Early origins of allergy and asthma (ARIES): study protocol for a prospective prenatal birth cohort in Chile

Caroll D Hernández, Paola Casanello, Paul R Harris, José A Castro-Rodríguez, Carolina Iturriaga, Guillermo Perez-Mateluna, Marcelo Farías, Marcela Urzúa, Cherie Hernandez, Carolina Serrano, Mauricio Sandoval, Rodrigo Hoyos-Bachiloglu, Ricardo Uauy, Arturo Borzutzky, Caroll D Hernández, Paola Casanello, Paul R Harris, José A Castro-Rodríguez, Carolina Iturriaga, Guillermo Perez-Mateluna, Marcelo Farías, Marcela Urzúa, Cherie Hernandez, Carolina Serrano, Mauricio Sandoval, Rodrigo Hoyos-Bachiloglu, Ricardo Uauy, Arturo Borzutzky

Abstract

Background: Growing evidence shows that atopic dermatitis (AD), food allergy (FA), allergic rhinitis, and asthma are largely determined during the first 1000 days (time elapsed from conception to the 2nd birthday). The ARIES birth cohort aims to determine prenatal and perinatal conditions, as well as genetic and epigenetic factors, that participate in the early setting of immune responses, and the role of these in the later determination of the risk of allergic diseases and asthma in the offspring.

Methods: We have designed a birth cohort of 250 families with prenatal recruitment (~ 14 weeks). We will genotype relevant allergy/asthma-associated variants in trios and will perform immunophenotyping and evaluation of allergy biomarkers in cord blood. At 1 and 2 years of age we will assess if infants have developed allergic sensitization, AD, FA, as well as biomarkers of asthma including the asthma predictive index. We will also evaluate how maternal conditions modify immune programming through epigenetic modifications and will then depict newborn epigenetic cues of allergy/asthma risk. Next, we will assess composition/diversity of maternal gut, placenta, breastmilk and infant gut microbiome and their association with immunophenotype and biomarkers at birth, and clinical outcomes at age 1 and 2. Finally, we plan to assess how environmental exposures (perinatal outdoor and indoor pollution, allergens and endotoxin) affect the incidence of allergic sensitization, AD, FA, and risk of asthma.

Discussion: The in-depth study of the ARIES birth cohort shall provide crucial information to understand the rising incidence of allergies and asthma in developing countries, and hopefully provide cues on how to prevent and treat these diseases.

Trial registration: clinicaltrials.gov NCT04186949, retrospectively registered on December 5, 2019.

Keywords: Allergy; Asthma; Atopic dermatitis; Birth cohort; Cohort study; Food allergy; Prenatal conditions.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Factors that influence the development of allergy and asthma. Diagrammatic representation of the hypothesis of the ARIES study
Fig. 2
Fig. 2
Recruitment and follow-up strategy used in the ARIES birth cohort. Patients that fulfill inclusion criteria will be invited to participate in their 1st antenatal visit and enter the study at 14 ± 6 weeks of gestation with follow-up until the child is 2 years old

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