Early Risk of Asthma in Children Exposed to In-utero Maternal Obesity

Overview

This study seeks a better understanding of the pathogenesis of asthma in early life. The aim of this project is to determine whether the offspring of obese mothers at 3 years of life have increased the risk of asthma compared to children whose mothers were not obese and whether this increased risk is associated with a programming altered immune reactivity at birth.

Full Title of Study: “Early Risk of Asthma in Children Exposed to In-utero Maternal Obesity: An Epigenetic-mediated Programming of Immune Function”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: April 2018

Detailed Description

The general objectives of this study are: 1. To determine whether the increased risk of asthma in children born from a pre-pregnant obese mother can be observed at 3 years of life and whether this increased risk associated with altered plasma levels of immune mediators at birth. 2. To explore in children born from pre-pregnant obese mother whether monocyte physiology and M1-M2 polarization present an altered response and expression of asthma-related immune-modulations at birth. 3. To study in neonates born from pre-pregnant obese mother whether the in vitro expression of TNFα, IL12, IL-10 and IL-4Rα in monocytes associates with changes in the DNA methylation status in the promoter regions of those genes. The study is performed in accordance with the Helsinki Declaration, and the study protocol was accepted by Institutional Review Boards at School of Medicine of the Pontificia Universidad Católica de Chile.

Arms, Groups and Cohorts

  • Newborn from obese and nonobese pregnant
    • Obese (BMI>30) or normal weight (BMI<25) women at their first antenatal visit were invited to participate in the study at the moment of delivery at Sotero del Rio Hospital, Santiago. Information regarding birth outcomes, parental history, as well as environmental conditions was collected at recruitment. Follow-up questionnaires by phone were completed every 6 months. Umbilical cord blood samples were collected to measure IL-12, TNF-α, IL-10, IL-4; to evaluate metabolic status; to isolated monocytes and macrophage differentiation; and for DNA methylation status of the promoter regions of the genes coding for TNF-α, IL-12, IL-10, and IL-4Rα. Also, fasting blood samples of the mothers within 48 hours after delivery; and blood samples and skin prick test were collected.

Clinical Trial Outcome Measures

Primary Measures

  • Risk of asthma (defined as “positive asthma predictive index” at 36 months of age)
    • Time Frame: 36 months of age

Secondary Measures

  • Allergy status (positive skin prick test)
    • Time Frame: 30-36 months of age

Participating in This Clinical Trial

Inclusion Criteria

  • Women who receive care in any of the 12 public health care centers in La Florida and Puente Alto and give birth in the Sotero del Río Hospital. – Singleton pregnancy of fewer than 14 weeks of gestation at the first antenatal visit. – 18 years or older Exclusion Criteria:

  • Pregnant women with overweight (BMI 25-30) before 14 weeks. – Women that have a premature birth, cardio-respiratory disorder or neurological defects of the neonate. – Women that develop gestational diabetes and hypertension during pregnancy

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 45 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Pontificia Universidad Catolica de Chile
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Jose A. Castro-Rodriguez, MD, PhD, Principal Investigator, Pontificia Universidad Catolica de Chile

Citations Reporting on Results

Castro-Rodriguez JA, Forno E, Casanello P, Padilla O, Krause BJ, Uauy R. Leptin in Cord Blood Associates with Asthma Risk at Age 3 in the Offspring of Women with Gestational Obesity. Ann Am Thorac Soc. 2020 Dec;17(12):1583-1589. doi: 10.1513/AnnalsATS.202001-080OC.

Cifuentes-Zuniga F, Arroyo-Jousse V, Soto-Carrasco G, Casanello P, Uauy R, Krause BJ, Castro-Rodriguez JA. IL-10 expression in macrophages from neonates born from obese mothers is suppressed by IL-4 and LPS/INFgamma. J Cell Physiol. 2017 Dec;232(12):3693-3701. doi: 10.1002/jcp.25845. Epub 2017 Apr 27.

Vega-Tapia F, Artigas R, Hernandez C, Uauy R, Casanello P, Krause BJ, Castro-Rodriguez JA. Maternal obesity is associated with a sex-specific epigenetic programming in human neonatal monocytes. Epigenomics. 2020 Nov;12(22):1999-2018. doi: 10.2217/epi-2020-0098. Epub 2020 Dec 4.

Jaramillo-Ospina A, Castano-Moreno E, Munoz-Munoz E, Krause BJ, Uauy R, Casanello P, Castro-Rodriguez JA. Maternal Obesity Is Associated With Higher Cord Blood Adipokines in Offspring Most Notably in Females. J Pediatr Gastroenterol Nutr. 2021 Aug 1;73(2):264-270. doi: 10.1097/MPG.0000000000003172.

Castro-Rodriguez JA, Forno E, Padilla O, Casanello P, Krause BJ, Borzutzky A. The asthma predictive index as a surrogate diagnostic tool in preschoolers: Analysis of a longitudinal birth cohort. Pediatr Pulmonol. 2021 Oct;56(10):3183-3188. doi: 10.1002/ppul.25592. Epub 2021 Jul 28.

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