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.

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. However, fundamental questions about causality, timing, duration, and severity of early ID remain unanswered. The proposed study will determine developmental/ behavioral effects of preventing ID depending on timing and duration of iron supplementation (i.e., pre- and/or early postnatally). The study will relate outcomes to severity of ID and consider reversibility of effects with iron therapy, depending on timing.

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 CDC-supported study involving 15,000 pregnant women in rural China (ClinicalTrials.gov identifier: NCT00133744).

Aims 1 & 2 entail 2 preventive RCTs to support causal inferences about timing and duration. Comparing available approaches - screening & treatment, iron supplementation and its timing, or multimicronutrients- will make the results highly relevant to global practice and policy.

Aim 1: To determine effects of timing of iron deficiency prevention on infant behavior and development. The 3-group design of the CDC-supported Prenatal Nutrition Study will support causal inferences about effects of prenatal iron supplementation (with or without multimicronutrients) on newborn behavior and development. A RCT of early postnatal iron supplementation will be added to focus on iron supplementation in the 1st 9 mo, when benefits of supplemental iron for breast-fed infants are unknown. Infants are assigned randomly (double-blind) within prenatal group to receive vitamins with or without iron from 6 wk to 9 mo. Development/behavior is evaluated at 9 and 18 mo, with outcomes in sensory, motor, cognitive, language, and social/ emotional domains. Using intention to treat, the groups are a) pre- and early postnatal iron, b) iron prenatal only, c) iron early postnatal only, d) neither, e) prenatal multimicronutrients and early postnatal iron, and f) prenatal micronutrients only. Comparisons of b) v. c) relative to d) will identify differential effects of preventing iron deficiency depending on timing and will support causal inferences regarding supplementation in each period. Comparing b) v. f) will determine if outcomes are better with prenatal multimicronutrients than iron alone.

Aim 2: To determine effects of duration of iron supplementation on infant behavior/development. Comparing groups a) pre- and early postnatal iron v. b) or c) will determine if the duration of iron supplementation has different behavioral/developmental effects. Comparing a) v. e) will determine if outcomes are better with than without prenatal multimicronutrients.

• Iron Deficiency Anemia
• Iron Deficiency

• Dietary Supplement: folic acid + iron prenatally, vits A & D + iron postnatally
• Dietary Supplement: folic acid + iron prenatally, vitamins A & D postnatally
• Dietary Supplement: folic acid prenatally, vitamins A & D + iron postnatally
• Dietary Supplement: folic acid prenatally, vitamins A & D postnatally
• Dietary Supplement: multimicronutrients prenatally, vits A&D+iron postnatally
• Dietary Supplement: multimicronutrients prenatally, vits A&D postnatally

• Experimental: pre- and early postnatal iron
• Experimental: iron prenatal only
• Experimental: iron early postnatal only
• Active Comparator: no iron pre- or postnatal
• Experimental: prenatal multimicronutrients and early postnatal iron
• Experimental: prenatal multimicronutrients only

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.