Intermittent preventive treatment for malaria in pregnancy and infant growth: a mediation analysis of a randomised trial.

IF 9.7 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EBioMedicine Pub Date : 2024-11-01 Epub Date: 2024-10-16 DOI:10.1016/j.ebiom.2024.105397

Yanwei Tong, Kalani Ratnasiri, Suhi Hanif, Anna T Nguyen, Michelle E Roh, Grant Dorsey, Abel Kakuru, Prasanna Jagannathan, Jade Benjamin-Chung

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Abstract

Background: Intermittent preventive treatment for malaria in pregnancy (IPTp) can improve birth outcomes, but whether it confers benefits to postnatal growth is unclear. We investigated the effect of IPTp on infant growth in Uganda and its pathways of effects using causal mediation analyses.

Methods: We analysed data from 633 infants born to mothers enrolled in a randomised trial of monthly IPTp with dihydroartemisinin-piperaquine (DP) vs. sulfadoxine-pyrimethamine (SP) (NCT02793622). Weight and length were measured from 0 to 12 months of age. Using generalised linear models, we estimated effects of DP vs. SP on gravidity-stratified mean length-for-age (LAZ) and weight-for-length Z-scores (WLZ). We investigated mediation by placental malaria, gestational weight change, maternal anaemia, maternal inflammation-related proteins, preterm birth, birth length, and birth weight. Mediation models adjusted for infant sex, gravidity, gestational age at enrolment, maternal age, maternal parasitaemia at enrolment, education, and wealth.

Findings: SP increased mean LAZ by 0.18-0.28 Z from birth through age 4 months compared to DP, while DP increased mean WLZ by 0.11-0.28 Z from 2 to 8 months compared to SP among infants of multigravidae; at these ages, confidence intervals for mean differences excluded 0. We did not observe differences among primigravida. Mediators of SP included birth weight, birth length, maternal stem cell factor, and DNER. Mediators of DP included placental malaria and birth length, maternal IL-18, CDCP1, and CD6 at delivery.

Interpretation: In high malaria transmission settings, this exploratory study suggests different IPTp regimens may influence infant growth among multigravidae, potentially through distinct pathways, in the exclusive breastfeeding period, when few other interventions are available.

Funding: Stanford Center for Innovation in Global Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bill & Melinda Gates Foundation.

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孕期疟疾间歇性预防治疗与婴儿成长：随机试验的中介分析。

背景：妊娠期疟疾间歇性预防治疗（IPTp）可改善出生结果，但它是否对产后生长有益尚不清楚。我们采用因果中介分析法调查了 IPTp 对乌干达婴儿生长的影响及其影响途径：我们分析了参加每月使用双氢青蒿素-哌喹 (DP) 与磺胺乙胺嘧啶 (SP) 的 IPTp 随机试验（NCT02793622）的母亲所生的 633 名婴儿的数据。体重和身长的测量从 0 个月到 12 个月不等。利用广义线性模型，我们估算了DP与SP对孕妇分层平均身长-年龄（LAZ）和体重-身长Z分数（WLZ）的影响。我们研究了胎盘疟疾、妊娠体重变化、母体贫血、母体炎症相关蛋白、早产、出生身长和出生体重的中介作用。中介模型对婴儿性别、孕酮、入学时的胎龄、母亲年龄、入学时的母亲寄生虫血症、教育程度和财富进行了调整：在多胎妊娠的婴儿中，从出生到 4 个月大，SP 与 DP 相比，LAZ 平均值增加了 0.18-0.28 Z，而从 2 个月到 8 个月大，DP 与 SP 相比，WLZ 平均值增加了 0.11-0.28 Z；在这些年龄段，平均值差异的置信区间不包括 0。SP的中介因素包括出生体重、出生身长、母体干细胞因子和DNER。DP的中介因素包括胎盘疟疾、出生时长、母体IL-18、CDCP1和CD6：在疟疾高度传播的环境中，这项探索性研究表明，在纯母乳喂养期间，当几乎没有其他干预措施可用时，不同的IPTp疗法可能会通过不同的途径影响多胎妊娠妇女的婴儿生长：斯坦福全球健康创新中心、尤妮斯-肯尼迪-施莱佛国家儿童健康与人类发展研究所、比尔及梅琳达-盖茨基金会。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.