Mother-child hemoglobin at preconception and first 1000 days and child development at 6 years

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Anemia is an important global health problem. Concerns about the validity of the cut-off values for hemoglobin (Hb) that WHO issued in 1968 have been raised. Several systematic reviews, including a recent one by Dr. Young (PI), reveal a paucity of data and insufficient evidence on relationships between anemia and functional consequences, especially child health and development (CHD). WHO has issued a call for analyses that can inform the appropriateness of its cut-off values for a variety of outcomes, including CHD. We have a unique opportunity to examine the relationships between maternal and child Hb measured across the continuum of preconception, pregnancy and early childhood and a battery of CHD measures. The data we will use are from a randomized, double-blinded, placebo-controlled trial of preconceptional micronutrient supplementation (NCT01665378; PRECONCEPT study; PI: Ramakrishnan) conducted in Vietnam. Prospective data are available from preconception (n=5011 women), through pregnancy and delivery for 1599 livebirths, and from birth to 6 y for 1290 children. To assess timing-specific influences of mother/child Hb, valid statistical methods are needed to generate uncorrelated estimates of Hb changes over time. We will apply innovative conditional modeling methods to answer the following questions. 1: Are maternal preconception Hb concentrations associated with CHD from birth through age 6y? Maternal preconception Hb concentrations will be positively associated with CHD outcomes [1. birth size, 2. Hb at 3, 12 and 24 mo, 3. motor and mental development (Bayley scales for infant development at 12 and 24 mo, and Wechsler scale for global intelligence, performance and verbal scores at 6y). 2: What is the role of timing of changes in maternal Hb across preconception to delivery on CHD? The relative importance of maternal Hb for CHD will vary across four periods: preconception, preconception - trimester 1, trimester 1 - 2, and trimester 2 - 3. 3: What is the role of timing of child Hb changes across the first 2 years of life on child cognition at 6y? The relative importance of child Hb on cognition will vary across three periods: 3mo, 3mo - 1y, and 1y - 2y. The proposed research will fill important gaps in current knowledge about relationships between maternal and child Hb before and during the 1st 1000 days of life and child cognitive functioning through the age of 6 years. Important strengths include availability of prospective, high quality data on a large sample of mother-child pairs from preconception through age 6 y, the application of innovative statistical methods and a highly qualified team that includes junior (PI: Young, early stage investigator) and senior experienced investigators from Emory University and Thai Nguyen University of Medicine and Pharmacy in Vietnam.