The Developmental Origins of Obesity

NCT06981676 | Recruiting

• 1 other identifier: 1221812
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Pregestational obesity (PGO, BMI ≥30) is a significant independent risk factor for the development of obesity in childhood and adolescence. Notably, elevated levels of IL-6 and leptin have been found in the cord blood of offspring born to women with PGO, along with increased body fat. Both our research and that of others have shown an upregulation of pro-inflammatory genes in cord blood monocytes and alterations in innate immune function, including a blunted response to pro-inflammatory stimuli. However, it remains unclear whether these effects are due to an altered immune response in differentiated immune cells or if they are programmed earlier in gestation, during the progenitor cell stage. Long-chain polyunsaturated fatty acids (LCPUFAs) are crucial for cellular function, acting as precursors to membrane components and signaling molecules involved in cardiovascular, metabolic, and immune processes. Modern dietary patterns have led to a relative deficiency in n-3 LCPUFAs, such as Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA). As a result, international health guidelines recommend LCPUFA supplementation during pregnancy. Studies have shown that increased intake of n-3 LCPUFAs during pregnancy exerts effective anti-inflammatory effects in the maternal circulation, adipose tissue, and placenta. The recently completed MIGHT study (NCT02574767), which involved 1005 women with overweight or PGO, investigated the effects of DHA supplementation during pregnancy (200 mg vs. 800 mg/day). A subgroup of the newborns from this cohort also participated in the EpiFat study (NCT04249635), conducted by our team (2017-2021). The findings demonstrated that maternal DHA supplementation (800 mg/day) significantly reduced body fat and improved adipose metabolic markers in offspring at birth, with these effects persisting until 4 months of age. Additionally, the cord blood monocytes of PGO offspring exhibited increased expression of pro-inflammatory genes (IL-6, MCP-1, TNF-α, IL-8), but these effects were completely reversed in the offspring of DHA-supplemented women. These results provide strong evidence of pro-inflammatory programming in innate immune cells and adiposity in offspring of women with PGO, and show that maternal PUFA supplementation during pregnancy can reverse these early obesity biomarkers. However, it remains unclear whether these effects persist into early childhood (5 years of age), particularly in high-risk populations such as those born to women with PGO. Moreover, we hypothesize that maternal obesogenic signals during early embryonic development may affect the progenitor cells of adipocytes (mesenchymal stem cells, MSC) and monocytes (hematopoietic stem cells, HSC), potentially leading to long-term effects on the offspring. This study hypothesizes that: "Maternal obesity increases the risk of childhood obesity by programming adipose and immune progenitor cells, an effect that may be mitigated by maternal supplementation with polyunsaturated fatty acids during pregnancy." To test this hypothesis, we propose: A pilot clinical study to examine whether maternal PGO affects the lineage commitment, number, TLR4 signaling, and epigenetic markers (ChIP-seq) of monocyte (HSC) and adipocyte (MSC) progenitor cells, and whether maternal supplementation with PUFAs during pregnancy can modify these effects. The OMEGA Stem study will invite 160 healthy women (80 with normal weight and 80 with pregestational obesity) with singleton pregnancies to participate. Participants will receive either 600 mg/day of EPA/DHA (1 capsule) or standard antenatal care. A trained midwife will enroll the women \<16 weeks of pregnancy, with data collection (sociodemographic information, clinical data and blood samples) at study initiation, 26-28 weeks, and at delivery. Neonatal body composition will be assessed by a trained midwife (24-48 hours after delivery) through anthropometric measurements and skinfold thickness, calculated using Catalano's formula.

Conditions

Maternal Obesity; Obesity

Keywords

Pregestational Obesity; Maternal Obesity; Omega 3; PUFAs; LCPUFAs

Outcome Measures

Primary Outcomes (2)

• PPARγ gene expression in mesenchymal stem cells isolated from the umbilical cord of newborns from normal-weight and obese mothers supplemented or not with DHA

  Adipogenic commitment will be assessed by qPCR measuring the expression of PPARγ. Unit of measure: PPARg gene expression (RQ-fold change) in mesenchymal cells

  At birth

• Myelopoietic commitment of hematopoietic stem cells (HSC) from umbilical cord blood of newborns from normal-weight and obese mothers supplemented or not with DHA

  Myelopoietic commitment will be assessed by flow cytometry, identifying the expression of CD38 in CD34+ HSC. Unit of Measure: Percentage (%) and Mean fluorescence intensity (MFI) of CD38 in HSC (CD34+ cells)

  At birth

Secondary Outcomes (3)

• Number of CD34+ hematopoietic stem cells (HSC) in cord blood.

  At birth

• Activation of LPS/TLR4/AKT pathway in hematopoietic stem cells (HSC).

  At birth

• Presence of "trained immunity epigenetic hallmarks" in hematopoietic stem cells (HSC).

  At birth

Other Outcomes (1)

• Neonatal fat mass at birth

  24 - 48 hours after birth

Study Arms (4)

Normalweight Group (NW)

NO INTERVENTION

Pregnant women with normal weight and pregnancy usual care

NW plus PUFAs group

EXPERIMENTAL

NW women, supplemented with high levels of PUFA (600 mg/day DHA/EPA).

Dietary Supplement: DHA and EPA

Pregestational obesity Group (PGO)

NO INTERVENTION

Pregnant women with PGO and pregnancy usual care

Pregestational obesity Group (PGO) plus PUFAs group

EXPERIMENTAL

Women with PGO with high PUFA supplementation (600 mg/day DHA/EPA)

Dietary Supplement: DHA and EPA

Interventions

DHA and EPA DIETARY_SUPPLEMENT

Women will receive daily supplementation of LCPUFAs (DHA and EPA) from first trimester until delivery

NW plus PUFAs group; Pregestational obesity Group (PGO) plus PUFAs group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• First prenatal visit \<14 weeks gestation
• Pregestational BMI between 18.5 and 24.9 for the NW groups and BMI \>30 for the PGO groups,
• To have singleton pregnancy,
• ≥18 years of age and plan to deliver at the Hospital Clínico UC- Christus

You may not qualify if:

• Preexisting diabetes
• GDM
• Preeclampsia,
• Multiple gestations
• Chronic cardio-respiratory disorder or neurological o genetic defects of the fetus
• History of an eating disorder, food allergy,
• Any high-risk pregnancy condition (MINSAL 2015)

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Red Salud UC Christus Hospital

Santiago, Santiago Metropolitan, 8330024, Chile

RECRUITING

MeSH Terms

Conditions

Pregnancy in Obesity; Obesity

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Paola Casanello, Ph.D.

CONTACT

+56 223548119; pcasane@uc.cl

Ivone Vargas

CONTACT

+56223542397; eticadeinvestigacion@uc.cl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Model Details: Pilot Randomized Controlled Trial

Study Record Dates

• First Submitted: January 20, 2025
• First Posted: May 21, 2025
• Study Start: July 25, 2023
• Primary Completion: March 30, 2026
• Study Completion (Estimated): March 30, 2027
• Last Updated: May 21, 2025

Record last verified: 2025-05

Locations

CL (1)