We report the largest population based study to date of respiratory illness in adults with a history of LBW. VLBW survivors had 83% higher odds of hospitalization for respiratory illnesses as young adults when compared with NBW individuals. For MLBW survivors, the odds were 34% higher. This risk remained present after adjusting for maternal sociodemographic characteristics including age, race, marital status and urban/rural residence, and infant factors, including sex and birth year. VLBW survivors were at greater risk for hospitalization for respiratory disease than MLBW survivors. This graded risk, with infants of lower birth weight at greater risk of later lung disease, is biologically plausible. Infants with a lower birth weight are more likely to be born at an earlier gestational age and are known to be at higher risk of lung injury and BPD (9
). We were unable to determine if gestational age modified the effect of birth weight on adult hospitalizations, as has been hypothesized (25
). Gestational age according to last menstrual period was available in our data but was not felt to be accurate. Others have reported the inaccuracies in estimation of gestational age estimation using the last menstrual period as well (26
). An increased risk of hospitalization was present across all three subgroups of respiratory illness: asthma, respiratory infections, and respiratory failure. Although the number of events was low, LBW survivors were at a particularly high risk of the most severe condition of respiratory failure requiring mechanical ventilation.
Maternal smoking may explain a small amount of the association between birth weight and risk of hospitalization. Adjustment for smoking status attenuated the OR for MLBW from 1.33 to 1.27 and for VLBW from 1.30 to 1.29 (). However, birth weight remained significantly associated with adult hospitalizations after adjustment for maternal smoking in MLBW survivors. The trend also remained significant.
The increased risk of hospitalization may be explained by poor lung development among LBW infants. Poor lung function in healthy term infants is associated with decreased lung function in young adults (29
). It is reasonable to assume this relationship would also be true for LBW survivors. Although we were unable to assess for a history of BPD, some LBW survivors in our study would have been at risk for “old” BPD. Old BPD is characterized by diffuse alveolar damage and neutrophilic inflammation leading to fibrosis (6
). Abnormal pulmonary anatomy has been seen on computed tomography scans in adult survivors of moderate to severe BPD (30
). The sequelae of lung injury may alter respiratory anatomy and physiology for years to come. This may predispose survivors to air trapping, poor airway clearance, or gas exchange disorders. LBW survivors may also be more likely to have upper airway problems, such as tracheal stenosis, tracheomalacia, or vocal cord paralysis placing them at higher risk of respiratory illness. Additionally, LBW in the absence of BPD may confer an increased risk of adult respiratory disease because hyaline membrane disease, which is associated with old BPD, was relatively uncommon in our study.
Young adult survivors of BPD have been reported to have abnormal pulmonary function. In 1990, Northway and colleagues reported mild airflow obstruction, airway hyperresponsiveness, and air trapping in 26 young adult survivors (31
). Others have reported mild airflow obstruction in extremely LBW (16
) and VLBW survivors (17
). Low normal range exercise capacity has been reported in LBW survivors (32
). Others have not found significant differences in pulmonary function between LBW survivors and NBW control subjects. Narang and colleagues recently reported that mean z-scores for FEV1
and FVC were slightly below normal among LBW survivors and NBW control subjects, but there were no significant differences between the two groups (25
). In addition to abnormal PFTs, LBW survivors have reported a greater prevalence of respiratory symptoms and doctor-diagnosed asthma compared with NBW survivors (16
Our data should be interpreted with some caution. We were unable to assess for differential migration out of WA in our control group. It is possible that NBW infants were more likely to move out of the state than LBW infants. If these control subjects had been hospitalized as young adults in other states, we would have missed these hospitalizations. However, we estimate that 14% of NBW control subjects would need to have been hospitalized outside of WA to eliminate the observed excess in respiratory disease hospitalizations for VLBW survivors. This seems unlikely because only about 0.3% of young adults are hospitalized for diseases of the respiratory system in any given year (33
). The use of linked databases has limitations. However, it seems unlikely that birth weight would have been recorded any differently for cases and control subjects, and any misclassification would tend to bias our estimates toward the null.
We were only able to assess maternal socio-economic status indirectly. Nevertheless, after adjustment for maternal age and sociodemographic characteristics, results were largely unaffected. We were also unable to assess for smoking exposure in adult survivors. If LBW survivors had smoked more than NBW survivors, they may have been at increased risk of respiratory disease. However, it is unknown if differences in smoking behavior exist between these two groups. Smoking has been reported to be more prevalent among LBW survivors compared with NBW survivors, although lung function did not differ between the groups (25
). Others have not found differences in smoking behavior between the two groups (8
). Finally, similar to all long-term follow-up studies, we identified a study population born in an era before the routine use of antenatal corticosteroids and surfactant therapy. These practices have decreased the incidence of old BPD. The incidence of “new” BPD, however, is increasing. New BPD is primarily a result of immature lung development and is associated with fewer, larger alveoli and disrupted capillary development. It is unknown if these survivors will have the same risk of adult respiratory illness as our study population.
We report a previously unrecognized excess risk of hospitalization for respiratory illness in young adults with a history of LBW. Our findings suggest that not only are VLBW and MLBW survivors at increased risk of long-term respiratory disorders but that these disorders are clinically significant and associated with increased health care utilization. In our study, the population attributable risk percent, the percentage of disease in a population attributable to a particular exposure, was estimated to be 1.8%. If this were extrapolated to the 1.2 million U.S. hospitalizations for respiratory illnesses per year for ages 18 to 44, low birth weight may account for over 21,000 adult hospitalizations per year, with charges in excess of $225 million per year (33
). The number of excess hospitalizations may grow in view of the improving survival and increasing prevalence of BPD. If confirmed, these findings suggest that internists, and not just pediatricians, need to be aware of their patient's birth history. Future studies should focus on identifying other risk factors that may modify this risk so that interventions can be designed to improve outcomes and reduce health care utilization costs.