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Sir,

We commend Zanardo et al.1 for their prospective study on chorioamnionitis, preterm premature rupture of membranes (PPROM) and respiratory outcome after preterm birth. However, two fundamental issues complicate the interpretation of their findings. The authors laudably explored the association between chorioamnionitis and chronic lung disease (CLD) in a multivariable model, adjusting for potential confounders. An intriguing interaction between chorioamnionitis, gestational age and subsequent development of CLD was reported, suggesting that the effect of chorioamnionitis on CLD risk is, in fact, dependent on gestational age. However, the characteristics of this interaction were not reported and, furthermore, no odds ratios or confidence intervals for the individual factors in the model were provided. Thus, the reader is unable to interpret both the direction and magnitude of the reported associations.

Secondly, from univariable analyses, the authors concluded that there is no reason to assume that chorioamnionitis influences lung maturation, as judged from similar incidences of respiratory distress syndrome (RDS) between infants with and without chorioamnionitis. This contradicts the compelling available evidence from both human studies and several animal models, which indicates that antenatal inflammation enhances lung maturation and decreases both RDS incidence and severity.2–4 We propose that the inability to detect an association between chorioamnionitis and RDS incidence might be a result of the lack of adjustment for potential confounders, the most important being gestational age.3 From the baseline data provided by the authors, it is clear that the gestational age in infants with chorioamnionitis is, on average, 2.6 weeks lower. The similar RDS incidence between the two groups in the presence of such a large and significant difference in gestational age – gestational age being the most important predictor of RDS incidence – suggests that chorioamnionitis may well decrease the RDS risk when adjusted for gestational age. Indeed, such an effect has been reported previously in several studies, as reviewed elsewhere.3

In conclusion, we feel that it is important for the authors to supply additional information on the interaction between chorioamnionitis, gestational age and CLD, taking into account that, in cohort studies, the presence of interaction precludes a direct interpretation of the related main effects (chorioamnionitis and gestational age in this case). Moreover, we would be interested to learn how an adjustment for important confounders, including gestational age, would affect the association between chorioamnionitis and RDS in the reported cohort.

References

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  2. References
  • 1
    Zanardo V, Vedovato S, Cosmi E, Litta P, Cavallin F, Trevisanuto D, et al. Preterm premature rupture of membranes, chorioamnion inflammatory scores and neonatal respiratory outcome. BJOG 2010;117:948.
  • 2
    Been JV, Rours IG, Kornelisse RF, Lima Passos V, Kramer BW, Schneider TA, et al. Histologic chorioamnionitis, fetal involvement, and antenatal steroids: effects on neonatal outcome in preterm infants. Am J Obstet Gynecol 2009;587:e18.
  • 3
    Been JV, Zimmermann LJ. Histological chorioamnionitis and respiratory outcome in preterm infants. Arch Dis Child Fetal Neonatal Ed 2009;94:F21825.
  • 4
    Kramer BW, Kallapur S, Newnham J, Jobe AH. Prenatal inflammation and lung development. Semin Fetal Neonatal Med 2009;14:27.