A nationwide longitudinal investigation on the role of prenatal exposure to infectious diseases on the onset of chronic conditions in children and adolescents in Brazil.

Background: In utero exposure to infections might set the stage for a chain of events leading to a wide spectrum of long-term health outcomes observed in children and adolescents. This proposal aims to investigate whether syphilis, zika, dengue and chikungunya during pregnancy can increase the risk of the offspring developing a non-infectious chronic condition during childhood and adolescence.

Objectives: 1) Estimate the risk of non-infectious chronic conditions associated to syphilis, zika, dengue and chikungunya during pregnancy and when appropriate, explore if the risk varies by timing during pregnancy when the infection is acquired (first, second or third trimester) and severity (such as severe or mild dengue); 2) Investigate whether in uterus exposure to maternal infection affects the growth pattern of children and adolescents; 3) Examine the extent to which the relationship between maternal infection and non-infectious chronic outcomes are mediated by intrauterine growth restriction and preterm birth.

Methods: We will compare health outcomes and growth trajectories of children and adolescents born to mothers with and without specific infections during pregnancy using conventional multivariable regression in the whole study population, in a within sibship design, using the subgroup of offspring with at least one sibling who is not exposed to the infection, and negative control outcome. Then we will decompose the direct and mediated effects (by preterm birth and small for gestational age) of maternal infection on chronic disorders.

Results and conclusions: The results from this study will advance our understanding of the relationship between infections during pregnancy and chronic disorders, with widespread implications enabling targeting of critical points along the path from in utero exposure to outcomes to avoid or mitigate illness and disability over the life course.