Cherkos Ashenafi S, LaCourse Sylvia M, Enquobahrie Daniel A, Richardson Barbra A, Bradford Sarah, Montepiedra Grace, Mmbaga Blandina T, Mbengeranwa Tapiwa, Masheto Gaerolwe, Jean-Phillippe Patrick, Chakhtoura Nahida, Theron Gerhard, Weinberg Adriana, Cassim Haseena, Raesi Mpho S, Jean Elsie, Wabwire Deo, Nematadzira Teacler, Stranix-Chibanda Lynda, Hesseling Anneke C, Aurpibul Linda, Gupta Amita, John-Stewart Grace
Biostatistics and Epidemiology Department, School of Public Health, University of North Texas Health Science Center, Fort Worth, TX, USA.
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
EClinicalMedicine. 2023 Mar 17;58:101912. doi: 10.1016/j.eclinm.2023.101912. eCollection 2023 Apr.
Isoniazid preventive therapy (IPT) initiation during pregnancy was associated with increased incidence of adverse pregnancy outcomes in the TB APPRISE trial. Effects of IPT exposure on infant growth are unknown.
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.
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.
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.
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.
在TB APPRISE试验中，孕期开始异烟肼预防性治疗（IPT）与不良妊娠结局发生率增加有关。IPT暴露对婴儿生长的影响尚不清楚。
这项事后分析使用了TB APPRISE试验的数据，这是一项多中心、双盲、安慰剂对照试验，在八个结核病高流行国家将女性随机分为从孕期开始的28周IPT（孕期IPT）或产后第12周（产后IPT）。参与者于2014年8月至2016年4月入组。基于改良意向性分析，我们仅分析了出生后至少有一次随访的活产婴儿，并在总体和按性别分层的多变量Cox比例风险回归中比较了两组至产后12周和48周婴儿生长发育迟缓的时间。最终模型中调整的因素包括婴儿性别、母亲的基线BMI、年龄、抗逆转录病毒治疗方案、病毒载量、CD4细胞计数、教育程度和家庭粮食不安全状况。
在898名暴露于HIV但未感染（HEU）的婴儿中，447名（49.8%）为女性。孕期IPT组的婴儿在12周时体重不足的风险比产后IPT组的婴儿高1.47倍（调整后风险比1.47 [95%置信区间：1.06, 2.03]）；产后48周时风险仍然增加（调整后风险比1.34 [95%置信区间：1.01, 1.78]）。母亲IPT时间与发育迟缓或消瘦无关。在按性别分层的分析中，孕期IPT组的男婴出生体重低（LBW）风险增加（调整后相对风险2.04 [95%置信区间：1.16, 3.68]）、早产风险增加（调整后相对风险1.81 [95%置信区间：1.04, 3.21]）以及在12周（调整后风险比2.02 [95%置信区间：1.29, 3.18]）和48周（调整后风险比1.82 [95%置信区间：1.23, 2.69]）时体重不足风险增加。母亲IPT时间不影响女婴的生长。
孕期母亲接受IPT与HEU婴儿，尤其是男婴出生体重低、早产和体重不足风险增加有关。这些数据补充了之前的TB APPRISE数据，表明孕期IPT会影响婴儿生长，这可为管理提供参考，并值得进一步研究其机制。
TB APPRISE研究由美国国立卫生研究院（NIH）（资助编号，UM1AI068632 [IMPAACT LOC]、UM1AI068616 [IMPAACT SDMC]和UM1AI106716 [IMPAACT LC]）通过国家过敏和传染病研究所资助，同时由尤妮斯·肯尼迪·施莱佛国家儿童健康与人类发展研究所（合同编号，HHSN275201800001I）和国家心理健康研究所共同资助。
