Preterm birth was associated with increased mortality in adolescents and adults age 50 and younger, compared to full-term birth, in a population-based cohort study that included more than 6 million people born in the Nordic Region.
Early preterm (<34 weeks) birth was associated with a 1.4-fold increased risk of death from all causes between the ages of 15 and 50 years, while late preterm birth (34-36 weeks) was associated with a 1.2-fold increase.
The association between earlier gestational age and preterm birth was stronger in women than in men, and preterm birth was associated with a roughly 2-fold increased risk for death from cardiovascular disease, diabetes, and lung disease in the study, published online January 8 in JAMA Network Open.
“The findings of this study strengthen the evidence of increased risk of death from noncommunicable diseases (NCD) in young adults born preterm,” wrote researchers Kari Risnes, MD, PhD, of the Norwegian University of Science and Technology, Trondheim, Norway, and colleagues. “Importantly, the increased death risk was found across gestational ages up to the ideal term date and includes the much larger group with early-term birth.”
The researchers noted that roughly 1 in 10 pregnancies involve birth before 37 weeks’ gestation and more than 90% of babies born preterm reach adulthood.
Until recently, they wrote, most studies of preterm birth outcomes have been limited to early adulthood and have focused on extreme (<28 weeks) and very (28-32 weeks) preterm birth. Recent studies suggest, however, that adverse long-term outcomes may not be limited to extreme preterm birth.
“The notion that early life is a vulnerable period, when even subtle disruptions in the development of organ systems may lead to adverse health outcomes in adulthood, is far from new,” Risnes and colleagues wrote. “…A growing body of evidence from clinical follow-up studies associates shorter gestation with higher levels of risk factors for noncommunicable diseases.”
Risnes and colleagues used nationwide birth cohorts from Norway, Sweden, Denmark, and Finland to identify people born between 1967 and 2002 who were followed for mortality from age 15 years to 2017.
Categories of gestational age included moderate preterm birth and earlier (23-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), full term (39-41 weeks) and post term (42-44 weeks). The main outcomes were all-cause mortality and cause-specific mortality from NCD, defined as cancer, diabetes, chronic lung disease, and cardiovascular disease (CVD).
A total of 6,263 286 people were followed up for mortality from age 15 years, including 339,403 (5.4%) who were born preterm. Roughly half of the cohort (48.7%) were women.
Among the main study findings:
- Compared with full-term birth, the adjusted hazard ratios (aHRs) for all-cause mortality were 1.44 (95% CI, 1.34-1.55) for moderate preterm birth and earlier; 1.23 (95% CI, 1.18-1.29) for late preterm birth; and 1.12 (95% CI, 1.09-1.15) for early-term birth.
- The association between gestational age and all-cause mortality was stronger in women than in men (P for interaction = 0.03).
- Preterm birth was associated with 2-fold increased risks of death from CVD (aHR, 1.89; 95% CI, 1.45-2.47), diabetes (aHR, 1.98; 95% CI, 1.44-2.73), and chronic lung disease (aHR, 2.28; 95% CI, 1.36-3.82).
- The main associations were replicated across countries and could not be explained by familial or individual confounding factors.
Casey Crump, MD, PhD, of the Mount Sinai, Icahn School of Medicine, New York City, recently published a systematic review of 6 studies examining mortality in adults born prematurely. In commentary published with the study by Risnes and colleagues, Crump wrote that the study findings corroborate those of the studies included in his review.
“All 6 previously published studies of cohorts born in the last 50 years (in Sweden, Norway, and Australia) found that preterm birth was associated with increased all-cause mortality in early adulthood after adjusting for other perinatal and sociodemographic factors,” Crump wrote, adding that the study’s risk estimates were also consistent with those of the previously published studies.
“Based on previous large population-based studies and new corroborating findings from Risnes et al, the evidence is now clear that preterm and early-term birth are important risk factors for premature mortality in adulthood,” Crump wrote. “The mechanisms are not fully established but may involve persistent epigenetic changes and impaired organ development that affect cardiometabolic function and most organ systems, consistent with the developmental origins of health and disease hypothesis.”
Crump noted that preterm and early-term birth should 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. Most knowledge about preterm birth outcomes has been relegated to the specialties of neonatology and pediatrics, with little integration so far into internal medicine or family medicine, the primary disciplines that will provide care for these patients in adulthood. Consequently, the growing evidence on long-term health sequelae has yet to be incorporated into clinical practice. Currently, clinicians seldom seek birth history in adult patients. History-taking and electronic health records (EHRs) for patients of all ages should routinely include birth history, including gestational age at birth, to provide important early-life context for understanding patients’ health.”
He concluded that integration of this new knowledge into clinical practice “is a crucial next step to improve long-term health in this growing population with increased health risks.”
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Early preterm (<34 weeks) birth was associated with a 1.4-fold increased risk of death from all causes between the ages of 15 and 50 years, while late preterm birth (34-36 weeks) was associated with a 1.2-fold increase.
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The association between earlier gestational age and preterm birth was stronger in women than in men, and preterm birth was associated with a roughly 2-fold increased risk for death from cardiovascular disease, diabetes, and lung disease.
Salynn Boyles, Contributing Writer, BreakingMED™
Funding for this study was provided by European Union horizon 2020, the Academy of Finland, the Foundation for Pediatric Research, and others.
Lead researcher Kari Risnes reported no relevant disclosures. Editorial writer Casey Crump reported receiving grant funding from the NHLBI.
Cat ID: 191
Topic ID: 83,191,730,914,191,41,138,192,925
