近日，澳大利亚皇家儿童医院Frank Shann团队研究了接种一剂BCG丹麦疫苗和口服脊髓灰质炎疫苗对印度体重小于2000 g新生儿死亡率的影响。2025年9月22日出版的《英国医学杂志》发表了这项成果。

为了检验体重为2000 g的新生儿接种一剂BCG丹麦疫苗和口服脊髓灰质炎疫苗（OPV）对全因新生儿死亡率（年龄≤28天）的影响，研究组在印度东南部三个三级新生儿重症监护病房（NICUs）中进行了一项多中心、开放标签、随机对照试验。

招募体重为2000克的新生儿，7067名被评估为合格，5420名被随机分组（2714名BCG-OPV， 2706名对照组）。干预措施为新生儿按1:1随机分组，接受0.1 mL丹麦卡介苗皮内加口服脊髓灰质炎疫苗（OPV），要么在入住NICU 48小时内（早期接种组），要么至少推迟到出院时（对照组）。按新生儿重症监护室、性别和出生体重（1000 g、1000-1499 g、1500-1999 g）进行分层。主要结局为全因新生儿死亡率。主要的次要结局，包括三分之一的试验，是由于感染造成的新生儿死亡率。

在5420名中位年龄为0.9天、中位出生体重为1560克的新生儿中，有9名未能随访。早期接种组2714名新生儿中有238名（8.8%）死亡，对照组2706名新生儿中有273名（10.1%）死亡。在按新生儿重症监护室分层并校正出生年龄、出生体重、性别和胎龄的意向治疗Cox生存分析中，早期接种组的新生儿死亡率为1.29，对照组为1.50(校正风险比0.83,95%可信区间（CI） 0.69 ~ 0.98；P = 0.03)。预防1例死亡所需的治疗人数为21人（95% CI 10 - 245）。早期接种组感染相关新生儿死亡率为每人每年0.40，对照组为0.73（校正风险比0.53,95% CI 0.40 ~ 0.70）。没有发生结核病死亡，也没有与疫苗接种相关的严重不良反应。

研究结果表明，在重症监护室中体重为2000克的新生儿中，中位年龄为0.9天时给予BCG-OPV降低了新生儿全因死亡率，原因是由于结核病以外的感染（非特异性或脱靶效应）导致的死亡减少。如果一名熟练的管理人员在高死亡率环境中，在出生当天或出生后不久，为高比例的新生儿接种疫苗，新生儿死亡率就可以大幅降低。

附：英文原文

Title: 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)

Author: Bethou Adhisivam, Chinnathambi Kamalarathnam, B Vishnu Bhat, Kumutha Jayaraman, Siva P Namachivayam, Frank Shann, Brent McSharry, Ponrani David, Raja, Mangalabharathi Sundaram

Issue&Volume: 2025/09/22

Abstract:

Objective To test the effect on all cause neonatal mortality (aged ≤28 days) of a dose of BCG Danish vaccine and oral polio vaccine (OPV) administered to newborn babies weighing <2000 g.

Design Multicentre, open label, randomised controlled trial

Setting Three tertiary neonatal intensive care units (NICUs) in southeast India.

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

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

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

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. 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. In intention-to-treat Cox 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 ratio 0.83, 95% confidence interval (CI) 0.69 to 0.98; P=0.03). The number needed to treat to prevent one death was 21 (95% CI 10 to 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 ratio 0.53, 95% CI 0.40 to 0.70). No deaths from tuberculosis occurred, and no serious adverse effects were associated with vaccination.

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). 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.

DOI: 10.1136/bmj-2025-084745

Source: https://www.bmj.com/content/390/bmj-2025-084745