<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/NCT02242188</url>
  </required_header>
  <id_info>
    <org_study_id>SIDBI study</org_study_id>
    <nct_id>NCT02242188</nct_id>
  </id_info>
  <brief_title>Supplementing Iron and Development in Breastfed Infants (SIDBI Study)</brief_title>
  <acronym>SIDBI</acronym>
  <official_title>Effect of Iron Supplementation on Psychomotor Development of Non-anemic Exclusively or Predominantly Breastfed Infants: Randomized, Double-blind, Placebo-controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Warsaw</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Warsaw</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      INTRODUCTION Exclusively breastfed infants are at risk of iron deficiency. American Academy&#xD;
      of Pediatrics (AAP) recommends iron supplementation in exclusively breastfed infants&#xD;
      beginning at 4 months of age. Uncertainty exists regarding the effects of iron&#xD;
      supplementation during infancy on neurodevelopmental outcomes in the absence of anemia.&#xD;
&#xD;
      AIM To establish whether psychomotor and mental development is influenced by early iron&#xD;
      supplementation in healthy, non-anemic, exclusively or predominantly breastfed infants.&#xD;
&#xD;
      METHODS Healthy term newborns will be recruited shortly after birth. If predominantly&#xD;
      breastfed (&gt;50% daily feedings) and non-anemic at 4 months, they will be randomized to&#xD;
      receive either an iron supplement (approx.1mg/kg/day) or placebo until 9 months of age.&#xD;
      Participants will be assessed with use of Bayley Scales of Infant and Toddler Development&#xD;
      (Bayley III) at 12, 24 and 36 months of age.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      INTRODUCTION Iron is a nutrient of essential importance to the human organism. It takes part&#xD;
      in energy production, oxygen transportation, and DNA synthesis and is indispensable for the&#xD;
      development of the central nervous system. Iron is required for the myelination and&#xD;
      production of neurotransmitters. It has been well documented that iron deficiency anemia&#xD;
      (IDA) impairs child development. If the diagnosis of IDA is delayed, the deficits may be&#xD;
      irreversible. Iron deficiency (ID) is the most common single nutrient deficiency and may&#xD;
      affect 12% of children &lt; 3 years of age in industrialized countries. ID has the potential to&#xD;
      negatively influence psychomotor development. However, a causal relationship is not as clear&#xD;
      as for IDA.&#xD;
&#xD;
      Previous studies have suggested that iron supplementation in healthy infants may enhance&#xD;
      psychomotor development. A meta-analysis carried out by our group (Szajewska et al. ) aimed&#xD;
      to evaluate the effects of iron supplementation in non-anemic pregnant women and in&#xD;
      non-anemic healthy children aged &lt;3 years on the mental performance and psychomotor&#xD;
      development of children. The authors identified 7 randomized controlled trials (RCTs), 5 of&#xD;
      which referred to supplementation during infancy. The polled results of 3 RCTs (n = 561)&#xD;
      showed significant improvement on the Psychomotor Development Index (PDI) of the Bayley&#xD;
      Scales of Infant Development at approximately 12 months of age in the iron-supplemented group&#xD;
      compared with the control group (mean difference: 4.21; 95% CI 2.31 to 6.12). No significant&#xD;
      effect of iron supplementation on the Mental Developmental Index (MDI) or behavior was found.&#xD;
      Since the meta-analysis was performed, one relevant new study has been published. In this&#xD;
      follow-up study, cognitive and school performance was measured at the age of 9 years. In the&#xD;
      original study, infants were randomized to receive daily supplementation of iron, zinc, iron&#xD;
      and zinc or placebo from 4 to 6 months of age and an assessment of iron and zinc status, as&#xD;
      well as growth, was performed. No statistically significant difference in cognitive&#xD;
      performance or school performance was reported between the four groups.&#xD;
&#xD;
      Given that ID is a common problem in small children, measures to prevent ID are being taken.&#xD;
      According to Committee of Nutrition of the European Society for Paediatric Gastroenterology,&#xD;
      Hepatology and Nutrition (ESPGHAN CoN), this should be achieved by the promotion of exclusive&#xD;
      breastfeeding, the use of iron-fortified formulas when formula feeding is needed, the&#xD;
      postponement of the introduction of whole cow milk as the main drink until the end of the&#xD;
      first year of life, and the promotion of consumption of complementary foods rich in iron.&#xD;
      More recently, the ESPGHAN CoN concluded that there is no convincing evidence that iron&#xD;
      supplements should be provided to normal birth weight, exclusively breastfed infants during&#xD;
      the first 6 months of life in populations with a low prevalence of IDA among 6-month-olds. In&#xD;
      contrast, the American Academy of Pediatrics (AAP) recommends iron supplementation (1 mg/kg)&#xD;
      in exclusively breastfed infants beginning at 4 months of age that should be continued until&#xD;
      iron from complementary foods is available. Since in partially breastfed infants iron intake&#xD;
      is uncertain, those who receive more than one half of their daily feedings as human milk,&#xD;
      should also be supplemented with 1mg/kg iron beginning at 4 months.&#xD;
&#xD;
      Interventional studies of good methodological quality evaluating the role of iron&#xD;
