<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03783104</url>
  </required_header>
  <id_info>
    <org_study_id>13795/001</org_study_id>
    <nct_id>NCT03783104</nct_id>
  </id_info>
  <brief_title>Maternal B12 Supplementation to Improve Infant B12 Deficiency and Neurodevelopment</brief_title>
  <acronym>MATCOBIND</acronym>
  <official_title>A Randomised Controlled Trial to Compare Two Different Doses of Maternal B12 Supplementation in Improving Infant B12 Deficiency and Neurodevelopment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sitaram Bhartia Institute of Science and Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Paropakar Maternity and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University College, London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Vitamin B12 plays a key role in the development and normal functioning of the brain and&#xD;
      nervous system. Unborn and new-born infants derive their vitamin B12 stores almost entirely&#xD;
      from maternal B12 stores. As such, infants who are born to vegetarian mothers and exclusively&#xD;
      breast fed are at a high-risk of B12 deficiency. This is because the best sources of vitamin&#xD;
      B12 are found in animal based or fortified foods (e.g. cheese, milk and eggs). Vitamin B12&#xD;
      deficiency is widely reported among antenatal mothers and children, particularly in Low and&#xD;
      Middle Income Countries (LMICs) where these food sources are uncommon.&#xD;
&#xD;
      So far, studies have shown that antenatal vitamin B12 deficiency in mothers may be associated&#xD;
      with poorer neurodevelopment in their children. Furthermore, vitamin B12 supplementation&#xD;
      during pregnancy and early lactation has been shown to increase maternal, breast milk, and&#xD;
      infant levels of vitamin B12. Although existing literature documents several studies on&#xD;
      maternal vitamin B12 supplementation, there is a lack of research on the causative effect of&#xD;
      maternal vitamin B12 supplementation on infant development. This project, funded by the&#xD;
      Medical Research Council (MRC), will undertake a multi-centric nutritional trial in Nepal and&#xD;
      India, as these are two LMICs where high incidence of vitamin B12 deficiency is reported.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The project is a multi-centric, double-blind and parallel two-armed randomised controlled&#xD;
      trial divided into two stages:&#xD;
&#xD;
      Stage 1:&#xD;
&#xD;
      A total of 720 recruited mothers across India and Nepal will be randomly allocated to 2 equal&#xD;
      groups (360 each). The patients, recruiters, developmental therapists, the laboratory and the&#xD;
      data analyst will be blinded to the randomization code for the duration of the trial. To&#xD;
      ensure blinding and allocation concealment, maternal supplements will be numbered&#xD;
      sequentially outside the trial sites by a neutral party using the randomization code supplied&#xD;
      by an offsite statistician. Group 1 (Intervention) will receive 250μg of vitamin B12&#xD;
      supplementation delivered daily to the mother from 12-weeks' gestation up to 6-months&#xD;
      post-partum. Group 2 (Control) will receive 50μg of vitamin B12 supplementation delivered&#xD;
      daily to the mother from 12-weeks' gestation up to 6- months post-partum. The mother's&#xD;
      profile will be recorded, including information on: age, height, weight, ethnicity,&#xD;
      education, socioeconomic status, maternal dietary assessment and intake of any supplements.&#xD;
      Mother's blood levels for vitamin B12 status and other deficiencies will also be recorded.&#xD;
&#xD;
      Within 48 hours enrolment women will be contacted as a part of follow-up. Relevant elements&#xD;
      of the clinical records including maternal weight, blood pressure, foetal growth and position&#xD;
      and reports of any screening tests for congenital infections/ chromosomal anomalies will be&#xD;
      recorded. Any acquired morbidity (including gestational diabetes, pregnancy induced&#xD;
      hypertension, and hypothyroidism) during the period from the last visit will be noted. Any&#xD;
      drugs or medicines started by the mother will be recorded. Both study sites will promote&#xD;
      exclusive breastfeeding by preparing the mothers for breastfeeding in the antenatal period&#xD;
      using structured counselling sessions led by an obstetrician or a specified health educator.&#xD;
&#xD;
      Stage 2:&#xD;
&#xD;
      The birth and post-delivery course of the new-born during hospital stay will be assessed by&#xD;
      the medical officer and/or paediatrician for any morbidity potentially influencing&#xD;
      neurodevelopment, such as growth retardation, congenital anomalies, seizures, neurological&#xD;
      problems, hypoglycemia, hypothermia, hearing deficits, vision and heart disease.&#xD;
&#xD;
      After discharge, all neonates will be routinely followed with preventive and vaccination care&#xD;
      as per standard protocols. As part of routine care, all new-borns will be screened for&#xD;
      metabolic disorders at 7-14 days.&#xD;
&#xD;
      During routine visits, anthropometric measurements including weight, length and head&#xD;
      circumference will be recorded and signs of micronutrient deficiency (especially anaemia and&#xD;
      rickets) will be noted. The child care teams at both sites will encourage the initiation and&#xD;
