This large, population‐based study identified an association between preterm birth, but not SGA status, and subsequent risk of clinical asthma among children <10 years of age. This effect was observed among children <5 years and 5–9 years of age. Among children with asthma, preterm birth also increased the risk of hospitalisation due to asthma. These data support previous studies that have identified an association between prematurity and changes in pulmonary function, including those that have found effects extending into adolescence1,5,7,23,24,25,26
and adult life.27
Futher, our stratified analyses suggest that previously reported associations are probably not solely due to preterm birth increasing the risk of respiratory tract infection.
Recent studies have found a relationship between intrauterine growth retardation and bronchopulmonary dysplasia.28,29,30
Pulmonary damage from bronchopulmonary dysplasia, in turn, has been associated with asthma,6,7,23,24,25
providing a potential mechanism by which low‐birth weight might increase the risk of asthma. All of these studies, however, evaluated the effect of asthma on lung function rather than clinical illness. Several studies evaluating clinical illness as an outcome have found an association between low‐birth weight and future asthma risk31,32,33
whereas others have not.5,34
These studies, however, did not evaluate the independent effect of prematurity and birth weight on asthma, or the association between SGA status and asthma. One study that evaluated gestational age and birth weight found that birth weight adjusted for gestational age was strongly associated with lung function, but that gestational age alone more accurately reflected respiratory illness.4
A second study found that after adjustment for confounding factors, birth weight was not associated with either adult lung function or asthma symptoms.35
Our results support existing evidence that low‐birth weight independent of gestational age does not increase the risk of clinically significant asthma.
but not all34,35
published studies have found that preterm birth leads to increased risk of clinical asthma or decreased lung function. Few studies, however, have attempted to quantify the effect of prematurity on asthma outcomes. Consistent with our results, a single study found that each additional week of gestation reduced the risk of severe wheezing by 10%.5
In our study, the largest effect occurred at <32 weeks of gestation. Nevertheless, some effect is observed between 32 and 36 weeks' gestation. As the occurrence of births is much greater at 32–36 than at <32 weeks' gestation, it is likely that the greatest effect on asthma will occur by extending these later gestation births.
Our study had several limitations. Because children were not necessarily continuously enrolled over the 4‐year study period, we may have missed children with milder asthma who presented infrequently for care, and thus our results may not be generalisable to this population; we controlled for this to some extent by limiting analysis to children enrolled for at least 365 days. Children born prematurely may have more opportunities to have asthma diagnosed and reported because they present more frequently with other medical conditions; this ascertainment bias may have overestimated the association between preterm birth and asthma. We studied only the Medicaid population and thus results may not be generalisable to other groups. We did not evaluate lung function. Finally, we could not evaluate the possibility of a causal link between respiratory infection and asthma.
We believe that this is the largest population‐based study yet conducted that has evaluated the association between birth outcomes and clinically relevant asthma. Among children born at <32 weeks, the 4‐year asthma prevalence was
10% regardless of whether children were <5 years or >5 years, although among those with asthma 15–43% required hospitalisation, depending on age. Consequently, preterm children should be evaluated for the development of asthma and treated aggressively when asthma is identified. Each additional week of gestation decreased the overall asthma risk by 7.6% and the risk of hospitalisation among children with asthma by 6.9%. Thus, measures that prolong gestation could possibly have a modest effect on asthma burden among children born preterm.