<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/NCT01728766</url>
  </required_header>
  <id_info>
    <org_study_id>2006-035</org_study_id>
    <nct_id>NCT01728766</nct_id>
  </id_info>
  <brief_title>Breast Milk Zinc Transfer to Appropriate- and Small-for-gestational-age Bangladeshi Infants</brief_title>
  <official_title>Longitudinal Studies of Breast Milk Zinc Transfer to Appropriate- and Small-for-gestational-age, Predominantly Breast Fed, Bangladeshi Infants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>International Centre for Diarrhoeal Disease Research, Bangladesh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, Davis</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>International Centre for Diarrhoeal Disease Research, Bangladesh</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Data collected from this study will provide information on the breast milk zinc&#xD;
      concentration, maternal and infant zinc status, and transfer of zinc from mothers breast milk&#xD;
      to infants during first six months of life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The International Atomic Energy Agency (IAEA) has reviewed published literature to collect&#xD;
      information for its Coordinated Research Project (CRP) on Zinc Nutrition During Early Life ,&#xD;
      and observed that there is limited information on: 1) the concentration of zinc in breast&#xD;
      milk of mothers in lower income countries at different times post-partum; 2) the total amount&#xD;
      of zinc transferred from mothers to infants at different ages in these settings, and 3) zinc&#xD;
      transfer from mother to infant born with appropriate-for-gestational-age (AGA) and&#xD;
      small-for-gestational-age (SGA). Therefore, IAEA has planned to assist local scientists to&#xD;
      collect such information from selected countries. The International Zinc Nutrition&#xD;
      Consultative Group (IZiNCG) has identified Bangladesh as a country with high risk of zinc&#xD;
      deficiency (IZiNCG, 2004), where the rate of SGA infants is &gt;30% - one of the highest in the&#xD;
      world (de Onis, 1998). Thus, Bangladesh is an appropriate candidate country to participate in&#xD;
      this CRP.&#xD;
&#xD;
      This study will enroll 50 healthy, full-term, newborn infants (&gt;37 weeks gestational age by&#xD;
      ultrasound) and their mothers if they plan to breast-feed exclusively for at least 4 months&#xD;
      and also to continue breast feeding for at least 12 months. The infants will be examined,&#xD;
      weighed and measured within 48 hours of birth, half of whom will be AGA (BW&gt;2800g) and the&#xD;
      other half SGA (BW&lt;2500g). Infants with any acute or chronic illnesses, or congenital&#xD;
      anomalies will not be eligible. Any mother with toxaemia, pregnancy-induced hypertension,&#xD;
      multiple pregnancies, previously diagnosed as positive for HIV/hepatitis B infections, or&#xD;
      habituated to smoking or alcohol consumption will also be excluded. The participants will be&#xD;
      recruited from Nandipara, Dhaka, an urban community where the ICDDRB has ongoing clinical&#xD;
      study facilities.&#xD;
&#xD;
      Each of the eligible mother-infant pairs will be studied in 3 separate rounds, at 4, 12 and&#xD;
      24 weeks post-partum. In each round, two-week studies of breast milk transfer from the mother&#xD;
      to the infant will be carried out, using the deuterium &quot;dose-to-the-mother&quot; technique. In&#xD;
      each round, the women will be requested to attend the Dhaka Hospital of ICDDR, B on day 0,&#xD;
      for collection of baseline saliva samples from mother-infant pairs and administration of&#xD;
      deuterium to the mothers. Study health workers will make home visits on days 1, 2, 3, 4, 13,&#xD;
      and 14 and collect saliva samples from the infants and their mothers on days 1, 2, 13 and 14,&#xD;
      of each round.&#xD;
&#xD;
      ~2 ml of saliva will be collected for each sample from both the mother and the infant.&#xD;
&#xD;
      On days 0 and 4 of each round, 5-10 ml of manually-expressed breast milk will be collected&#xD;
      for determining their zinc concentration. The total zinc transfer from mother to infant will&#xD;
      be calculated as the product of the mean daily milk volume, as determined from the deuterium&#xD;
      studies, and the mean milk zinc concentration on the days of milk collection.&#xD;
&#xD;
      On the first day of each of the rounds at 4, 12 and 24 week post-partum 2.0 ml of venous&#xD;
      blood will be collected from both the mothers and infants for serum zinc assay.&#xD;
&#xD;
      Body weight, length and head circumference of infants, and body weight and height of mothers&#xD;
      will be measured on day 0 at 4, 12 and 24 week post-partum.&#xD;
&#xD;
      Breast milk volume and zinc concentration, and total zinc transfer from mothers to infants&#xD;
      will be the major outcome variables, which will be examined for conformance to the normal&#xD;
      distribution and transformed if required. Means of the major outcome variables will be&#xD;
      compared for AGA and SGA infants for each time points, using repeated measures ANOVA.&#xD;
      Repeated measures analysis of covariance will be used to assess if these relationships change&#xD;
      with age. Analyses will be done with SAS Release 9 and SPSS version 10.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2006</start_date>
  <completion_date type="Actual">October 2008</completion_date>
  <primary_completion_date type="Actual">October 2008</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Amount of zinc transferred through breast milk</measure>
    <time_frame>at 4, 12 and 24 weeks after delivery of the infants</time_frame>
    <description>During each round of study, a milk sample was collected during the visit to icddr,b on study day 1 and 5. On each occasion, the breast was cleansed with soap and water and rinsed with copious amounts of deionized water. The milk sample was then collected ~2-3 minutes after the feeding was initiated by momentarily removing the infant from the breast, so the study assistant could manually express 5-10 mL milk into a zinc-free beaker. The milk sample was then transferred to a plastic screw cap vial and transported to the laboratory, as described above for the saliva samples. The milk zinc concentration was measured by atomic absorption spectrometer (AAS, AA6501S, Shimadzu, Kyoto, Japan). The total zinc transfer from mother to infant was calculated as the product of the mean daily milk volume, as determined from the deuterium tracer studies, and the mean milk zinc concentration on the corresponding milk collection days.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma zinc content of both the mother and the infant</measure>
