Many studies have investigated risk factors for asthma and allergic diseases;however there is little consensus on modifiable risk factors. Early life exposure appears to be crucial in the development of the immune system and delayed maturation increases the tendency to develop asthma and allergic disease. In addition, recent evidence suggests that the in utero period and the first two years of life are key periods in the development of the adult pattern of immune response. In particular, the fetal cytokine environment seems to play a key role in regulating the prenatal development of immune function and may be affected by toxic exposures during pregnancy. High concentrations of cytokines, e.g. interferon gamma (IFN3) and interleukin (IL)-4 in the fetal circulation appears to be a good indicator of the maturation of immune competence in the developing fetus. Omega-3 polyunsaturated fatty acid (n-3 PUFA) intake during pregnancy and early infancy has been suggested to play an important role in preventing the development of allergic diseases;however data are inconsistent and little is known about the mechanism by which n-3 PUFA could have a beneficial effect on preventing atopy and asthma. We therefore propose to determine the impact of n-3 PUFA supplementation during pregnancy on the incidence of atopy, asthma and lung growth in children. We will take advantage of an on-going randomized double-blind controlled trial (RCT) of supplementation conducted among women supplemented from the 22nd week of pregnancy through delivery with either docosahexaenoic acid (DHA), 400 mg per day or placebo up to delivery. In particular we plan to determine: 1) Whether n-3 PUFA supplementation during pregnancy accelerates maturation of immune competence at birth as determined by level of exemplary cytokines (IFN3 and IL-4) in cord blood. 2) Whether n-3 PUFA supplementation during pregnancy decreases the risk of allergen sensitization and asthma and improves lung growth in the first 60 months of life. This study is derived from the largest RCT to date (n=1094) to determine the impact of n-3 PUFA supplementation on child growth and development (NIH Grant Number: 1580566256A1, Ramakrishnan PI) .We will evaluate the impact of n-3 PUFA supplementation (DHA) on the risk of atopy, asthma and lung function growth in childhood and whether this impact differs by the maternal atopic status, assessed using an objective measure (specific IgE).

Public Health Relevance

Over the past few decades, the prevalence of asthma and other allergic diseases has been increasing worldwide;these conditions are responsible for significant morbidity and health care costs. In Latin America and Mexico, these diseases also constitute a major public health problem. While many studies have investigated risk factors for asthma and allergic diseases, there is little consensus on modifiable risk factors. Early life exposure appears to be crucial in the development of the immune system and delayed maturation increases the tendency to develop asthma and allergic disease. In addition, recent evidence suggests that the in utero period and the first two years of life are key periods in the development of the adult pattern of immune response. In particular, the fetal cytokine environment seems to play a key role in regulating the prenatal development of immune function and may be affected by toxic exposures during pregnancy. High concentrations of cytokines, e.g. interferon gamma (IFN3) and interleukin (IL)-4 in the fetal circulation appears to be a good indicator of the maturation of immune competence in the developing fetus. There is now an urgent need to identify modifiable environmental factors that might influence immune regulatory pathways in early life and the propensity for allergic disease. Omega-3 fatty acid (n-3 FA) intake during pregnancy and early infancy has been suggested to play an important role in preventing the development of allergic diseases;however data are inconsistent and little is known about the mechanism by which n-3 FA could have a beneficial effect on preventing atopy and asthma. Therefore it is of particular relevance to assess if supplementation with n-3 PUFA provided during pregnancy, thus before atopy is established, might play a protective role. In this project, we will take advantage of an on-going randomized double-blind controlled trial (RCT) of supplementation conducted among women supplemented from the 22nd week of pregnancy through delivery with either docosahexaenoic acid (DHA), 400 mg per day or placebo up to delivery. Our study will be the largest to date to evaluate the impact of n-3 PUFA on allergic diseases and lung growth in children. In addition, because of the low level of n-3 PUFA intake in the Mexican women population, this trial provides the best setting in which the potential beneficial effect of supplementation can be established and would provide a large benefit to the offsprings.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD058818-04
Application #
8331284
Study Section
Integrative Nutrition and Metabolic Processes Study Section (INMP)
Program Officer
Raiten, Daniel J
Project Start
2009-09-01
Project End
2013-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$212,325
Indirect Cost
$15,728
Name
Mexico National Institute of Public Health
Department
Type
DUNS #
812222776
City
Cuernavaca
State
Country
Mexico
Zip Code
62100
Lee, Ho-Sun; Barraza-Villarreal, Albino; Hernandez-Vargas, Hector et al. (2013) Modulation of DNA methylation states and infant immune system by dietary supplementation with ýý-3 PUFA during pregnancy in an intervention study. Am J Clin Nutr 98:480-7
Hernandez, Evelia; Barraza-Villarreal, Albino; Escamilla-Nunez, Maria Consuelo et al. (2013) Prenatal determinants of cord blood total immunoglobulin E levels in Mexican newborns. Allergy Asthma Proc 34:e27-34