Fetal Programming of Immune Response and Body Fat by Maternal Obesity

NCT04249635 | Completed

• 1 other identifier: 1171406
• Study Type: observational
• Target: 247
• Locations: 1 country
• Sites: 1

Brief Summary

According to the Chilean National Health Survey 2009-2010, 60% of woman in reproductive age are overweight or obese with detrimental consequences on women as well as offspring´s health at long term. New efforts are required to clarify how increased maternal body fat and obesity previous and during pregnancy impinge an increased cardiometabolic and obesity risk in the progeny. Nowadays it is clear that obesity in adults constitute a chronic state of sub-clinical inflammation characterized by an increased infiltration of monocytes in the adipose tissue as well as an imbalance between increased pro- (M1) and decreased anti- (M2) inflammatory macrophage polarization. Increased inflammatory markers have been found in obese children as young as 3 years of age, but if these markers are present at birth is completely unknown. Therefore, unveiling the mechanisms implicated in the capability of monocytes to differentiate into pro-inflammatory macrophages at birth would contribute to establish early markers of the potential risk to develop cardio-metabolic diseases. In this context, modulation of M1-M2 polarization seems to be crucial for the development of altered immune response, and this process would be tightly regulated by epigenetic mechanisms. On the other hand, long chain polyunsaturated fatty acids (LCPUFAs) play a role as precursors of cellular membrane components and modifiers, and as precursors of a plethora of signaling molecules that participates in cardiovascular, metabolic and immune functions. Additionally, DHA regulates gene expression in monocytes and macrophages altering the M1/M2 polarization. The supplementation with DHA in a high risk population of pregestational obese mothers, with known low n-3 intake, would have an important impact on newborn and infant % body fat. An improvement in the n-6/n-3 LCPUFA ratio during pregnancy in humans could represent a primary prevention strategy to revert fetal and neonatal high body fat and a healthy immune system maturation. The hypothesis of this proposal is that neonates born from obese mothers supplemented with DHA during pregnancy show a reduction in specific markers of high-risk of obesity. These markers would be evidenced as a lower percent of body fat at birth and at 4 months of age, as well as the reversion of functional and epigenetic changes in neonatal monocytes at birth, compared to neonates from obese mothers with low DHA intake.

Conditions

Body Composition; Obesity

Keywords

Maternal obesity; Body composition; DHA; n-3 LCPUFA

Outcome Measures

Primary Outcomes (2)

• Newborn body fat percentage

  Percentage of body fat obtained by skinfold measures and calculated using Catalano et al (1996) formula.

  24 hours to 48 hours after birth.

• Infant body fat

  Percentage and fat mass obtained by Air Displacement Plethysmography (PEA POD)

  4 Months of age.

Secondary Outcomes (2)

• Epigenetic-driven inflammatory response of neonatal monocytes & macrophages in vitro.

  At birth

• DHA antiinflammatory effects in neonatal monocytes

  At birth

Study Arms (3)

Reference Group

Healthy term (\> 37 weeks of gestation) newborns of women with pregestational body mass index (BMI) ≥18,5 and \<24,9 in the first prenatal visit.

Maternal obesity (MO) Group

Newborns of women with pregestational BMI ≥30 that received 200 mg/dayDHA supplementation.

Dietary Supplement: DHA

MO+DHA Group

Newborns from women with pregestational BMI ≥30 that received 800 mg/day DHA supplementation.

Dietary Supplement: DHA

Interventions

DHA DIETARY_SUPPLEMENT

Women received supplementation of Based on Schizochytrium oil, 100% DHA (DSM) from 14 weeks of pregnancy until delivery.

MO+DHA Group; Maternal obesity (MO) Group

Eligibility Criteria

• Age: 24 Hours - 4 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Pregnant women of Puente Alto district of Santiago, Chile.

You may qualify if:

• Healthy term (\> 37 weeks of gestation) newborns of: women with pregestational BMI ≥18,5 and \<24,9 in the first prenatal visit (Reference Group); newborns of women with pregestational BMI ≥30 with customary DHA supplementation (200 mg/day) (Maternal obesity, MO Group); newborns from women with pregestational BMI ≥30 with 800 mg/day DHA supplementation (MO+DHA Group); all with singleton and healthy pregnancies.

You may not qualify if:

• Newborns with low birth weight (\<2500 g), complications at delivery, or those requiring long-term hospital admission.
• Newborns of women with preexisting diabetes, premature labor, gestational diabetes, preeclampsia, multiple gestation, chronic cardio-respiratory disorder or neurological o genetic defects of the fetus; any high risk pregnancy condition according to national guidelines,

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (1)

Red Salud UC Christus Hospital

Santiago, Santiago Metropolitan, 8330024, Chile

Location

Biospecimen

Retention: SAMPLES WITH DNA

Maternal blood (plasma \& serum) Umbilical cord blood (plasma, serum and cord blood mononuclear cells) Placental tissue (biopsies and IHQ) Infant blood samples at 4 months (plasma \& serum)

MeSH Terms

Conditions

Obesity; Pregnancy in Obesity

Condition Hierarchy (Ancestors)

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

Study Officials

• Paola Casanello, Ph.D.

  Pontificia Universidad Catolica de Chile

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2020
• First Posted: January 31, 2020
• Study Start: June 9, 2016
• Primary Completion: March 30, 2020
• Study Completion: June 1, 2020
• Last Updated: June 24, 2020

Record last verified: 2020-06

Locations

CL (1)