ABSTRACT
Objectives: The potential adverse impact of prenatal multiple micronutrient supplementation (MMN) versus iron-folic acid (IFA) on perinatal mortality is concerned. It has been speculated that MMN might survive frail fetuses to late pregnancy or early infancy, resulting in an increase in perinatal death. If the speculation holds true, MMN would prevent miscarriages. We aimed to assess the speculation. Methods: Pubmed, Embase, Web of Knowledge, and Cochrane Library were searched. Primary outcome was miscarriages. Secondary outcomes were stillbirths, perinatal deaths, and infant deaths; death events combined with miscarriages. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were estimated with fixed- or random-effect model, depending on heterogeneity tests. Pre-specified stratified and sensitivity analyses were planned to assess whether results varied by maternal baseline or trial characteristics. Results: In total, 15 trials were identified. MMN versus IFA significantly reduced miscarriage risk (RR 0.91, 95% CI 0.83-1.00). MMN significantly reduced infant death risk within 90 days (RR 0.86, 95% CI 0.78-0.95); this reduction remained when miscarriage and stillbirth were included (RR 0.88, 95% CI 0.82-0.94). MMN insignificantly increased perinatal death risk (RR 1.08, 95% CI 0.93-1.25), but the increased risk vanished when miscarriages were included (RR 0.99, 95% CI 0.89-1.10). No difference for other death events between groups was observed, irrespective of whether miscarriages were accounted for. Conclusions: MMN versus IFA supplementation prevented miscarriages and infant deaths within 90 days. The modestly increased perinatal mortality risk is a fallacy due to the survival bias resulting from protective effect on miscarriages.
ABSTRACT
Objectives: We investigated whether daily supplementation with low-dose B vitamins in healthy elderly improves Framingham risk score (FRS), a cardiovascular disease predictor. Methods: A double-blind randomized controlled trial was conducted in a rural area of North China during 2007-2012. 390 healthy participants aged 60-74 were randomly allocated to receive daily vitamin C (50 mg; control) or vitamin C plus B vitamins (400 μg folic acid, 2 mg B6, and 10 μg B12) for 12 months. The outcome was FRS. Results: Compared with control, supplementation with B vitamins reduced FRS by 3.7% (mean difference, -0.38; 95% CI -1.06, 0.31; P=0.279) at 6 months, 7.6% (-0.77; 95% CI -1.47, -0.06; P=0.033) at 12 months, but this reduction effect vanished 6 months later after stopping supplementation (-0.7%; -0.07; 95% CI -0.80, 0.66; P=0.855). The reduction in FRS at 12 months after supplementation was more pronounced in individuals with folate deficiency (11.0%; -1.38; 95% CI -2.56, -0.20; P=0.023) than those without folate deficiency (5.0%; -0.47; 95% CI -1.20, 0.26; P=0.206). B vitamins elevated high-density lipoprotein cholesterol by 3.4% (0.04 mmol/L; 95% CI -0.02, 0.10; P=0.155) at 6 months, 9.2% (0.11 mmol/L; 95% CI 0.04, 0.18; P=0.003) at 12 months; the change magnitude declined to 3.3% (0.04 mmol/L; 95% CI -0.02, 0.10; P=0.194) after stopping supplementation, compared with control. Conclusions: Daily supplementation with low-dose B vitamins for 12 months reduced FRS, particularly in healthy elderly with folate deficiency. These reduction effects declined after stopping supplementation, indicating a need for persistent supplementation to maintain the benefits.