Randomized Trial of Vitamin B12 in Pregnant Indian Women

Not Applicable

Completed

Conditions: Pregnancy

Interventions: Other: Placebo
Dietary Supplement: Vitamin B12

Registration Number: NCT00641862

Lead Sponsor: Harvard School of Public Health (HSPH)

Brief Summary: This study is a randomized, double-blind trial among 300 pregnant Indian women in order to determine the effectiveness of vitamin B12 supplementation in improving maternal B12 status. Secondary aims for this trial include maternal hemoglobin, maternal weight gain during pregnancy and infant birthweight. All women will receive standard of prenatal obstetric care, including routine supplementation with iron and folate.

Detailed Description: The incidence of poor fetal growth and adverse maternal and infant birth outcomes is quite high in India, and several lines of evidence suggest that maternal nutritional status may be an important factor. We have previously performed extensive evaluations of poor fetal and infant outcomes in other settings, and found that maternal micronutrient supplementation (B vitamins including vitamin B12, plus vitamins C and E) in HIV positive Tanzanian mothers decreased the risk of low birthweight (\<2500 g) by 44% (RR (95% CI) 0.56 (0.38-0.82)), severe preterm birth (\<34 weeks of gestation) by 39% (RR 0.61 (0.38-0.96)), and small size for gestational age at birth by 43% (RR 0.57 (0.39-0.82)). In a prospective cohort study of 410 pregnant Indian women, we recently found a strong relationship between maternal serum vitamin B12 concentration and risk of infant intrauterine growth retardation (IUGR). Compared to women in the highest tertile of serum B12 concentration, women in the lowest tertile were significantly more likely to have IUGR infants, after controlling for maternal age, weight, education, and parity (OR (95% CI) 5.98 (1.72-20.74)). We now propose a randomized, double-blind trial among 300 pregnant Indian women in order to determine the effectiveness of vitamin B12 supplementation (50 µg daily) in improving maternal B12 status. Secondary aims for this exploratory trial include maternal hemoglobin, maternal weight gain during pregnancy and infant birthweight. All women will receive standard of prenatal obstetric care, including routine supplementation with iron and folate. The study will be a collaborative effort between the Division of Nutrition, St John's Research Institute, Bangalore, India, and the Department of Nutrition, Harvard School of Public Health, Boston, US.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 366

Inclusion Criteria

Pregnant women at or before 14 weeks gestational age.

Exclusion Criteria

Women who anticipate moving outside of the study area before study completion
Those with twin or multiple pregnancies
Those who test positive for hepatitis B (HepBSAg), HIV or Syphilis (VDRL)
Those taking vitamin supplements in addition to folate and iron
Those with a serious pre-existing medical condition, defined as conditions that require chronic or daily medical therapy such as connective tissue diseases, hypertension not related to pregnancy, inflammatory bowel disease, active tuberculosis, symptomatic heart disease, and insulin dependent diabetes.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo
Vitamin B12	Vitamin B12	Vitamin B12

Primary Outcome Measures

Name	Time	Method
Changes in Maternal Serum B12 Concentration From 1st to 3rd Trimester	from 1st to 3rd trimester

Secondary Outcome Measures

Name	Time	Method
Receptive Language Scale, Bayley Scales of Infant Development, 3rd Edition	9 months	The Receptive Language Scale is a single scale that measures the ability of the child to recognize sounds and understand spoken words and directions. Higher values represent better performance. The interquartile range provides adequate assessment of the variability of the data. The minimum possible score is 0 and the maximum possible score is 49.
Fine Motor Scale, Bayley Scales of Infant Development, 3rd Edition	9 months	The Fine Motor Scale is a single scale that measures prehension, perceptual-motor integration, motor planning and speed, visual tracking, reaching, object grasping, object manipulation, functional hand skills, and responses to tactile information. Higher values represent better performance. The interquartile range provides adequate assessment of the variability of the data. The minimum possible value is 0 and the maximum possible value is 66.
Vineland Social Maturity Scale (VSMS)	60-72 months	This scale has 8 main domains which include, Self Help General, Self Help Dressing, Self Direction, Occupation, Communication, Locomotion and Socialization. It is possible to calculate Social age and Social quotient from VSMS which will provide a good idea about the social maturity of the infant. VSMS will be used in conjunction with KABC at age 60-72 months of age.
The Brief P Test	66 months postpartum	The Brief P test is a measure of infant executive function based on parental rating. It will be administered at 66 months postpartum.
Cognitive Scale, Bayley Scales of Infant Development, 3rd Edition	9 months	The cognitive scale is a single scale that measures sensorimotor integration, concept formation, attention, habituation, and memory. Higher values represent better performance. The interquartile range provides an adequate assessment of the variability of the data. The minimum possible score of the cognitive scale is 0 and the maximum possible score is 91.
Expressive Language Scale, Bayley Scales of Infant Development, 3rd Edition	9 months	The Expressive Language Scale is a single scale that measures the ability of the child to communicate using sounds, gestures, or words. Higher scores represent better performance. The interquartile range provides adequate assessment of the variability of the data. The minimum possible value is 0 and the maximum possible value is 48.
Kaufman's Assessment Battery for Children (KABC)	60-72 months	This test is used for assessing child intelligence
Gross Motor Scale, Bayley Scales of Infant Development, 3rd Edition	9 months	The Gross Motor Scale is a single scale that measures movement of the limbs and torso, static positioning (e.g., sitting, standing), dynamic movement including locomotion and coordination, balance, and motor planning. Higher values represent better performance. The interquartile range provides adequate assessment of the variability of the data. The minimum possible value is 0 and the maxiumum possible value is 72.
The Wechsler Preschool and Primary Scale of Intelligence (WPPSI)	78 months	WPPSI is an intelligence test designed for children ages 2 years 6 months to 7 years 7 months. It is a paper-pencil test that will be administered during the 78 month follow up to assess child's intellectual functioning.
Parental Version of Strengths and Difficulties Questionnaire (SDQ)	78 months	Administered at 78 months to assess childhood behavioral problems. The SDQ has 25 items and generates 5 scales: emotional problem, conduct problem, hyperactivity/inattention, peer relationship problems and pro-social behavior.
Bradley Infant-Toddler Home Tools	60 months	Home tools used to analyze aspects of home environment. This scale captures information on parenting behavior under 6 domains: responsivity, acceptance, organization, learning materials, parental involvement, and variety of stimulation at home). Trained study personnel will administer this questionnaire to participating families at 60 months.