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Abstract：
According to global prevalence analysis studies, acute upper respiratory tract infections (URTIs) are the most common acute infectious disease in children, especially in preschool children. Acute URTIs lead to an economic burden on families and society. Vitamin A refers to the fat-soluble compound all-trans-retinol and also represents retinol and its active metabolites. Vitamin A interacts with both the innate immune system and the adaptive immune system and improves the host\'s defences against infections. Correlation studies show that serum retinol deficiency was associated with a higher risk of respiratory tract infections. Therefore, vitamin A supplementation may be important in preventing acute URTIs.
To assess the effectiveness and safety of vitamin A supplements for preventing acute upper respiratory tract infections in children up to seven years of age.
We searched CENTRAL, MEDLINE, Embase, the Chinese Biomedical Literature Database, and two trial registration platforms to 8 June 2023. We also checked the reference lists of all primary studies and reviewed relevant systematic reviews and trials for additional references. We imposed no language or publication restrictions.
We included randomised controlled trials (RCTs), which evaluated the role of vitamin A supplementation in the prevention of acute URTIs in children up to seven years of age.
We used the standard methodological procedures expected by Cochrane.
We included six studies (27,351 participants). Four studies were RCTs and two were cluster-RCTs. The included studies were all conducted in lower-middle-income countries (two in India, two in South Africa, one in Ecuador, and one in Haiti). Three studies included healthy children who had no vitamin A deficiency, one study included children born to HIV-infected women, one study included low-birthweight neonates, and one study included children in areas with a high local prevalence of malnutrition and xerophthalmia. In two studies, vitamin E was a co-treatment administered in addition to vitamin A. We judged the included studies to be at either a high or unclear risk of bias for random sequence generation, incomplete outcome data, and blinding. Primary outcomes Six studies reported the incidence of acute URTIs during the study period. Five studies reported the number of acute URTIs over a period of time, but there was population heterogeneity and the results were presented in different forms, therefore only three studies were meta-analysed. We are uncertain of the effect of vitamin A supplementation on the number of acute URTIs over two weeks (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.92 to 1.09; I2 = 44%; 3 studies, 22,668 participants; low-certainty evidence). Two studies reported the proportion of participants with an acute URTI. We are uncertain of the effect of vitamin A supplementation on the proportion of participants with an acute URTI (2 studies, 15,535 participants; low-certainty evidence). Only one study (116 participants) reported adverse events. No infant in either the placebo or vitamin A group was found to have feeding difficulties (failure to feed or vomiting), a bulging fontanelle, or neurological signs before or after vitamin A administration (very low-certainty evidence). Secondary outcomes Two studies (296 participants) reported the severity of subjective symptoms, presented by the mean duration of acute URTI. Vitamin A may have little to no effect on the mean duration of acute URTI (very low-certainty evidence).
The evidence for the use of vitamin A supplementation to prevent acute URTI is uncertain, because population, dose and duration of interventions, and outcomes vary between studies. From generally very low- to low-certainty evidence, we found that there may be no benefit in the use of vitamin A supplementation to prevent acute URTI in children up to seven years of age. More RCTs are needed to strengthen the current evidence. Future research should report over longer time frames using validated tools and consistent reporting, and ensure adequate power calculations, to allow for easier synthesis of data. Finally, it is important to assess vitamin A supplementation for preschool children with vitamin A deficiency.
To assess the effectiveness and safety of vitamin A supplements for preventing acute upper respiratory tract infections in children up to seven years of age.
We searched CENTRAL, MEDLINE, Embase, the Chinese Biomedical Literature Database, and two trial registration platforms to 8 June 2023. We also checked the reference lists of all primary studies and reviewed relevant systematic reviews and trials for additional references. We imposed no language or publication restrictions.
We included randomised controlled trials (RCTs), which evaluated the role of vitamin A supplementation in the prevention of acute URTIs in children up to seven years of age.
We used the standard methodological procedures expected by Cochrane.
