Hemoglobin during pregnancy does not mediate the relationship between nutrition supplements and intrauterine growth: A secondary data analysis of Women First Preconception Nutrition Trial.
Sumera Aziz Ali, Linda Valeri, Ka Kahe, Jeanine M Genkinger, Sarah Saleem, Saleem Jessani, Robert L Goldenberg, Jamie E Westcott, Jennifer F Kemp, Ana L Garcés, Lester Figueroa, Shivaprasad S Goudar, Sangappa M Dhaded, Richard J Derman, Antoinette Tshefu, Adrien L Lokangaka, Melissa S Bauserman, Elizabeth M McClure, Marion Koso Thomas, Louise Kuhn, Nancy F Krebs
{"title":"Hemoglobin during pregnancy does not mediate the relationship between nutrition supplements and intrauterine growth: A secondary data analysis of Women First Preconception Nutrition Trial.","authors":"Sumera Aziz Ali, Linda Valeri, Ka Kahe, Jeanine M Genkinger, Sarah Saleem, Saleem Jessani, Robert L Goldenberg, Jamie E Westcott, Jennifer F Kemp, Ana L Garcés, Lester Figueroa, Shivaprasad S Goudar, Sangappa M Dhaded, Richard J Derman, Antoinette Tshefu, Adrien L Lokangaka, Melissa S Bauserman, Elizabeth M McClure, Marion Koso Thomas, Louise Kuhn, Nancy F Krebs","doi":"10.1016/j.tjnut.2025.04.036","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>We examined whether hemoglobin (Hb) during pregnancy could be a potential mechanism through which multiple micronutrient-fortified SQ-LNS improve intrauterine growth.</p><p><strong>Methods: </strong>We used data collected from women and newborns in a randomized controlled trial conducted in Pakistan, India, the Democratic Republic of Congo, and Guatemala. Women were randomized 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=2,075) and 32 weeks of gestation (n=2,157). Causal mediation analysis was employed to estimate direct and indirect effects.</p><p><strong>Results: </strong>Hemoglobin levels at 12 or 32 weeks of gestation did not mediate the relation between the SQ-LNS and intrauterine growth. Indirect effects of preconception SQ-LNS (Arm 1) vs. Arm 3, mediated by Hb at 12 weeks of gestation, were 0.02 (95% 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 weeks of gestation confirmed the findings of no statistically significant mediated effects of Hb during pregnancy.</p><p><strong>Conclusions: </strong>The observed main effect of multiple micronutrient-fortified SQ-LNS on intrauterine growth was not mediated by Hb levels at 12 or 32 weeks of gestation. The findings suggest exploring other pathways implicated in the association between the SQ-LNS and intrauterine growth.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov #NCT01883193; https://clinicaltrials.gov/ct2/show/NCT01883193?term=01883193&rank=1.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nutrition","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.tjnut.2025.04.036","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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.
Objective: We examined whether hemoglobin (Hb) during pregnancy could be a potential mechanism through which multiple micronutrient-fortified SQ-LNS improve intrauterine growth.
Methods: We used data collected from women and newborns in a randomized controlled trial conducted in Pakistan, India, the Democratic Republic of Congo, and Guatemala. Women were randomized 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=2,075) and 32 weeks of gestation (n=2,157). Causal mediation analysis was employed to estimate direct and indirect effects.
Results: Hemoglobin levels at 12 or 32 weeks of gestation did not mediate the relation between the SQ-LNS and intrauterine growth. Indirect effects of preconception SQ-LNS (Arm 1) vs. Arm 3, mediated by Hb at 12 weeks of gestation, were 0.02 (95% 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 weeks of gestation confirmed the findings of no statistically significant mediated effects of Hb during pregnancy.
Conclusions: The observed main effect of multiple micronutrient-fortified SQ-LNS on intrauterine growth was not mediated by Hb levels at 12 or 32 weeks of gestation. The findings suggest exploring other pathways implicated in the association between the SQ-LNS and intrauterine growth.
期刊介绍:
The Journal of Nutrition (JN/J Nutr) publishes peer-reviewed original research papers covering all aspects of experimental nutrition in humans and other animal species; special articles such as reviews and biographies of prominent nutrition scientists; and issues, opinions, and commentaries on controversial issues in nutrition. Supplements are frequently published to provide extended discussion of topics of special interest.