Association between preterm birth and asthma and atopic dermatitis in preschool children: a nationwide population-based study

Asthma and atopic dermatitis (AD) are representative chronic diseases in childhood. This study aimed to investigate the impact of preterm birth on the incidence and severity of asthma and AD in children, as well as to identify neonatal risk factors for asthma and AD. We used health claims data recorded between 2007 and 2014 in the Korean National Health Insurance Service database. We recruited 2,224,476 infants born between 2007 and 2014 and divided them into three groups: 3518 of extremely preterm (EP) infants (< 28 weeks of gestational age (GA)), 82,579 of other preterm (OP) infants (28-36 weeks of GA), and 2,138,379 of full-term (FT) infants (> 37 weeks of GA). We defined asthma as > 3 episodes of clinical visits in a year before 6 years of age, early asthma as onset at < 2 years of age, and severe asthma as > 1 event of status asthmaticus or admission to a hospital via an emergency room. AD was defined as ≥ 3 diagnoses in a year before 6 years of age, early AD as onset at < 2 years of age, and severe AD as prescription of high-potency topical steroids or immunosuppressants. An association of preterm birth with asthma and AD was assessed using inverse probability of treatment-weighted multivariable Cox regression analysis. Cardiorespiratory conditions, such as respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, and pulmonary hypertension, significantly increased the risk of asthma. Specifically, bronchopulmonary dysplasia emerged as a significant risk factor for both severe and early-onset asthma (odds ratio (OR) 1.36, 95% CI 1.21-1.37 for severe asthma; OR 1.55, 95% CI 1.30-1.85 for early asthma), while it was associated with a decreased risk of AD (OR 0.86, 95% CI 0.80-0.92). Neonatal sepsis, jaundice, and retinopathy of prematurity were also identified as significant risk factors for later asthma. A stepwise increase in the risk of asthma with an increasing degree of prematurity was observed, with the OP group showing an adjusted hazard ratio (aHR) of 1.24 (95% CI: 1.22-1.26) and the EP group showing an aHR of 1.51 (95% CI: 1.41-1.63). Conversely, preterm birth was inversely associated with the risk of AD, with aHRs of 0.73 (95% CI: 0.67-0.79) for the OP group and 0.88 (95% CI: 0.87-0.89) for the EP group. Conclusion Preterm children have a significantly higher risk of asthma and lower risk of AD, with cardiorespiratory conditions significantly increasing the risk of asthma. Thus, we highlight the need for targeted respiratory management strategies for this high-risk population. What is Known: •Asthma and atopic dermatitis are prevalent chronic diseases in childhood, reducing the quality of life of children. •Preterm birth was associated with an increased risk of asthma, but few large nationwide studies. •Research on the relationship between preterm birth and pediatric atopic dermatitis is controversial, with few large nationwide studies. What is New: • Preterm children, especially born before 28 weeks of gestational age, had a significantly higher risk of asthma and lower risk of atopic dermatitis. • Cardiorespiratory comorbidities such as RDS, BPD, PDA, and pulmonary hypertension in neonatal period are prominent risk factors for asthma. • Preterm children are vulnerable to both early-onset and severe asthma.