# Hemoglobin During Pregnancy Does Not Mediate the Relationship between Nutrition Supplements and Intrauterine Growth: A Secondary Data Analysis of Women First Preconception Nutrition Trial

## TL;DR

This study found that hemoglobin levels during pregnancy do not explain how nutrition supplements improve baby growth in the womb.

## Contribution

The study shows hemoglobin is not a key mechanism for how nutrition supplements affect fetal growth.

## Key findings

- Hemoglobin levels at 12 or 32 weeks of pregnancy did not mediate the effects of SQ-LNS on intrauterine growth.
- Direct effects of SQ-LNS on birth outcomes were significant, but indirect effects through hemoglobin were not.
- Findings suggest other biological pathways may explain the benefits of nutrition supplements during pregnancy.

## Abstract

Nutrition supplements such as multiple micronutrient-fortified small-quantity lipid-based nutrient supplementation (SQ-LNS) consumed either before or during pregnancy have been shown to improve intrauterine growth, but the mechanisms through which the supplements improve intrauterine growth remain unclear.

We examined whether hemoglobin (Hb) during pregnancy could be a potential mechanism through which multiple micronutrient-fortified SQ-LNS improve intrauterine growth.

We used data collected from women and newborns in a randomized controlled trial conducted in Pakistan, India, the Democratic Republic of the Congo, and Guatemala. Women were randomly assigned to consume multiple micronutrient-fortified SQ-LNS from preconception until birth (arm 1); consume the SQ-LNS from the second trimester of pregnancy until birth (arm 2); or no supplement (arm 3). Intrauterine growth, expressed as birth length, weight, and head circumference Z-scores, was the outcome. The mediator was Hb (g/dL) measured at 12 (n = 2075) and 32 wk of gestation (n = 2157). Causal mediation analysis was employed to estimate direct and indirect effects.

Hb levels at 12 or 32 wk of gestation did not mediate the relation between the SQ-LNS and intrauterine growth. Indirect effects of preconception SQ-LNS (arm 1) compared with arm 3, mediated by Hb at 12 wk of gestation, were 0.02 [95% confidence interval (CI): –0.02, 0.01], 0.01 (95% CI: –0.01, 0.02), and 0.01 (95% CI: –0.01, 0.02) for length, weight, and head circumference Z-scores, respectively. The corresponding direct effects (95% CIs), not mediated by Hb, were 0.18 (0.09, 0.33), 0.12 (0.03, 0.23), and 0.06 (–0.03, 0.20), respectively. Site-specific and gestational age-adjusted data analyses at 12 and 32 wk of gestation confirmed the findings of no statistically significant mediated effects of Hb during pregnancy.

The observed main effect of multiple micronutrient-fortified SQ-LNS on intrauterine growth was not mediated by Hb levels at 12 or 32 wk of gestation. The findings suggest exploring other pathways implicated in the association between the SQ-LNS and intrauterine growth.

This trial was registered at clinicaltrials.gov as #NCT01883193 (https://clinicaltrials.gov/ct2/show/NCT01883193?term=01883193&rank=1).