We included six studies (27,351 participants). Four studies were RCTs and two were cluster-RCTs. The included studies were all conducted in lower-middle-income countries (two in India, two in South Africa, one in Ecuador, and one in Haiti). Three studies included healthy children who had no vitamin A deficiency, one study included children born to HIV-infected women, one study included low-birthweight neonates, and one study included children in areas with a high local prevalence of malnutrition and xerophthalmia. In two studies, vitamin E was a co-treatment administered in addition to vitamin A. We judged the included studies to be at either a high or unclear risk of bias for random sequence generation, incomplete outcome data, and blinding. Primary outcomes Six studies reported the incidence of acute URTIs during the study period. Five studies reported the number of acute URTIs over a period of time, but there was population heterogeneity and the results were presented in different forms, therefore only three studies were meta-analysed. We are uncertain of the effect of vitamin A supplementation on the number of acute URTIs over two weeks (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.92 to 1.09; I2 = 44%; 3 studies, 22,668 participants; low-certainty evidence). Two studies reported the proportion of participants with an acute URTI. We are uncertain of the effect of vitamin A supplementation on the proportion of participants with an acute URTI (2 studies, 15,535 participants; low-certainty evidence). Only one study (116 participants) reported adverse events. No infant in either the placebo or vitamin A group was found to have feeding difficulties (failure to feed or vomiting), a bulging fontanelle, or neurological signs before or after vitamin A administration (very low-certainty evidence). Secondary outcomes Two studies (296 participants) reported the severity of subjective symptoms, presented by the mean duration of acute URTI. Vitamin A may have little to no effect on the mean duration of acute URTI (very low-certainty evidence).
The evidence for the use of vitamin A supplementation to prevent acute URTI is uncertain, because population, dose and duration of interventions, and outcomes vary between studies. From generally very low- to low-certainty evidence, we found that there may be no benefit in the use of vitamin A supplementation to prevent acute URTI in children up to seven years of age. More RCTs are needed to strengthen the current evidence. Future research should report over longer time frames using validated tools and consistent reporting, and ensure adequate power calculations, to allow for easier synthesis of data. Finally, it is important to assess vitamin A supplementation for preschool children with vitamin A deficiency.