      establishment of exclusive breastfeeding while minimizing the use of formula feeds by&#xD;
      providing support and counselling during hospital stay. Maternal and infant tolerance for the&#xD;
      supplementation including any gastrointestinal symptoms will be recorded at each visit.&#xD;
      Supplementation of the mother in both groups will be stopped at 6 months after childbirth. At&#xD;
      9 months, the neurodevelopmental, complementary feeding practices and home environment will&#xD;
      be assessed and infant vitamin B12 status will be determined.&#xD;
&#xD;
      Data will be checked and encrypted after removing any &quot;patient identifiable information&quot;.&#xD;
      These data will be sent with the group coding sheet to a statistician blinded to intervention&#xD;
      or control grouping. Data will be analysed using the neurodevelopmental scores at 9 months as&#xD;
      the primary efficacy outcome variable. Biochemical prevalence of B12 deficiency in mothers&#xD;
      during the first and third trimesters and infants after 9 months of birth will be analysed as&#xD;
      the secondary outcome variables. Although no safety issues are expected, infant linear growth&#xD;
      and incidence of adverse events will be the mainly safety outcomes. Data on maternal&#xD;
      tolerance of B12 supplementation will also be collected. All primary analyses will be&#xD;
      conducted on an intention to treat basis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 27, 2019</start_date>
  <completion_date type="Anticipated">December 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_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.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>double-blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Infant neurodevelopment</measure>
    <time_frame>9 months in all infant subjects</time_frame>
    <description>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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maternal B12 status</measure>
    <time_frame>First trimester (&lt;12 weeks gestation) and third trimester (≥ 27 weeks)</time_frame>
    <description>The change in biochemical parameters of maternal B12 status between first (&lt;12 weeks gestation) and third trimester (≥ 27 weeks gestation) as measured by vitamin B12, homocysteine and holotranscobalamin levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infant B12 status</measure>
    <time_frame>9 months (± 2 weeks) of age after birth</time_frame>
    <description>The change in biochemical parameters of infant B12 status at 9 months (± 2 weeks) after birth as compared to low dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin levels and infant anthropometry</measure>
    <time_frame>Between first and third trimester</time_frame>
    <description>The change in hemoglobin levels in the mother</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin levels and infant anthropometry</measure>
    <time_frame>At 9 months after birth</time_frame>
    <description>The change in hemoglobin levels in the infant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin levels and infant anthropometry</measure>
    <time_frame>At 1, 2, 3, 4, 6 and 9 months after birth</time_frame>
    <description>The change in infant anthropometry including weight, length, and head circumference (c)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Socio-economic mediators of the relationship between maternal B12 status, supplementation and infant neurodevelopment</measure>
    <time_frame>At study enrolment</time_frame>
    <description>Income, education, profession</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of maternal diet</measure>
    <time_frame>During the third trimester (27 weeks of gestation)</time_frame>
    <description>The effect of the intervention on maternal vitamin B12 status, infant B12 status and infant neurodevelopment</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of type of milk feeding on infant vitamin B12 status</measure>
    <time_frame>At 9 months (± 2 weeks) infant age</time_frame>
    <description>Assessed by measuring blood levels of B12</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of type of milk feeding on infant neurodevelopment</measure>
    <time_frame>At 9 months (± 2 weeks) infant age</time_frame>
    <description>Assessed using the Developmental Assessment Scales for Indian Infants (DASII)</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of infant complementary feeding on infant vitamin B12 status</measure>
    <time_frame>At 9 months (± 2 weeks) infant age</time_frame>
    <description>Assessed by measuring blood levels of B12</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of infant complementary feeding on infant neurodevelopment</measure>
    <time_frame>At 9 months (± 2 weeks) infant age</time_frame>
    <description>Assessed using the Developmental Assessment Scales for Indian Infants (DASII)</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of maternal iron</measure>
    <time_frame>In first and third trimester and at 9 months (± 2 weeks) infant age</time_frame>
    <description>Determining any effect of maternal iron levels in first and third trimester on the relationship between infant vitamin B12 status and infant neurodevelopment</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of maternal vitamin D status</measure>
    <time_frame>In first and third trimester and at 9 months (± 2 weeks) infant age</time_frame>
