Saleem Javeria, Zakar Rubeena, Butt Muhammad Salman, Kaleem Rameeza, Chaudhary Asif, Chandna Jaya, Jolliffe David A, Piper Joseph, Abbas Zaigham, Tang Jonathan C Y, Fraser William D, Freemantle Nick, Prendergast Andrew J, Martineau Adrian R
Department of Public Health, University of the Punjab, Lahore, Punjab, Pakistan.
Institute of Nursing and Health Research, Ulster University, Belfast, UK.
Nat Commun. 2025 Mar 15;16(1):2554. doi: 10.1038/s41467-025-57803-9.
We have previously shown that high-dose vitamin D improved weight gain and neurodevelopmental indices in children receiving standard therapy for uncomplicated severe acute malnutrition (SAM). Here we present results of a randomised placebo-controlled trial in Lahore, Pakistan, to determine whether two oral doses of 200,000 international units (IU) vitamin D (the first administered on or before the day of hospital discharge and the second administered 14 days later) would benefit children aged 6-59 months during the convalescent phase of complicated SAM. Eligible participants were individually randomised to intervention vs. control arms with a one-to-one allocation ratio and stratification by hospital of recruitment using computer-generated random sequences. Double-blinding to treatment allocation was maintained by concealing allocation from participants' parents or guardians, their medical care providers, and all trial staff. The primary outcome was mean weight-for-height or -length z-score (WHZ) at 2-month follow-up. Secondary efficacy outcomes included mean WHZ at 6-month follow-up and mean lean mass index, Malawi Development Assessment Tool (MDAT) scores and serum 25-hydroxyvitamin D (25[OH]D) concentrations at 2- and 6-month follow-up. The trial has now completed. 259 children were randomised (128 to vitamin D, 131 to placebo), of whom 251 (96.9%) contributed data to analysis of the primary outcome (123 allocated to vitamin D, 128 to placebo). At 2-month follow-up, participants allocated to vitamin D had significantly higher mean serum 25(OH)D concentrations than those allocated to placebo (adjusted mean difference [aMD] 100.0 nmol/L, 95% confidence interval [CI] 72.2-127.8 nmol/L). This was not associated with an inter-arm difference in mean WHZ at 2-month follow-up (aMD 0.02, 95% CI -0.20 to 0.23), or in any anthropometric or neurodevelopmental secondary outcome assessed at 2- or 6-month follow-up. The intervention was safe. In conclusion, high-dose vitamin D elevated mean serum 25(OH)D concentrations in children receiving standard therapy for complicated SAM in Pakistan, but did not influence any anthropometric or neurodevelopmental outcome studied. The trial was registered at ClinicalTrials.gov with the identifier NCT04270643.
我们之前已经表明，高剂量维生素D可改善接受单纯性重度急性营养不良（SAM）标准治疗的儿童的体重增加和神经发育指标。在此，我们展示了在巴基斯坦拉合尔进行的一项随机安慰剂对照试验的结果，以确定两次口服200,000国际单位（IU）维生素D（第一次在出院当天或之前给药，第二次在14天后给药）是否会使6至59个月大的复杂SAM恢复期儿童受益。符合条件的参与者通过计算机生成的随机序列以一对一的分配比例和招募医院分层，被随机分配到干预组和对照组。通过对参与者的父母或监护人、他们的医疗服务提供者以及所有试验工作人员隐瞒分配情况，维持对治疗分配的双盲。主要结局是2个月随访时的平均身高别体重或身长Z评分（WHZ）。次要疗效结局包括6个月随访时的平均WHZ以及2个月和6个月随访时的平均瘦体重指数、马拉维发育评估工具（MDAT）评分和血清25-羟基维生素D（25[OH]D）浓度。该试验现已完成。259名儿童被随机分组（128名接受维生素D，131名接受安慰剂），其中251名（96.9%）为主要结局分析提供了数据（123名被分配接受维生素D，128名接受安慰剂）。在2个月随访时，分配接受维生素D的参与者的平均血清25(OH)D浓度显著高于分配接受安慰剂的参与者（调整后平均差异[aMD] 100.0 nmol/L，95%置信区间[CI] 72.2 - 127.8 nmol/L）。这与2个月随访时组间平均WHZ的差异无关（aMD 0.02，95% CI -0.20至0.23），也与2个月或6个月随访时评估的任何人体测量或神经发育次要结局无关。该干预措施是安全的。总之，高剂量维生素D提高了在巴基斯坦接受复杂SAM标准治疗的儿童的平均血清25(OH)D浓度，但并未影响所研究的任何人体测量或神经发育结局。该试验已在ClinicalTrials.gov注册，标识符为NCT04270643。
