CHICAGO - The largest-ever study of the long-term consequences of premature birth finds that children born early have higher death rates in childhood and are more likely to be childless in adulthood.
Experts called the research significant because it followed 1.2 million Norwegian births over decades. It also raises questions about future risks for even tinier babies saved today by modern medicine.
New drugs and therapies first used widely in the 1990s now save smaller and sicker babies. So the babies in the study may have been healthier, on average, than children born premature in recent years, experts said.
"Are we improving their survival but at the expense of significant problems down the road?" asked study leader Dr. Geeta Swamy of Duke University Medical Center.
Most preemies grow up to have good health and normal reproduction, but the researchers found heightened risks compared with babies born at full term from 1967 to 1988. The findings add to known consequences of prematurity such as lung problems, disabilities, mental handicap and school delays.
U.S. rates of premature births climbed steadily during the past two decades reaching an estimated 12.8 per cent of births in 2006, government figures show. More than 540,000 babies were born premature that year. Fertility treatments that result in multiple births and older mothers contributed to the rise. (The rate of premature births in Norway that year was seven per cent.)
"In the United States, there is an epidemic of preterm birth, and prevention is absolutely critical," said Dr. Alan Fleischman of the March of Dimes. He was not involved in the study.
Fleischman said prevention efforts include hormone treatment for women with a history of giving premature birth, avoiding inducing labour unless medically necessary and reducing the number of embryos implanted at one time during fertility treatments.
In the study, appearing in Wednesday's Journal of the American Medical Association, more than 60,000 Norwegian children were born premature, about five per cent overall. Only single births were included.
As expected, babies born early were more likely to die during the first year of life compared with babies born at term.
Surprisingly, their increased risk of death persisted as they aged.
The children who were born five to nine weeks early (28 to 32 weeks into the pregnancy) showed a doubled risk of death from ages one to five compared with children born at normal term. (The overall risk of death was low: 33 of the 5,880 children in the premature group died.)
When the researchers looked at boys and girls separately, they found a stronger link in boys between premature birth and higher death rates in childhood.
The causes of childhood deaths are still being analyzed, but birth defects and childhood cancers played a role, Swamy said.
In adulthood, other differences showed up. Prematurity was linked to lower levels of education and more childlessness in both men and women in a subset of more than 580,000 births from 1967 through 1976.
Women who were preemies had a higher risk of giving birth to premature babies themselves. The risk of next-generation premature births increased with the severity of prematurity in the mothers.
The study didn't examine reasons for these greater risks. Possible culprits include genetic differences, birth defects, economic factors and social obstacles, Swamy said.
As in other studies, there were more premature births among single mothers and those with less education.
The research was based on data from Norwegian birth, death and other records.
Norway's homogenous population and its universal access to medical care make the findings a "best-case scenario," said Dr. Wanda Barfield of the Centers for Disease Control and Prevention. She co-authored an accompanying editorial in the journal.
In the United States, premature birth rates among black mothers are higher than among white mothers, she said.
The findings suggest people may want to tell their doctors if they were born early.
"That may help doctors to manage adult health and reproductive conditions for future generations," Barfield said.
Abstract
Context Preterm birth is a major cause of infant morbidity and mortality. Less is known about long-term health among persons born preterm.
Objective To determine the long-term effects of preterm birth on survival, reproduction, and next-generation preterm birth.
Design, Setting, and Participants Population-based, observational, longitudinal study using registry data from 1 167 506 singleton births in the Medical Birth Registry of Norway in 1967-1988. The cohort was followed up through 2002 for survival. The cohort was truncated to births from 1967-1976 for assessment of educational achievement and reproductive outcomes through 2004.
Main Outcome Measures In relation to sex and gestational age at birth, absolute mortality, risk of fetal, infant, child, and adolescent mortality, and incidence and risk of reproduction and next-generation preterm birth. Singleton term (37-42 weeks) fetal deaths and live births, stratified by sex, served as the reference group for all analyses.
Results The percentage who were born preterm was higher among boys (5.6%) than among girls (4.7%). Preterm 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 (95% confidence interval [CI], 2.0-14.2) and 7.0 (95% CI, 2.3-22.0), respectively. The mortality rate for girls born at 22 to 27 weeks was 1.71% for early childhood death, with an RR of 9.7 (95% CI, 4.0-23.7); there were no late childhood deaths. 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 (95% CI, 1.6-3.7) and 2.3 (95% CI, 1.3-4.1), respectively. Girls born at 28 to 32 weeks did not have a significantly increased risk of childhood mortality. Reproduction was diminished for index participants born preterm. For men and women born at 22 to 27 weeks, absolute reproduction was 13.9% and 25%, with RRs of 0.24 (95% CI, 0.17-0.32) and 0.33 (95% CI, 0.26-0.42), respectively. For 28 to 32 weeks, absolute reproduction was 38.6% and 59.2% for men and women, with RRs of 0.7 (95% CI, 0.66-0.74) and 0.81 (95% CI, 0.78-0.85), respectively. Preterm women but not men were at increased risk of having preterm offspring.
Conclusion In persons born in Norway in 1967-1988, preterm birth was associated with diminished long-term survival and reproduction.