    <description>Determine any effect of maternal vitamin D status in first and third trimester on the relationship between infant vitamin B12 status and infant neurodevelopment</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">720</enrollment>
  <condition>Child Developmental Delay</condition>
  <condition>Child Malnutrition</condition>
  <condition>Maternal Exposure</condition>
  <condition>Vitamin B 12 Deficiency</condition>
  <arm_group>
    <arm_group_label>250μg of vitamin B12 supplementation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>50μg of vitamin B12 supplementation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>B12 Supplement</intervention_name>
    <description>Differential doses of vitamin B 12 supplementation in a two-armed randomised controlled trial</description>
    <arm_group_label>250μg of vitamin B12 supplementation</arm_group_label>
    <arm_group_label>50μg of vitamin B12 supplementation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able and willing to give full consent (record if verbal consent is being used)&#xD;
&#xD;
          -  First presentation of the mother to the antenatal clinic &lt;12 weeks of gestation&#xD;
             (mothers presenting later not included as the investigators may miss a proportion of&#xD;
             the brain growth period)&#xD;
&#xD;
          -  Vegetarian mothers (higher risk of deficiency; defined as self-reported dietary&#xD;
             pattern that includes vegans and/or people who do eat egg and/or people who do consume&#xD;
             milk and/or meat/fish &lt; once a month)&#xD;
&#xD;
          -  Mother is expecting singleton birth&#xD;
&#xD;
          -  Living within an a-priori defined geographical area (to enhance efficiency of&#xD;
             follow-up): Delhi - National Capital Region; Nepal - 10km radius of Paropakar&#xD;
             Maternity &amp; Women's Hospital, Kathmandu valley including the three districts of&#xD;
             Kathmandu, Bhaktapur and Lalitpur.&#xD;
&#xD;
          -  Is familiar with English, Hindi, or Nepalese&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Younger mothers (&lt;18 years; higher risk of neonatal morbidity)&#xD;
&#xD;
          -  Maternal Age&gt;35 years ( higher risk of neonatal morbidity)&#xD;
&#xD;
          -  Mothers already on medicinal B12 supplementation including as B-complex or&#xD;
             multivitamins (confounder)&#xD;
&#xD;
          -  Women with multiple gestation, those diagnosed with chronic medical conditions&#xD;
             (diabetes mellitus, hypertension, heart disease, neurological disease or thyroid&#xD;
             disease), and those who tested positive for hepatitis B, HIV or syphilis (associated&#xD;
             with prematurity, intrauterine growth restriction (IUGR) and other neonatal&#xD;
             morbidities which could influence neurodevelopment)&#xD;
&#xD;
          -  Women who anticipate moving out of the city before/ after delivery (follow-up&#xD;
             difficult/not possible, 16% delivered outside Sitaram Bhartia Institute of Science &amp;&#xD;
             Research (SBISR) in earlier work done by Principle Investigator) (3)&#xD;
&#xD;
          -  Women treated for infertility (higher risk of prematurity and neonatal complications&#xD;
&#xD;
          -  Women with known pre-diagnosed mental health disorder including depression, drug or&#xD;
             alcohol abuse likely to affect participation in the study&#xD;
&#xD;
          -  Participation in another study within 4 weeks prior to trial start&#xD;
&#xD;
          -  Allergy to B12 or another supplement constituent&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Only pregnant women are eligible.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Monica Lakhanpaul</last_name>
    <role>Principal Investigator</role>
    <affiliation>University College, London</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Monica Lakhanpaul</last_name>
    <phone>+442079052259</phone>
    <phone_ext>42322</phone_ext>
    <email>m.lakhanpaul@ucl.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Sitaram Bhartia Institute for Science and Research</name>
      <address>
        <city>New Delhi</city>
        <zip>110016</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jitender Nagpal, Dr</last_name>
      <phone>011-42111244</phone>
      <email>jitendernagpal@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Paropakar Maternity and Women's Hospital</name>
      <address>
        <city>Kathmandu</city>
        <zip>44600</zip>
        <country>Nepal</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rajendra P Pant, Dr</last_name>
      <phone>+977-9851046646</phone>
      <email>Rajendrapant8@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Jageshwor Gautam, Prof</last_name>
      <phone>+977-9851027419</phone>
      <email>drjgautam48@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>India</country>
    <country>Nepal</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>July 19, 2019</last_update_submitted>
  <last_update_submitted_qc>July 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vitamin B12</keyword>
  <keyword>Maternal nutrition</keyword>
  <keyword>Neurodevelopment</keyword>
  <keyword>Supplementation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malnutrition</mesh_term>
    <mesh_term>Vitamin B 12 Deficiency</mesh_term>
    <mesh_term>Child Nutrition Disorders</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03783104
org study id: 13795/001
nct id: NCT03783104
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention 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.
