Iron DeficiencyNCT00642863
Brain and Behavior Depending on Timing of Iron Deficiency in Human Infants
A study testing Ferrous Sulfate (liquid) + vitamins A and D, vitamins A and D and Ferrous sulfate (liquid) in people with Iron Deficiency and Iron Deficiency Anemia, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in China.
Trial summary
It is common in many populations that babies develop iron deficiency or iron deficiency anemia (that is, too few healthy red blood cells due to lack of iron). This is due to rapid growth in infancy combined with limited sources of iron in the infant diet. Read more about this study
- Who is it for?
- Ages Up to 5 days
- Conditions the study is for
- Iron Deficiency, Iron Deficiency Anemia
- What is being tested?
- Ferrous Sulfate (liquid) + vitamins A and D, vitamins A and D and Ferrous sulfate (liquid)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,614 participants
- Where
- 1 siteChina
- Study dates
- Apr 2008to Jun 2014
- 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 Up to 5 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- infants born at Maternity and Children's Hospitals of Fuyang city in China
- healthy term newborns from uncomplicated pregnancies for hematology screening
- healthy full-term singleton infants with cord Hb and ferritin in the low-marginal or normal range for developmental testing
Who cannot join
- perinatal complications
Trial locations and contacts
1 site in 1 country.
China1 site
Children's Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003
About this study
It is common in many populations that babies develop iron deficiency or iron deficiency anemia (that is, too few healthy red blood cells due to lack of iron). This is due to rapid growth in infancy combined with limited sources of iron in the infant diet. The amount of iron the baby receives across the placenta during pregnancy is another important factor. This study focuses on infants who are born with less than the usual amount of iron in their bodies. The purposes of the study are to assess effects of lower iron at birth on infant behavior and development and to determine if providing iron supplements to such infants beginning at 6 weeks fosters healthier development. Another part of the study will determine the effects of iron deficiency anemia at different times during infant development.
Read the detailed description
The project focuses on brain-behavior effects depending on the timing of iron deficiency (ID) and iron repletion in human infants. Iron deficiency (ID) is the world's most common single nutrient disorder, differentially affecting pregnant women and infants everywhere. The study promises to be the first systematic investigation of brain and behavior effects of prenatal dietary iron deficiency in human infants. The design will support comparisons of brain/behavior effects depending on the timing and duration of ID. The study will assess reversibility of effects, depending on timing of ID and its treatment, and examine maternal vs. fetal iron regulatory mechanisms in placenta and white blood cells. State-of-the-art neurophysiologic and behavioral measures will test specific hypotheses regarding effects of ID on sensory, motor, cognitive, affective-social and regulatory functions related to impaired myelination of sensory/motor systems and altered structure, neurotransmitter function and neurometabolism in targeted brain regions (basal ganglia and hippocampus). The study will be conducted in China, a rapidly developing country where ID often occurs among pregnant women and infants in the absence of generalized undernutrition. Cord blood hemoglobin (Hb) and ferritin concentrations will be measured in 1300 rural full-term infants, with iron status determined again at 9 and 18 mo. Brain-behavior assessments in the perinatal period will involve 359 infants ("newborn cohort"): 59 with low Hb ("low birth iron" group) will receive iron; 200 with marginal Hb or low cord ferritin ("marginal birth iron" group) will be randomly assigned at 6 wk, 50 to iron therapy and 150 to vitamins only; and 100 with normal cord Hb and ferritin levels ("normal birth iron" group) will receive vitamins only. The remaining 763 infants with cord blood testing will form the "blood screen cohort." At 9 and 18 mo, the newborn cohort will be reassessed, along with IDA infants from the blood screen cohort - about 58 at 9 mo ("early postnatal IDA") and 48 at 18 mo ("late postnatal IDA"). Approximately 39 marginal-birth-iron vitamins only-treated infants in the newborn cohort may also have IDA at 9 mo ("combined ID"). IDA infants will be treated with vitamins with iron. Differential effects and/or reversibility depending on timing of ID or treatment could inform health policy and practice worldwide. However, the effects of prenatal iron deficiency have received very little study in human infants due in large part to previous thinking, no longer accepted, that the infant was protected. Up to 75% of pregnant women worldwide are anemic, with about half due to ID. An estimated 20-25% of 6- to 24-mo-old infants have IDA, and more have ID without anemia. Thus, the public health implications of study findings could be profound.
