Fever in Pregnancy and Offspring Mortality—A Longitudinal Study of a Cohort From 1927 to 1937 on the Faroe Islands

Abstract

Adverse influences in utero may have a causal relationship with adult health. Size at birth appears to be associated with morbidity and mortality later in life, and a number of reports have suggested that infections occurring during pregnancy may be associated with preterm birth or stillbirth and other adverse perinatal effects as well as the subsequent development of disease in adults. This cohort study investigated the relationship between pregnancy complications, specifically fever in utero, and adult health in a birth cohort comprised of individuals born during 1927-1937 in an isolated island community with high birth weight. Complete medical records including maternal data, complications during pregnancy and birth, and newborn data were extracted from medical registries. Dates of death and identifiable ICD-recorded causes of death were also extracted. Multiple Cox regression was used for mortality analyses. The final dataset contained 4208 individuals, including 2234 were men and 1974 were women, who were followed-up from 1949 to 2002. During the study period, 521 men in the birth cohort died, of whom 319 had an ICD-classified cause of death. Fever during the pregnancy of male offspring was associated with increased all-cause mortality (rate ratio [RR], 1.505; 95% confidence interval [CI], 1.084-1.926; P = 0.057). There was also an association with increased rates of premature death (RR, 1.943; 95% CI, 1.486-2.400; P = 0.004) and cancer (RR, 2.625; 95% CI, 1.845-3.405; P = 0.015). Complete mortality data were available for the 250 women in the cohort who had died; 139 had an ICD-classified cause of death. Unlike male offspring, no association was found with all-cause mortality or premature death, and only a slight trend was found with cancer death. In both male and female offspring, there was no association between fever during pregnancy and the occurrence of death from ischemic heart disease. These findings are the first to show that fever as an indicator of infection during pregnancy is associated with increased disease-specific mortality among offspring in adult life.