Preterm birth linked to elevated risk for premature death in adulthood

Adults who were born prematurely may be at an elevated risk for premature death from all causes, as well as death from noncommunicable diseases such as CVD, chronic lung disease and diabetes, according to research published in JAMA Network Open.

“So far, studies investigating long-term health and disease after preterm birth have mostly been limited to early adulthood among those with the highest risk, namely those born extremely (< 28 weeks) and very (28 weeks to 32 weeks) preterm,” Kari Risnes, MD, PhD, a professor at the Norwegian University of Science and Technology in Norway, and colleagues wrote. “However, recent reports suggest that adverse long-term outcomes are not confined to extreme gestational ages, considering that children born just a few weeks before term or even early term had higher risk.”

Risnes and colleagues conducted a population-based cohort study of national birth cohorts in Denmark, Finland, Norway and Sweden. Individuals included in the study were born from 1967 through 2002. They were identified at birth and followed up from 15 years of age through death or 2017.

The researchers categorized gestational age as moderately preterm or earlier (23 weeks to 33 weeks gestation), late preterm (34 weeks to 36 weeks gestation), early term (37 weeks to 38 weeks gestation), full term (39 weeks to 41 weeks gestation) and post term (42 weeks to 44 weeks gestation).

Of the 6,263,286 people evaluated in the study, 5.4% were born preterm.

Risnes and colleagues determined that the risk for all-cause mortality after 15 years of age was greater in those with moderate preterm birth (adjusted HR = 1.44; 95% CI, 1.34-1.55), late preterm birth (adjusted HR = 1.23; 95% CI, 1.18-1.29), and early term birth (adjusted HR = 1.12; 95% CI, 1.09-1.15).

They found that associations between gestational age and all-cause mortality were stronger in women compared with men.

Additionally, Risnes and colleagues determined that preterm birth (before 37 weeks gestation), compared with full-term birth, was associated with doubled risks for death from CVD (adjusted HR = 1.89; 95% CI, 1.45-2.47), diabetes (adjusted HR = 1.98; 95% CI, 1.44-2.73) and chronic lung disease (adjusted HR = 2.28; 95% CI, 1.36-3.82).

The researchers noted that the findings were replicated across the four countries, and that the observed associations were not explained by individual cofounding factors, familial genetic and environmental factors, congenital malformations or socioeconomic factors.

In an editorial accompanying the study, Casey Crump, MD, PhD, a professor in the departments of family medicine and community health and population health science and policy at Icahn School of Medicine at Mount Sinai, wrote that the study corroborates findings from other large cohort studies, and “the evidence is now clear that preterm and early-term birth are important risk factors for premature mortality in adulthood.”

He noted that while the mechanisms behind these associations are not fully realized, it may be due to impaired organ development and epigenetic changes that affect cardiometabolic function and organ systems.

“Preterm and early-term birth should now be recognized as chronic conditions that require long term clinical follow-up for preventive actions, monitoring and treatment of health sequelae across the life course,” Crump wrote.

References:

• Risnes K, et al. JAMA Netw Open. 2021;doi:10.1001/jamanetworkopen.2020.32779.
• Crump C, et al. JAMA Netw Open. 2021;doi:10.1001/jamanetworkopen.2020.33361.