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 fullterm 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.

Association of Preterm Birth With Myocardial Fibrosis and Diastolic Dysfunction in Young Adulthood

“…As such, ECV is now recognized as a novel prognostic marker independent of noninfarction scar in the myocardium ( 27 ). In our present study of normotensive individuals, we identified that nearly 9% of the preterm population had ECV of 30% or greater, which may contribute to their greater risk for early heart failure ( 4 ) and early cardiovascular-related mortality ( 7 ). Our finding of greater ECV with no change in native T1 in the preterm-born adults suggests a specific association with collagen deposition.…”

“…Preterm birth (<37 gestational weeks) affects >10% of live births worldwide ( 1 ) and abruptly interrupts the trajectory of cardiac development, leading to neonatal ( 2 ) and long-term ( 3 ) morbidity. Large-scale birth registries investigating the impact of being born preterm have shown an increased risk for cardiovascular diseases by childhood and adulthood, including heart failure ( 4 , 5 ), ischemic heart disease ( 6 ), and early cardiovascular-related mortality ( 7 ).…”

Low Birth Weight as an Early-Life Risk Factor for Adult Stroke Among Men

“…Two previous studies evaluated the association between short gestation and the risk of stroke. No significant association was seen for prematurity and the risk of fatal stroke (21) or stroke events (22). In the present study, we included men born between 1945 and 1961, but because information on gestational age was J o u r n a l P r e -p r o o f not available, prematurity could not be assessed.…”

Postnatal inflammation in ApoE−/− mice is associated with immune training and atherosclerosis

“…Atherosclerosis may develop from early childhood onwards, but manifests symptomatically as cardiovascular disease (CVD) in adulthood (1, 2) and it remains the most common cause of death globally (3,4). Preterm infants are at increased risk for developing CVD in adulthood (5,6), with some estimates suggesting a doubling of risk compared to those born at term (7). This heightened risk may reflect the increased inflammatory exposures that characterise pregnancies that culminate in preterm birth, including prenatal inflammation (chorioamnionitis) and that arising from early life infections, which are highly prevalent in preterm infants (8).…”