Measles-Mumps-Rubella Vaccination and Asthma-like Disease in Early Childhood

Anders Hviid; Mads Melbye

Disclosures

Am J Epidemiol. 2008;168(11):1277-1283. 

In This Article

Results

A total of 871,234 children (among whom 85% were MMR-vaccinated before the end of follow-up) were included in the cohort. During 2,926,406 person-years of follow-up, we identified 26,880 asthma hospitalizations among 17,885 children. Status asthmaticus accounted for 406 hospitalizations among 354 children. The follow-up of 15,914 children was prematurely terminated because of death (n = 5,455), emigration (n = 10,159), or disappearance (n = 300).

A total of 600,938 children (among whom 84% were MMR-vaccinated before the end of follow-up) had information on prescription medication use. During 1,858,199 person-years of follow-up, we identified 833,424 uses of anti-asthma medication among 248,907 users (uses-to-users ratio (UR), 3.35). Steroid inhalants accounted for 315,965 uses among 67,731 users (UR, 4.66); short-acting β2-agonist inhalants accounted for 211,103 uses among 78,668 users (UR, 2.68); long-acting β2-agonist inhalants accounted for 5,445 uses among 1,363 users (UR, 4.00); systemic β2-agonists accounted for 431,672 uses among 203,865 users (UR, 2.12); and other anti-asthma medications accounted for 6,482 uses among 1,498 users (UR, 4.33). Note that when adding the number of uses across medication categories, this number exceeds the uses of "all anti-asthma medication," a consequence of the 20-event counting limit per person described above in Materials and Methods. The follow-up of 12,552 children was prematurely terminated because of death (n = 4,681), emigration (n = 7,710), or disappearance (n = 161).

In Table 1 , we present rate ratios for all asthma hospitalizations according to MMR vaccination status. We found that vaccination protected children against hospitalization, corresponding to a 25% reduction in the "all asthma hospitalizations" rate and a 37% reduction in the "severe asthma hospitalization" rate. The protective effect against all asthma hospitalizations was greatest in the youngest children, in those with the longest time spent at the hospital in infancy, in girls, in low birth weight children, in children with 1 older sibling, and in children living in rural areas. Including only asthma diagnoses in the construction of infant hospitalization propensity yielded similar rate ratios. The protective effect was greatest (rate ratio = 0.59, 95% confidence interval (CI): 0.55, 0.64) among children who had spent the most time (18 days-1 year) at the hospital for asthma in infancy, as compared with those who had spent little time (≤1 day) at the hospital for asthma (rate ratio = 0.83, 95% CI: 0.80, 0.88). We further analyzed the MMR effect according to age at vaccination: Rate ratios were 0.75 (95% CI: 0.71, 0.79), 0.74 (95% CI: 0.71, 0.76), 0.84 (95% CI: 0.92, 1.01), 0.92 (95% CI: 0.84, 1.01), and 0.90 (95% CI: 0.81, 1.01) for vaccination at ages <15 months, 15-18 months, 19-22 months, 23-26 months, and 27 months, respectively.

In Table 2 , we present rate ratios for use of anti-asthma medication according to MMR vaccination status. We found that vaccination was associated with less use of anti-asthma medication, corresponding to an 8% reduction in "all anti-asthma medication" use. This effect varied according to category of medication, from a 39% reduction in the use of "other anti-asthma medications" to no reduction in the use of systemic β2-agonists. The reduced use of all anti-asthma medication was greatest in the youngest children, in those with all infant vaccinations, in those with less affluent fathers, in boys, in children with no older siblings or only 1 older sibling, and in children living in rural areas. We further analyzed the MMR effect according to age at vaccination. These incidence rate ratios were 0.94 (95% CI: 0.93, 0.95), 0.91 (95% CI: 0.90, 0.91), 0.98 (95% CI: 0.97, 0.99), 1.00 (95% CI: 0.98, 1.01), and 1.01 (95% CI: 0.99, 1.03) for vaccination at ages <15 months, 15-18 months, 19-22 months, 23-26 months, and ≥27 months, respectively.

Further analyses were conducted using only the first asthma outcomes. In this case, follow-up was terminated after the first outcome in children with asthma outcomes. This included termination of follow-up for children with a first asthma outcome before vaccination or before 1 year of age (the start of follow-up). In this case, the asthma hospitalization rate ratio was 0.80 (95% CI: 0.77, 0.83). The rate ratio for first use of anti-asthma medication was 0.93 (95% CI: 0.92, 0.94).

Information on maternal smoking during pregnancy was available for a subgroup of children in the cohort. Among children born since 1994 whose mothers smoked during pregnancy, the rate ratio for "all asthma hospitalizations" was 0.69 (95% CI: 0.65, 0.72), as compared with 0.82 (95% CI: 0.78, 0.85) among children whose mothers had not smoked during pregnancy and 0.81 (95% CI: 0.72, 0.90) among children whose mothers had an unknown or unreported status for smoking during pregnancy.

Among approximately 100,000 children in the cohort who also participated in the Danish National Birth Cohort study,[15] we analyzed receipt of MMR vaccine according to parental asthma and atopy. Receipt of MMR vaccine was 92% and was independent of parental asthma or parental atopy.

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