The project is expected to continue with a 5-year follow-up (Aug 2013-July 2017).
- Conditions
- Iron Deficiency, Iron Deficiency Anemia
- Being tested
- Ferrous Sulfate (liquid) + vitamins A and D, vitamins A and D, Ferrous sulfate (liquid)
- Keywords
- iron deficiency, iron deficiency anemia, infant, development, behavior
- Medical subject headings
- Iron Deficiencies, Anemia, Iron-Deficiency, Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferrous Sulfate (liquid) + vitamins A and DDietary supplement
a single daily dose of 1-2 mg/kg of elemental iron (5 mg from 6 wk to 9 mo and 15 mg from 9 to 18 mo.) and 1500 IU vitamin A and 500 IU vitamin D from 6 wk to 18 mo.
vitamins A and DDietary supplement
a single daily dose (liquid) of 1500 IU vitamin A and 500 IU vitamin D from 6 wk to 18 mo.
Ferrous sulfate (liquid)Dietary supplement
Infants who become iron deficient/anemic at 9 or 18 mo will take a single daily dose of 3 mg/kg of elemental iron for 3 months.
| Study group | Role | What they receive |
|---|---|---|
| Low birth iron | Experimental | Infants with low birth iron who receive vitamins A and D + iron Receives: Dietary Supplement: Ferrous Sulfate (liquid) + vitamins A and D |
| Marginal birth iron 1 | Experimental | Infants with marginal birth iron randomized to receive vitamins A and D + iron Receives: Dietary Supplement: Ferrous Sulfate (liquid) + vitamins A and D |
| Marginal birth iron 2 | Active comparator | Infants with marginal birth iron randomized to receive vitamins A and D without iron Receives: Dietary Supplement: vitamins A and D |
| Normal birth iron | Active comparator | Infants with normal birth iron who receive vitamins A and D without iron Receives: Dietary Supplement: vitamins A and D |
| Combined ID | Experimental | Marginal-birth-iron vitamins only-treated infants who have IDA at 9 mo. Receives: Dietary Supplement: Ferrous sulfate (liquid) |
| Early postnatal IDA | Experimental | Infants with IDA at 9 months whose cord blood was collected at birth but who were not assessed and assigned to vitamins with or without iron at 6 weeks Receives: Dietary Supplement: Ferrous sulfate (liquid) |
| Late postnatal IDA | Experimental | Infants with IDA at 18 months whose cord blood was collected at birth but who were not assessed and assigned to vitamins with or without iron at 6 weeks. These infants were also not anemic when screened at 9 months. Receives: Dietary Supplement: Ferrous sulfate (liquid) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infant behavior and development
Measured: 6 weeks; 9 and 18 months
Secondary outcomes (2)
Low or marginal birth iron
Measured: 6 weeks
Infant anemia
Measured: 9 and 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2008 (estimated)
- Study startApr 2008
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Iron DeficiencyStudies of the same condition, open and under way.
- 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
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,614 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Betsy Lozoff, MD, Principal investigator, University of MichiganJie Shao, MD, Study director, The Children's Hospital of Zhejiang University School of MedicineZhengyan Zhao, MD, Study director, The Children's Hospital of Zhejiang University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00642863
- Sponsor's protocol ID
- 2P01HD039386-06A1
- Other IDs
- 2P01HD039386-06A1
- Status last verified
- Mar 2014
- First submitted
- 21 Mar 2008
- Last updated
- 29 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Clark KM, Li M, Zhu B, Liang F, Shao J, Zhang Y, Ji C, Zhao Z, Kaciroti N, Lozoff B. Breastfeeding, Mixed, or Formula Feeding at 9 Months of Age and the Prevalence of Iron Deficiency and Iron Deficiency Anemia in Two Cohorts of Infants in China. J Pediatr. 2017 Feb;181:56-61. doi: 10.1016/j.jpeds.2016.10.041. Epub 2016 Nov 8.
