Early Childhood Obesity Programming by Intrauterine Growth Restriction

Molecular Basis of Early Childhood Obesity Programming by Intrauterine Growth Restriction

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.

Study Overview

• Status: Recruiting
• Conditions: Childhood Obesity; Epigenetics

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Sandra Reznik, MD; Phone Number: 718-904-2947; Email: sreznik@montefiore.org

Study Locations

• United States
  • New York
    • The Bronx, New York, United States, 10461
      • Recruiting
      • Jack D. Weiler Hospital
      • Contact: Mamta Fuloria, MD; Phone Number: 718-904-4105; Email: mfuloria@montefiore.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 hour to 2 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Term AGA and IUGR singleton infants

Description

Mother-infant pairs will be recruited for this study.

Inclusion Criteria:

• Healthy singleton term intrauterine growth restricted (IUGR) and appropriate for gestational age (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. Infants will be classified as IUGR if birth weight is <10th percentile for gestational age and gender based on World Health Organization (WHO) growth curves. Infants will be classified as AGA if birth weight percentile is >10th and <90th percentile
• Reproductive age women, healthy enough to achieve pregnancy
• Deliver a single healthy live term infant at ≥37 weeks' gestational age (GA)
• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

Exclusion Criteria:

• Multiple gestation
• Maternal depression
• Maternal renal disease
• History of maternal smoking in the 2nd and 3rd trimester of pregnancy
• Maternal gestational diabetes / Type 2 Diabetes (T2D)
• Preterm birth (less than 37 weeks' gestation)
• Known chromosomal or congenital anomaly
• Infants in extremis
• Low Apgar scores (Apgar score <7 at 5 minutes of age)
• Known congenital bacterial or non-bacterial infections
• Known inborn errors of metabolism

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
IUGR infants; Intrauterine growth restricted infants will be enrolled. There are no interventions.
AGA infants; Appropriate for gestational age infants will be enrolled. There are no interventions.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Icahn School of Medicine at Mount Sinai; University of Wisconsin, Madison; University of California, San Francisco; Hackensack Meridian Health Center for Discovery and Innovation; Gencove
• Investigators: Principal Investigator: Sandra Reznik, MD, Montefiore Medical Center/Albert Einstein College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: January 10, 2018
• First Submitted That Met QC Criteria: January 17, 2018
• First Posted (Actual): January 18, 2018

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Obesity; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Pediatric Obesity
• Other Study ID Numbers: 2018-8749; R01HD092533 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No