Carter Center, Niamey, Niger.
Centre de Recherche et Interventions en Santé Publique, Birni N'Gaoure, Niger.
JAMA Netw Open. 2021 Dec 1;4(12):e2139351. doi: 10.1001/jamanetworkopen.2021.39351.
Mass azithromycin distributions may decrease childhood mortality, although the causal pathway is unclear. The potential for antibiotics to function as growth promoters may explain some of the mortality benefit.
To investigate whether biannual mass azithromycin distributions are associated with increased childhood growth.
DESIGN, SETTING, AND PARTICIPANTS: This cluster-randomized trial was performed from December 2014 until March 2020 among 30 rural communities in Boboye and Loga departments in Niger, Africa, with populations from 200 to 2000 individuals. Communities were randomized in a 1:1 ratio to biannual mass distributions of azithromycin or placebo for children ages 1 to 59 months. Participants, field-workers, and study personnel were masked to treatment allocation. Height and weight changes from baseline to follow-up at 4 years were compared between groups. Data were analyzed from June through November 2021.
Participants received azithromycin at 20 mg/kg using height-based approximation or by weight for children unable to stand every 6 months at the participants' households. Placebo contained the vehicle of the azithromycin suspension.
Longitudinal anthropometric assessments were performed on a random sample of children before the first treatment and then annually for 5 years. Height and weight were the prespecified primary outcomes.
Among 3936 children enrolled from 30 communities, baseline characteristics were similar between 1299 children in the azithromycin group and 2637 children in the placebo group (mean 48.2% [95% CI, 45.5% to 50.8%] girls vs 48.0% [95% CI, 45.7% to 50.3%] girls; mean age, 30.8 months [95% CI, 29.5 to 32.0 months] vs 30.6 months [95% CI, 29.2 to 31.6 months]). Baseline anthropometric assessments were performed among 2230 children, including 985 children in the azithromycin group and 1245 children in the placebo group, of whom follow-up measurements were available for 789 children (80.1%) and 1063 children (85.4%), respectively. At the prespecified 4-year follow-up visit, children in the azithromycin group gained a mean 6.7 cm (95% CI, 6.5 to 6.8 cm) in height and 1.7 kg (95% CI, 1.7 to 1.8 kg) in weight per year and children in the placebo group gained a mean 6.6 cm (95% CI, 6.4 to 6.7 cm) in height and 1.7 kg (95% CI, 1.7 to 1.8 kg) in weight per year. Height at 4 years was not statistically significantly different between groups when adjusted for baseline height (0.08 cm [95% CI, -0.12 to 0.28 cm] greater in the azithromycin group; P = .45), and neither was weight when adjusted for height and baseline weight (0.02 kg [95% CI, -0.10 to 0.06 kg] less in the azithromycin group; P = .64). However, among children in the shortest quartile of baseline height, azithromycin was associated with a 0.4 cm (95% CI, 0.1 to 0.7 cm) increase in height compared with placebo.
This study did not find evidence of an association between mass azithromycin distributions and childhood growth, although subgroup analysis suggested some benefit for the shortest children. These findings suggest that the mortality benefit of mass azithromycin distributions is unlikely to be due solely to growth promotion.
ClinicalTrials.gov Identifier: NCT02048007.
大规模阿奇霉素分发可能会降低儿童死亡率，尽管因果关系尚不清楚。抗生素作为生长促进剂的潜在作用可能解释了一些死亡率获益的原因。
调查每半年为 1 至 59 个月的儿童进行两次大规模阿奇霉素分发是否与儿童生长增加有关。
设计、地点和参与者：本项集群随机试验于 2014 年 12 月至 2020 年 3 月在非洲尼日尔的博约耶和洛加地区的 30 个农村社区进行，社区人口从 200 人到 2000 人不等。社区按 1:1 的比例随机分为两组，一组接受每半年一次的阿奇霉素或安慰剂的大规模分发，一组接受阿奇霉素或安慰剂的大规模分发。参与者、现场工作人员和研究人员对治疗分配情况进行了掩蔽。比较两组在 4 年随访时的身高和体重变化。数据分析于 2021 年 6 月至 11 月进行。
参与者每 6 个月在家中按身高（身高为 20mg/kg）或体重（无法站立的儿童）使用阿奇霉素进行治疗。安慰剂含有阿奇霉素混悬剂的载体。
在第一次治疗前，对 30 个社区中的 3936 名儿童进行了随机抽样的纵向人体测量评估，然后每年进行 5 年的随访。身高和体重是预先设定的主要结果。
在从 30 个社区招募的 3936 名儿童中，阿奇霉素组的 1299 名儿童和安慰剂组的 2637 名儿童的基线特征相似（平均 48.2%[95%置信区间，45.5%至 50.8%]为女孩，vs 48.0%[95%置信区间，45.7%至 50.3%]为女孩；平均年龄为 30.8 个月[95%置信区间，29.5 至 32.0 个月]，vs 30.6 个月[95%置信区间，29.2 至 31.6 个月]）。在基线人体测量评估中，包括阿奇霉素组的 985 名儿童和安慰剂组的 1245 名儿童，其中有 789 名儿童（80.1%）和 1063 名儿童（85.4%）可获得随访测量。在规定的 4 年随访时，阿奇霉素组儿童每年身高增长 6.7 厘米（95%置信区间，6.5 至 6.8 厘米），体重增加 1.7 公斤（95%置信区间，1.7 至 1.8 公斤），而安慰剂组儿童每年身高增长 6.6 厘米（95%置信区间，6.4 至 6.7 厘米），体重增加 1.7 公斤（95%置信区间，1.7 至 1.8 公斤）。身高在经过基线身高调整后，两组之间没有统计学上的显著差异（阿奇霉素组高 0.08 厘米[95%置信区间，-0.12 至 0.28 厘米]；P=0.45），体重在经过身高和基线体重调整后也没有统计学上的显著差异（阿奇霉素组少 0.02 公斤[95%置信区间，-0.10 至 0.06 公斤]；P=0.64）。然而，在基线身高处于最短四分位数的儿童中，与安慰剂相比，阿奇霉素组的身高增加了 0.4 厘米（95%置信区间，0.1 至 0.7 厘米）。
本研究没有发现大规模阿奇霉素分发与儿童生长之间存在关联的证据，尽管亚组分析表明最短的儿童可能有一些益处。这些发现表明，大规模阿奇霉素分发的死亡率获益不太可能仅仅是由于生长促进。
ClinicalTrials.gov 标识符：NCT02048007。
