Fetal and neonatal risk factors for diseases caused by disturbances in the function of the immune system

Abstract

Diseases caused by disturbances in the function of the immune system are a heterogeneous group of disorders, including e g allergic and autoimmune diseases. Several of these diseases have become increasingly common during the last decades. The reasons for this increase in prevalence are mostly unknown. However, environmental factors must contribute, since no genetic changes can explain the rapid changes in occurrence. Many of the diseases are supposed to have a long latency period before manifest symptoms. Thus the perinatal period, during which the immune system undergoes a rapid development, may be an especially vulnerable period for the influence of environmental factors causing immunological disturbances.

The aim of this thesis was to study the associations between factors and events during the fetal and neonatal period, and the risk of diseases during childhood caused by inappropriate immune responses. We have studied autoimmune diabetes mellitus (T1DM), coeliac disease, inflammatory bowel disease (IBD), and bronchial asthma (asthma) by use of large, population based, Swedish health registers. These registers make it possible to identify prospectively collected risk determinants for rare diseases.

We have found a significant positive trend in odds ratio for T1DM and birth weight, with intrauterine growth retardation being associated with a decreased risk. Low birth weight and being small for gestational age are instead associated with an increased risk of asthma and coeliac disease. Severe infections during the neonatal period are associated with an increased risk of coeliac disease, IBD, and asthma. Maternal smoking during early pregnancy is associated with a decreased risk of IBD, but an increased risk of asthma and coeliac disease. Low maternal age is linked to an increased risk of coeliac disease and hospitalization due to asthma. High maternal educational level is instead associated with a decreased risk of hospitalization for asthma. Being the first born child is linked to a decreased risk of coeliac disease, but an increased risk of asthma. Several complications during the fetal and neonatalperiod are associated with an increased risk of asthma, including pre-eclampsia, maternal diabetes during pregnancy, prematurity, caesarean section, instrumental vaginal delivery, low Apgar score, and respiratory problems. Phototherapy and/or neonatal icterus are risk determinants for asthma.

In conclusion, there are several possible fetal and neonatal risk factors for diseases caused by immunological disturbances. These associations warrant further research, which may provide help to prevent disease in childhood.