Preterm, Large or Small for Gestational Age Births Associated with Increased AFib Risk

Krisztina László, PhD
Credit: Karolinska Institutet

New data from an analysis of more than 8 million individuals with follow-up up to middle age provides an overview of the risk of atrial fibrillation associated with preterm, large for gestational age (LGA), and small for gestational age (SGA) births.

Results of the study, which contained 174.4 million person-years of follow-up data, indicate there were 30%, 55%, and 71% increases in risk for atrial fibrillation observed for preterm, LGA, and SGA births, respectively.¹

“We found that individuals born preterm and those who were large for gestational age at birth had a slightly higher risk of developing atrial fibrillation up to middle-age than those with corresponding normal birth outcomes,” said principal investigator Krisztina László, PhD, associate professor at the Department of Global Public Health, Karolinska Institutet, and senior lecturer at the Department of Public Health and Caring Sciences at Uppsala University.² “Individuals who were small for gestational age at birth had an increased risk of atrial fibrillation up to the age of 18, but not later in adulthood.”

According to László and investigators, despite a considerable amount of research performed examining associations between adverse birth outcomes and risk of cardiovascular disease, there is a lack of contemporary evidence related to adverse birth outcomes and their associations with atrial fibrillation. With this in mind, investigators designed the current study to estimate potential risk for atrial fibrillation later in life associated with preterm birth, SGA, or LGA.¹

To do so, investigators designed a multinational cohort study leveraging data from national health registries pertaining to birth and outcomes for citizens of Denmark, Sweden, and Finland. Of note, Danish registries provided information related to live singleton births from 1978-2016, with follow-up through December 31, 2016. Swedish registries provided information related to live singleton births from 1973-2014 with follow-up through December 31, 2021. Finnish registries provided information related to live singleton births from 1987-2014 with follow-up through 2016.¹

The primary outcome of interest for the study was the diagnosis of atrial fibrillation. For the purpose of analysis, investigators used multivariable Cox proportional hazards models and flexible paramedics survival models to estimate hazard ratios (HR) for atrial fibrillation based on preterm birth, SGA, and LGA.¹

Overall, the cohort included 8,012,433 participants with a maximum age of 49 years and a median age of 21 years. From this cohort, investigators obtained a total of 174.4 million person-years of follow-up data. During the follow-up period, 11,464 participants had a diagnosis of atrial fibrillation, with a median age at diagnosis of 29.3 years.¹

Upon analysis, results indicated both preterm birth and LGA were associated with increased risk in both the full population cohort and in the sibling analyses, with multivariate HRs from the cohort analyses of 1.30 (95% CI, 1.18-1.42) and 1.55 (95% CI, 1.46-1.63), respectively. Further analysis suggested preterm birth was more strongly associated with atrial fibrillation in childhood than adulthood and children born SGA had an increased risk during the first 18 years of life, but this risk did not persist into adulthood.¹

“Atrial fibrillation at a young age may involve a heavy socioeconomic burden for the affected individuals and we need to learn more about the underlying causes of the disease,” said lead investigator Fen Yang, doctoral student at the Department of Global Health, Karolinska Institutet.² “Our findings may highlight the need to monitor and prevent the disease in individuals with an elevated risk of atrial fibrillation.”

References:

1. Yang F, Janszky I, Gissler M, et al. Preterm Birth, Small for Gestational Age, and Large for Gestational Age and the Risk of Atrial Fibrillation Up to Middle Age. JAMA Pediatr. Published online April 24, 2023. doi:10.1001/jamapediatrics.2023.0083
2. Lindberg F. New insights on the risk for atrial fibrillation in children and young adults. Karolinska Institutet. https://news.ki.se/new-insights-on-the-risk-for-atrial-fibrillation-in-children-and-young-adults. Published April 24, 2023. Accessed April 24, 2023.