Effect of pregnancy versus postpartum maternal isoniazid preventive therapy on infant growth in HIV-exposed uninfected infants: a post-hoc analysis of the TB APPRISE trial
Year: 2023
Type: article
Abstract: Background: IPT exposure on infant growth are unknown. Methods: This post-hoc analysis used data from the TB APPRISE trial, a multicentre, double-blind, placebo-controlled trial, which randomised women to 28-week IPT starting in pregnancy (pregnancy-IPT) or postpartum week 12 (postpartum-IPT) in eight countries with high tuberculosis prevalence. Participants were enrolled between August 2014 and April 2016. Based on modified intent-to-treat analyses, we analysed only live-born babies who had at least one follow-up after birth and compared time to infant growth faltering between arms to 12 weeks and 48 weeks postpartum in overall and sex-stratified multivariable Cox proportional hazards regression. Factors adjusted in the final models include sex of infant, mother's baseline BMI, age in years, ART regimen, viral load, CD4 count, education, and household food insecurity. Results: Among 898 HIV-exposed uninfected (HEU) infants, 447 (49.8%) were females. Infants in pregnancy-IPT had a 1.47-fold higher risk of becoming underweight by 12 weeks (aHR 1.47 [95% CI: 1.06, 2.03]) than infants in the postpartum-IPT; increased risk persisted to 48 weeks postpartum (aHR 1.34 [95% CI: 1.01, 1.78]). Maternal IPT timing was not associated with stunting or wasting. In sex-stratified analyses, male infants in the pregnancy-IPT arm experienced an increased risk of low birth weight (LBW) (aRR 2.04 [95% CI: 1.16, 3.68), preterm birth (aRR 1.81 [95% CI: 1.04, 3.21]) and becoming underweight by 12 weeks (aHR 2.02 [95% CI: 1.29, 3.18]) and 48 weeks (aHR 1.82 [95% CI: 1.23, 2.69]). Maternal IPT timing did not influence growth in female infants. Interpretation: Maternal IPT during pregnancy was associated with an increased risk of LBW, preterm birth, and becoming underweight among HEU infants, particularly male infants. These data add to prior TB APPRISE data, suggesting that IPT during pregnancy impacts infant growth, which could inform management, and warrants further examination of mechanisms. Funding: The TB APPRISE study Supported by the National Institutes of Health (NIH) (award numbers, UM1AI068632 [IMPAACT LOC], UM1AI068616 [IMPAACT SDMC], and UM1AI106716 [IMPAACT LC]) through the National Institute of Allergy and Infectious Diseases, with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract number, HHSN275201800001I) and the National Institute of Mental Health.
Source: EClinicalMedicine
Authors: Ashenafi S. Cherkos, Sylvia M. LaCourse, Daniel A. Enquobahrie, Barbra A. Richardson, Sarah Bradford, Grace Montepiedra, Blandina T. Mmbaga, Tapiwa Mbengeranwa, Gaerolwe Masheto, Patrick Jean–Phillippe, Nahida Chakhtoura, Gerhard Theron, Adriana Weinberg, Haseena Cassim, Mpho S. Raesi, Elsie Jean, Deo Wabwire, Teacler Nematadzira, Lynda Stranix-Chibanda, Anneke C. Hesseling, Linda Aurpibul, Amita Gupta, Grace John-Stewart, Timothy R. Sterling, Renee Browning, Katie McCarthy, Lisa Aaron, Katherine Shin, Amanda Golner, Bonnie Zimmer, Jyoti S. Mathad, Savita Pahwa, Vandana Kulkarni, Diane Costello, Vivian Rexroad, Monica Gandhi, Joan Du Plessis, Amy James Loftis
Institutions: University of North Texas Health Science Center, University of Washington, Family Health International 360, Harvard University, Kilimanjaro Christian Medical Centre, Kilimanjaro Clinical Research Institute, University of Zimbabwe, Botswana Harvard AIDS Institute Partnership, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Stellenbosch University, University of Colorado Anschutz, University of Colorado Denver, University of the Witwatersrand, Perinatal HIV Research Unit, Gheskio Centers, MUJHU Research Collaboration, Chiang Mai University, Johns Hopkins University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,000
Funders: International Maternal Pediatric Adolescent AIDS Clinical Trials Network, National Institutes of Health, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1220961632, G1781567339, G1857750563, Impact of maternal HIV on Mycobacterium tuberculosis infection among peripartum women and their infants, G3045663399, G3262353703, G32641939, G3342746445, G3373432187, G3665517470, G4064436708, The effect of HIV exposure and infection on immunity to TB in children, G4853082081, G4927240118, G5602729146, UZ-UCSF Clinical Trials Unit, G6571807012, G6585143688, G7502524018, G765734810, G803170016, G826259428, G8500352392, G8922259349, G9000030691, G9000153711, G9000155056, SDMC - IMPAACT Leadership Group, Botswana-Harvard T.H. Chan School of Public Health AIDS Initiative Partnership CTU, Thailand HIV/AIDS and Infectious Disease Clinical Trials Unit (THAI CTU)
OpenAlex ID: W4327831237