Wheezing lower respiratory disease and vaccination of premature infants.

Purpose: Premature infants are at increased risk of wheezing in association with respiratory syncytial virus (RSV) and rhinovirus infections. We assess possible associations between wheezing and routine vaccinations of premature infants.

Methods: We conducted a self-controlled case series (SCCS) study of premature infants born at five health maintenance organizations (HMO's) from 1997 to 2002 (N=18,628). Episodes of medically attended wheezing lower respiratory diseases (WLRD) were ascertained from ICD-9 coded database records. Relative risks of WLRD during post-vaccination exposure windows were estimated by Cox proportional hazard regression with time-dependent vaccine exposure variables, adjusted for age, season, and frequency of well-baby visits.

Results: WLRD hazard ratios (HR) were not significantly elevated for any vaccine type among non-fragile or fragile premature infants. Among non-fragile infants the 8-14 days HR was significantly reduced for live attenuated MMR (0.68, 0.52-0.88) and Varicella (0.71, 0.53-0.94) vaccines, and similarly but insignificantly reduced for infrequently used live attenuated OPV vaccine (0.70, 0.46-1.06). There was a smaller significant reduction (0.83, 0.69-0.998) in the 15-30 days HR for MMR and a similar but not significant reduction (0.86, 0.71-1.05) in the 31-44 days HR for MMR. Hepatitis B vaccine (HBV), which is not a live vaccine, had significantly reduced 8-14 days (0.84, 0.72-0.98) and 31-44 days (0.88, 0.78-0.98) HRs among non-fragile infants. The apparent protective effect of HBV may be confounded by live vaccines administered simultaneously with the third dose of HBV. Among fragile infants there was a large significant reduction in the 8-14 days HR for live attenuated OPV vaccine (0.40, 0.23-0.70) and smaller significant reductions in the 8-14 days HR for inactivated DTaP (0.82, 0.71-0.95), Hib (0.83, 0.73-0.96), and PCV7 (0.84, 0.70-0.997) vaccines. Delays in vaccinating fragile infants may have made simultaneous administration of live vaccines and third doses of these inactivated vaccines more likely.

Conclusions: We found no evidence of increased WLRD risk following routine vaccinations of premature infants. WLRD risk among non-fragile premature infants appears to be reduced for a few weeks after live attenuated vaccinations.