      supplementation of infants without anemia on their mental and psychomotor development are&#xD;
      still needed.&#xD;
&#xD;
      MATERIALS AND METHODS&#xD;
&#xD;
      This is a randomized, double-blind, placebo-controlled trial.&#xD;
&#xD;
        -  Participants Healthy singleton newborns born at term in a university hospital (St. Anna&#xD;
           Mazowiecka Hospital, Department of Gynecology and Obstetrics, The Medical University of&#xD;
           Warsaw, Poland) will be considered for inclusion. Their mothers will be approached&#xD;
           shortly after birth and informed consent will be obtained. Parents will be contacted&#xD;
           after approximately 3 months in order to establish weather an infant is being&#xD;
           exclusively breastfed. If so, the infant will be randomised to receive either an iron&#xD;
           supplement or a placebo from the age of 4 completed months until 9 months of age.&#xD;
           Infants will also be recruited in well-baby clinics. Apart from recruitment, all study&#xD;
           procedures will be pursued in The Department of Paediatrics, The Medical University of&#xD;
           Warsaw, Poland.&#xD;
&#xD;
        -  Sample size Sample size was calculated with the main outcome of fine and gross motor&#xD;
           scales, cognitive and language development of the Bayley Scales of Infant and Toddler&#xD;
           Development (Bayley III). In the previous editions of the test, these elements of the&#xD;
           assessment were combined into Psychomotor Developmental Index (PDI) and Mental&#xD;
           Developmental Index (MDI). To detect a difference of 5 points between the study groups&#xD;
           with a power of 80% and α =0.05, a sample of 91 infants is needed in each study group.&#xD;
           To account for 20% of loss to follow up, we aim to recruit 220 infants for the study.&#xD;
&#xD;
        -  Interventions Infant in the experimental group will receive ferric pyrophosphate (7mg,&#xD;
           10mg or 15 mg depending on body weight daily, i.e. approx.1 mg/kg/day) or placebo from 4&#xD;
           months to 9 months of age.&#xD;
&#xD;
        -  Allocation concealment and blinding A computer-generated randomisation list will be&#xD;
           prepared. Blocks of ten will be applied. Randomisation will be stratified by infant's&#xD;
           gender. Consecutive randomisation numbers (each number assigned to intervention or&#xD;
           placebo in a blinded way) will be given to participants at enrollment. The study&#xD;
           products will be delivered to the centre in boxes labelled with the letters A and B&#xD;
           (meaning of A and B blinded, information deposited in a sealed envelope in a safe at the&#xD;
           administrative part of the department). The boxes will also carry the information on the&#xD;
           specific dose (7, 10 or 15mg). Subsequently, the letters A and B will be removed from&#xD;
           the boxes by an independent person unrelated to the study planning and conduct, and&#xD;
           replaced with numeric codes corresponding to the randomisation numbers, e.g. 001 - 7mg,&#xD;
           001 - 10mg, 001 - 15mg, 002 - 7mg, 002 - 10mg, 002 - 15mg etc. Sachets containing the&#xD;
           study product will be packed in small packages of 30 pieces each. Neither the collective&#xD;
           packages, nor the sachets will carry any labelling and all the unused sachets will&#xD;
           always be returned by parents before switching to higher dose. The active product and&#xD;
           placebo will be packed in identical sachets and the content will look and taste the&#xD;
           same. Researchers, caregivers, outcome assessors, and a person responsible for the&#xD;
           statistical analysis will be blinded to the intervention until a statistical report for&#xD;
           the 12-months' developmental assessment is available. After that, both the caregivers&#xD;
           and main outcome assessor will remain blinded until the completion of the study. The&#xD;
           information on intervention assignment will be stored in a sealed envelope in a safe in&#xD;
           the administrative part of the department.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2015</start_date>
  <completion_date type="Anticipated">June 2019</completion_date>
  <primary_completion_date type="Anticipated">January 2019</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Psychomotor development</measure>
    <time_frame>12, 24 and 36 months of age</time_frame>
    <description>Psychomotor development will be assessed with the Bayley Scales of Infant and Toddler Development (Bayley III or BSID III) at 12 and 24 months of age.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hematological and iron status</measure>
    <time_frame>4, 12 and 24 months</time_frame>
    <description>Samples will be analyzed for hemoglobin (Hb) concentration, mean corpuscular volume (MCV), hematocrit (HCT), reticulocytes (RET) concentration, serum ferritin, hepcidin, soluble transferrin receptor and calculated soluble transfferin receptor ratio (sTfR), reticulocyte hemoglobin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Growth</measure>
    <time_frame>4, 6, 9, 12, 24 and 36 months</time_frame>
    <description>Weight, length and head circumference will be recorded at 4, 6, 9, 12, 24 and 36 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Behaviour</measure>
    <time_frame>36 months</time_frame>
    <description>Behaviour will be assessed with use of child behavioral checklist (CBCL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>untill 9 months of age (during intervention)</time_frame>
