Lancet. 1998 Oct 17;352(9136):1257-63.
The benefits and safety of vitamin A supplementation linked to immunisation in infancy need to be assessed before it can be widely recommended. We assessed the safety and benefits of maternal postpartum and infant vitamin A supplementation administered with each of the three diphtheria-tetanus-pertussis (DPT) and poliomyelitis immunisations and with a fourth dose with measles immunisation.
From January, 1995, we enrolled 9424 mother-infant pairs from Ghana, India, and Peru in this randomised, double-blind, placebo-controlled trial. 4716 mothers of infants in the vitamin A group received 200000 IU vitamin A, and their infants were given 25000 IU vitamin A with each of the first three doses of DPT/poliomyelitis immunisation at 6, 10, and 14 weeks. In the control group, 4708 mothers and their infants received placebo at the same times. At 9 months, with measles immunisation, infants in the vitamin A group were given a further dose of 25000 IU and those in the control group received 100000 IU vitamin A. Infants were followed up to age 12 months. The primary outcome measures were vitamin A status, signs of acute toxic effects, anthropometric indicators, and severe morbidity. Analysis was by intention to treat.
3933 (93%) of the eligible 4212 infants on vitamin A and 3938 (93%) of the eligible 4227 controls received all four study doses. At the 6-month follow-up, there was a small decrease in vitamin A deficiency in the vitamin A group compared with controls (serum retinol < or =0.70 micromol/L 101 [29.9%] vs 122 [37.1%; 95% CI of the difference -14.3% to -0.2%]). This effect was no longer apparent at 9 and 12 months. There were no significant between-group differences in mortality throughout the study. The rate ratio to compare all deaths up to age 9 months in the two groups was 0.96 (95% CI 0.73 to 1.27). Fewer than 1% of the infants had bulging fontanelle. The intervention had no effect on anthropometric status, or on overall or severe morbidity.
The trial confirmed the safety of the intervention, but shows no sustained benefits in terms of vitamin A status beyond age 6 months or infant morbidity.
在能够广泛推荐婴儿期与免疫接种相关的维生素A补充剂之前，需要评估其益处和安全性。我们评估了产妇产后及婴儿补充维生素A与三种白喉-破伤风-百日咳（DPT）和脊髓灰质炎疫苗接种以及第四剂麻疹疫苗接种联合使用时的安全性和益处。
从1995年1月起，我们在这项随机、双盲、安慰剂对照试验中纳入了来自加纳、印度和秘鲁的9424对母婴。维生素A组中4716名婴儿的母亲接受200000国际单位维生素A，其婴儿在6周、10周和14周时，在前三次DPT/脊髓灰质炎疫苗接种时各给予25000国际单位维生素A。在对照组中，4708名母亲及其婴儿在相同时间接受安慰剂。在9个月时进行麻疹疫苗接种，维生素A组的婴儿再给予25000国际单位，对照组的婴儿接受100000国际单位维生素A。对婴儿随访至12个月龄。主要结局指标为维生素A状态、急性毒性作用体征、人体测量指标和严重发病率。分析采用意向性分析。
维生素A组4212名符合条件的婴儿中有3933名（93%），对照组4227名符合条件的婴儿中有3938名（93%）接受了全部四剂研究药物。在6个月随访时，与对照组相比，维生素A组维生素A缺乏症略有下降（血清视黄醇≤0.70微摩尔/升，分别为101例[29.9%]和122例[37.1%]；差异的95%置信区间为-14.3%至-0.2%）。在9个月和12个月时，这种效果不再明显。在整个研究过程中，两组之间的死亡率没有显著差异。两组中9个月龄前所有死亡的发生率比值为0.96（95%置信区间为0.73至1.27）。不到1%的婴儿有囟门隆起。该干预对人体测量状态、总体或严重发病率没有影响。
该试验证实了干预措施的安全性，但在6个月龄后维生素A状态或婴儿发病率方面未显示出持续益处。
