Brain and Behavior Depending on Timing of Iron Deficiency in Human Infants

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00642863
First received: March 21, 2008
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
Iron Deficiency
Iron Deficiency Anemia
Dietary Supplement: Ferrous Sulfate (liquid) + vitamins A and D
Dietary Supplement: vitamins A and D
Dietary Supplement: Ferrous sulfate (liquid)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Brain and Behavior Depending on Timing of Iron Deficiency in Human Infants

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Infant behavior and development [ Time Frame: 6 weeks; 9 and 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Low or marginal birth iron [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Infant anemia [ Time Frame: 9 and 18 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 1300
Study Start Date: April 2008
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low birth iron
Infants with low birth iron who receive vitamins A and D + iron
Dietary Supplement: Ferrous Sulfate (liquid) + vitamins A and D
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.
Experimental: Marginal birth iron 1
Infants with marginal birth iron randomized to receive vitamins A and D + iron
Dietary Supplement: Ferrous Sulfate (liquid) + vitamins A and D
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.
Active Comparator: Marginal birth iron 2
Infants with marginal birth iron randomized to receive vitamins A and D without iron
Dietary Supplement: vitamins A and D
a single daily dose (liquid) of 1500 IU vitamin A and 500 IU vitamin D from 6 wk to 18 mo.
Active Comparator: Normal birth iron
Infants with normal birth iron who receive vitamins A and D without iron
Dietary Supplement: vitamins A and D
a single daily dose (liquid) of 1500 IU vitamin A and 500 IU vitamin D from 6 wk to 18 mo.
Experimental: Combined ID
Marginal-birth-iron vitamins only-treated infants who have IDA at 9 mo.
Dietary Supplement: 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.
Experimental: Early postnatal IDA
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
Dietary Supplement: 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.
Experimental: Late postnatal IDA
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.
Dietary Supplement: 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.

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).

  Eligibility

Ages Eligible for Study:   up to 5 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • perinatal complications
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00642863

Contacts
Contact: Betsy Lozoff, MD 7347642443 blozoff@umich.edu

Locations
China, Zhejiang
Children's Hospital, Zhejiang University School of Medicine Recruiting
Hangzhou, Zhejiang, China, 310003
Contact: Zhengyan Zhao, MD    86-571-8706-1007    zhaozy@zju.edu.cn   
Contact: Jie Shao, MD    86-571-8702-3391    shaojie@zju.edu.cn   
Principal Investigator: Zhengyan Zhao, MD         
Sponsors and Collaborators
Investigators
Principal Investigator: Betsy Lozoff, MD University of Michigan
Study Director: Jie Shao, MD Children's Hospital, Zhejiang University School of Medicine
Study Director: Zhengyan Zhao, MD Children's Hospital, Zhejiang University School of Medicine
  More Information

No publications provided

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00642863     History of Changes
Other Study ID Numbers: 2 P01 HD039386-06A1, 2 P01 HD039386-06A1
Study First Received: March 21, 2008
Last Updated: March 19, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
iron deficiency
iron deficiency anemia
infant
development
behavior

Additional relevant MeSH terms:
Anemia
Anemia, Iron-Deficiency
Anemia, Hypochromic
Deficiency Diseases
Hematologic Diseases
Malnutrition
Nutrition Disorders
Iron Metabolism Disorders
Metabolic Diseases
Vitamin A
Vitamins
Vitamin D
Iron
Retinol palmitate
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Anticarcinogenic Agents
Antineoplastic Agents
Therapeutic Uses
Trace Elements
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 28, 2014