Heart Failure Risk Among Children Born Preterm Persists Through Adulthood

Casey Crump, MD, PhD

New research from an international team of clinicians suggests survivors of preterm birth were at an increased risk of new-onset heart failure that persists through adulthood.

An analysis of data from nearly 4.2 million patients in a Swedish birth registry dating back to 1973, results of the study indicate being born before 37 weeks gestational age was associated with a greater risk of heart failure at multiple stages of life—underlining the need for greater follow-up and monitoring of this patient population.

“To our knowledge, this is the largest population-based study of preterm birth in association with HF risks and the first to examine such risks into mid-adulthood or include cosibling analyses,” wrote investigators.

Spurred by an interest in furthering the understanding of preterm birth and cardiovascular risk later in life, a team led by Casey Crump, MD, PhD, of the Ichan School of Medicine at Mount Sinai, sought to address these apparent knowledge gaps using data from the Swedish Birth Register. Using a time frame of 1973-2018, the registry provided investigators with data related to 4,193,069 live singleton births, including 210,039 preterm births.

The median age of the study cohort was 22.5 years and the maximum age was 43 years. In total, investigators obtained data related to 85.0 million person-years of follow-up. Of those born preterm, 8324 were considered extremely preterm (22-27 weeks), 44,373 were moderately preterm (28-33 weeks), 157,342 were late preterm (34-36 weeks), and 740,391 were early term (37-38 weeks). In regard to the remaining patients, 2,896,444 were considered fullterm births and 346,195 were considered postterm births.

The primary outcome measure of the study was incident heart failure. For the purpose of analysis, investigates planned to use Cox regression to determine hazard ratios associated with each gestational age group while adjusting for perinatal and maternal factors. Investigators also planned additional cosibling analyses to assess for potential confounding by unmeasured familial factors.

Upon analysis, investigators identified 4158 patients as having heart failure. These patients had a median age at diagnosis of 15.4 (IQR, 28.0) years at diagnosis. Adjusted analyses indicated preterm birth, defined as earlier than 37 weeks, was associated with an increased risk of heart failure at ages younger than 1 year (aHR, 4.49; 95% CI, 3.86-5.22), 1-17 years (aHR, 3.42; 95% CI, 2.75-4.27), and 18-43 years (aHR, 1.42; 95% CI, 1.19-1.71) when compared to fullterm births.

At ages 18-43 years, the hazard ratios stratified by gestational age were 4.72 (95% CI, 2.11-10.52) for extremely preterm births, 1.93 (95% CI, 1.37-2.71) for moderately preterm births, 1.24 (95% CI, 1.00-1.54) for late preterm births, and 1.09 (95% CI, 0.97-1.24) for early term births. Investigators noted the corresponding incidence rates for patients at 18-43 years were 31.7, 13.8, 8.7, and 7.3, respectively, compared with 6.6 for full-term births

Investigators included 3.5 million individuals in their cosibling analyses. Results of these analyses were similar to that of the primary analyses when assessing risk among patients younger than 18 years but substantially lower risks were no longer significant at ages 18-43 years.

In an editorial comment, Mandy Brown Belfort, MD, MPH, of Brigham and Women’s Hospital, and Suzanne Brown Sacks, MD, MS, of Vanderbilt University School of Medicine, commended investigators on bringing attention to the importance of shifting focus to long-term health of survivors of preterm birth.

“The findings by Crump et al shed new light on heart failure as a long-term consequence of preterm birth and highlight opportunities for clinicians caring for preterm-born infants across the lifespan to understand their unique health risks and tailor their preventive and disease-specific care accordingly,” wrote the pair.

This study, “Association of Preterm Birth With Long-term Risk of Heart Failure Into Adulthood,” was published in JAMA Pediatrics.