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

Kari Risnes,Josephine Funck Bilsteen,Eero Kajantie,Sven Sandin,Paul Brown,Anne-Marie Nybo Andersen,Signe Opdahl,Anna Pulakka

doi:10.1001/jamanetworkopen.2020.32779

Abstract

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

Highlights

15 million pregnancies each year, 1 in 10, result in preterm birth, ie, birth before 37 weeks of gestation.[1,2] Improved survival after preterm birth is among the most striking advances of modern health care, and in recent birth cohorts, more than 90% of those born preterm reach adulthood.[2]
The adjusted hazard ratios for all-cause mortality were 1.44 for moderate preterm birth and earlier; 1.23 for late preterm birth; and 1.12 for early-term birth
Preterm birth was associated with 2-fold increased risks of death from cardiovascular disease (CVD), diabetes, and chronic lung disease

Summary

Introduction

15 million pregnancies each year, 1 in 10, result in preterm birth, ie, birth before 37 weeks of gestation.[1,2] Improved survival after preterm birth is among the most striking advances of modern health care, and in recent birth cohorts, more than 90% of those born preterm reach adulthood.[2]. 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.[7,8] While many studies that have followed up individuals born in the mid to late 20th century demonstrate robust associations between lower birth weight and higher cardiometabolic disease risk and mortality,[9,10] only some could assess preterm birth as a factor associated with these outcomes. Results are mixed, and their generalizability to individuals entering adulthood today may be limited.[9,11,12] A growing body of evidence from clinical follow-up studies associates shorter gestation with higher levels of risk factors for noncommunicable diseases (NCDs).[13,14,15] For cancer, studies on associations with gestational age are few,[16] while larger birth size has been associated with higher adult cancer risk.[10,17]

Methods

Results

Discussion

Conclusion