摘要：
背景：根据全球患病率分析研究，急性上呼吸道感染(URTIs)是儿童最常见的急性感染性疾病,尤其是学龄前儿童。急性URTIs导致家庭和社会的经济负担。维生素A是指脂溶性化合物全反式视黄醇,也代表视黄醇及其活性代谢物。维生素A与先天免疫系统和适应性免疫系统相互作用，并改善宿主对感染的防御能力。相关研究表明，血清视黄醇缺乏与呼吸道感染的高风险相关。因此,补充维生素A对预防急性URTIs可能很重要.
目的：评估维生素A补充剂预防7岁以下儿童急性上呼吸道感染的有效性和安全性。
方法：我们搜索了CENTRAL，MEDLINE,Embase,中国生物医学文献数据库,和两个试用注册平台至2023年6月8日。我们还检查了所有主要研究的参考列表，并回顾了相关的系统评价和试验以获得更多参考。我们没有语言或出版物限制。
方法：我们纳入了随机对照试验（RCT），评估了补充维生素A在预防7岁以下儿童急性URTIs中的作用。
方法：我们使用了Cochrane预期的标准方法学程序。
结果：我们纳入了6项研究（27,351名参与者）。四项研究为随机对照试验，两项为簇状随机对照试验。纳入的研究都是在中低收入国家进行的(印度有两项，两个在南非，一个在厄瓜多尔，和一个在海地）。三项研究包括没有维生素A缺乏的健康儿童，一项研究包括感染艾滋病毒的妇女所生的孩子，一项研究包括低出生体重的新生儿，一项研究纳入了当地营养不良和干眼症患病率高的地区的儿童。在两项研究中，维生素E是除维生素A外的联合治疗。我们判断纳入的研究具有高或不清楚的随机序列生成偏倚风险，不完整的结果数据，和致盲。主要结果6项研究报告了研究期间急性URTI的发生率。五项研究报告了一段时间内急性URTI的数量，但是存在种群异质性，结果以不同的形式呈现，因此,只有三项研究进行了荟萃分析.我们不确定补充维生素A对两周内急性URTIs数量的影响（风险比（RR）1.00，95％置信区间（CI）0.92至1.09；I2=44％；3项研究，22,668名参与者；低确定性证据)。两项研究报告了急性URTI参与者的比例。我们不确定补充维生素A对急性URTI参与者比例的影响（2项研究，15535名参与者；低确定性证据)。只有一项研究（116名参与者）报告了不良事件。安慰剂组或维生素A组的婴儿均未发现喂养困难（无法进食或呕吐），鼓鼓的fontanelle，或维生素A给药之前或之后的神经系统症状（非常低的确定性证据）。次要结果两项研究（296名参与者）报告了主观症状的严重程度，以急性URTI的平均持续时间表示。维生素A可能对急性URTI的平均持续时间几乎没有影响（非常低的确定性证据）。
结论：使用补充维生素A预防急性URTI的证据尚不确定，因为人口，干预的剂量和持续时间，和结果不同的研究。从通常非常低到低确定性的证据，我们发现,对于7岁以下的儿童,使用维生素A补充剂预防急性URTI可能没有益处.需要更多的RCT来加强当前的证据。未来的研究应该使用经过验证的工具和一致的报告在更长的时间范围内进行报告，并确保足够的功率计算，以便更容易地合成数据。最后,评估维生素A缺乏学龄前儿童的维生素A补充情况非常重要.
目的：评估维生素A补充剂预防7岁以下儿童急性上呼吸道感染的有效性和安全性。
方法：我们搜索了CENTRAL，MEDLINE,Embase,中国生物医学文献数据库,和两个试用注册平台至2023年6月8日。我们还检查了所有主要研究的参考列表，并回顾了相关的系统评价和试验以获得更多参考。我们没有语言或出版物限制。
方法：我们纳入了随机对照试验（RCT），评估了补充维生素A在预防7岁以下儿童急性URTIs中的作用。
方法：我们使用了Cochrane预期的标准方法学程序。
结果：我们纳入了6项研究（27,351名参与者）。四项研究为随机对照试验，两项为簇状随机对照试验。纳入的研究都是在中低收入国家进行的(印度有两项，两个在南非，一个在厄瓜多尔，和一个在海地）。三项研究包括没有维生素A缺乏的健康儿童，一项研究包括感染艾滋病毒的妇女所生的孩子，一项研究包括低出生体重的新生儿，一项研究纳入了当地营养不良和干眼症患病率高的地区的儿童。在两项研究中，维生素E是除维生素A外的联合治疗。我们判断纳入的研究具有高或不清楚的随机序列生成偏倚风险，不完整的结果数据，和致盲。主要结果6项研究报告了研究期间急性URTI的发生率。五项研究报告了一段时间内急性URTI的数量，但是存在种群异质性，结果以不同的形式呈现，因此,只有三项研究进行了荟萃分析.我们不确定补充维生素A对两周内急性URTIs数量的影响（风险比（RR）1.00，95％置信区间（CI）0.92至1.09；I2=44％；3项研究，22,668名参与者；低确定性证据)。两项研究报告了急性URTI参与者的比例。我们不确定补充维生素A对急性URTI参与者比例的影响（2项研究，15535名参与者；低确定性证据)。只有一项研究（116名参与者）报告了不良事件。安慰剂组或维生素A组的婴儿均未发现喂养困难（无法进食或呕吐），鼓鼓的fontanelle，或维生素A给药之前或之后的神经系统症状（非常低的确定性证据）。次要结果两项研究（296名参与者）报告了主观症状的严重程度，以急性URTI的平均持续时间表示。维生素A可能对急性URTI的平均持续时间几乎没有影响（非常低的确定性证据）。
结论：使用补充维生素A预防急性URTI的证据尚不确定，因为人口，干预的剂量和持续时间，和结果不同的研究。从通常非常低到低确定性的证据，我们发现,对于7岁以下的儿童,使用维生素A补充剂预防急性URTI可能没有益处.需要更多的RCT来加强当前的证据。未来的研究应该使用经过验证的工具和一致的报告在更长的时间范围内进行报告，并确保足够的功率计算，以便更容易地合成数据。最后,评估维生素A缺乏学龄前儿童的维生素A补充情况非常重要.