PubMed 27836288
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain and Behavior Depending on Timing of Iron Deficiency in Human Infants
- ClinicalTrials.gov ID
- NCT00642863
- Acronym / sponsor ID
- 2P01HD039386-06A1
- Conditions
- Iron Deficiency, Iron Deficiency Anemia
- Keywords
- iron deficiency, iron deficiency anemia, infant, development, behavior
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,614 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- Apr 2008
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 25 Mar 2008 (estimated)
- 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.
It is common in many populations that babies develop iron deficiency or iron deficiency anemia (that is, too few healthy red blood cells due to lack of iron). This is due to rapid growth in infancy combined with limited sources of iron in the infant diet. The amount of iron the baby receives across the placenta during pregnancy is another important factor. This study focuses on infants who are born with less than the usual amount of iron in their bodies. The purposes of the study are to assess effects of lower iron at birth on infant behavior and development and to determine if providing iron supplements to such infants beginning at 6 weeks fosters healthier development. Another part of the study will determine the effects of iron deficiency anemia at different times during infant development.
Detailed description
The project focuses on brain-behavior effects depending on the timing of iron deficiency (ID) and iron repletion in human infants. Iron deficiency (ID) is the world's most common single nutrient disorder, differentially affecting pregnant women and infants everywhere. The study promises to be the first systematic investigation of brain and behavior effects of prenatal dietary iron deficiency in human infants. The design will support comparisons of brain/behavior effects depending on the timing and duration of ID. The study will assess reversibility of effects, depending on timing of ID and its treatment, and examine maternal vs. fetal iron regulatory mechanisms in placenta and white blood cells. State-of-the-art neurophysiologic and behavioral measures will test specific hypotheses regarding effects of ID on sensory, motor, cognitive, affective-social and regulatory functions related to impaired myelination of sensory/motor systems and altered structure, neurotransmitter function and neurometabolism in targeted brain regions (basal ganglia and hippocampus). The study will be conducted in China, a rapidly developing country where ID often occurs among pregnant women and infants in the absence of generalized undernutrition. Cord blood hemoglobin (Hb) and ferritin concentrations will be measured in 1300 rural full-term infants, with iron status determined again at 9 and 18 mo. Brain-behavior assessments in the perinatal period will involve 359 infants ("newborn cohort"): 59 with low Hb ("low birth iron" group) will receive iron; 200 with marginal Hb or low cord ferritin ("marginal birth iron" group) will be randomly assigned at 6 wk, 50 to iron therapy and 150 to vitamins only; and 100 with normal cord Hb and ferritin levels ("normal birth iron" group) will receive vitamins only. The remaining 763 infants with cord blood testing will form the "blood screen cohort." At 9 and 18 mo, the newborn cohort will be reassessed, along with IDA infants from the blood screen cohort - about 58 at 9 mo ("early postnatal IDA") and 48 at 18 mo ("late postnatal IDA"). Approximately 39 marginal-birth-iron vitamins only-treated infants in the newborn cohort may also have IDA at 9 mo ("combined ID"). IDA infants will be treated with vitamins with iron. Differential effects and/or reversibility depending on timing of ID or treatment could inform health policy and practice worldwide. However, the effects of prenatal iron deficiency have received very little study in human infants due in large part to previous thinking, no longer accepted, that the infant was protected. Up to 75% of pregnant women worldwide are anemic, with about half due to ID. An estimated 20-25% of 6- to 24-mo-old infants have IDA, and more have ID without anemia. Thus, the public health implications of study findings could be profound.
