Low gestational age at birth appears to be strongly associated with higher mortality during young adulthood, independently of fetal growth and other perinatal and socioeconomic factors, according to a study in the Sept. 21 issue of JAMA.
The robust association was observed even among "late" preterm births at 34-36 weeks, said Dr. Casey Crump of the department of medicine at Stanford (Calif.) University, and his associates.
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A new study has found a strong association between low gestational age at birth and higher mortality during adulthood.
"To our knowledge, this is the first study to report the specific contribution of gestational age at birth on mortality in adulthood. The results underscore the persistent long-term health sequelae of preterm birth," the investigators said (JAMA 2011;306:1233-40).
"Clinicians will increasingly encounter the health sequelae of preterm birth throughout the life course and will need to be aware of the long-term effects on the survivors, their families, and society," they noted.
Previous studies have examined the relationship between low birth weight and adult mortality, but have not assessed the contribution of gestational age. To do so, Dr. Crump and his colleagues performed a cohort study of 674,820 singleton infants born in 1973-1979 in Sweden, who were followed throughout their lives for all-cause and cause-specific mortality.
The study subjects were aged 29-36 years at the most recent follow-up. The prevalence of preterm birth in Sweden in the late 1970s was 5%. The prevalence in this cohort was 4.1% (27,979 preterm births).
There were 7,095 deaths among the study subjects. Mortality strongly correlated with low gestational age (LGA) at birth during early childhood, an association that disappeared in late childhood and adolescence but reappeared in young adulthood.
The relationship was robust and linear in young adulthood at ages 18-36 years. Adjusting the data to account for numerous possible confounders – including the subject’s sex, birth year, and birth order; the mother’s age at delivery; the mother’s marital status; and both parents’ educational status – had little effect on the risk estimates.
An analysis that excluded subjects born with congenital malformations also did not affect the correlation between LGA at birth and increased mortality in young adulthood. Mortality was increased even among subjects born at the end of the preterm period at 34-36 weeks, the investigators said.
When the data were analyzed by cause of death, LGA at birth was most strongly associated with mortality due to respiratory and endocrine disorders, followed by cardiovascular disorders. In contrast, it was not significantly associated with death from neurological disorders, cancer, or injury.
This finding is consistent with reports in the literature that LGA correlates with asthma, hypertension, diabetes, and hypothyroidism in later life, Dr. Crump and his associates said.
"The underlying mechanisms are still largely unknown but may involve a complex interplay of fetal and postnatal nutritional abnormalities; other intrauterine exposures, including glucocorticoid and sex hormone alterations; and common genetic factors," they said.
The researchers noted that the prevalence of preterm birth in the United States at present exceeds 12%, more than double the prevalence in this cohort. Most survivors "have a high level of function and self-reported quality of life," but the results of this study show that increased long-term morbidities and mortality also can be expected, Dr. Crump and his associates said.
However, it should be noted that today’s preterm infants may differ in important ways from the subjects in this study because neonatal care has advanced during the interim. "It is unclear to what extent our findings are generalizable to later cohorts, and any such comparison should be made with caution," they noted.
This study was supported by the U.S. National Institute of Child Health and Human Development, the Swedish Research Council, the Swedish Council for Working Life and Social Research, and the Avtal om Läkarutbildning och Forskning (Agreement on Medical Training and Research), Lund, Sweden. The authors reported no financial conflicts of interest.