Preterm birth linked to increased mortality risk from infancy to adulthood

Study shows higher mortality rates among individuals born preterm, with risks varying by gestational age and highest in early childhood.

Study: Short-Term and Long-Term Mortality Risk After Preterm Birth. Image Credit: sruilk/Shutterstock.com

In a recent study published in the JAMA Network Open, researchers assessed the association between preterm birth (PTB) and all-cause and cause-specific mortality from birth through early adulthood.

Background

PTB, defined as birth before 37 weeks’ gestation, is a leading cause of neonatal mortality, affecting approximately 10% of births globally. PTB is linked to rising mortality rates due to increased reporting of extremely preterm births, physician-initiated PTB, and assisted reproductive techniques.

Prematurity disrupts multiple organ systems, leaving individuals vulnerable to lifelong health risks, with mortality rates inversely associated with gestational age. While most preterm infants survive into adulthood, evidence suggests a persistent increased mortality risk.

However, studies have largely focused on European populations, highlighting the need for research in North America to address population-specific differences.

About the study

The present study utilized population-based vital statistics data from Statistics Canada to create a comprehensive birth cohort. Live births in Canada from January 1, 1983, to December 31, 1996, were included, with follow-up extending until December 31, 2019.

Exclusions were made for missing or invalid gestational age (GA) data, births with GA under 24 weeks, and post-term births beyond 41 weeks.

The study linked the Canadian Vital Statistics—Birth and Death databases, ensuring data confidentiality through deidentification and secure access. Ethical approval was obtained, and informed consent was waived due to the use of anonymized data.

PTB was defined as birth before 37 weeks’ gestation and further categorized into extremely preterm (24-27 weeks), very preterm (28-31 weeks), moderately preterm (32-33 weeks), and late preterm (34-36 weeks).

All-cause and cause-specific mortality data were derived from death records classified using standard International Classification of Diseases codes. Baseline characteristics, such as sex, parental age, birth plurality, and origin, were matched using coarsened exact matching to minimize confounding.

Statistical analyses included incidence rates, cumulative mortality curves, and risk estimates, with regression models accounting for sibling clustering. Sensitivity analyses considered variations by sex, birth year, and socioeconomic factors.

Study results

The study included 5,370,770 live births in Canada between 1983 and 1996. After excluding births with missing or invalid GA data, post-term births beyond 41 weeks, and births before 24 weeks’ gestation, the final cohort comprised 4,998,560 individuals, of which 6.9% (342,580) were preterm.

Among these, 0.3% were extremely preterm (24-27 weeks), 0.6% very preterm (28-31 weeks), 0.8% moderately preterm (32-33 weeks), and 5.1% late preterm (34-36 weeks). Compared to those born at term, preterm individuals were more likely to be male, born in multiple births, or to mothers who were younger than 20 or 35 years or older, single, or multiparous.

Matched cohort analyses, which balanced baseline characteristics, included 4,350,210 individuals, with no significant differences in baseline characteristics remaining after matching.

During a median follow-up of 29 years, 72,662 deaths were recorded (14,312 preterm and 58,350 term). The annual all-cause mortality incidence rate between ages 1 and 36 years was 5.94 per 10,000 person-years for preterm births and 3.73 for term births.

Mortality risks were inversely associated with GA, with individuals born preterm at higher risk, particularly in the early years of life. By age 36, 1.7% of preterm individuals had died compared to 1.1% of term individuals, with the highest mortality rates among the most preterm groups.

In the first year of life, preterm infants experienced significantly higher mortality rates, with an average monthly incidence of 23.9 deaths per 10,000 child-months compared to 1.82 for term infants. The mortality rate was highest among extremely preterm infants, with 26.2% dying within the first year, compared to 0.2% for term infants.

The matched cohort analysis confirmed increased all-cause mortality risks for preterm births across all age periods, with the strongest associations in early childhood (ages 1-5 years) and diminishing during late adolescence and early adulthood. Kaplan-Meier estimates showed consistently higher mortality among preterm individuals across all age categories.

Cause-specific mortality analyses revealed heightened risks for preterm individuals, particularly for respiratory, digestive, circulatory, nervous system, endocrine, and infectious diseases, as well as cancers and congenital malformations. The highest hazard ratios were observed for conditions originating in the perinatal period and digestive system disorders.

Secondary analyses showed consistent findings across sex and birth year strata, with minor variations. Accounting for socioeconomic factors such as family income and rural residence did not substantially alter the results.

Conclusions

To summarize, this cohort study found that individuals born preterm faced increased mortality risks from birth to early adulthood, with the highest risks in infancy declining with age and rising slightly after 30 years.

Mortality was inversely associated with GA, with those born before 28 weeks at greatest risk. PTB was linked to deaths from respiratory, circulatory, digestive, and nervous system disorders, infections; congenital conditions; cancers, and perinatal complications.

Advances in neonatal care have improved survival over time, and males showed higher absolute but lower relative risks.