SEARCHRCTobstetrics and gynecology, pediatrics

RCT·obstetrics and gynecology, pediatrics, infectious disease, epidemiology, clinical trial·PMC10031034

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

eClinicalMedicine · 23 authors, 24 centres

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TL;DR

The study found that starting IPT during pregnancy was associated with a higher risk of infants becoming underweight, especially in male infants.

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This study is a post-hoc analysis of the TB APPRISE trial, a multicentre, double-blind, placebo-controlled RCT that randomized HIV-positive women to 28-week IPT starting in pregnancy or postpartum week 12. The analysis included 898 HIV-exposed uninfected infants and compared growth faltering to 12 and 48 weeks postpartum using multivariable Cox regression. The central finding was that infants in the pregnancy-IPT arm had a 1.47-fold higher risk of becoming underweight by 12 weeks (aHR 1.47) and a 1.34-fold higher risk by 48 weeks (aHR 1.34) compared to infants in the postpartum-IPT arm. Maternal IPT timing was not associated with stunting or wasting. Limitations include the post-hoc design and the lack of a no-IPT comparator after 12 weeks. The findings suggest that in utero IPT exposure may have sex-differential negative effects on infant growth.

STUDY TYPE

RCT

SPECIALTY

obstetrics and gynecology

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AI pipeline

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100% · A

ORIGINAL PAPER

PMC10031034

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

eClinicalMedicine

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ABSTRACT

Summary Background Isoniazid preventive therapy (IPT) initiation during pregnancy was associated with increased incidence of adverse pregnancy outcomes in the TB APPRISE trial. Effects of in utero 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. Keywords: Pregnancy isoniazid, HEU growth, In utero IPT and growth, IPT and Adverse birth effects Abbreviations: IPT, Isoniazid preventive therapy; LBW, Low birth weight; SGA, Small for gestational age; WAZ, Weight-for-age z-score; WLZ, Weight-for-length z-score; LAZ, Length-for-age z-score; WLWH, Women living with HIV; HEU, HIV-exposed uninfected

CITATION EXPORT

Ashenafi S Cherkos, Sylvia M LaCourse, Daniel A Enquobahrie et al.. 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. eClinicalMedicine. (2023). https://doi.org/10.1016/j.eclinm.2023.101912

AUTHORS

23 · 24 CENTRES

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

aBiostatistics and Epidemiology Department, School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, USA
bDepartment of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA
cDepartment of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA
dDepartment of Global Health, School of Public Health, University of Washington, Seattle, WA, USA
eDepartment of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA
fFHI 360, Durham, NC, USA
gCenter for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA
hDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
iKilimanjaro Clinical Research Institute -Kilimanjaro Christian Medical Centre and Kilimanjaro Christian Medical University College, Moshi, Tanzania
jUniversity of Zimbabwe College of Health Sciences-Clinical Trials Research Centre, Harare, Zimbabwe
kBotswana Harvard AIDS Institute Partnership, Gaborone, Botswana
lNational Institute of Allergy and Infectious Diseases, Bethesda, MD, USA
mNIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD, Bethesda, MD, USA
nDepartment of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
oDepartments of Pediatrics, Medicine and Pathology, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, CO, USA
pPerinatal HIV Research Unit, University of the Witwatersrand, South Africa
qDepartment of Pediatrics, GHESKIO Centers, Port-au-Prince, Haiti
rMakerere University – Johns Hopkins University Research Collaboration, Kampala, Uganda
sUniversity of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe
tDepartment of Paediatrics and Child Health, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe
uDesmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, South Africa
vResearch Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand
wJohns Hopkins University, School of Medicine, Baltimore, MD, USA
xDepartment of Pediatrics, University of Washington, Seattle, WA, USA