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

Study Overview
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Brief Summary
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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.

Detailed Description
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The general objectives of this study are: 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. 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. 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.

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

Conditions
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Asthma, Children, Obesity, Maternal

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Newborn from obese and nonobese pregnant<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of asthma (defined as positive asthma predictive index at 36 months of age) |  | 36 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Allergy status (positive skin prick test) |  | 30-36 months of age |