Micronutrient supplements in pregnancy: an urgent priority

Abstract

We read with concern the Comment by Anura V Kurpad and Harshpal Singh Sachdev (June, 2022).1Kurpad AV Sachdev HS Precision in prescription: multiple micronutrient supplements in pregnancy.Lancet Glob Health. 2022; 10: e780-e781Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar The authors described some limitations of the recent 2022 study by Caniglia and colleagues inherent to observational studies.2Caniglia EC Zash R Swanson SA et al.Iron, folic acid, and multiple micronutrient supplementation strategies during pregnancy and adverse birth outcomes in Botswana.Lancet Glob Health. 2022; 10: e850-e861Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar This robust programmatic evaluation adds to the existing strong evidence of benefit of antenatal multiple micronutrient supplements (MMS) compared with iron–folic acid supplements (IFAS) alone from a meta-analysis of 17 randomised controlled trials,3Smith ER Shankar AH Wu LSF et al.Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality: a meta-analysis of individual patient data from 17 randomised trials in low-income and middle-income countries.Lancet Glob Health. 2017; 5: e1090-e1100Summary Full Text Full Text PDF PubMed Scopus (124) Google Scholar and accounts for access and adherence in real-world programmes. The difference in mean birthweight shown in the study is consistent with the shown benefit of MMS versus IFAS. Shifts in the lower tail of the birthweight distribution can occur without large changes in mean birthweight, and are highly beneficial because low birthweight or preterm neonates have increased risks of death and poor growth and development.4Katz J Lee ACC Kozuki N et al.Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis.Lancet. 2013; 382: 417-425Summary Full Text Full Text PDF PubMed Scopus (488) Google Scholar Kurpad and Sachdev call for an individualised prescription of prenatal MMS, according to type and extent of micronutrient deficiencies. Although aspirational, this proposition has yet to be achieved in any nation. Furthermore, mapping of micronutrient deficiencies to provide individualised tailored products remains infeasible in most low-income and middle-income countries (LMICs), where even population-level micronutrient deficiencies data are scarce. When such data are available, they clearly justify MMS, as multiple micronutrient deficiencies coexist during pregnancy. Kurpad and Sachdev raised concerns about excessive doses of micronutrients in the UN International Multiple Micronutrient Antenatal Preparation (UNIMMAP) MMS formulation. We previously showed that this formulation does not result in excessive concerning micronutrient intakes, even when paired with adequate diets—which are not accessible to most pregnant women in LMICs.5Gernand AD The upper level: examining the risk of excess micronutrient intake in pregnancy from antenatal supplements.Ann N Y Acad Sci. 2019; 1444: 22-34Crossref PubMed Scopus (13) Google Scholar In fact, data from the largest MMS trial revealed that MMS, although reducing adverse birth outcomes and improving micronutrient status, was unable to eliminate deficiencies, suggesting that higher—not lower—micronutrient doses might be needed to replete pregnant women in LMICs.6Schulze KJ Mehra S Shaikh S et al.Antenatal multiple micronutrient supplementation compared to iron-folic acid affects micronutrient status but does not eliminate deficiencies in a randomized controlled trial among pregnant women of rural Bangladesh.J Nutr. 2019; 149: 1260-1270Crossref PubMed Scopus (23) Google Scholar Iron intake beyond the daily requirement might increase oxidative stress, but it is of more concern for IFAS providing 60 mg of iron, than for UNIMMAP MMS providing 30 mg of iron. Research on subclinical metabolic risks would be useful, and current evidence suggests that MMS—versus IFAS—might decrease metabolic risk for the mother and offspring.7Priliani L Oktavianthi S Prado EL Malik SG Shankar AH Maternal biomarker patterns for metabolism and inflammation in pregnancy are influenced by multiple micronutrient supplementation and associated with child biomarker patterns and nutritional status at 9–12 years of age.PLoS One. 2020; 15e0216848Crossref PubMed Scopus (3) Google Scholar Dietary adequacy with appropriate quantity and quality of diverse foods remains central, yet still lags due to access and cost constraints in many LMICs. This paucity makes MMS an urgent, important, cost-effective, and complementary intervention to improve pregnancy and birth outcomes. We declare no competing interests. Precision in prescription: multiple micronutrient supplements in pregnancyThe programmatic possibility of introducing multiple micronutrient supplements (MMS), which include iron and folic acid, for routine antenatal care in low-income and middle-income countries (LMIC) has been enthusiastically welcomed by many, but it is equally opposed by others. This is reflected in the language of the WHO recommendation,1 which states that more rigorous research is required, specifically, using early ultrasound to date pregnancies accurately and to rigorously evaluate outcomes and the follow-up of infants into childhood. Full-Text PDF Open Access