Mortality Among Young Adults Born Preterm and Early Term in 4 Nordic Nations

Abstract

Importance: Adverse long-term outcomes in individuals born before full gestation are not confined to individuals born at extreme gestational ages. Little is known regarding mortality patterns among individuals born in the weeks close to ideal gestation, and the exact causes are not well understood; both of these are crucial for public health, with the potential for modification of risk.

Objective: To examine the risk of all-cause and noncommunicable diseases (NCD) deaths among young adults born preterm and early term.

Design, setting, and participants: This multinational population-based cohort study used nationwide birth cohorts from Norway, Sweden, Denmark, and Finland for individuals born between 1967 and 2002. Individuals identified at birth who had not died or emigrated were followed up for mortality from age 15 years to 2017. Analyses were performed from June 2019 to May 2020.

Exposures: Categories of gestational age (ie, 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]).

Main outcomes and measures: All-cause mortality and cause-specific mortality from NCD, defined as cancer, diabetes, chronic lung disease, and cardiovascular disease (CVD).

Results: A total of 6 263 286 individuals were followed up for mortality from age 15 years. Overall, 339 403 (5.4%) were born preterm, and 3 049 100 (48.7%) were women. 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 were stronger in women than in men (P for interaction = .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.

Conclusions and relevance: The findings of this study strengthen the evidence of increased risk of death from NCDs in young adults born preterm. 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. Excess mortality associated with shorter gestational age was most pronounced for CVDs, chronic lung disease, and diabetes.

Figure 1.. All-Cause Mortality

Figure 2.. Cumulative Hazard of Death by Sex and Gestational Age Category in Data Sets from Norway and Sweden

Figure 3.. Noncommunicable Disease Mortality

NA indicates not applicable.

Figure 4.. Cardiovascular Disease Mortality