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: Universal prenatal iron-folic acid and other micronutrient supplements are recommended to prevent anemia during pregnancy, but the evidence of their effect on iron status among women with mild or no anemia is limited. This study is to describe the iron status [serum ferritin (SF), serum transferrin receptor (sTfR), and body iron (BI)] before and after micronutrient supplementation during pregnancy. Methods: Among 834 pregnant women with mild or no anemia (Hb >110 g/L) from a subset of participants in a randomized, double-blind trial in China, women were randomly assigned to daily 400 µg folic acid (FA) (control), folic acid plus 30mg iron (IFA,), or folic acid, iron, plus 13 additional multiple micronutrients (MM) provided before 20 weeks gestation to delivery. Venous blood was collected during study enrollment (<20 weeks gestation) and at 28-32 weeks gestation. Results: At 28-32 weeks gestation , compared to FA group, both the IFA and MM group showed significantly lower prevalence of iron deficiency (ID) no matter which indicator (SF, sTfR, or BI) was used for defining ID. The prevalence of ID at 28-32 weeks gestation for IFA, MM, and FA were 35.3%, 42.7%, and 59.6% respectively using low SF; were 53.6%, 59.9%, and 69.9% respectively using high sTfR; and were 34.5%, 41.2%, and 59.6% respectively using low BI. However, there was no difference on anemia prevalence between FA and IFA or MM groups. Conclusions: Compared to FA alone, prenatal IFA and MM supplements provided to women with no or mild anemia improved later pregnancy iron status but did not affect perinatal anemia.