    <time_frame>at 4, 12 and 24 weeks after the delivery of the infants</time_frame>
    <description>On the first morning of each round, 2 mL of venous blood was drawn from both the mother and infant for plasma zinc analyses, using stainless steel needles and certified trace element-free, evacuated collection tubes (Sarstedt LiH monovette, Sarstedt, Newton, NC, USA). The infant samples were drawn 90 minutes after the first morning feeding, but the mothers' samples were not timed in relation to meals. The plasma was separated within 60 minutes and stored at -20o C until analysis. The plasma samples were diluted (1:12) with distilled, deionized water, vortexed, and analyzed using the same AAS described above. The plasma samples were also compared with commercially available standard zinc nitrate solution (BDH, England), bi-level control serum (Cat # 66816; UTAK Laboratories Inc, Valencia, CA), and pooled serum to determine the accuracy and precision of the analyses.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">76</enrollment>
  <condition>Small for Gestational Age at Delivery</condition>
  <condition>Post-term Infant, Not Heavy-for-dates</condition>
  <arm_group>
    <arm_group_label>Infants under-6 months and their mothers</arm_group_label>
    <description>Small for gestational age at delivery. Post-term Infant, Not Heavy-for-dates.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Small for gestational age at delivery</intervention_name>
    <description>Small for gestational age at delivery. gestational age at &gt;37 weeks by and birth weight &lt;2500 g</description>
    <arm_group_label>Infants under-6 months and their mothers</arm_group_label>
    <other_name>Small-for-Gestational Age (SGA)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Post-term Infant, Not Heavy-for-dates</intervention_name>
    <description>Appropriate for gestational age at delivery. Gestational age at &gt;37 weeks and birth weight &gt;2800 g</description>
    <arm_group_label>Infants under-6 months and their mothers</arm_group_label>
    <other_name>Appropriate-for-gestational age (AGA)</other_name>
  </intervention>
  <biospec_retention>None Retained</biospec_retention>
  <biospec_descr>
    <textblock>
      Breast milk Plasma&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The participants were 46 mothers and their term infants, 20 of whom were classified as&#xD;
        appropriate for gestational age (AGA, birth weight &gt;2800 g at ≥37 weeks of gestation) and&#xD;
        26 of whom were classified as small for gestational age (SGA, birth weight &lt;2500 g at ≥37&#xD;
        weeks of gestation). Gestational age was assessed by ultrasonography at ~32 weeks of&#xD;
        gestation. Only mothers who were planning to breast feed exclusively for at least four&#xD;
        months were included in the study. Mothers with pregnancy-induced hypertension, multiple&#xD;
        pregnancies, known HIV or hepatitis B infection, or use of tobacco products or alcohol were&#xD;
        excluded from the study, as were infants with congenital abnormalities, chronic infections,&#xD;
        or acute illnesses at the time of enrollment.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  AGA, birth weight &gt;2800 g at ≥37 weeks of gestation&#xD;
&#xD;
          -  SGA, birth weight &lt;2500 g at ≥37 weeks of gestation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other than the above birth weight&#xD;
&#xD;
          -  Any congenital anomalies abnormalities, chronic infections as were infants with c, or&#xD;
             acute illnesses at the time of enrollment&#xD;
&#xD;
          -  Mothers with pregnancy-induced hypertension, multiple pregnancies, known HIV or&#xD;
             hepatitis B infection, or use of tobacco products or alcohol were excluded from the&#xD;
             study,&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>6 Months</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dr M Munirul Islam, MBBS, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Associate Scientist</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>International Centre for Diarrhoeal Disease Research, Bangladesh ( icddr,b),</name>
      <address>
        <city>Dhaka</city>
        <zip>1212</zip>
        <country>Bangladesh</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bangladesh</country>
  </location_countries>
  <verification_date>November 2012</verification_date>
  <study_first_submitted>November 4, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <last_update_submitted>June 1, 2017</last_update_submitted>
  <last_update_submitted_qc>June 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Breast milk zinc transfer</keyword>
  <keyword>Bangladeshi infants</keyword>
  <keyword>appropriate-for-gestational-age</keyword>
  <keyword>small-for-gestational-age</keyword>
  <keyword>plasma zinc</keyword>
  <!-- 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/NCT01728766
org study id: 2006-035
nct id: NCT01728766
lead sponsor: 
collaborator: 
has dmc: No
Data collected from this study will provide information on the breast milk zinc
      concentration, maternal and infant zinc status, and transfer of zinc from mothers breast milk
      to infants during first six months of life.
The International Atomic Energy Agency (IAEA) has reviewed published literature to collect
      information for its Coordinated Research Project (CRP) on Zinc Nutrition During Early Life ,
      and observed that there is limited information on: 1) the concentration of zinc in breast
      milk of mothers in lower income countries at different times post-partum; 2) the total amount
      of zinc transferred from mothers to infants at different ages in these settings, and 3) zinc
      transfer from mother to infant born with appropriate-for-gestational-age (AGA) and
      small-for-gestational-age (SGA). Therefore, IAEA has planned to assist local scientists to
      collect such information from selected countries. The International Zinc Nutrition
      Consultative Group (IZiNCG) has identified Bangladesh as a country with high risk of zinc
      deficiency (IZiNCG, 2004), where the rate of SGA infants is >30% - one of the highest in the
      world (de Onis, 1998). Thus, Bangladesh is an appropriate candidate country to participate in
      this CRP.

