ABSTRACT. Background. Perinatal factors, including gestational age and birth weight, influence the development of atopy in early life. However, the role of these factors in the development of asthma in later life among children who do not develop perinatal respiratory disease remains unclear.Methods. Four hundred fifty-four infants who had a history of allergy or asthma in at least 1 parent, were born in the 36th week of gestation or later, and did not develop perinatal respiratory distress were monitored for at least 6 years. Associations between predictor variables and asthma and wheeze were assessed with multivariate logistic regression and repeated-event analyses.Results. Although we previously observed a relationship between low birth weight and persistent wheeze in the first 1 year of life, we did not observe similar associations between low birth weight and asthma at 6 years of age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 0.40 -2.73). However, a strong relationship was found between low-normal gestational age and asthma at 6 years of age (OR: 4.7; 95% CI: 2.1-10.5). The effects of low-normal gestational age were significantly greater among boys than among girls (boys: OR: 8.15; 95% CI: 2.98 -22.3; girls: OR: 1.90; 95% CI: 0.38 -13.83). Longitudinal analysis of the relationship between gestational age and wheeze during the 6 years of observation confirmed these gender differences.Conclusions. Among children at high risk of developing atopic disease, late prematurity might be an important additional determinant of asthma later in life, and these effects are gender specific. Pediatrics 2004; 114:e327-e332. URL: http://www.pediatrics.org/cgi/ content/full/114/3/e327; asthma, gestational age, birth weight, longitudinal studies.ABBREVIATIONS. IgE, immunoglobulin E; OR, odds ratio; CI, confidence interval. T here is substantial evidence that perinatal factors contribute to the development of both atopic disease and asthma. Although it is well established that prematurity is a major risk factor for the development of chronic lung disease, as a result of bronchopulmonary dysplasia, 1,2 and that extremely premature infants more frequently demonstrate persistent airway hyperresponsiveness in early childhood, 3 the influence of less extreme prematurity on the development of asthma among otherwise healthy children remains unresolved. Both low birth weight and prematurity were directly associated with the development of wheeze or asthma in several studies, 4-7 whereas other studies either failed to demonstrate an association [8][9][10][11] or demonstrated inverse relationships. 12 Although several of those studies were prospective, 6,8 most of the studies that demonstrated important effects included very premature infants (Ͻ36 weeks of gestation) in their analyses, making it difficult to separate the effects of prematurity from those associated with mechanical ventilation and respiratory distress syndrome. Moreover, few of those studies examined gender-differing effects, despite evidence of important gende...