Onset and Persistence of Childhood Asthma: Predictors From Infancy
Authors: Klinnert Mary D. , Nelson Harold S. , Price Marcella R. , Adinoff Allen D. , Leung Donald Y. M. , Mrazek David A. 
Published: August 2004

Objective.
In a prospective study of children with a family history of asthma, asthma onset by 3 years of age was found previously to be positively associated with variables from the first year of life, including elevated total immunoglobulin E (IgE), frequent respiratory infections, and parenting difficulties. We followed this cohort of genetically at-risk children to investigate the relationship between factors assessed in infancy and asthma, allergy, and psychological status at school age.

Methods.
A cohort of 150 children who were at risk for developing asthma were identified prenatally on the basis of the mothers' having asthma. For 28 children, the father had asthma as well, putting them at bilateral genetic risk. Families primarily were middle and upper middle class Caucasians. Parents came to the clinic during the third trimester of pregnancy for assessments of medical and psychosocial functioning. A home visit took place when the infant was 3 weeks old, when parenting risk was assessed before the onset of any asthma symptoms. Parenting difficulties included problems with infant caregiving as well as components of maternal functioning, such as postpartum depression and inadequate marital support. Blood was drawn for serum IgE at 6 months of age. Parents and offspring subsequently came to the clinic multiple times, with the last clinic visit during the child's sixth year. Follow-up at age 6 involved a clinic visit for allergy and psychosocial evaluations, consisting of interviews and a behavior questionnaire. Seventy-seven children received the allergy and psychosocial evaluation, 26 received the psychosocial evaluation in the clinic, and 30 families received telephone interviews and mailed in questionnaires. Additional monitoring of families by telephone and mail was maintained over the next 2 years, until the children were 8, to ensure accurate characterization of the course of illness. Comprehensive medical records were obtained and reviewed for all health care contacts. Children were designated as having asthma when there was documentation in medical records of physician-diagnosed asthma, observed wheezing, and/or prescription of asthma medications during the time period when the child was between 6 and 8 years of age. Parental reports of the occurrence of asthma corroborated the medical record data.

Results.
Data regarding asthma status were available for 145 children through 8 years of age. Forty (28%) of the children manifested asthma between 6 and 8 years of age. Among variables previously reported to predict asthma onset by age 3, 3 proved to have significant univariate relationships with asthma between ages 6 and 8: elevated IgE levels measured when the children were 6 months of age, global ratings of parenting difficulties measured when infants were 3 weeks old, and higher numbers of respiratory infections in the first year of life. Among these offspring of mothers with asthma, paternal asthma showed a significant association with asthma between ages 6 and 8. Eczema in the first year was not significantly related to later asthma. Multiple logistic regression showed that the model that best predicted asthma at ages 6 to 8 from infancy variables included 2 main effects. The adjusted odds ratio for 6-month IgE was 2.15 (1.51, 3.05) and for parenting difficulties was 2.07 (1.15, 3.71). Although socioeconomic status (SES) was not associated with asthma at ages 6 to 8, families of lower SES were more likely to be rated as having parenting difficulties early in the child's life. The mothers of lower SES breastfed for a shorter period of time and were more likely to smoke during their infant's first year. There were more respiratory infections during the first year of life among infants whose mother was rated as having more parenting difficulties. Mothers who reported smoking breastfed their infants for a shorter length of time. Male gender was significantly associated with higher IgE levels when infants were 6 months of age. Laboratory testing was completed for 77 children at age 6. Total serum IgE levels were significantly higher for the children with asthma between ages 6 and 8. Skin-prick testing showed that the children with asthma had significantly more positive skin test reactions than did the children without asthma. Psychosocial interview data at 6 years of age were available for 103 families, and behavioral questionnaires were available for 133 families. On the basis of 6-year interviews, children with asthma were rated as being at greater psychological risk than were the children without asthma. Mothers' Child Behavior Checklist (CBCL) ratings of their children's behavior indicated higher internalizing scores for the children with asthma as compared with the children without asthma. Like the 6-month IgE, 6-year IgE was higher for boys. IgE levels measured at 6 months of age were significantly correlated with 6-year IgE levels. Parenting difficulties measured at 3 weeks were significantly correlated with 6-year measures of maternal depression, CBCL Internalizing score, and Child Psychological Risk (CPR) score. There also were significant correlations among the psychosocial variables assessed when the children were 6 years of age; maternal depression was significantly associated with child CBCL Internalizing score and CPR score, and the last 2 also were significantly correlated. Multiple logistic regression showed that 2 concurrently measured variables entered the model showing the strongest associations with asthma at ages 6 to 8. The adjusted odds ratio for CPR score was 3.21 (1.29–7.96) and for 6-year IgE was 1.71 (1.04–2.80).

Conclusions.
This study of the natural history of childhood asthma focused on the development of asthma into the school-age years in a genetically at-risk group of children. The relationships between biological and psychosocial variables in the first year and school-age asthma support the formulation of asthma as beginning early in life, with the developing immune system interacting with environmental influences. The data provide support for the possible contribution of psychosocial factors to asthma onset and persistence into childhood.