Pre-, Peri- and Postnatal Programming and Origins of Disease: Early Targeting the Epidemics of Allergy and Overweight

Overview

Combined programme: Nutrition, Allergy, Mucosal immunology and Intestinal microbiota (NAMI) was created with the objective to reverse the rising trend of chronic inflammatory diseases, such as allergic disease and obesity, by control of the internal and external environments of the infant. To approach this problem, the project aims to characterize * how immunology is regulated during pregnancy and early infancy, * how the immune interaction between mother and child is influenced by nutritional and microbial factors, and * how the regulation is related to disease risk.

While allergic diseases comprise the most common chronic disease in childhood, obesity is the most prevalent nutritional disorder among children throughout the world. In Europe, an estimated 20% of children and adolescents are overweight with one-third of these being considered obese. Moreover, escalation of these problems is expected in the future, since the velocity of propagation is highest in children. Although genetic factors can determine the propensity of an individual to become allergic or obese, these unlikely explain the recent and progressive worldwide increases in incidence. Rather, it would appear that the environmental changes more directly shape the risk during a critical period of life when the scene is set for the consolidation of the immune responder type. Prenatal environmental exposures may alter gene expression via epigenetic mechanisms, heritable changes in gene expression occurring without alterations in the DNA sequences. Specifically current research interest is directed towards health promotion and reducing the risk of disease evaluating the probiotic effects with specific foods and nutrients, and assessing their interactions in optimal combination and food matrix. For this purpose a series of interventions studies evaluate the both the optimal timing of probiotic intervention and the optimal mode of administration. Sections: Prenatal RCT 2 Randomized, parallel-design clinical trial of 3 groups. Pregnant women (n=256) from families with at least one member having an allergic disease have been recruited from maternal welfare clinics and randomly assigned to control group or one of the intervention groups. Mothers in the dietary intervention groups received dietary counselling with specific attention to the quality and quantity of fat in the diet. To promote the achievement of current dietary recommendations, mothers have been provided with foods which have a favourable fat composition (e.g. spreads). The subjects in the intervention groups have been further randomized (double-blind randomization) to receive either placebo or a probiotic preparation, 1010 cfu of both Lactobacillus rhamnosus GG and Bifidobacterium lactis and controls received placebo in a single-blind manner. Dietary food products and probiotic supplementation have been continued from the 1st trimester of pregnancy until the end of exclusive breast feeding, maximum of 6 months. Perinatal RCT 1 Randomized double-blind, placebo-controlled study of 2 groups. Pregnant women (n=159) have been randomized into one of the study groups 2-4 weeks before term to receive placebo (microcrystalline cellulose) or probiotic Lactobacillus rhamnosus GG (ATCC 53103; 1010 cfu). After delivery probiotics/ placebo were administered orally to the infants for 6 months. General information to prevent allergy has been given in written form to all: to breast-feed for at least 4-6 months; to begin solid foods at 4-6 months; no smoking by caretakers. RCT 3 Randomized double-blind, placebo-controlled clinical trial of 3 groups. Pregnant women (n=241) with a history of atopic diseases have been assigned to one of the treatment groups: to receive for 2 months before delivery and for 2 months thereafter, when they are breast-feeding, either placebo or Lactobacillus rhamnosus and Bifidobacterium longum or Lactobacillus paracasei and Bifidobacterium longum. Postnatal RCT 4 Randomized double-blind, placebo-controlled study of 3 groups. Neonates (n=94) fulfilling the following criteria: gestational age at birth between 32nd and 36th weeks, weight over 1500 g and no congenital defects of gastrointestinal system or other defects that prevent enteral nutrition, have been randomized to receive either placebo (microcrystalline cellulose) or a probiotic preparation (Lactobacillus rhamnosus GG, ATCC 53103) or a prebiotic preparation (a mixture of Polydextrose and Galacto-oligosaccharideOS in a 1:1 ratio). The treatment continues for 2 months. RCT 5 Randomized double-blind, placebo-controlled clinical trial of 2 groups. 2-6 weeks old formula- and breast-fed colic infants (n=30), who cry without medical cause for 3h/d, for 3days/week, have been randomized to receive either placebo (microcrystalline cellulose) or a probiotic preparation (Lactobacillus rhamnosus GG, ATCC 53103) for 4 weeks. Formula-fed infants receive extensively hydrolysed formula and mothers of breast-fed infants avoid cow's milk in their diet.