Our study examined the association of late-preterm birth with asthma in the first 18 months of life. We demonstrated that children born late preterm were at increased risk for persistent asthma and use of an inhaled corticosteroid. Children born late preterm with asthma also had increased utilization, as measured on the basis of acute respiratory outpatient visits. In addition, we found that diagnoses of asthma and inhaled corticosteroid were more common among children with low-normal gestational age, compared with term children. Extending previous work that focused on infants <1 year of age, this study documents an association of asthma severity with late prematurity.
Previous studies on asthma and preterm birth focused on the impact of gestational age for very preterm infants (≤32 weeks) or all preterm infants (<37 weeks), and the magnitude of the association varied substantially between studies.16–22
Mechanistically, it has been proposed that chorioamnionitis, because of the associated proinflammatory state and heightened immune response, might play a role in asthma development for infants born preterm.20,29
The few studies of late prematurity and the development of asthma showed mixed results. Using survey data from a nationally representative sample, Abe et al24
did not find an association with late-preterm birth when asthma was assessed on the basis of caregiver reports. Escobar et al,25
using a large cohort from Kaiser Permanente, did find a statistically significant association between late prematurity and recurrent wheeze in children up to 3 years of age; recurrent wheeze was defined as a composite measure on the basis of ICD-9 codes, prescription utilization, and visit history.
Our study specifically evaluated the association of birth at 34 to 36 weeks of gestation with asthma in a practice-based setting, using physician classifications of severity as well as utilization measures. Our findings that late-preterm children were more likely to have persistent asthma diagnosed and to be given inhaled corticosteroids indicate that late-preterm birth is associated with differences in asthma disease severity and health resource utilization for asthma. The implication that late-preterm children have a propensity for more-severe illness is consistent with the results of previous studies that demonstrated higher rehospitalization rates and higher hospital costs for late-preterm infants, compared with term infants, in the first year of life.12,13
Our findings also suggest that low-normal gestational ages of 37 to 38 weeks might confer increased risk of early childhood asthma, compared with gestational ages of ≥39 weeks, as suggested in other studies.25,26
This association is noteworthy, given recent epidemiological trends in gestational length for US births. Since the 1990s, the distribution of gestational ages has shifted downward; 39, rather than 40, weeks is now the most common length of gestation.47
The proportion of births at severely preterm gestational ages has remained stable in the past 2 decades, whereas there have been increases primarily in the proportions of births at 37 to 39 weeks and 34 to 36 weeks of gestation.1,47
The reasons for this trend are likely multifactorial, including increases in labor induction and cesarean delivery rates, patient and provider preferences, and obesity and other demographic changes.47–50
Given the large contributions of late-preterm and low-normal gestation deliveries to the total volume of US births, associations of asthma with these gestational-age groups could have a significant public health impact, which warrants further investigation.
This study had several limitations, primarily related to regression adjustment for nonrandomization. We lacked data on certain prenatal and postnatal risk factors, including chorioamnionitis, maternal smoking, and family history. Although more-detailed information on obstetric and neonatal histories, including the indications for delivery, was available for some infants, such data were documented inconsistently and therefore were not reliable for analysis. Although such unobserved factors might have influenced selection into gestational-age groups and biased results, the large ORs make these unmeasured variables less likely to account for observed differences between groups. We also acknowledge that there might have been errors in ICD-9 coding that led to misclassification bias. However, this would be minimized by the fact that each ICD-9 code in the chronic problem list was paired with a physician-documented diagnosis in the medical records, which we used as a cross-reference. An additional limitation is that we were unable to assess outcomes beyond 18 months of age; therefore, we missed asthma diagnoses made after that time. Although diagnosis of asthma in younger age groups can be difficult, our study used an EHR that provides a unique, standardized approach for physicians to measure and to document asthma symptoms among infants and young children; the validity of this approach was demonstrated previously.30,32
Strengths of this study include racial and socioeconomic diversity of the sample, which contributes to the generalizability of results. This birth cohort, in which all patients were born in 2007, reflects recent trends in late-preterm birth rates and asthma.