    <description>Parents will be asked to fill out a form of possible adverse events of the intervention daily. The symptoms listed in the form will include diarrhoea, vomiting, constipation, discolouration of the stool, fever, and respiratory tract infections. The forms will be collected at each check-up visit during the intervention.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">220</enrollment>
  <condition>Iron Deficiency</condition>
  <arm_group>
    <arm_group_label>Iron</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ferric pyrophosphate (powder preparation in sachets: Actiferol, SunActive Fe, Sequoia, Poland) in a single daily dose. Three doses will be used: 7 mg for infants up to 7 kg of body weight, 10 mg for infants from 7 to 10 kg of body weight, and 15 mg for those exceeding the weight of 10 kg. Caregivers will be instructed to administer the daily dose at the same time of a day, after mixing the content of the sachet with a little amount of breastmilk or milk formula.&#xD;
The intervention will last from 4 months to 9 months of age.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Maltodextrin prepared in sachets. Caregivers will be instructed to administer the daily dose at the same time of a day, after mixing the content of the sachet with a little amount of breastmilk or milk formula.&#xD;
The intervention will last from 4 months to 9 months of age.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Iron</intervention_name>
    <description>Ferric pyrophosphate (powder preparation in sachets: Actiferol, SunActive Fe, Sequoia, Poland) in a single daily dose. Three doses will be used: 7 mg for infants up to 7 kg of body weight, 10 mg for infants from 7 to 10 kg of body weight, and 15 mg for those exceeding the weight of 10 kg. Caregivers will be instructed to administer the daily dose at the same time of a day, after mixing the content of the sachet with a little amount of breastmilk or milk formula.&#xD;
The intervention will last from 4 months to 9 months of age.</description>
    <arm_group_label>Iron</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Maltodextrin (packed in identical sachets as active products)</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Maltodextrin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Term singleton infants (&gt;37 weeks gestational age)&#xD;
&#xD;
          -  Birth weight &gt; 2500g&#xD;
&#xD;
          -  Healthy at inclusion&#xD;
&#xD;
          -  Breastfed exclusively or predominantly (&gt;50% meals) at inclusion&#xD;
&#xD;
          -  No previous iron supplementation&#xD;
&#xD;
          -  No previous blood transfusion&#xD;
&#xD;
          -  Informed consent given&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  preterm delivery (&lt;37 weeks of gestation)&#xD;
&#xD;
          -  birth weight &lt; 2500 g&#xD;
&#xD;
          -  multiple pregnancy&#xD;
&#xD;
          -  major illness or congenital anomaly&#xD;
&#xD;
          -  being &lt;50% breastfed at the time of inclusion&#xD;
&#xD;
          -  food allergy&#xD;
&#xD;
          -  anaemia (Hb &lt;105 g/L [10.5 g/dL]) at inclusion, lack of informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Weeks</minimum_age>
    <maximum_age>18 Weeks</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anna M Chmielewska, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Medical University of Warsaw</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Anna M Chmielewska, MD, PhD</last_name>
    <phone>0048602677037</phone>
    <email>anna.chmielewska@umu.se</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Pediatrics, The Medical University of Warsaw</name>
      <address>
        <city>Warsaw</city>
        <zip>02091</zip>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna M Chmielewska, MD, PhD</last_name>
      <phone>+48602677037</phone>
      <email>anna.chmielewska@umu.se</email>
    </contact>
    <contact_backup>
      <last_name>Radosław Dryl, MD</last_name>
      <phone>+48791547086</phone>
      <email>radoslawdryl@onet.eu</email>
    </contact_backup>
    <investigator>
      <last_name>Anna M Chmielewska, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Hania Szajewska, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Radosław Dryl, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Małgorzata Pieścik-Lech, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Grzegorz Chmielewski, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>September 14, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>February 21, 2017</last_update_submitted>
  <last_update_submitted_qc>February 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Warsaw</investigator_affiliation>
    <investigator_full_name>Anna Chmielewska</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Breastfeeding</keyword>
  <keyword>Iron supplementation</keyword>
  <keyword>Psychomotor development</keyword>
  <keyword>Safety</keyword>
  <keyword>infants</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Iron Deficiencies</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>This has not been discussed in the study team.</ipd_description>
  </patient_data>
  <!-- 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/NCT02242188
org study id: SIDBI study
nct id: NCT02242188
lead sponsor: 
has dmc: No
INTRODUCTION Exclusively breastfed infants are at risk of iron deficiency. American Academy
      of Pediatrics (AAP) recommends iron supplementation in exclusively breastfed infants
      beginning at 4 months of age. Uncertainty exists regarding the effects of iron
      supplementation during infancy on neurodevelopmental outcomes in the absence of anemia.

