Early Childhood Obesity Programming by Intrauterine Growth Restriction

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.

Primary outcomes

• Growth velocity [Until 24 months of age]: Change in growth velocity based on DNA methylation marks and functional profiles of CD3+ T-cells
• DNA methylation of CD3+ T-cells [At birth and 24 months of age]: Change in DNA methylation of CD3+ T-cells in the first 24 months of life in IUGR infants
• T-cell function [At birth, 12 and 24 months of age]: Change in T-cell function in the first 24 months of life in IUGR infants

Sex: All, ages: 1 Hour to 24 Months, accepts healthy volunteers

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

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• Results publication: Akinyemi AJ, Du XQ, Aguilan J, Sidoli S, Hirsch D, Wang T, Reznik S, Fuloria M, Charron MJ. Human cord plasma proteomic analysis reveals sexually dimorphic proteins associated with intrauterine growth restriction. Proteomics. 2024 Apr;24(7):e2300260. doi: 10.1002/pmic.202300260. Epub 2023 Dec 7. PMID 38059784
• Results publication: Reznik SE, Akinyemi AJ, Harary D, Latuga MS, Fuloria M, Charron MJ. The effect of cesarean delivery on the neonatal gut microbiome in an under-resourced population in the Bronx, NY, USA. BMC Pediatr. 2024 Jul 13;24(1):450. doi: 10.1186/s12887-024-04908-7. PMID 38997672

• Sandra Reznik, MD, Principal investigator, Montefiore Medical Center/Albert Einstein College of Medicine

NIH grants: R01HD092533, R16GM145586, S10OD030286