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Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials

BMJ 2016; 355 doi: https://doi.org/10.1136/bmj.i5044 (Published 12 October 2016) Cite this as: BMJ 2016;355:i5044

Re: Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials

We apologize to Doctor Rosenbloom for not being clear in our prior reply.

In most of the included studies RDS was defined as the presence of clinical signs of respiratory distress with an oxygen requirement and a chest radiograph showing reticulogranular infiltrates. Transient tachypnea of the newborn was defined, in most of the included trials, as respiratory distress without diffuse reticulogranular infiltrate resolved spontaneously by 72 hours of age.

In our review we reported data for mild RDS, moderate RDS, as well as severe RDS (i.e. our primary outcome). It means that the definition of Porto et used for TTN overall the definition of our review for mild RDS.

Therefore babies with TTN (as defined by Porto et al.) included in the Porto trial met the criteria for mild RDS of our review. Therefore we included them in the outome ''overall RDS'' as per our definition. The two babies with ''RDS'' as defined by Porto et al. met the criteria for severe RDS of our review. Therefore, you should not add up events of one outcome with events of a different outcome, given that these events are not mathematically exclusive. Participant may be included in the ''RDS outcome'' but also in the ''TTN'' outcome, depends on the definition used.

An example can be clear for this situation. In a cohort of 50 women with 10 women who delivered preterm, five at 27 weeks, and 5 at 31 weeks, we will have the following outcomes:
PTB <37 weeks: 10/50
PTB<34 weeks: 10/50
PTB <28 weeks: 5/50
The total number of women who delivered preterm is still 10 and not 25 (10+10+5) because we have overlapping in the events.

In summary, as we stated in our review, the major shortcoming of the meta-analysis was the different definitions used for respiratory morbidity in the different trials and, therefore, the high clinical and statistically heterogeneity within the trials.

To completely clarify the effect of late preterm steroids on respiratory morbidity a IPD meta-analysis with level-patient data is necessary. With an IPD we may report all the events using clear and planned definition.

An aggregate meta-analysis indeed is limited by the shortcomings highlighted above and cannot explore the heterogeneity or subgroup analyses.

We hope that such a study will be performed soon.

Thanks

Gabriele

Competing interests: No competing interests

14 November 2017
Gabriele Saccone
MD
Univerisity of Naples Federico II