Effect of BCG Danish and oral polio vaccine on neonatal mortality in newborn babies weighing less than 2000 g in India: multicentre open label randomised controlled trial (BLOW2).

Methods

Multicentre, open label, randomised controlled trialSETTING: Three tertiary neonatal intensive care units (NICUs) in southeast India.

多中心、开放标签、随机对照试验。地点：印度东南部的三家三级新生儿重症监护病房(NICUs)。

population

Newborn babies weighing <2000 g. 7067 were assessed for eligibility and 5420 were randomised (2714 BCG-OPV, 2706 control).

体重低于2000克的新生儿共有7067名被评估是否符合入选标准，其中5420名被随机分配（2714名接受BCG-OPV，2706名对照组）。

Methods

Newborns were randomised 1:1 to receive 0.1 mL of BCG Danish intradermally plus OPV, either within 48 hours of admission to the NICU (early vaccination group) or delayed until at least the time of discharge (control group).

新生儿按照1:1的比例随机分配，接受0.1毫升丹麦产BCG疫苗皮内注射加上口服脊髓灰质炎疫苗（OPV），要么在入新生儿重症监护病房（NICU）后48小时内（早期疫苗接种组），要么延迟至至少出院时（对照组）。

Stratification was by NICU, sex, and birth weight (<1000 g, 1000-1499 g, 1500-1999 g).

分层因素包括新生儿重症监护病房(NICU)、性别以及出生体重（<1000克、1000-1499克、1500-1999克）。

The primary outcome was all cause neonatal mortality.

主要结局指标为新生儿全因死亡率。

The main secondary outcome, included a third of the way through the trial, was neonatal mortality due to infection.

主要次要结果，包括在试验进行到三分之一时，是由于感染导致的新生儿死亡率。

Results

Of the 5420 newborn babies randomised at a median age of 0.9 days and with a median birth weight of 1560 g, nine were lost to follow-up.

在中位年龄为0.9天、中位出生体重为1560克的5420名新生儿中，有九名失访。

Deaths occurred in 238 (8.8%) of 2714 newborn babies in the early vaccination group and 273 (10.1%) of 2706 in the control group.

在早期接种组的2714名新生儿中，有238名（8.8%）死亡，在对照组的2706名新生儿中，有273名（10.1%）死亡。

In intention-to-treatCox survival analysis stratified by NICU and adjusted for postnatal age, birth weight, sex, and gestational age, neonatal mortality per person year was 1.29 in the early vaccination group and 1.50 in the control group (adjusted hazard ratio0.83, 95% confidence interval(CI) 0.69 to 0.98; P=0.03).

在按新生儿重症监护病房（NICU）分层并根据产后年龄、出生体重、性别和胎龄进行调整的意向治疗Cox生存分析中，早期接种组的新生儿每年人年死亡率为1.29，对照组为1.50（调整后的风险比为0.83，95%置信区间（CI）为0.69至0.98；P=0.03）。

The number needed to treat to prevent one death was 21 (95% CI 10 to 245).

预防每例死亡所需的治疗人数为21（95% CI 10至245）。

Infection related neonatal mortality per person year was 0.40 in the early vaccination group and 0.73 in the control group (adjusted hazard ratio0.53, 95% CI 0.40 to 0.70).

早期疫苗接种组的感染相关新生儿每年人年死亡率为0.40，对照组为0.73（调整后风险比0.53，95% CI 0.40至0.70）。

No deaths from tuberculosis occurred, and no serious adverse effects were associated with vaccination.

未发生因结核病导致的死亡，也未出现与接种疫苗相关的严重不良反应。

Conclusions

In newborn babies weighing <2000 g in intensive care, BCG-OPV administered at a median age of 0.9 days reduced all cause neonatal mortality owing to a decrease in deaths due to infections other than tuberculosis (a non-specific or off-target effect).

在体重不足2000克的新生儿重症监护病房中，中位年龄为0.9天接种BCG-OPV后，由于非结核感染导致的死亡率下降，从而降低了所有原因的新生儿死亡率（一种非特异性或非靶向效应）。

A substantial reduction in neonatal mortality could be achieved if a skilled administrator vaccinated a high proportion of newborn babies in high mortality settings on the day of, or soon after, birth.

如果熟练的管理员在高死亡率环境中，在出生当天或不久后为高比例的新生儿接种疫苗，可以显著降低新生儿死亡率。

trial_registration

Clinical Trials Registry India CTRI/2017/01/007676.

临床试验注册印度 CTRI/2017/01/007676。