Child Developmental DelayMATCOBINDNCT03783104
Maternal B12 Supplementation to Improve Infant B12 Deficiency and Neurodevelopment
A study testing B12 Supplement in people with Child Developmental Delay and Child Malnutrition, run by University College, London at 2 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Child Developmental Delay, Child Malnutrition, Maternal Exposure
- What is being tested?
- B12 Supplement
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 720 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 27 Apr 2019to 1 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
India1 site, 1 recruiting
- Recruiting
Sitaram Bhartia Institute for Science and Research
New Delhi, 110016
Jitender Nagpal, Dr, 011-42111244, jitendernagpal@gmail.com
Nepal1 site, 1 recruiting
- Recruiting
Paropakar Maternity and Women's Hospital
Kathmandu, 44600
Rajendra P Pant, Dr, +977-9851046646, Rajendrapant8@gmail.com
Jageshwor Gautam, Prof, +977-9851027419, drjgautam48@gmail.com
About this study
Official title: A Randomised Controlled Trial to Compare Two Different Doses of Maternal B12 Supplementation in Improving Infant B12 Deficiency and Neurodevelopment
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.
Read the detailed description
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:
The birth and post-delivery course of the new-born during hospital stay will be assessed by the medical officer and/or paediatrician for any morbidity potentially influencing neurodevelopment, such as growth retardation, congenital anomalies, seizures, neurological problems, hypoglycemia, hypothermia, hearing deficits, vision and heart disease.
After discharge, all neonates will be routinely followed with preventive and vaccination care as per standard protocols. As part of routine care, all new-borns will be screened for metabolic disorders at 7-14 days.
During routine visits, anthropometric measurements including weight, length and head circumference will be recorded and signs of micronutrient deficiency (especially anaemia and rickets) will be noted. The child care teams at both sites will encourage the initiation and establishment of exclusive breastfeeding while minimizing the use of formula feeds by providing support and counselling during hospital stay. Maternal and infant tolerance for the supplementation including any gastrointestinal symptoms will be recorded at each visit. Supplementation of the mother in both groups will be stopped at 6 months after childbirth. At 9 months, the neurodevelopmental, complementary feeding practices and home environment will be assessed and infant vitamin B12 status will be determined.
Data will be checked and encrypted after removing any "patient identifiable information". These data will be sent with the group coding sheet to a statistician blinded to intervention or control grouping. Data will be analysed using the neurodevelopmental scores at 9 months as the primary efficacy outcome variable. Biochemical prevalence of B12 deficiency in mothers during the first and third trimesters and infants after 9 months of birth will be analysed as the secondary outcome variables. Although no safety issues are expected, infant linear growth and incidence of adverse events will be the mainly safety outcomes. Data on maternal tolerance of B12 supplementation will also be collected. All primary analyses will be conducted on an intention to treat basis.
- Being tested
- B12 Supplement
- Keywords
- Vitamin B12, Maternal nutrition, Neurodevelopment, Supplementation
- Medical subject headings
- Learning Disabilities, Child Nutrition Disorders, Vitamin B 12 Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
B12 SupplementDietary supplement
Differential doses of vitamin B 12 supplementation in a two-armed randomised controlled trial
| Study group | Role | What they receive |
|---|---|---|
| 250μg of vitamin B12 supplementation | Experimental | 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. Receives: Dietary Supplement: B12 Supplement |
| 50μg of vitamin B12 supplementation | Active comparator | 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. Receives: Dietary Supplement: B12 Supplement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infant neurodevelopment
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
Measured: 9 months in all infant subjects
Secondary outcomes (5)
Maternal B12 status
The change in biochemical parameters of maternal B12 status between first (<12 weeks gestation) and third trimester (≥ 27 weeks gestation) as measured by vitamin B12, homocysteine and holotranscobalamin levels
Measured: First trimester (<12 weeks gestation) and third trimester (≥ 27 weeks)
Infant B12 status
The change in biochemical parameters of infant B12 status at 9 months (± 2 weeks) after birth as compared to low dose
Measured: 9 months (± 2 weeks) of age after birth
Hemoglobin levels and infant anthropometry
The change in hemoglobin levels in the mother
Measured: Between first and third trimester
Hemoglobin levels and infant anthropometry
The change in hemoglobin levels in the infant
Measured: At 9 months after birth
Hemoglobin levels and infant anthropometry
The change in infant anthropometry including weight, length, and head circumference (c)
Measured: At 1, 2, 3, 4, 6 and 9 months after birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2018
- Study start27 Apr 2019
- Primary completion1 Dec 2021 (estimated)
