Vitamin B12 Supplementation to Improve B12 Status and Child Development

Not Applicable

Completed

• Conditions: Early Pregnancy
• Interventions: Dietary Supplement: Plain UHT milk; Dietary Supplement: Vitamin B12 fortified UHT milk

• Registration Number: NCT03258385
• Lead Sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh

Brief Summary

Impaired vitamin B12 (B12) status during pregnancy is associated with increased risk of birth defects and common complications (e.g. intrauterine growth restriction, neural tube defects), and possibly immune function impairment. The newborns and infants of B12-deficient mothers have low B12 stores at birth, further exacerbated by a very low concentration of B12 in breast milk that may hinder their growth and development. In regions such as Bangladesh, many women of reproductive age have inadequate B12 status, probably due to low intake of animal source food. Vitamin B12 intake and status in pregnancy and lactation is potentially insufficient to prevent impaired child development and immune function related to inadequate B12 status. The investigators hypothesize that prolonged vitamin B12 supplementation through fortified milk starting from early pregnancy up to 6 mo-postpartum will improve: (1) biomarkers of vitamin B12 status in mothers-infant pairs (2) vaccine specific adaptive immunity in infants; (3) neurological and cognitive function in infants.

Detailed Description

The investigators aim to conduct a double-blind, randomized trial, to investigate the effects of B12-fortified milk on maternal and infant B12 status, immune function and child development. Pregnant women (n=148) will be randomized to receive B12-fortified milk (100 μg/day) or milk without fortification. The daily supplementation beginning at the baseline visit (GW 11-14) will continue until 6 mo-postpartum. Biomarkers of B12 status will be measured in mothers (GW 11-14 and 6-mo postpartum) and infants (3 and 6-mo). Infant development (6 and 12-mo) will be evaluated by Bayley Scales of Infant and Toddler Development. Immune responses will be measured in infant at 3 and 6-mo. Data on socioeconomic status, dietary diversity, and anthropometric indices will be recorded at baseline. Additional tests in mothers include screening for H. pylori and plasma gastrin.

Study Timeline

• Study First Submitted: 2017-08-13
• Study First Submitted QC: 2017-08-20
• Study First Posted: 2017-08-23
• Study Start: 2017-09-01
• Status Verified: 2021-04
• Primary Completion: 2021-10-30
• Study Completion: 2021-10-30
• Last Update Submitted: 2023-01-15
• Last Update Posted: 2023-01-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 155

Inclusion Criteria

1. 18 - 35 y old 2. 11-14 wk pregnant (based on last menstrual period) 3. Willing to stay in Dhaka during pregnancy and remain in the area for the 12 mo following recruitment 4. Willing to be admitted in the clinic for delivery 5. Intends to exclusively or predominantly breastfeed infant until 6 mo of age

Exclusion Criteria

1. Women with severe anemia; Hb concentration <70 g/L 2. History or presence of systemic disease such as Diabetes mellitus, Hypertension 3. History of previous complicated pregnancies, pre-term delivery, or abortion 4. Current use of supplements containing vitamin B12 5. Children with acute illness or features suggestive of any chronic disease such as tuberculosis, any congenital anomalies such as cleft lip or palate.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Plain UHT milk	Plain UHT milk	Placebo group (N=74) that will receive plain UHT milk daily
Vitamin B12-fortified UHT milk	Vitamin B12 fortified UHT milk	Supplementation group (N=74) that will receive vitamin B12 fortified UHT milk daily

Primary Outcome Measures

Name	Time	Method
Cognitive, Language and Motor Composite Score	12 months	The outcomes are measured by Bayley-III test
Change in concentrations of biomarkers of vitamin B12 in mother-child pairs	Baseline and 6 months postpartum	The investigators will determine the change in concentrations of biomarkers of B12 ( based on measurement of B12, MMA, tHcy, holoTC, cB12, folate in plasma; B12 in breast milk)
Vaccine specific immunity in infants	6 months	The investigators will determine the concentrations of vaccine specific IgA and IgG in plasma
Nuroinflammatory cytokines	12 months	The investigators will determine the change in concentrations of EGF and TNF-α in plasma

Trial Locations

Locations (1)

Maternal and Child Health Training Institute; 🇧🇩 Dhaka, Bangladesh