Determinantes prenatales y postnatales de la rápida ganancia ponderal en los primeros 3 meses de vida y alteraciones en el transcriptoma intestinal

Abstract

Rapid weight gain (RWG) in the first months of life increases the risk of obesity and other diseases in the future, so it is important to identify the predisposing factors. This is a crucial stage for intestinal maturation and RWG in this period could influence gut gene expression. Objectives: The objectives of this study were to analyse the prevalence of RWG from 0 to 3 months in the study cohort, to examine the prenatal and postnatal factors related to RWG and to analyse the differences in gut transcriptome using a non-invasive method in 3-month-old infants with RWG compared to a control group. Methodology: 611 mother-infant pairs participating in the NELA cohort from the Region of Murcia were included. RWG was defined as an increase in weight z-score greater than 0.67 SD from 0 to 3 months. Sociodemographic, lifestyle, anthropometric and analytical variables collected during pregnancy, delivery, birth, 3 and 18 months were analysed. In a subgroup of 61 children, 23 with RWG and 38 controls, gut transcriptome was analysed by microarray using stool exfoliated cells following a non-invasive method optimized by our group. Results: The prevalence of RWG from 0 to 3 months was 18.7% using the WHO charts. The regression model with the highest prediction index included maternal incomplete secondary education or lower, occasional alcohol consumption in the third trimester, low pregestational BMI, and low birthweight z-score. Mothers of children with RWG showed higher percentage of smoking, a diet characterized by higher caloric, total fat and carbohydrate intake, as well as lower adherence to the Mediterranean diet, but these variables were not significant in the regression model. Children with RWG had higher weight z-score, weight-for-length z-score and percentage of fat mass at 3 months, and they also had 11 times greater risk of developing overweight/obesity at 18 months. Gut gene expression was different in infants with RWG from 0 to 3 months, who presented genes related to ribosomal proteins and mitochondrial genes that participate in oxidative phosphorylation downregulated. These genes were also related to RWG from 0 to 18 months, although ribosomal genes were more important in this case. Conclusions: Children with RWG have a distinctive gene expression, characterized by an energy thrift pattern that could support the theory of a pathological postnatal response to a situation of intrauterine malnutrition. Maternal variables such as pregestational BMI, education, and alcohol consumption, along with lower birthweight z-score, increase the risk of RWG, so hygienic and dietetic measures should be recommended for these mothers, and they should be closely monitored during their pregnancy.