The project is expected to continue with a 5-year follow-up (Aug 2013-July 2017).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Low birth iron | Experimental | Dietary Supplement: Ferrous Sulfate (liquid) + vitamins A and DInfants with low birth iron who receive vitamins A and D + iron |
| Marginal birth iron 1 | Experimental | Dietary Supplement: Ferrous Sulfate (liquid) + vitamins A and DInfants with marginal birth iron randomized to receive vitamins A and D + iron |
| Marginal birth iron 2 | Active comparator | Dietary Supplement: vitamins A and DInfants with marginal birth iron randomized to receive vitamins A and D without iron |
| Normal birth iron | Active comparator | Dietary Supplement: vitamins A and DInfants with normal birth iron who receive vitamins A and D without iron |
| Combined ID | Experimental | Dietary Supplement: Ferrous sulfate (liquid)Marginal-birth-iron vitamins only-treated infants who have IDA at 9 mo. |
| Early postnatal IDA | Experimental | Dietary Supplement: Ferrous sulfate (liquid)Infants with IDA at 9 months whose cord blood was collected at birth but who were not assessed and assigned to vitamins with or without iron at 6 weeks |
| Late postnatal IDA | Experimental | Dietary Supplement: Ferrous sulfate (liquid)Infants with IDA at 18 months whose cord blood was collected at birth but who were not assessed and assigned to vitamins with or without iron at 6 weeks. These infants were also not anemic when screened at 9 months. |
Who may qualify
- Ages
- Up to 5 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- infants born at Maternity and Children's Hospitals of Fuyang city in China
- healthy term newborns from uncomplicated pregnancies for hematology screening
- healthy full-term singleton infants with cord Hb and ferritin in the low-marginal or normal range for developmental testing
Key exclusion criteria (1 listed)
- perinatal complications
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 |
|---|---|---|
| Ferrous Sulfate (liquid) + vitamins A and Da single daily dose of 1-2 mg/kg of elemental iron (5 mg from 6 wk to 9 mo and 15 mg from 9 to 18 mo.) and 1500 IU vitamin A and 500 IU vitamin D from 6 wk to 18 mo. | Dietary supplement | Low birth iron, Marginal birth iron 1 |
| vitamins A and Da single daily dose (liquid) of 1500 IU vitamin A and 500 IU vitamin D from 6 wk to 18 mo. | Dietary supplement | Marginal birth iron 2, Normal birth iron |
| Ferrous sulfate (liquid)Infants who become iron deficient/anemic at 9 or 18 mo will take a single daily dose of 3 mg/kg of elemental iron for 3 months. | Dietary supplement | Combined ID, Early postnatal IDA, Late postnatal IDA |
Primary outcome
Infant behavior and development
Time frame: 6 weeks; 9 and 18 months
2 secondary outcomes
Low or marginal birth iron
Time frame: 6 weeks
Infant anemia
Time frame: 9 and 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2014.
- Derived from this study: PubMed 27836288Clark KM, Li M, Zhu B, Liang F, Shao J, Zhang Y, Ji C, Zhao Z, Kaciroti N, Lozoff B. Breastfeeding, Mixed, or Formula Feeding at 9 Months of Age and the Prevalence of Iron Deficiency and Iron Deficiency Anemia in Two Cohorts of Infants in China. J Pediatr. 2017 Feb;181:56-61. doi: 10.1016/j.jpeds.2016.10.041. Epub 2016 Nov 8.
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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.
Betsy Lozoff, MD principal investigator
University of Michigan
Jie Shao, MD study director
The Children's Hospital of Zhejiang University School of Medicine
Zhengyan Zhao, MD study director
The Children's Hospital of Zhejiang University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ferrous Sulfate (liquid) + vitamins A and D, vitamins A and D and Ferrous sulfate (liquid) in people with Iron Deficiency and Iron Deficiency Anemia, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in China.
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 3 inclusion and 1 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: finished, as of the sponsor's last update on 29 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infant behavior and development (time frame: 6 weeks; 9 and 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00642863, which also lists 1 linked publication.
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 29 Oct 2014.