      AIM To establish whether psychomotor and mental development is influenced by early iron
      supplementation in healthy, non-anemic, exclusively or predominantly breastfed infants.

      METHODS Healthy term newborns will be recruited shortly after birth. If predominantly
      breastfed (>50% daily feedings) and non-anemic at 4 months, they will be randomized to
      receive either an iron supplement (approx.1mg/kg/day) or placebo until 9 months of age.
      Participants will be assessed with use of Bayley Scales of Infant and Toddler Development
      (Bayley III) at 12, 24 and 36 months of age.
INTRODUCTION Iron is a nutrient of essential importance to the human organism. It takes part
      in energy production, oxygen transportation, and DNA synthesis and is indispensable for the
      development of the central nervous system. Iron is required for the myelination and
      production of neurotransmitters. It has been well documented that iron deficiency anemia
      (IDA) impairs child development. If the diagnosis of IDA is delayed, the deficits may be
      irreversible. Iron deficiency (ID) is the most common single nutrient deficiency and may
      affect 12% of children < 3 years of age in industrialized countries. ID has the potential to
      negatively influence psychomotor development. However, a causal relationship is not as clear
      as for IDA.

      Previous studies have suggested that iron supplementation in healthy infants may enhance
      psychomotor development. A meta-analysis carried out by our group (Szajewska et al. ) aimed
      to evaluate the effects of iron supplementation in non-anemic pregnant women and in
      non-anemic healthy children aged <3 years on the mental performance and psychomotor
      development of children. The authors identified 7 randomized controlled trials (RCTs), 5 of
      which referred to supplementation during infancy. The polled results of 3 RCTs (n = 561)
      showed significant improvement on the Psychomotor Development Index (PDI) of the Bayley
      Scales of Infant Development at approximately 12 months of age in the iron-supplemented group
      compared with the control group (mean difference: 4.21; 95% CI 2.31 to 6.12). No significant
      effect of iron supplementation on the Mental Developmental Index (MDI) or behavior was found.
      Since the meta-analysis was performed, one relevant new study has been published. In this
      follow-up study, cognitive and school performance was measured at the age of 9 years. In the
      original study, infants were randomized to receive daily supplementation of iron, zinc, iron
      and zinc or placebo from 4 to 6 months of age and an assessment of iron and zinc status, as
      well as growth, was performed. No statistically significant difference in cognitive
      performance or school performance was reported between the four groups.

