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SurE for surfactant: response to letter

We would like to thank Nobile et al for their interest in our network metaanalysis comparing the efficacy of methods for surfactant administration. The authors raised concerns by giving emphasis on the combination of various study designs. However, our network metaanalysis implemented a parametric designadjusted metaanalysis in order to incorporate both randomised and nonrandomised evidence in the analysis, as suggested by Efthimiou et al. Following this approach, various weights were placed on observational studies, enabling the evaluation of their effects on the overall outcome. Combining randomised and nonrandomised evidence resulted in similar effects compared with randomised controlled trials, increasing the precision of the effect estimates. Moreover, the authors commented about the inclusion of a study that was subsequently retracted. Nonetheless, it should be noted that the reason for retraction was its overlap with another study that was not included in the metaanalysis. Therefore, no risk of data duplication was present. Furthermore, the validity of the metaanalysis outcomes is questioned given the variability of baseline patients’ characteristics, especially caesarean delivery rates and antenatal steroid administration. However, it is important to note that the distributions of potential confounding factors (ie, gender, median gestational age, birth weight, 5minute Apgar score, mode of delivery, administration of antenatal steroids, chorioamnionitis, premature rupture of membranes and time from birth to surfactant administration) were compared across interventions, indicating no significant differences. As a result, the transitivity assumption was satisfied and the internal validity of the metaanalysis was not threatened. Lastly, among all the less invasive surfactant methods, the one using the thin catheter is most studied and practised. However, we agree that data for neonates <28 weeks are not as robust as for higher gestation age group due to a smaller number of neonates, 5 and we need more data for this vulnerable population. In addition, lung recruitment before surfactant administration (INRECSURE) represents a promising novel alternative; hence, future randomized evidence directly comparing it to less invasive surfactant administration with thin catheters is warranted to draw conclusions concerning the optimal method of surfactant treatment, especially among extremely low gestational age newborns.