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

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

doi:10.1016/j.ebiom.2024.105397

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

EBioMedicine. 2024 Oct 16:109:105397. doi: 10.1016/j.ebiom.2024.105397. Online ahead of print.

Authors

Yanwei Tong¹, Kalani Ratnasiri², Suhi Hanif³, Anna T Nguyen³, Michelle E Roh⁴, Grant Dorsey⁵, Abel Kakuru⁶, Prasanna Jagannathan⁷, Jade Benjamin-Chung⁸

Affiliations

¹ Department of Statistics, Stanford University, Stanford, United States.
² Department of Epidemiology and Population Health, Stanford University, Stanford, United States; Department of Microbiology and Immunology, Stanford University, Stanford, United States.
³ Department of Epidemiology and Population Health, Stanford University, Stanford, United States.
⁴ Institute for Global Health Sciences, University of California San Francisco, San Francisco, United States; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, United States.
⁵ Department of Medicine, Division of HIV, ID, and Global Medicine, University of California San Francisco, San Francisco, United States.
⁶ Infectious Diseases Research Collaboration, Kampala, Uganda.
⁷ Department of Medicine, Stanford University, Stanford, United States.
⁸ Department of Epidemiology and Population Health, Stanford University, Stanford, United States; Chan Zuckerberg Biohub, San Francisco, United States. Electronic address: [email protected].

PMID: 39418986
DOI: 10.1016/j.ebiom.2024.105397

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.

Keywords: Child growth; Intermittent preventive treatment; Malaria; Mediation.