A Randomised Controlled Trial to Compare Two Different Doses of Maternal B12 Supplementation in Improving Infant B12 Deficiency and Neurodevelopment
试验速览
- 阶段
- 不适用
- 入组人数
- 720
- 试验地点
- 4
- 主要终点
- Infant neurodevelopment
研究概览
简要总结
Vitamin B12 plays a key role in the development and normal functioning of the brain and nervous system. Unborn and new-born infants derive their vitamin B12 stores almost entirely from maternal B12 stores. As such, infants who are born to vegetarian mothers and exclusively breast fed are at a high-risk of B12 deficiency. This is because the best sources of vitamin B12 are found in animal based or fortified foods (e.g. cheese, milk and eggs). Vitamin B12 deficiency is widely reported among antenatal mothers and children, particularly in Low and Middle Income Countries (LMICs) where these food sources are uncommon.
So far, studies have shown that antenatal vitamin B12 deficiency in mothers may be associated with poorer neurodevelopment in their children. Furthermore, vitamin B12 supplementation during pregnancy and early lactation has been shown to increase maternal, breast milk, and infant levels of vitamin B12. Although existing literature documents several studies on maternal vitamin B12 supplementation, there is a lack of research on the causative effect of maternal vitamin B12 supplementation on infant development. This project, funded by the Medical Research Council (MRC), will undertake a multi-centric nutritional trial in Nepal and India, as these are two LMICs where high incidence of vitamin B12 deficiency is reported.
详细描述
The project is a multi-centric, double-blind and parallel two-armed randomised controlled trial divided into two stages:
Stage 1:
A total of 720 recruited mothers across India and Nepal will be randomly allocated to 2 equal groups (360 each). The patients, recruiters, developmental therapists, the laboratory and the data analyst will be blinded to the randomization code for the duration of the trial. To ensure blinding and allocation concealment, maternal supplements will be numbered sequentially outside the trial sites by a neutral party using the randomization code supplied by an offsite statistician. Group 1 (Intervention) will receive 250μg of vitamin B12 supplementation delivered daily to the mother from 12-weeks' gestation up to 6-months post-partum. Group 2 (Control) will receive 50μg of vitamin B12 supplementation delivered daily to the mother from 12-weeks' gestation up to 6- months post-partum. The mother's profile will be recorded, including information on: age, height, weight, ethnicity, education, socioeconomic status, maternal dietary assessment and intake of any supplements. Mother's blood levels for vitamin B12 status and other deficiencies will also be recorded.
Within 48 hours enrolment women will be contacted as a part of follow-up. Relevant elements of the clinical records including maternal weight, blood pressure, foetal growth and position and reports of any screening tests for congenital infections/ chromosomal anomalies will be recorded. Any acquired morbidity (including gestational diabetes, pregnancy induced hypertension, and hypothyroidism) during the period from the last visit will be noted. Any drugs or medicines started by the mother will be recorded. Both study sites will promote exclusive breastfeeding by preparing the mothers for breastfeeding in the antenatal period using structured counselling sessions led by an obstetrician or a specified health educator.
Stage 2:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
double-blinded
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Able and willing to give full consent (record if verbal consent is being used)
- •First presentation of the mother to the antenatal clinic <12 weeks of gestation (mothers presenting later not included as the investigators may miss a proportion of the brain growth period)
- •Vegetarian mothers (higher risk of deficiency; defined as self-reported dietary pattern that includes vegans and/or people who do eat egg and/or people who do consume milk and/or meat/fish < once a month)
- •Mother is expecting singleton birth
- •Living within an a-priori defined geographical area (to enhance efficiency of follow-up): Delhi - National Capital Region; Nepal - 10km radius of Paropakar Maternity & Women's Hospital, Kathmandu valley including the three districts of Kathmandu, Bhaktapur and Lalitpur.
- •Is familiar with English, Hindi, or Nepalese
排除标准
- •Younger mothers (<18 years; higher risk of neonatal morbidity)
- •Maternal Age>35 years ( higher risk of neonatal morbidity)
- •Mothers already on medicinal B12 supplementation including as B-complex or multivitamins (confounder)
- •Women with multiple gestation, those diagnosed with chronic medical conditions (diabetes mellitus, hypertension, heart disease, neurological disease or thyroid disease), and those who tested positive for hepatitis B, HIV or syphilis (associated with prematurity, intrauterine growth restriction (IUGR) and other neonatal morbidities which could influence neurodevelopment)
- •Women who anticipate moving out of the city before/ after delivery (follow-up difficult/not possible, 16% delivered outside Sitaram Bhartia Institute of Science & Research (SBISR) in earlier work done by Principle Investigator) (3)
- •Women treated for infertility (higher risk of prematurity and neonatal complications
- •Women with known pre-diagnosed mental health disorder including depression, drug or alcohol abuse likely to affect participation in the study
- •Participation in another study within 4 weeks prior to trial start
- •Allergy to B12 or another supplement constituent
研究组 & 干预措施
250μg of vitamin B12 supplementation
Group 1 (Intervention) will receive 250μg of vitamin B12 supplementation delivered daily to the mother from 12 weeks gestation up to 6 months post-partum.
干预措施: B12 Supplement (Dietary Supplement)
50μg of vitamin B12 supplementation
Group 2 (Control) will receive 50μg of vitamin B12 supplementation delivered daily to the mother from 12 weeks gestation up to 6 months post-partum.
干预措施: B12 Supplement (Dietary Supplement)
结局指标
主要结局
Infant neurodevelopment
时间窗: 9 months in all infant subjects
The effect of higher dose oral maternal vitamin B12 supplementation on infant neurodevelopment as measured by Developmental Assessment Scales for Indian Infants (DASII) at age 9 months, as compared to low dose
次要结局
- Infant B12 status(9 months (± 2 weeks) of age after birth)
- Maternal B12 status(First trimester (<12 weeks gestation) and third trimester (≥ 27 weeks))
- Hemoglobin levels and infant anthropometry(At 1, 2, 3, 4, 6 and 9 months after birth)