Clinical trial NCT00641862: Randomized Trial of Vitamin B12 in Pregnant Indian Women
Official title: Randomized Trial of Vitamin B12 in Pregnant Indian Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pregnancy
Keywords: Pregnancy
Maternal Nutritional Status
Vitamin B12
Lead sponsor: Harvard School of Public Health (HSPH)
Sponsor class: OTHER
Collaborators: name: St. John's Research Institute
First posted: 2008-03-24
Enrollment: 366
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in Maternal Serum B12 Concentration From 1st to 3rd Trimester
timeFrame: from 1st to 3rd trimester
Secondary outcomes:
measure: Cognitive Scale, Bayley Scales of Infant Development, 3rd Edition
timeFrame: 9 months
measure: Receptive Language Scale, Bayley Scales of Infant Development, 3rd Edition
timeFrame: 9 months
measure: Expressive Language Scale, Bayley Scales of Infant Development, 3rd Edition
timeFrame: 9 months
measure: Fine Motor Scale, Bayley Scales of Infant Development, 3rd Edition
timeFrame: 9 months
measure: Gross Motor Scale, Bayley Scales of Infant Development, 3rd Edition
timeFrame: 9 months
measure: Kaufman's Assessment Battery for Children (KABC)
timeFrame: 60-72 months
measure: The Wechsler Preschool and Primary Scale of Intelligence (WPPSI)
timeFrame: 78 months
measure: Vineland Social Maturity Scale (VSMS)
timeFrame: 60-72 months
measure: The Brief P Test
timeFrame: 66 months postpartum
measure: Parental Version of Strengths and Difficulties Questionnaire (SDQ)
timeFrame: 78 months
measure: Bradley Infant-Toddler Home Tools
timeFrame: 60 months
Other outcomes:
Locations:
city: Bangalore
country: India
facility: St. John's Medical Research Institute, St. John's National Academy of Health Sciences
state: Karnataka
Study officials:
affiliation: Harvard School of Public Health (HSPH)
name: Christopher P Duggan, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: St. John's Research Institute
name: Anura Kurpad, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. John's Research Institute
name: Krishnamachari Srinivasan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Muthayya S, Dwarkanath P, Mhaskar M, Mhaskar R, Thomas A, Duggan C, Fawzi WW, Bhat S, Vaz M, Kurpad A. The relationship of neonatal serum vitamin B12 status with birth weight. Asia Pac J Clin Nutr. 2006;15(4):538-43.
citation: Muthayya S, Kurpad AV, Duggan CP, Bosch RJ, Dwarkanath P, Mhaskar A, Mhaskar R, Thomas A, Vaz M, Bhat S, Fawzi WW. Low maternal vitamin B12 status is associated with intrauterine growth retardation in urban South Indians. Eur J Clin Nutr. 2006 Jun;60(6):791-801. doi: 10.1038/sj.ejcn.1602383. Epub 2006 Jan 11.
citation: Srinivasan K, Thomas S, Anand S, Jayachandra M, Thomas T, Strand TA, Kurpad AV, Duggan CP. Vitamin B-12 Supplementation during Pregnancy and Early Lactation Does Not Affect Neurophysiologic Outcomes in Children Aged 6 Years. J Nutr. 2020 Jul 1;150(7):1951-1957. doi: 10.1093/jn/nxaa123.
citation: Anand S, Thomas S, Jayachandra M, Thomas T, Strand TA, Kurpad AV, Duggan CP, Srinivasan K. Effects of maternal B12 supplementation on neurophysiological outcomes in children: a study protocol for an extended follow-up from a placebo randomised control trial in Bangalore, India. BMJ Open. 2019 Feb 19;9(2):e024426. doi: 10.1136/bmjopen-2018-024426.
citation: Winje BA, Kvestad I, Krishnamachari S, Manji K, Taneja S, Bellinger DC, Bhandari N, Bisht S, Darling AM, Duggan CP, Fawzi W, Hysing M, Kumar T, Kurpad AV, Sudfeld CR, Svensen E, Thomas S, Strand TA. Does early vitamin B12 supplementation improve neurodevelopment and cognitive function in childhood and into school age: a study protocol for extended follow-ups from randomised controlled trials in India and Tanzania. BMJ Open. 2018 Feb 22;8(2):e018962. doi: 10.1136/bmjopen-2017-018962.
citation: Duggan C, Srinivasan K, Thomas T, Samuel T, Rajendran R, Muthayya S, Finkelstein JL, Lukose A, Fawzi W, Allen LH, Bosch RJ, Kurpad AV. Vitamin B-12 supplementation during pregnancy and early lactation increases maternal, breast milk, and infant measures of vitamin B-12 status. J Nutr. 2014 May;144(5):758-64. doi: 10.3945/jn.113.187278. Epub 2014 Mar 5.
citation: Lukose A, Ramthal A, Thomas T, Bosch R, Kurpad AV, Duggan C, Srinivasan K. Nutritional factors associated with antenatal depressive symptoms in the early stage of pregnancy among urban South Indian women. Matern Child Health J. 2014 Jan;18(1):161-170. doi: 10.1007/s10995-013-1249-2.