      This study will enroll 50 healthy, full-term, newborn infants (>37 weeks gestational age by
      ultrasound) and their mothers if they plan to breast-feed exclusively for at least 4 months
      and also to continue breast feeding for at least 12 months. The infants will be examined,
      weighed and measured within 48 hours of birth, half of whom will be AGA (BW>2800g) and the
      other half SGA (BW<2500g). Infants with any acute or chronic illnesses, or congenital
      anomalies will not be eligible. Any mother with toxaemia, pregnancy-induced hypertension,
      multiple pregnancies, previously diagnosed as positive for HIV/hepatitis B infections, or
      habituated to smoking or alcohol consumption will also be excluded. The participants will be
      recruited from Nandipara, Dhaka, an urban community where the ICDDRB has ongoing clinical
      study facilities.

      Each of the eligible mother-infant pairs will be studied in 3 separate rounds, at 4, 12 and
      24 weeks post-partum. In each round, two-week studies of breast milk transfer from the mother
      to the infant will be carried out, using the deuterium "dose-to-the-mother" technique. In
      each round, the women will be requested to attend the Dhaka Hospital of ICDDR, B on day 0,
      for collection of baseline saliva samples from mother-infant pairs and administration of
      deuterium to the mothers. Study health workers will make home visits on days 1, 2, 3, 4, 13,
      and 14 and collect saliva samples from the infants and their mothers on days 1, 2, 13 and 14,
      of each round.

