Association of Pre-Term Birth with Long-Term Survival, Reproduction, and Next Generation Pre-Term Birth
Pre-term birth (birth <37 weeks) is a major cause of infant morbidity and mortality. This study was conducted to assess the long-term health consequences of those persons who were themselves born pre-term . The authors hypothesized that pre-term birth is associated with not only fetal, infant, and childhood morbidity and mortality but also with adverse outcomes that persist throughout adulthood. This hypothesis was tested in a population-based, observational, longitudinal study using registry data from 1,167,506 singleton births in the Medical Birth Registry of Norway in 1967-1988 and followed through 2002. Index cohort ( 22 weeks of gestation or weighing at least 500 g) was selected from 1967 through 1988. The Medical Birth Registry of Norway (MBRN) requires mandatory registry of all fetal deaths and live births in Norway.
• The percentage of pre-term birth was higher among boys (5.6%) than among girls (4.7%).
• There was no association between maternal or paternal age and pre-term birth
• Pre-term participants had an increased risk of mortality throughout childhood.
• For boys born at 22 to 27 weeks, mortality rates were 1.33% and 1.01% for early and late childhood death, with relative risks (RRs) of 5.3.
• The mortality rate for girls born at 22 to 27 weeks was 1.71% for early childhood death, with an RR of 9.7. For 28 to 32 weeks, the early and late childhood mortality rates among boys were 0.73% and 0.37%, with RRs of 2.5. Girls born at 28 to 32 weeks did not have a significantly increased risk of childhood mortality.
• Increased relative mortality persisted into childhood for all pre-term gestational age categories.
• Increased risk of death was again detected for post-term boys in the late childhood period, with a mortality rate of 0.23%, an AR of 0.07%, and an RR of 1.4 (95% CI, 1.1-1.8).
• The lower the gestational age of the index participant, the greater the risk of having less than a high school education and the lower the risk of having graduate education.
• With regard to reproduction, only 25.0% of women who had been born at 22 to 27 weeks had subsequently reproduced in contrast to approximately 68% of women born at term. Similar findings were noted for index men, with reproductive rates of 13.9% and 50.4% for men who had been born at 22 to 27 weeks and at term, respectively. Female but not male index participants had an increased risk of recurrent pre-term birth following a dose-response pattern such that increasing severity of prematurity was associated with an increasing risk of adverse outcomes among their offspring.
• Reproduction was diminished for index participants born pre-term. For men and women born at 22 to 27 weeks, absolute reproduction was 13.9% and 25%, with RRs of 0.24. For 28 to 32 weeks, absolute reproduction was 38.6% and 59.2% for men and women, with RRs of 0.7 and 0.81, respectively.
• Pre-term women but not men were at increased risk of having pre-term offspring.
The authors concluded that In persons born in Norway in 1967-1988, pre-term birth was associated with diminished long-term survival and reproduction.
This is a provocative study demonstrating diminished long term survival and reproduction in pre-term birth children. It is widely recognized that assisted reproductive technologies are associated with increased incidence of higher gestation pregnancies. Higher order pregnancies are associated with increased prematurity. Prematurity is associated with increase morbidity and costs. The current study indicates that ultimately, the quality of life of premature offspring may be adversely affected. The author’s discussion is thoughtful and raises appropriate concerns regarding their study. As immediate morbidities associated with pre-term birth are more effectively treated and mortality rates decrease, will there be greater long term sequela. Thus, the potential long term consequences of our treatments (ART) and our interventions should be a source of concern and certainly warrant further investigation.