New Evidence Should Inform WHO Guidelines on Multiple Micronutrient Supplementation in Pregnancy.

Recent data from an individual patient data (IPD) meta-analysis of 17 randomized control trials including >100,000 women living in low- and middle-income countries found that multiple micronutrient supplementation (MMS) in pregnancy reduced the risk of low birth weight, preterm birth, and being born small for gestational age. Further, MMS reduced the risk of neonatal and infant mortality for females, and there was no evidence of increased risk among the 26 subgroups examined. The 2016 WHO antenatal care guidelines, which were released before the IPD meta-analysis, did not universally recommend MMS, noting: "There is some evidence of additional benefit … but there is also some evidence of risk." The guidelines suggest that MMS may increase the risk of neonatal mortality based on an exploratory subgroup analysis of 6 randomized trials. However, we identified several issues with this subgroup analysis. In this report we correct and update the subgroup analysis and show that there is no evidence that MMS increases the risk of neonatal mortality. There is growing scientific consensus that MMS containing iron and folic acid (IFA) is superior to IFA alone. The WHO guidelines currently state that "policy-makers in populations with a high prevalence of nutritional deficiencies might consider the benefits of MMN [multiple micronutrient] supplements on maternal health to outweigh the disadvantages, and may choose to give MMN supplements that include iron and folic acid." This equivocal guidance has created confusion about the best course of action for public health programs in low- and middle-income countries. Given the new evidence, WHO should review their statements regarding the potential neonatal mortality risks and re-evaluate the overall potential benefits of implementing MMS as a public health program.