      ~2 ml of saliva will be collected for each sample from both the mother and the infant.

      On days 0 and 4 of each round, 5-10 ml of manually-expressed breast milk will be collected
      for determining their zinc concentration. The total zinc transfer from mother to infant will
      be calculated as the product of the mean daily milk volume, as determined from the deuterium
      studies, and the mean milk zinc concentration on the days of milk collection.

      On the first day of each of the rounds at 4, 12 and 24 week post-partum 2.0 ml of venous
      blood will be collected from both the mothers and infants for serum zinc assay.

      Body weight, length and head circumference of infants, and body weight and height of mothers
      will be measured on day 0 at 4, 12 and 24 week post-partum.

      Breast milk volume and zinc concentration, and total zinc transfer from mothers to infants
      will be the major outcome variables, which will be examined for conformance to the normal
      distribution and transformed if required. Means of the major outcome variables will be
      compared for AGA and SGA infants for each time points, using repeated measures ANOVA.
      Repeated measures analysis of covariance will be used to assess if these relationships change
      with age. Analyses will be done with SAS Release 9 and SPSS version 10.
observational model: Cohort
time perspective: Prospective
measure: Amount of zinc transferred through breast milk
time frame: at 4, 12 and 24 weeks after delivery of the infants
description: During each round of study, a milk sample was collected during the visit to icddr,b on study day 1 and 5. On each occasion, the breast was cleansed with soap and water and rinsed with copious amounts of deionized water. The milk sample was then collected ~2-3 minutes after the feeding was initiated by momentarily removing the infant from the breast, so the study assistant could manually express 5-10 mL milk into a zinc-free beaker. The milk sample was then transferred to a plastic screw cap vial and transported to the laboratory, as described above for the saliva samples. The milk zinc concentration was measured by atomic absorption spectrometer (AAS, AA6501S, Shimadzu, Kyoto, Japan). The total zinc transfer from mother to infant was calculated as the product of the mean daily milk volume, as determined from the deuterium tracer studies, and the mean milk zinc concentration on the corresponding milk collection days.
measure: Plasma zinc content of both the mother and the infant
time frame: at 4, 12 and 24 weeks after the delivery of the infants
description: On the first morning of each round, 2 mL of venous blood was drawn from both the mother and infant for plasma zinc analyses, using stainless steel needles and certified trace element-free, evacuated collection tubes (Sarstedt LiH monovette, Sarstedt, Newton, NC, USA). The infant samples were drawn 90 minutes after the first morning feeding, but the mothers' samples were not timed in relation to meals. The plasma was separated within 60 minutes and stored at -20o C until analysis. The plasma samples were diluted (1:12) with distilled, deionized water, vortexed, and analyzed using the same AAS described above. The plasma samples were also compared with commercially available standard zinc nitrate solution (BDH, England), bi-level control serum (Cat # 66816; UTAK Laboratories Inc, Valencia, CA), and pooled serum to determine the accuracy and precision of the analyses.
arm group label: Infants under-6 months and their mothers
description: Small for gestational age at delivery. Post-term Infant, Not Heavy-for-dates.
intervention type: Other
intervention name: Small for gestational age at delivery
description: Small for gestational age at delivery. gestational age at >37 weeks by and birth weight <2500 g
arm group label: Infants under-6 months and their mothers
other name: Small-for-Gestational Age (SGA)
intervention type: Other
intervention name: Post-term Infant, Not Heavy-for-dates
description: Appropriate for gestational age at delivery. Gestational age at >37 weeks and birth weight >2800 g
arm group label: Infants under-6 months and their mothers
other name: Appropriate-for-gestational age (AGA)
Breast milk Plasma
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Day
maximum age: 6 Months
healthy volunteers: Accepts Healthy Volunteers
last name: Dr M Munirul Islam, MBBS, PhD
role: Principal Investigator
affiliation: Associate Scientist
facility: 
country: Bangladesh
responsible party type: Sponsor