Vitamin B12 is required for healthy infant growth and development, but low and marginal vitamin B12 status is endemic in low-income and middle-income countries. We aimed to measure the effect of vitamin B12 supplementation from early pregnancy until 6 months post partum on infant growth and neurodevelopment. In this community-based, double-blind, placebo-controlled trial, we randomly assigned (1:1) 800 pregnant women (aged 20–40 years) who were up to 15 weeks pregnant—recruited from home visits and outpatient departments at three hospitals in Nepal—to daily supplementation with 50 μg oral vitamin B12 or placebo until 6 months postpartum. Independent scientists generated the list that linked allocation to participants' study identification number. Participants were masked to group assignment and all investigators were masked until data cleaning was completed. The primary outcomes were length-for-age Z score (LAZ) at age 12 months and the cognitive composite score of the Bayley Scales of Infant and Toddler Development (3rd edition) at age 6 months and 12 months. The primary and secondary outcomes, including adverse events, were assessed in the intention-to-treat population, for all participants with available outcome data. This trial is registered with , . 800 eligible pregnant women were enrolled in the trial between March 28, 2017, and Oct 15, 2020, with 400 women randomly assigned to each group. Follow-up was completed on May 18, 2022. At baseline, 569 (71%) of 800 women had plasma vitamin B12 indicating low or marginal status (<221 pmol/L). We found no effect of vitamin B12 on the primary outcomes. The mean LAZ at age 12 months were –0·57 (SD 1·03) in the B12 group and –0·55 (1.03) in the placebo group (366 infants in the vitamin B12 group 363 infants in the placebo group) with a mean difference of –0·02 (95% CI –0·16 to 0·13). The mean cognitive composite scores were 97·7 (SD 10·5) in the B12 group and 97·1 (10·2) in the placebo group, with a mean difference of 0·5 (95% CI –0·6 to 1·7) measured in 364 and 361 infants. Stillbirths or infant deaths occurred in three (1%) of 374 women in the vitamin B12 group and nine (2%) of 379 women in the placebo group. Although vitamin B12 deficiency was prevalent in our study population and vitamin B12 supplementation from early pregnancy substantially improved vitamin B12 status, supplementation did not improve infant growth or neurodevelopment. Our findings support the current WHO recommendations of no routine vitamin B12 supplementation during pregnancy. Research Council of Norway.

中文翻译：

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怀孕期间补充维生素 B12 对尼泊尔婴儿生长发育的影响：一项基于社区的双盲、随机、安慰剂对照试验

婴儿健康生长和发育需要维生素 B12，但维生素 B12 水平较低和边缘水平在低收入和中等收入国家普遍存在。我们的目的是测量从怀孕早期到产后 6 个月补充维生素 B12 对婴儿生长和神经发育的影响。在这项基于社区的双盲安慰剂对照试验中，我们随机分配（1:1）800 名怀孕 15 周以内的孕妇（年龄 20-40 岁）——从家访和门诊部门招募，年龄为 3 岁。尼泊尔的医院——每天补充 50 μg 口服维生素 B12 或安慰剂，直至产后 6 个月。独立科学家生成了将分配与参与者的研究识别号联系起来的列表。参与者被蒙蔽以了解分组情况，所有研究人员都被蒙蔽，直到数据清理完成。主要结局是 12 个月时的年龄别身长 Z 评分 (LAZ) 以及 6 个月和 12 个月时贝利婴幼儿发展量表（第三版）的认知综合评分。对于所有具有可用结果数据的参与者，在意向治疗人群中评估了主要和次要结局，包括不良事件。该试验已在 , 注册。2017年3月28日至2020年10月15日期间，800名符合条件的孕妇参加了试验，每组有400名妇女随机分配。随访于 2022 年 5 月 18 日完成。基线时，800 名女性中有 569 名 (71%) 的血浆维生素 B12 水平较低或处于边缘状态 (<221 pmol/L)。我们发现维生素 B12 对主要结果没有影响。B12 组 12 个月大时的平均 LAZ 为 –0·57 (SD 1·03)，安慰剂组为 –0·55 (1.03)（维生素 B12 组 366 名婴儿，安慰剂组 363 名婴儿）平均差异为 –0·02（95% CI –0·16 至 0·13）。B12 组的平均认知综合评分为 97·7 (SD 10·5)，安慰剂组为 97·1 (10·2)，平均差异为 0·5（95% CI –0·6 至1·7）在 364 名和 361 名婴儿中进行了测量。维生素 B12 组 374 名女性中有 3 名 (1%) 发生死产或婴儿死亡，安慰剂组 379 名女性中有 9 名 (2%) 发生死产或婴儿死亡。尽管维生素 B12 缺乏症在我们的研究人群中普遍存在，并且从怀孕早期开始补充维生素 B12 可以显着改善维生素 B12 的状况，但补充并不能改善婴儿的生长或神经发育。我们的研究结果支持目前世界卫生组织关于怀孕期间不常规补充维生素 B12 的建议。挪威研究委员会。