      Given that ID is a common problem in small children, measures to prevent ID are being taken.
      According to Committee of Nutrition of the European Society for Paediatric Gastroenterology,
      Hepatology and Nutrition (ESPGHAN CoN), this should be achieved by the promotion of exclusive
      breastfeeding, the use of iron-fortified formulas when formula feeding is needed, the
      postponement of the introduction of whole cow milk as the main drink until the end of the
      first year of life, and the promotion of consumption of complementary foods rich in iron.
      More recently, the ESPGHAN CoN concluded that there is no convincing evidence that iron
      supplements should be provided to normal birth weight, exclusively breastfed infants during
      the first 6 months of life in populations with a low prevalence of IDA among 6-month-olds. In
      contrast, the American Academy of Pediatrics (AAP) recommends iron supplementation (1 mg/kg)
      in exclusively breastfed infants beginning at 4 months of age that should be continued until
      iron from complementary foods is available. Since in partially breastfed infants iron intake
      is uncertain, those who receive more than one half of their daily feedings as human milk,
      should also be supplemented with 1mg/kg iron beginning at 4 months.

      Interventional studies of good methodological quality evaluating the role of iron
      supplementation of infants without anemia on their mental and psychomotor development are
      still needed.

      MATERIALS AND METHODS

      This is a randomized, double-blind, placebo-controlled trial.

        -  Participants Healthy singleton newborns born at term in a university hospital (St. Anna
           Mazowiecka Hospital, Department of Gynecology and Obstetrics, The Medical University of
           Warsaw, Poland) will be considered for inclusion. Their mothers will be approached
           shortly after birth and informed consent will be obtained. Parents will be contacted
           after approximately 3 months in order to establish weather an infant is being
           exclusively breastfed. If so, the infant will be randomised to receive either an iron
           supplement or a placebo from the age of 4 completed months until 9 months of age.
           Infants will also be recruited in well-baby clinics. Apart from recruitment, all study
           procedures will be pursued in The Department of Paediatrics, The Medical University of
           Warsaw, Poland.

        -  Sample size Sample size was calculated with the main outcome of fine and gross motor
           scales, cognitive and language development of the Bayley Scales of Infant and Toddler
           Development (Bayley III). In the previous editions of the test, these elements of the
           assessment were combined into Psychomotor Developmental Index (PDI) and Mental
           Developmental Index (MDI). To detect a difference of 5 points between the study groups
           with a power of 80% and α =0.05, a sample of 91 infants is needed in each study group.
           To account for 20% of loss to follow up, we aim to recruit 220 infants for the study.

        -  Interventions Infant in the experimental group will receive ferric pyrophosphate (7mg,
           10mg or 15 mg depending on body weight daily, i.e. approx.1 mg/kg/day) or placebo from 4
           months to 9 months of age.

