Role of preconception nutrition supplements in maternal anemia and intrauterine growth: a systematic review and meta-analysis of randomized controlled trials.

Background: Impaired intrauterine growth, a significant global health problem, contributes to a higher burden of infant morbidity and mortality, mainly in resource-poor settings. Maternal anemia and undernutrition, two important causes of impaired intrauterine growth, are prioritized by global nutrition targets of 2030. We synthesized the evidence on the role of preconception nutrition supplements in reducing maternal anemia and improving intrauterine growth.

Methods: We undertook a review of the randomized controlled trials (RCTs) assessing the effect of preconception nutrition supplements on maternal hemoglobin, an indicator to estimate maternal anemia, and markers of intrauterine growth including birth weight, length, head circumference, and small for gestational age. Additionally, we examined preterm birth as an important perinatal outcome. We searched PubMed, CINAHL, Web of Science, Cochrane Central, and Embase. We computed summary mean differences and risk ratios (RR) with 95% confidence intervals (CIs) using random-effect models. We employed I² and Cochran's Q test statistics to assess heterogeneity. We used a revised Cochrane risk-of-bias (RoB version 2.0) and GRADE (grading of recommendations, assessment, development, and evaluation) tools to assess the risk of bias and quality of evidence of eligible RCTs, respectively.

Results: We identified 20 eligible RCTs (n = 27,659 women). Preconception nutrition supplements (iron and folic acid, multiple micronutrients, and a lipid-based nutrient supplement) overall increased maternal hemoglobin by 0.30 g/dL ((0.03, 0.57); I² = 79%; n=9). However, we did not find a significant effect of the supplements on birth weight (12.25 gm ((- 22.66, 47.16); I² = 55%; n=10)), length (0.15 cm (- 0.26, 0.56); I² = 68%; n = 5), head circumference (- 0.23 cm (- 0.88, 0.43); I² = 84%; n=4), small for gestational age (RR 0.91 (0.80, 1.04); I² = 31%; n=8), or preterm birth (RR 0.93 (0.69,1.25); I² = 57%; n=12). In general, the quality of evidence was assessed as very low to moderate.

Conclusion: Preconception nutrition supplements studied to date appear to reduce maternal anemia. However, it is uncertain whether there are beneficial effects of the supplements on intrauterine growth. Low quality of evidence warrants future well-designed RCTs to produce solid scientific data, particularly of a more comprehensive package of preconception nutrition supplements that include both macro- and micronutrients.

Systematic review registration: PROSPERO CRD42023464966.