtin had no significant change in glucose levels and AUC. It was also verified that neem oil treatment contributed to increase the frequency of malformation/variation, in particular the visceral in their fetuses, while neither significant result was observed in TAP group. CONCLUSION: In conclusion, neem seed oil treatment administered during pregnancy caused abnormalities in rat fetuses, showing teratogenic effect but the Azadirachtin (active principle) presented no impairment in the fetuses.

Treatment with Azadirachta indica in diabetic pregnant rats: negative effects on maternal outcome.

ETHNOPHARMACOLOGICAL RELEVANCE: The role of Azadirachta indica (neem) against Chagas disease and its antibiotic and antidiabetic action have been demonstrated in non-pregnant animals. However, the effects of neem on lipid metabolism and oxidative stress during pregnancy remain to be investigated. The objective of this study was to evaluate the effects of Azadirachta indica (neem) on maternal reproductive performance and biochemical parameters in non-diabetic and streptozotocin-induced mild diabetic rats (MD). MATERIALS AND METHODS: Pregnant rats were randomly distributed into six experimental groups: ND=non-treated non-diabetic (n=13); NDOil=non-diabetic treated with 1.2 mL/day neem seed oil (n=12); NDPA=non-diabetic treated with 1.0mg/mL/day azadirachtin (n=12); D=non-treated diabetic (n=13); DOil: diabetic treated with neem seed oil (n=12), and DPA=diabetic treated with azadirachtin, n=13. Treatment with either neem oil (1.2 mL/day) or azadirachtin (1.0mg/mL/day) was orally administered throughout pregnancy. Glucose test tolerance (GTT) was performed at day 17 of pregnancy and used as an inclusion criterion. At term pregnancy, maternal reproductive outcomes, lipid profile and oxidative stress status were assessed. RESULTS: Treatment with neem oil and azadirachtin during pregnancy (1) had no hypoglycemic and anti-hyperglycemic effects on non-diabetic and diabetic rats, respectively; (2) affected OGTT glycemic levels in diabetic rats; (3) increased the proportion of fetuses classified as small for pregnancy age (SPA) in all groups; and (4) did not interfere with the lipid profile in non-diabetic dams. Neem oil reduced the rate of total cholesterol and NEFA in diabetic animals. Both neem oil and azadirachtin increased lipoperoxidation, characterized by increased MDA levels in non-diabetic rats. CONCLUSION: Both neem seed oil and azadirachtin impaired intrauterine development and altered antioxidant/oxidative status during pregnancy.