Early Childhood Obesity Programming by Intrauterine Growth Restriction

Study Overview
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Brief Summary
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The molecular mechanisms underlying developmental programming of childhood obesity remain poorly understood. Here, the investigators address major questions about early childhood obesity programming by studying CD3+ T-cells from intrauterine growth restricted (IUGR) newborns who have an increased risk for obesity and other metabolic disorders in adult life.

Detailed Description
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Epidemiological studies of multiple cohorts suggest an increased risk for obesity, cardiovascular disease-related death and type 2 diabetes in low birth weight infants. However, the molecular mechanisms underlying developmental programming of childhood obesity remain poorly understood. Alterations in DNA methylation during fetal life have been proposed to be one of the mechanisms that regulate this phenotype. Here, the investigators address major questions about early childhood obesity programming by studying purified subpopulations of CD3+ T-cells from intrauterine growth restricted (IUGR) newborns who have an increased risk for obesity and other metabolic disorders in adult life. The investigators will correlate altered CD3+ T-cell DNA methylation profiles in cord and peripheral blood samples and functional changes in CD3+ T-cells with adiposity in childhood.

Official Title
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Molecular Basis of Early Childhood Obesity Programming by Intrauterine Growth Restriction

Conditions
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Childhood Obesity, Epigenetics

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy singleton term IUGR and AGA infants whose mothers are followed by the Obstetric Department of Montefiore Medical Center and who deliver at the Weiler Division of Montefiore Medical Center. Exclusion Criteria: Multiple gestation, maternal depression, maternal renal disease, infants in extremis, Apgar score <7 at 5 min and umbilical artery pH ≤7.25, chromosomal/ congenital abnormalities, congenital infections and inborn errors of metabolism. We will also exclude infants born to mothers with a history of maternal smoking in the 2nd and 3rd trimester of pregnancy and maternal gestational diabetes/T2D.

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| IUGR infants<br>Intrauterine growth restricted infants will be enrolled. There are no interventions. | |
| AGA infants<br>Appropriate for gestational age infants will be enrolled. There are no interventions. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth velocity | Change in growth velocity based on DNA methylation marks and functional profiles of CD3+ T-cells | Until 24 months of age | 
| DNA methylation of CD3+ T-cells | Change in DNA methylation of CD3+ T-cells in the first 24 months of life in IUGR infants | At birth and 24 months of age | 
| T-cell function | Change in T-cell function in the first 24 months of life in IUGR infants | At birth, 12 and 24 months of age |