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: double-blinded
measure: Infant neurodevelopment
time frame: 9 months in all infant subjects
description: 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
measure: Maternal B12 status
time frame: First trimester (<12 weeks gestation) and third trimester (≥ 27 weeks)
description: 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
measure: Infant B12 status
time frame: 9 months (± 2 weeks) of age after birth
description: The change in biochemical parameters of infant B12 status at 9 months (± 2 weeks) after birth as compared to low dose
measure: Hemoglobin levels and infant anthropometry
time frame: Between first and third trimester
description: The change in hemoglobin levels in the mother
measure: Hemoglobin levels and infant anthropometry
time frame: At 9 months after birth
description: The change in hemoglobin levels in the infant
measure: Hemoglobin levels and infant anthropometry
time frame: At 1, 2, 3, 4, 6 and 9 months after birth
description: The change in infant anthropometry including weight, length, and head circumference (c)
measure: Socio-economic mediators of the relationship between maternal B12 status, supplementation and infant neurodevelopment
time frame: At study enrolment
description: Income, education, profession
measure: Effect of maternal diet
time frame: During the third trimester (27 weeks of gestation)
description: The effect of the intervention on maternal vitamin B12 status, infant B12 status and infant neurodevelopment
measure: Effect of type of milk feeding on infant vitamin B12 status
time frame: At 9 months (± 2 weeks) infant age
description: Assessed by measuring blood levels of B12
measure: Effect of type of milk feeding on infant neurodevelopment
time frame: At 9 months (± 2 weeks) infant age
description: Assessed using the Developmental Assessment Scales for Indian Infants (DASII)
measure: Effect of infant complementary feeding on infant vitamin B12 status
time frame: At 9 months (± 2 weeks) infant age
description: Assessed by measuring blood levels of B12
measure: Effect of infant complementary feeding on infant neurodevelopment
time frame: At 9 months (± 2 weeks) infant age
description: Assessed using the Developmental Assessment Scales for Indian Infants (DASII)
measure: Effect of maternal iron
time frame: In first and third trimester and at 9 months (± 2 weeks) infant age
description: Determining any effect of maternal iron levels in first and third trimester on the relationship between infant vitamin B12 status and infant neurodevelopment
measure: Effect of maternal vitamin D status
time frame: In first and third trimester and at 9 months (± 2 weeks) infant age
description: Determine any effect of maternal vitamin D status in first and third trimester on the relationship between infant vitamin B12 status and infant neurodevelopment
arm group label: 250μg of vitamin B12 supplementation
arm group type: Experimental
description: 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.
arm group label: 50μg of vitamin B12 supplementation
arm group type: Active Comparator
description: 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.
intervention type: Dietary Supplement
intervention name: B12 Supplement
description: Differential doses of vitamin B 12 supplementation in a two-armed randomised controlled trial
arm group label: 250μg of vitamin B12 supplementation
arm group label: 50μg of vitamin B12 supplementation
criteria: 
gender: Female
gender based: Yes
gender description: Only pregnant women are eligible.
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Monica Lakhanpaul
role: Principal Investigator
affiliation: University College, London
last name: Monica Lakhanpaul
phone: +442079052259
phone ext: 42322
email: m.lakhanpaul@ucl.ac.uk
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: India
country: Nepal
responsible party type: Sponsor
mesh term: Malnutrition
mesh term: Vitamin B 12 Deficiency
mesh term: Child Nutrition Disorders