Early Life Risk Factors for Incident Atrial Fibrillation in the Helsinki Birth Cohort Study

Abstract

BackgroundEarly life risk factors are associated with cardiometabolic disease, but have not been fully studied in atrial fibrillation (AF). There are discordant results from existing studies of birth weight and AF, and the impact of maternal body size, gestational age, placental size, and birth length is unknown.Methods and ResultsThe Helsinki Birth Cohort Study includes 13 345 people born as singletons in Helsinki in the years 1934–1944. Follow‐up was through national registries, and ended on December 31, 2013, with 907 incident cases. Cox regression analyses stratified on year of birth were constructed for perinatal variables and incident AF, adjusting for offspring sex, gestational age, and socioeconomic status at birth. There was a significant U‐shaped association between birth weight and AF (P for quadratic term=0.01). The lowest risk of AF was found among those with a birth weight of 3.4 kg (3.8 kg for women [85th percentile] and 3.0 kg for men [17th percentile]). High maternal body mass index (≥30 kg/m2) predicted offspring AF; hazard ratio 1.36 (95% CI 1.07–1.74, P=0.01) compared with normal body mass index (<25 kg/m2). Maternal height was associated with early‐onset AF (<65.3 years), hazard ratio 1.47 (95% CI 1.24–1.74, P<0.0001), but not with later onset AF. Results were independent of incident coronary artery disease, hypertension, or diabetes mellitus.ConclusionsHigh maternal body mass index during pregnancy and maternal height are previously undescribed predictors of offspring AF. Efforts to prevent maternal obesity might reduce later AF in offspring. Birth weight has a U‐shaped relation to incident AF independent of other perinatal variables.

Genetics of height and risk of atrial fibrillation: A Mendelian randomization study

“…Observational designs have limited these studies, due to the possibility of residual confounding. The Helsinki Birth Cohort Study partially addressed this limitation by considering the effect of maternal height on risk of atrial fibrillation in offspring, but was limited by a small, homogenous sample [35]. We further build on those prior findings using the MR framework, considering both summary-level and individual-level genetic data, examining genetic variants associated with height and atrial fibrillation to provide a causal estimate for the effect of increasing height on risk of atrial fibrillation.…”

Maternal exercise intervention in obese pregnancy improves the cardiovascular health of the adult male offspring

“…These statistics demonstrate the scale of the problem and highlight the importance of intervention strategies not only for the immediate [7] but also the long-term health of both the mother and her child. Studies in humans have consistently shown that long-term cardiovascular health is compromised in offspring exposed to an obese pregnancy [8] , [9] , [10] , [11] , [12] . Due to rising levels of obesity worldwide, it is critical to investigate a targeted intervention achievable during an obese pregnancy to prevent transmission of poor cardiometabolic health from mother to child.…”

Causal Association Between Birth Weight and Atrial Fibrillation: Evidence from a Two-Sample Mendelian Randomization Analysis

“…[9][10][11][12][13] However, only four previous studies have assessed the potential association between BW and the risk of AF, with con icting results. [14][15][16][17] The Women's Health Study of 27,982 women, including 735 AF cases during a median follow-up of 14.5 years, indicated that BW was signi cantly associated with the incident AF among women. [14] The Atherosclerosis Risk in Communities cohort of 10,132 individuals, identifying 882 AF cases during an average follow-up of 10.3 years, demonstrated that low BW was independently associated with increased risk of AF.…”

“…[16] The Helsinki Birth Cohort Study of 13,345 individuals, including 907 incident cases during 70.5 years of follow-up, suggested a signi cant U-shaped association between BW and AF. [17] Although several recognized confounding factors have been adjusted in these studies, the in uence of unmeasured confounders was inevitable, which may account for the divergent results. MR analysis can avoid the potential unmeasured confounders thus making stronger causal inference.…”

“…To our knowledge, only four previous studies have explored the association between BW and AF, with discordant results. [14][15][16][17] Further investigation is warranted to reveal whether this association is causal. [18] Mendelian randomization (MR) analysis has been increasingly used to infer the causation.…”