Study Suggests Individuals Born Preterm Are at Increased Risk of Death Until Third, Fourth Decade of Life

Preterm birth (PTB), or birth prior to 37 weeks’ gestation, is a leading cause of neonatal mortality and the second leading cause of death among children younger than 5 years. Despite this, research is somewhat limited. Authors of research published in JAMA Network Open evaluated the associations between preterm birth and all-cause and cause-specific mortality from birth through adulthood (23-36 years of age).

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For this cohort study, the investigators created a population-based birth cohort using vital statistics from Statistics Canada. Data on live births in Canada between January 1, 1983, and December 31, 1996, were included, and those with missing information on baseline covariates or missing or invalid gestational age (GA), births with GAs less than 24 weeks, and post-term births more than 41 weeks’ gestation were excluded. The cohort was followed up until December 31, 2019, allowing for minimum and maximum follow-ups of 23 years and 36 years, respectively, depending on date of birth.

Information about GA at birth was available from a birth database and was completed by parents and health care professionals. PTB was defined as birth earlier than 37 weeks and was organized into the following categories: extremely preterm (24-27 weeks); very preterm (28-31 weeks), moderately preterm (32-33 weeks); and late preterm (34-36 weeks). Additionally, birth at term was defined as 37 to 41 weeks’ gestation.

Both all-cause and cause-specific mortality were recorded in the study. All-cause mortality was defined as death from any cause during the follow-up period, whereas cause-specific mortality was categorized according to the underlying cause of death, such as respiratory system disorders, circulatory disorders, infectious diseases, and cancer, among others.

Further, participants were matched on the following baseline covariates: sex; birth plurality (eg, singleton, multiple); province of birth; birth year; parental age at birth; maternal marital status (single, married, other [included widowed, divorced, or separated], or missing information); maternal parity (0, 1, 2, 3, or ≥4 previous live births); and parental origin of birth based on the Statistical Classification of Countries and Areas of Interest for social statistics. Additionally, the authors noted using statistics data and a matched cohort design to account for multiple sociodemographic characteristics.

The study authors identified a total of 4,998,560 live births in Canada between 1983 and 1996 which were included in the final analysis. Of these, approximately 6.9% were preterm (n = 342,580), with 0.3% (n = 14,130) born at 24 to 27 weeks’ gestation, 0.6% (n = 30,640) at 28 to 31 weeks, 0.8% (n = 40,560) 32 to 33 weeks’, and 5.1% (n = 257,250) at 34 at 36 weeks’. Individuals born preterm were more likely to be male (54.2%), a twin, or a higher-order multiple birth compared with their at-term counterparts. Mothers who gave birth preterm were more likely to be younger than 20 years or 35 years and older, single or missing marital status, and have 4 or more previous live births.

At a median follow-up of 29 years, 72,662 individuals died, of which 14,312 were born preterm and the remaining 58,350 were at term. At all age intervals, PTB was associated with an increased risk of death, with the highest risk differences (RDs) and risk ratios (RRs) observed from birth through infancy (ages 0-11 months; RD, 2.29% [95% CI, 2.23%-2.35%]; RR, 11.61 [95% CI, 11.09-12.15]) and in early childhood (ages 1-5 years; RD, 0.34% [95% CI, 0.31%-0.36%]; RR, 2.79 [95% CI, 2.61-2.98]). The lowest RDs and RRs were observed among those between ages 18 and 28 years (RD, 0.07% [95% CI, 0.04%-0.10%]; RR, 1.13 [95% CI, 1.07-1.19]).

Further, the authors also observed than increased risks of mortality were associated with several causes, such as respiratory, circulatory, and digestive system disorders; nervous system, endocrine, and infectious diseases; cancers; congenital malformations; and conditions that originated during the perinatal period. The highest hazard ratios (HRs) were observed for conditions that originated during the perinatal period (HR, 37.50 [95% CI, 29.80-47.20]) and for digestive and respiratory disorders, nervous system diseases, congenital malformations, and infections (HRs ranged from 2.34 [95% CI, 1.94-2.83] to 3.27 [95% CI, 2.97-3.61]). There were no associations found for external causes of deaths.

Limitations of the study include potential measurement errors in GA data and the lack of generalizability of 1980s through 1990s births compared with recent or present-day births. Further, the authors acknowledged that data may have missed deaths that occurred early in the neonatal period, notably those who were born near the threshold of viability. They suggested that follow-up studies should be conducted to assess any potential adverse effects of PTB into adulthood.

REFERENCE

Ahmed AM, Grandi SM, Pullenayegum E, et al. Short-Term and Long-Term Mortality Risk After Preterm Birth. JAMA Netw Open. 2024;7(11):e2445871. doi:10.1001/jamanetworkopen.2024.45871