A randomised controlled trial to compare two different doses of maternal B12 supplementation in improving infant B12 deficiency and neurodevelopment

一项随机对照试验，比较两种不同剂量的母亲维生素 B12 补充剂在改善婴儿维生素 B12 缺乏和神经发育方面的作用

• 批准号: MR/R020396/1
• 负责人: Monica Lakhanpaul
• 金额: $ 50.64万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR020396%2F1
• 关键词: randomised; controlled; trial; compare; two

Vitamin B12, also called cobalamin, is a water-soluble vitamin that has a key role in the normal functioning of the brain and nervous system. Up to 74% women are reported deficient during antenatal period in some populations. Deficiency of B12 in newborns is problematic given the role Vitamin B12 plays in neuronal health (brain and nerve cells health) and in the development of foetal and infant brain. We propose this research to compare two different doses (a treatment dose in comparison with a dose known to just prevent further deficiency) of maternal Vitamin B12 supplementation in terms of their effectiveness in removing infant B12 deficiency and neurodevelopment.We propose to undertake a multi-centric trial in India and Nepal as these are countries where high incidence of deficiency is reported. We will recruit 720 pregnant women from the antenatal clinics of the department of Gynaecology and Obstetrics at Sitaram Bhartia institute of Science and Research, New Delhi and Paropakar Indrarajayalaxmi Maternity Hospital, Kathmandu, Nepal. The subjects will be recruited at their first presentation to the antenatal clinic and should be vegetarian as they are at high-risk of B12 deficiency. Mothers who are >35 years of age, are already on B12 supplementation, have multiple gestation, chronic medical conditions, known psychological illnesses or those who anticipate moving out of the city before/after delivery will be excluded from the study. Recruited mothers will be randomly allocated to 2 equal groups (360 each). Group 1 (Intervention) will receive daily 250 micrograms Vitamin B12 supplementation to the mother through pregnancy and up to 6 months post-partum. Group 2 (Control) will receive 50 micrograms Vitamin B12 supplementation to the mother through pregnancy and up to 6 months post-partum. The profile information of the mother including age, height, weight, ethnicity, education, socioeconomic status, maternal dietary assessment (by Food Frequency Questionnaire), intake of any supplements (iron, folate, Vitamin-D) etc. will be recorded. Vitamin B12 dosage will be provided at enrolment and then monthly to mothers. Mother's blood levels for Vitamin B12 status and other deficiencies will be drawn. Sampling for these biochemical tests will be combined with other routine tests at these stages to avoid any additional discomfort for the mother. At childbirth, the delivery and post-delivery course of the new-born will be monitored and documented for any problems potentially influencing neurodevelopment. After discharge, all neonates will be routinely followed with preventive and vaccination care as per standard protocols. During routine visits, anthropometric measurements including weight, length and head circumference will be recorded and signs of micronutrient deficiency (especially anaemia and rickets) will be noted. Any illnesses suffered by the child in the intervening period will be recorded. Supplementation of the mother in both groups will be stopped at 6 months after childbirth followed by evaluation at 9 months. The neurodevelopmental assessment and home environment assessment will be done by a developmental therapist and complementary feeding assessment by a nutritionist. Along with routine sampling for Hb screening at 9 months, infant B12 levels status will be determined. The assessment of the infant neurodevelopment scores, the biochemical measures of B12 status of the infant and those of the mother will then be compared between the two groups to see if the neurodevelopment and/or B12 status in the group receiving the higher dose (250 mcg) is better and safe. A positive or a negative result will generate scientific evidence on whether B12 should be supplemented in vegetarian pregnant women with a view to preventing B12 deficiency and its neurodevelopmental consequences in the infant. This will also allow the development of policies and frameworks for routine/wider usage of this supplement in high-risk populations

维生素B12，也被称为钴胺素，是一种水溶性维生素，在大脑和神经系统的正常功能中起着关键作用。据报告，在一些人群中，高达74%的妇女在产前缺乏维生素d。鉴于维生素B12在神经元健康（大脑和神经细胞健康）以及胎儿和婴儿大脑发育中所起的作用，新生儿缺乏B12是一个问题。我们提出这项研究，以比较两种不同剂量（治疗剂量与已知仅用于预防进一步缺乏的剂量）的母亲维生素B12补充剂在消除婴儿B12缺乏症和神经发育方面的有效性。我们建议在印度和尼泊尔进行多中心试验，因为这两个国家报告的缺乏率很高。我们将从新德里Sitaram Bhartia科学研究所妇产科和尼泊尔加德满都Paropakar Indrarajayalaxmi妇产医院的产前诊所招募720名孕妇。受试者将在他们第一次到产前诊所就诊时被招募，并且应该是素食者，因为他们是B12缺乏症的高危人群。年龄在35岁以下、已经在补充B12、有多胎妊娠、慢性疾病、已知的心理疾病或预计在分娩前后搬离城市的母亲将被排除在研究之外。被招募的母亲将被随机分为两组（每组360人）。第一组（干预）将在怀孕期间和产后6个月每天向母亲补充250微克维生素B12。第二组（对照组）将在怀孕期间和产后6个月期间向母亲补充50微克维生素B12。记录母亲的个人资料信息，包括年龄、身高、体重、种族、教育程度、社会经济状况、母亲的饮食评估（通过食物频率问卷）、任何补充剂（铁、叶酸、维生素d）的摄入量等。维生素B12剂量将在入组时提供，然后每月向母亲提供。母亲血液中的维生素B12水平和其他缺陷将被检测出来。在这些阶段，这些生化测试的抽样将与其他常规测试相结合，以避免给母亲带来任何额外的不适。分娩时，新生儿的分娩和产后过程将被监测并记录任何可能影响神经发育的问题。出院后，所有新生儿将按照标准方案进行常规预防和疫苗接种护理。在常规访问期间，将记录人体测量数据，包括体重、长度和头围，并注意微量营养素缺乏的迹象（特别是贫血和佝偻病）。在此期间，孩子所患的任何疾病都将被记录下来。两组在分娩后6个月停止补充母体，并在9个月时进行评估。神经发育评估和家庭环境评估将由发育治疗师完成，补充喂养评估将由营养学家完成。在9个月时进行常规Hb筛查，确定婴儿B12水平状态。婴儿神经发育评分的评估，婴儿和母亲的B12状态的生化指标将在两组之间进行比较，以确定接受较高剂量（250微克）的组的神经发育和/或B12状态是否更好、更安全。结果是阳性还是阴性将为素食孕妇是否应该补充B12提供科学证据，以预防B12缺乏症及其对婴儿神经发育的影响。这也将允许制定政策和框架，以便在高危人群中常规/更广泛地使用这种补充剂

项目成果

Efficacy of maternal B12 supplementation in vegetarian women for improving infant neurodevelopment: protocol for the MATCOBIND multicentre, double-blind, randomised controlled trial.

素食女性补充 B12 对改善婴儿神经发育的功效：MATCOBIND 多中心、双盲、随机对照试验方案。

• DOI: 10.1136/bmjopen-2019-034987
• 发表时间: 2020
• 期刊: BMJ open
• 影响因子: 2.9
• 作者: Nagpal J

327 Maternal B-12 supplementation in vegetarian pregnant women improves maternal B-12 status and infant neurodevelopment: The MATCOBIND multi-centric double-blind randomised-control-trial

327 素食孕妇补充 B-12 可改善母亲 B-12 状态和婴儿神经发育：MATCOBIND 多中心双盲随机对照试验

• DOI: 10.1136/archdischild-2023-rcpch.486
• 发表时间: 2023
• 作者: Nagpal J