Healthy Infant Development Project

NCT ID: NCT00613717

Last Updated: 2014-10-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 2371 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2014-06-30

Brief Summary

The Healthy Infant Development Project will determine if providing micronutrient supplements to mothers during pregnancy and infants in the first 9 months fosters healthy behavior and development in babies.

Detailed Description

Iron deficiency (ID) is the most common single nutrient disorder in the world, and pregnant women and infants are at highest risk. With long-lasting differences in prior studies, effects on the developing brain and infant behavior and development are among the most worrisome concerns. The proposed study will determine developmental/ behavioral effects of preventing ID depending on timing (Aim 1) and duration (Aim 2) of iron supplementation (i.e., pre- and/or early postnatally). The study will relate outcomes to severity of ID (Aim 3) and consider reversibility of effects with iron therapy, depending on timing (Aim 4). We expect different neurobehavioral effects when ID occurs or is prevented/treated during different phases of brain development (proliferation and growth phase primarily prenatally and regional diversification and interconnection largely in infancy). The project entails 2 randomized controlled trials (RCTs) to support causal inferences about preventing ID pre- and/or early postnatally. The project builds on a large US CDC-supported study (Pregnancy Nutrition Study) involving pregnant women in rural China (ClinicalTrials.gov identifier: NCT00133744). Study groups of infants in the proposed RCTs combined are a) pre- and early postnatal iron, b) prenatal iron, c) early postnatal iron, and d) neither (n = 500/group, total 2000, at study end). Iron status and sensitive sensory, motor, cognitive, language, and social-emotional outcomes will be assessed at birth, 9 and 18 mo. Results of Aims 1 & 2 will determine the best window to prevent ID effects and whether breast-fed infants benefit from iron before 6 mo. Aim 3 (severity) will determine the level of ID at which different developmental domains are adversely affected. If ill effects of ID without anemia are documented, there could be major policy implications; screening is currently only for anemia. Detecting more or less vulnerable domains may also point to other interventions in addition to iron therapy. To identify reversibile effects, depending on age of treatment (Aim 4), outcomes at 18 mo will be compared for infants 1) never iron-deficient, 2) poor iron status at birth and assigned to postnatal iron, 3) maternal IDA (anemia) treated in the 1st or 2nd trimester, 4) infant IDA treated at 9 mo, and 5) IDA treated at 18 mo. The results will be highly relevant to global practice and policy regarding ID, which differentially affects poor and/or minority women and infants everywhere.

The project is expected to continue with a 5-year follow-up (Nov 2014- Oct 2019).

Conditions

Iron Deficiency Anemia; Iron Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

a

pre- and early postnatal iron

Group Type: EXPERIMENTAL

folic acid + iron prenatally, vits A & D + iron postnatally

Intervention Type: DIETARY_SUPPLEMENT

Prenatally: pills by mouth, one per day, from the first prenatal visit until delivery, 400 mcg folic acid, 30 mg Fe.

Postnatally: liquid by mouth, once per day, from 6 weeks old until 9 months old, 1 mg/kg/day Fe, 1500 IU vitamin A, 500 IU vitamin D.

b

iron prenatal only

Group Type: EXPERIMENTAL

folic acid + iron prenatally, vitamins A & D postnatally

Intervention Type: DIETARY_SUPPLEMENT

Prenatally: pills by mouth, one per day, from the first prenatal visit until delivery, 400 mcg folic acid, 30 mg Fe.

Postnatally: liquid by mouth, once per day, from 6 weeks old until 9 months old, 1500 IU vitamin A, 500 IU vitamin D.

c

iron early postnatal only

Group Type: EXPERIMENTAL

folic acid prenatally, vitamins A & D + iron postnatally

Intervention Type: DIETARY_SUPPLEMENT

Prenatally: pills by mouth, one per day, from the first prenatal visit until delivery, 400 mcg folic acid.

Postnatally: liquid by mouth, once per day, from 6 weeks old until 9 months old, 1 mg/kg/day Fe, 1500 IU vitamin A, 500 IU vitamin D.

d

no iron pre- or postnatal

Group Type: ACTIVE_COMPARATOR

folic acid prenatally, vitamins A & D postnatally

Intervention Type: DIETARY_SUPPLEMENT

Prenatally: pills by mouth, one per day, from the first prenatal visit until delivery, 400 mcg folic acid.

Postnatally: liquid by mouth, once per day, from 6 weeks old until 9 months old, 1500 IU vitamin A, 500 IU vitamin D.

Interventions

folic acid + iron prenatally, vits A & D + iron postnatally

Prenatally: pills by mouth, one per day, from the first prenatal visit until delivery, 400 mcg folic acid, 30 mg Fe.

Postnatally: liquid by mouth, once per day, from 6 weeks old until 9 months old, 1 mg/kg/day Fe, 1500 IU vitamin A, 500 IU vitamin D.

Intervention Type: DIETARY_SUPPLEMENT

folic acid + iron prenatally, vitamins A & D postnatally

Prenatally: pills by mouth, one per day, from the first prenatal visit until delivery, 400 mcg folic acid, 30 mg Fe.

Postnatally: liquid by mouth, once per day, from 6 weeks old until 9 months old, 1500 IU vitamin A, 500 IU vitamin D.

Intervention Type: DIETARY_SUPPLEMENT

folic acid prenatally, vitamins A & D + iron postnatally

Prenatally: pills by mouth, one per day, from the first prenatal visit until delivery, 400 mcg folic acid.

Postnatally: liquid by mouth, once per day, from 6 weeks old until 9 months old, 1 mg/kg/day Fe, 1500 IU vitamin A, 500 IU vitamin D.

Intervention Type: DIETARY_SUPPLEMENT

folic acid prenatally, vitamins A & D postnatally

Prenatally: pills by mouth, one per day, from the first prenatal visit until delivery, 400 mcg folic acid.

Postnatally: liquid by mouth, once per day, from 6 weeks old until 9 months old, 1500 IU vitamin A, 500 IU vitamin D.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Full-term healthy neonates born to study mothers from CDC's Prenatal Nutrition Study with randomly selected lot numbers.

Exclusion Criteria

• birth weight < 2500 g
• gestational age ≤ 37 wk
• major perinatal complications
• major congenital anomaly
• multiple birth.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 5 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centers for Disease Control and Prevention

FED

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Betsy Lozoff, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Li Ming, MD

Role: STUDY_DIRECTOR

Peking University First Hospital

Locations

Peking University First Hospital

Beijing, , China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 27836288 (View on PubMed)

Lozoff B, Jiang Y, Li X, Zhou M, Richards B, Xu G, Clark KM, Liang F, Kaciroti N, Zhao G, Santos DC, Zhang Z, Tardif T, Li M. Low-Dose Iron Supplementation in Infancy Modestly Increases Infant Iron Status at 9 Mo without Decreasing Growth or Increasing Illness in a Randomized Clinical Trial in Rural China. J Nutr. 2016 Mar;146(3):612-21. doi: 10.3945/jn.115.223917. Epub 2016 Jan 20.

Reference Type: DERIVED

PMID: 26791556 (View on PubMed)

Other Identifiers

1R01HD052069-01A2

Identifier Type: NIH

Identifier Source: secondary_id

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1R01HD052069-01A2

Identifier Type: NIH

Identifier Source: org_study_id

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