- Study completion1 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Child Developmental DelayStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A total of 720 recruited mothers across India and Nepal will be randomly allocated to 2 equal groups (360 each). 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 720 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Sitaram Bhartia Institute of Science and Research, Paropakar Maternity and Women's Hospital
- Responsible party
- Sponsor
- Investigators
- Monica Lakhanpaul, Principal investigator, University College, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03783104
- Sponsor's protocol ID
- 13795/001
- Acronym
- MATCOBIND
- Status last verified
- Jul 2019
- First submitted
- 17 Dec 2018
- Last updated
- 22 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial to Compare Two Different Doses of Maternal B12 Supplementation in Improving Infant B12 Deficiency and Neurodevelopment
- ClinicalTrials.gov ID
- NCT03783104
- Acronym / sponsor ID
- MATCOBIND / 13795/001
- Keywords
- Vitamin B12, Maternal nutrition, Neurodevelopment, Supplementation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 720 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Sitaram Bhartia Institute of Science and Research, Paropakar Maternity and Women's Hospital
- Study start
- 27 Apr 2019 (actual)
- Primary completion
- 1 Dec 2021 (estimated)
- Study completion
- 1 Dec 2021 (estimated)
- First posted
- 20 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
The birth and post-delivery course of the new-born during hospital stay will be assessed by the medical officer and/or paediatrician for any morbidity potentially influencing neurodevelopment, such as growth retardation, congenital anomalies, seizures, neurological problems, hypoglycemia, hypothermia, hearing deficits, vision and heart disease.
After discharge, all neonates will be routinely followed with preventive and vaccination care as per standard protocols. As part of routine care, all new-borns will be screened for metabolic disorders at 7-14 days.
During routine visits, anthropometric measurements including weight, length and head circumference will be recorded and signs of micronutrient deficiency (especially anaemia and rickets) will be noted. The child care teams at both sites will encourage the initiation and establishment of exclusive breastfeeding while minimizing the use of formula feeds by providing support and counselling during hospital stay. Maternal and infant tolerance for the supplementation including any gastrointestinal symptoms will be recorded at each visit. Supplementation of the mother in both groups will be stopped at 6 months after childbirth. At 9 months, the neurodevelopmental, complementary feeding practices and home environment will be assessed and infant vitamin B12 status will be determined.
Data will be checked and encrypted after removing any "patient identifiable information". These data will be sent with the group coding sheet to a statistician blinded to intervention or control grouping. Data will be analysed using the neurodevelopmental scores at 9 months as the primary efficacy outcome variable. Biochemical prevalence of B12 deficiency in mothers during the first and third trimesters and infants after 9 months of birth will be analysed as the secondary outcome variables. Although no safety issues are expected, infant linear growth and incidence of adverse events will be the mainly safety outcomes. Data on maternal tolerance of B12 supplementation will also be collected. All primary analyses will be conducted on an intention to treat basis.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A total of 720 recruited mothers across India and Nepal will be randomly allocated to 2 equal groups (360 each). 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.
| Arm | Type | Receives |
|---|---|---|
| 250μg of vitamin B12 supplementation | Experimental | Dietary Supplement: B12 SupplementGroup 1 (Intervention) will receive 250μg of vitamin B12 supplementation delivered daily to the mother from 12 weeks gestation up to 6 months post-partum. |
| 50μg of vitamin B12 supplementation | Active comparator | Dietary Supplement: B12 SupplementGroup 2 (Control) will receive 50μg of vitamin B12 supplementation delivered daily to the mother from 12 weeks gestation up to 6 months post-partum. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| B12 SupplementDifferential doses of vitamin B 12 supplementation in a two-armed randomised controlled trial | Dietary supplement | 250μg of vitamin B12 supplementation, 50μg of vitamin B12 supplementation |
Primary outcome
Infant neurodevelopment
Time frame: 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
5 secondary outcomes
Maternal B12 status
Time frame: First trimester (<12 weeks gestation) and third trimester (≥ 27 weeks)
Infant B12 status
Time frame: 9 months (± 2 weeks) of age after birth
Hemoglobin levels and infant anthropometry
Time frame: Between first and third trimester
Hemoglobin levels and infant anthropometry
Time frame: At 9 months after birth
Hemoglobin levels and infant anthropometry
Time frame: At 1, 2, 3, 4, 6 and 9 months after birth
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Monica Lakhanpaul principal investigator
University College, London
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing B12 Supplement in people with Child Developmental Delay and Child Malnutrition, run by University College, London at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in India, Nepal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Monica Lakhanpaul (+442079052259 ext. 42322, m.lakhanpaul@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infant neurodevelopment (time frame: 9 months in all infant subjects). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2019.