Ali Sumera Aziz, Valeri Linda, Kahe Ka, Genkinger Jeanine M, Saleem Sarah, Jessani Saleem, Goldenberg Robert L, Westcott Jamie E, Kemp Jennifer F, Garcés Ana L, Figueroa Lester, Goudar Shivaprasad S, Dhaded Sangappa M, Derman Richard J, Tshefu Antoinette, Lokangaka Adrien L, Bauserman Melissa S, McClure Elizabeth M, Koso Thomas Marion, Kuhn Louise, Krebs Nancy F
Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Department of Biostatistics, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
J Nutr. 2025 Jul;155(7):2385-2397. doi: 10.1016/j.tjnut.2025.04.036. Epub 2025 May 19.
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).
孕期前或孕期服用多种微量营养素强化的小剂量脂质基营养补充剂（SQ-LNS）等营养补充剂已被证明可促进子宫内生长，但这些补充剂促进子宫内生长的机制尚不清楚。
我们研究了孕期血红蛋白（Hb）是否可能是多种微量营养素强化的SQ-LNS促进子宫内生长的潜在机制。
我们使用了在巴基斯坦、印度、刚果民主共和国和危地马拉进行的一项随机对照试验中收集的妇女和新生儿数据。妇女被随机分配从孕前至分娩服用多种微量营养素强化的SQ-LNS（组1）；从妊娠中期至分娩服用SQ-LNS（组2）；或不服用补充剂（组3）。以出生时的身长、体重和头围Z评分表示的子宫内生长情况为研究结果。中介变量是在妊娠12周（n = 2075）和32周（n = 2157）时测量的Hb（g/dL）。采用因果中介分析来估计直接和间接效应。
妊娠12周或32周时的Hb水平并未介导SQ-LNS与子宫内生长之间的关系。与组3相比，妊娠12周时由Hb介导的孕前SQ-LNS（组1）对身长、体重和头围Z评分的间接效应分别为0.02 [95%置信区间（CI）：-0.02，0.01]、0.01（95% CI：-0.01，0.02）和0.01（95% CI：-0.01，0.02）。相应的未由Hb介导的直接效应（95% CI）分别为0.18（0.09，0.33）、0.12（0.03，0.23）和0.06（-0.03，0.20）。在妊娠12周和32周时进行的特定地点和孕周调整数据分析证实了孕期Hb无统计学显著介导效应的结果。
多种微量营养素强化的SQ-LNS对子宫内生长的观察到的主要效应并非由妊娠12周或32周时的Hb水平介导。这些发现提示应探索SQ-LNS与子宫内生长之间关联中涉及的其他途径。该试验已在clinicaltrials.gov注册，注册号为#NCT01883193（https://clinicaltrials.gov/ct2/show/NCT01883193?term=01883193&rank=1）。
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