Comment on Transient Tachypnea of the Newborn Is Associated With an Increased Risk of Hospitalization Due to Respiratory Syncytial Virus Bronchiolitis

To the Editors:

We read with interest the article by Heinonen et al¹ in which a relation between transient tachypnea of the newborn (TTN) and the risk of respiratory syncytial virus (RSV) hospitalization within the first year of life was demonstrated. In this population-based study, 2 large national database registries were linked to identify children with TTN and RSV hospitalization based on International Classification of Diseases, 9th revision, codes. Multivariable logistic regression analysis was used in which a significantly increased risk was found for TTN and the occurrence of RSV hospitalization after correction for potentially confounding factors. The authors suggest that both entities may share the underlying pathophysiologic defect in sodium-driven pulmonary fluid transport explaining this association.

Despite their large study population, the usage of registry data has limitations such as the lack of data on RSV viral detection. Furthermore, using International Classification of Diseases codes for diagnosis often results in the underdetection of disease compared with using medical chart data, especially for milder conditions.² This could have occurred as well for a temporary, mild condition such as TTN, which is often not the primary cause of hospital admission. In contrast, however, the authors reported an incidence of TTN of 1.57%, which is much higher compared with the incidence of 0.4%–0.6% described for term born infants.^3,4 We speculate that perhaps children with mild infant respiratory distress syndrome were included, because distinguishing between these 2 entities can be difficult.

We seek to validate their results in the RISK study,⁵ a prospective birth cohort study in 4072 late preterm infants (32–35 weeks gestational age) of whom 181 (4.4%) children were hospitalized with RSV-confirmed infection during their first year of life. Although preterm born infants have an increased risk of both TTN³ and RSV hospitalization, we attempted replicating the findings of Heinonen and colleagues in our population. We defined TTN as having received isolated oxygen or low-flow nasal cannula oxygenation therapy or as having received continuous or bilevel positive airway pressure (CPAP/BiPAP) for a maximum duration of 1 day. We excluded patients from our definition if they had received prolonged continuous positive airway pressure, mechanical ventilation, surfactant or a full course of antibiotics, or if they were diagnosed with meconium aspiration syndrome, pneumothorax or pneumonia at birth.

TTN was diagnosed in 222 (5.5%) children in our study, which is comparable to the 4.6%–6.4% incidence shown in late preterm infants in literature.³ Univariate and adjusted multivariable analyses did not show an association between TTN and RSV hospitalization (Table 1).

TABLE 1.: Adjusted ORs and Rates of Hospitalizations Due to RSV Bronchiolitis During the First Year of Life in Children With and Without History of TTN Stratified by Age at the Time of RSV Diagnosis

We acknowledge that our population differs from the study by Heinonen et al with respect to the risk of respiratory disease.³ Perhaps the multifactorial increased risk of respiratory disease in prematurely born infants overshadows the individual contribution of epithelial ion transport dysfunction in this population. Even though we could not confirm the results by Heinonen et al in our population of late preterm infants, we are interested to see whether their hypothesis can be investigated further in other prospective birth cohort studies in term born infants.

Lieke W. P. C. G. van de Kam, BSc
Koos Korsten, MD
Joanne G. Wildenbeest, PhD
Louis J. Bont, PhD
Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands