Early Life Thiamine Supplementation for Infant Neurocognitive Benefits: a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,972
- 试验地点
- 1
- 主要终点
- Mullen's Scales of Early Learning "Early Learning Composite" T-score (MSEL-ELC)
研究概览
简要总结
Thiamine (vitamin B1) is an important nutrient needed for energy metabolism, brain development, and overall health. However, low thiamine intake is a concern in countries where white rice is the main staple since it contains little thiamine. If pregnant or breastfeeding women do not eat enough thiamine, their babies may also become deficient. Severe thiamine deficiency can cause beriberi, which can be life-threatening. Milder deficiency during early life may affect brain development.
Healthy pregnant women should eat 1.4 mg thiamine daily. In a previous study in rural Cambodia, study investigators found that giving breastfeeding mothers a higher dose of thiamine (10mg per day) improved their infants' brain development at six months of age. However, supplementation began two weeks after birth. Since much of an infant's brain development occurs in utero, starting mother's supplementation earlier - in pregnancy - may provide greater benefits.
Study investigators are now conducting a study with pregnant women in Cambodia. Participants will receive either the usual amount of thiamine found in multiple micronutrient supplements or a higher dose, beginning in pregnancy and continuing until their child is 18 months old. The primary outcome is cognition at 18 months, to see whether higher thiamine intake during pregnancy and early childhood leads to measurable improvements in early brain development.
详细描述
Please see attached study protocol for full details.
Background:
Thiamine (vitamin B1) is an essential micronutrient crucial for normal physiological functioning and healthy child development. Thiamine requirements increase with carbohydrate-rich diets (e.g. white rice) and during periods of high metabolism (e.g. perinatal women, infancy). The limited data available show that the prevalence of thiamine deficiency is high in women of childbearing age and their infants in several low- and middle-income settings, notably in South and Southeast Asia, where white rice is the dietary staple, but also in several African countries. Thiamine-deficient pregnant and lactating women produce breastmilk low in thiamine, putting their breastfed infants at risk of deficiency, and potentially fatal beriberi. In addition, recent evidence suggests that sub-clinical thiamine deficiency may be conferred prenatally, placing millions of infants at risk of neurocognitive deficits, undercutting life-long well-being and productivity.
Preliminary Data:
In coordination with the Cambodian Ministry of Health, study investigators undertook a four-parallel-arm, randomized, controlled trial (NCT03616288) in rural Cambodia to estimate the dose of maternal thiamine required postpartum to optimize breastmilk thiamine concentrations; secondary exploratory outcomes included neurocognitive assessments. Mothers were randomized to consume 0, 1.2, 2.4, or 10 mg daily thiamine from 2 weeks through 6 months postnatal. While milk thiamine concentrations were significantly higher in all thiamine groups compared to placebo, critically, at 6 months postnatal, only infants in the 10 mg/d group showed robust neurocognitive benefits. Additionally, infants whose mothers had higher milk thiamine concentrations at our pre-supplementation baseline (2 weeks postpartum) showed significantly improved neurocognitive outcomes at 6 months postnatal, suggesting that infants' prenatal access to adequate thiamine may have critical benefits for neurocognitive development.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •This community-based trial will take place in villages throughout Kampong Thom province, Cambodia. Using convenience sampling, pregnant women (either primi- or multi-gravida) will be recruited from antenatal care programs within local health centers in Kampong Thom province.
- •Inclusion Criteria:
- •women aged 18-45 years
- •12(+0) to 15(+6) weeks pregnant, based on last menstrual period
- •planning to breastfeed for at least 6 months
排除标准
- •consumed thiamine-containing supplements in the preceding 3 months
- •planning on moving out of province in the next year
研究组 & 干预措施
Standard of Care +
multiple micronutrient supplement formulations containing the RNI for thiamine: 1.4 mg/d for pregnant/lactating women (from 12-16 weeks pregnancy through 6 months postnatal), and 0.5 mg/d for children (6-18 months postnatal)
干预措施: Multiple micronutrient supplementation (Dietary Supplement)
High-thiamine MMS
multiple micronutrient supplement formulations containing a higher dose of daily thiamine: 10 mg/d for pregnant/lactating women (12-16 weeks pregnancy through 6 months postnatal), and 5 mg/d for children (6-18 months postnatal)
干预措施: Multiple micronutrient supplementation (Dietary Supplement)
结局指标
主要结局
Mullen's Scales of Early Learning "Early Learning Composite" T-score (MSEL-ELC)
时间窗: 18 months postnatal
Early Learning Composite (ELC) Standard Score is derived from the sum of the age adjusted T-scores for all but the Gross Motor scales: ELC Standard Score = Visual Reception T-Score + Fine Motor T-Score + Receptive Language T-Score + Expressive Language T-Score ELC Standard Score Mean = 100 ELC Standard Score SD = 15 ELC Standard Score Range (Min/Max) = 49 to 155
次要结局
未报告次要终点
研究者
Kyly Whitfield
Associate Professor, Department of Applied Human Nutrition
Mount Saint Vincent University