Cherkos Ashenafi S, LaCourse Sylvia M, Enquobahrie Daniel A, Escudero Jaclyn N, Mecha Jerphason, Matemo Daniel, Kinuthia John, John-Stewart Grace
Biostatistics and Epidemiology Department, School of Public Health, University of North Texas Health Science Center, Fort Worth, Texas, USA.
Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, USA.
medRxiv. 2023 Oct 20:2023.10.19.23297259. doi: 10.1101/2023.10.19.23297259.
Isoniazid preventive therapy (IPT) decreases risk of tuberculosis (TB) disease; impact on long-term infant growth is unknown. In a recent randomized trial (RCT), we assessed IPT effects on infant growth without known TB exposure.
The infant TB Infection Prevention Study (iTIPS) trial was a non-blinded RCT among HIV-exposed uninfected (HEU) infants in Kenya. Inclusion criteria included age 6-10 weeks, birthweight ≥2.5 kg, and gestation ≥37 weeks. Infants in the IPT arm received 10 mg/kg isoniazid daily for 12 months, while the control trial received no intervention; post-trial observational follow-up continued through 24 months of age. We used intent-to-treat linear mixed-effects models to compare growth rates (weight-for-age z-score [WAZ] and height-for-age z-score [HAZ]) between trial arms.
Among 298 infants, 150 were randomized to IPT, 47.6% were females, median birthweight was 3.4 kg (interquartile range [IQR] 3.0-3.7), and 98.3% were breastfed. During the 12-month intervention period and 12-month post-RCT follow-up, WAZ and HAZ declined significantly in all children, with more HAZ decline in male infants. There were no growth differences between trial arms, including in sex-stratified analyses. In longitudinal linear analysis, mean WAZ (β=0.04 [95% CI:-0.14, 0.22]), HAZ (β=0.14 [95% CI:-0.06, 0.34]), and WHZ [β=-0.07 [95% CI: -0.26, 0.11]) z-scores were similar between arms as were WAZ and HAZ growth trajectories. Infants randomized to IPT had higher monthly WHZ increase (β to 24 months 0.02 [95% CI:0.01, 0.04]) than the no-IPT arm.
IPT administered to HEU infants did not significantly impact growth outcomes in the first two years of life.
异烟肼预防性治疗（IPT）可降低结核病（TB）发病风险；其对婴儿长期生长的影响尚不清楚。在最近一项随机试验（RCT）中，我们评估了IPT对未接触已知TB的婴儿生长的影响。
婴儿结核病感染预防研究（iTIPS）试验是在肯尼亚对未感染艾滋病毒（HEU）的婴儿进行的一项非盲法随机对照试验。纳入标准包括年龄6 - 10周、出生体重≥2.5千克和孕周≥37周。IPT组婴儿每天接受10毫克/千克异烟肼治疗，持续12个月，而对照组不进行干预；试验后观察性随访持续至24个月龄。我们使用意向性分析线性混合效应模型比较试验组之间的生长速率（年龄别体重z评分[WAZ]和年龄别身高z评分[HAZ]）。
在298名婴儿中，150名被随机分配到IPT组，47.6%为女性，出生体重中位数为3.4千克（四分位间距[IQR] 3.0 - 3.7），98.3%为母乳喂养。在12个月的干预期和随机对照试验后12个月的随访期间，所有儿童的WAZ和HAZ均显著下降，男婴的HAZ下降更多。试验组之间在生长方面没有差异，包括在按性别分层的分析中。在纵向线性分析中，平均WAZ（β = 0.04 [95% CI：-0.14, 0.22]）、HAZ（β = 0.14 [95% CI：-0.06, 0.34]）和WHZ [β = -0.07 [95% CI：-0.26, 0.11]] z评分在两组之间相似，WAZ和HAZ的生长轨迹也相似。随机分配到IPT组的婴儿每月WHZ增加幅度（至24个月龄的β为0.02 [95% CI：0.01, 0.04]）高于未接受IPT组。
对HEU婴儿给予IPT在生命的头两年对生长结果没有显著影响。