        -  Allocation concealment and blinding A computer-generated randomisation list will be
           prepared. Blocks of ten will be applied. Randomisation will be stratified by infant's
           gender. Consecutive randomisation numbers (each number assigned to intervention or
           placebo in a blinded way) will be given to participants at enrollment. The study
           products will be delivered to the centre in boxes labelled with the letters A and B
           (meaning of A and B blinded, information deposited in a sealed envelope in a safe at the
           administrative part of the department). The boxes will also carry the information on the
           specific dose (7, 10 or 15mg). Subsequently, the letters A and B will be removed from
           the boxes by an independent person unrelated to the study planning and conduct, and
           replaced with numeric codes corresponding to the randomisation numbers, e.g. 001 - 7mg,
           001 - 10mg, 001 - 15mg, 002 - 7mg, 002 - 10mg, 002 - 15mg etc. Sachets containing the
           study product will be packed in small packages of 30 pieces each. Neither the collective
           packages, nor the sachets will carry any labelling and all the unused sachets will
           always be returned by parents before switching to higher dose. The active product and
           placebo will be packed in identical sachets and the content will look and taste the
           same. Researchers, caregivers, outcome assessors, and a person responsible for the
           statistical analysis will be blinded to the intervention until a statistical report for
           the 12-months' developmental assessment is available. After that, both the caregivers
           and main outcome assessor will remain blinded until the completion of the study. The
           information on intervention assignment will be stored in a sealed envelope in a safe in
           the administrative part of the department.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Psychomotor development
time frame: 12, 24 and 36 months of age
description: Psychomotor development will be assessed with the Bayley Scales of Infant and Toddler Development (Bayley III or BSID III) at 12 and 24 months of age.
measure: Hematological and iron status
time frame: 4, 12 and 24 months
description: Samples will be analyzed for hemoglobin (Hb) concentration, mean corpuscular volume (MCV), hematocrit (HCT), reticulocytes (RET) concentration, serum ferritin, hepcidin, soluble transferrin receptor and calculated soluble transfferin receptor ratio (sTfR), reticulocyte hemoglobin.
measure: Growth
time frame: 4, 6, 9, 12, 24 and 36 months
description: Weight, length and head circumference will be recorded at 4, 6, 9, 12, 24 and 36 months.
measure: Behaviour
time frame: 36 months
description: Behaviour will be assessed with use of child behavioral checklist (CBCL)
measure: Adverse events
time frame: untill 9 months of age (during intervention)
description: Parents will be asked to fill out a form of possible adverse events of the intervention daily. The symptoms listed in the form will include diarrhoea, vomiting, constipation, discolouration of the stool, fever, and respiratory tract infections. The forms will be collected at each check-up visit during the intervention.
arm group label: Iron
arm group type: Experimental
description: Ferric pyrophosphate (powder preparation in sachets: Actiferol, SunActive Fe, Sequoia, Poland) in a single daily dose. Three doses will be used: 7 mg for infants up to 7 kg of body weight, 10 mg for infants from 7 to 10 kg of body weight, and 15 mg for those exceeding the weight of 10 kg. Caregivers will be instructed to administer the daily dose at the same time of a day, after mixing the content of the sachet with a little amount of breastmilk or milk formula.
The intervention will last from 4 months to 9 months of age.
arm group label: Placebo
arm group type: Placebo Comparator
description: Maltodextrin prepared in sachets. Caregivers will be instructed to administer the daily dose at the same time of a day, after mixing the content of the sachet with a little amount of breastmilk or milk formula.
The intervention will last from 4 months to 9 months of age.
intervention type: Drug
intervention name: Iron
description: Ferric pyrophosphate (powder preparation in sachets: Actiferol, SunActive Fe, Sequoia, Poland) in a single daily dose. Three doses will be used: 7 mg for infants up to 7 kg of body weight, 10 mg for infants from 7 to 10 kg of body weight, and 15 mg for those exceeding the weight of 10 kg. Caregivers will be instructed to administer the daily dose at the same time of a day, after mixing the content of the sachet with a little amount of breastmilk or milk formula.
The intervention will last from 4 months to 9 months of age.
arm group label: Iron
intervention type: Dietary Supplement
intervention name: Placebo
description: Maltodextrin (packed in identical sachets as active products)
arm group label: Placebo
other name: Maltodextrin
criteria: 
gender: All
minimum age: 16 Weeks
maximum age: 18 Weeks
healthy volunteers: Accepts Healthy Volunteers
last name: Anna M Chmielewska, MD, PhD
role: Principal Investigator
affiliation: The Medical University of Warsaw
last name: Anna M Chmielewska, MD, PhD
phone: 0048602677037
email: anna.chmielewska@umu.se
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
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country: Poland
responsible party type: Principal Investigator
investigator affiliation: Medical University of Warsaw
investigator full name: Anna Chmielewska
investigator title: MD, PhD
mesh term: Iron Deficiencies
sharing ipd: Undecided
ipd description: This has not been discussed in the study team.