Respiratory support does not improve outcomes in preemies with irregular breathing

Among very preterm infants who fail to demonstrate regular breathing during deferred cord clamping, breathing support through intermittent positive pressure ventilation (IPPV) is safe but has no impact on transfusion rates or clinical outcomes, according to a recent study.

The study included 105 infants who had received the intended 50-second deferred cord clamping. The IPPV intervention was given to 54 participants, whose rate of blood transfusion was 28 percent. Of the remaining 51 infants who received the standard intervention, 30 percent were transfused. [J Pediatr 2022;doi:10.1016/j.jpeds.2022.09.025]

Statistical modelling showed that the difference between the groups failed to reach significance (odds ratio [OR], 0.90, 95 percent confidence interval [CI], 0.39–2.01; p=0.79). Analyses were carried out on an intention-to-treat basis.

Similarly, the median number of transfusions received was comparable between the IPPV and control arms (p=0.33), as was the median difference in the total mL/kg/red cells received (difference, 10 mL, 95 percent CI, –5 to 25; p=0.6).

As a key secondary endpoint, the researchers investigated the impact of IPPV on a composite of clinical indicators including death, chronic lung disease, and severe intraventricular haemorrhage (rated grade 3 or 4).

The composite outcome occurred in 46 percent of preemies in the IPPV arm, as opposed to 38 percent among control comparators. The resulting likelihood estimate showed that IPPV increased the likelihood of such an endpoint, but not significantly so (OR, 1.39, 95 percent CI, 0.66–2.95; p=0.45). Haemoglobin levels at days 1 and 7 were likewise comparable between arms.

“We found no difference between groups in any of the transfusion measures or measured haemoglobin levels. These findings suggest there was no difference in placental transfusion,” the researchers said, conceding that “we expected improved placental transfusion in the intervention group related to respiration, and that IPPV would facilitate this.”

Nevertheless, using a colorimetric carbon dioxide detector showed that gas exchange occurred successfully in 70 percent of cases where IPPV was applied. However, the time to fully establish respiration did not significantly differ between groups.

A longer clamping time?

The researchers then asked, “Would a period longer than 50 seconds prior to cord clamping in our study have altered the results?”

A previous systematic review suggested that 30 seconds of deferred cord clamping was enough to yield transfusion benefits in preterm infants. Meanwhile, a 2020 study found that cord clamping based on physiological measures (ie, when the infant had achieved stabilized breathing and heart rate) was at least noninferior to a time-based delayed cord clamping protocol. [Am J Obstet Gynecol 2018;218:1-8; Resuscitation 2020;147:26-33]

Regardless, the research team decided against extending the clamp time to more than 50 seconds “as we were studying a group of preterm infants who were not breathing and could be deemed at increased risk of adverse outcome,” they explained.

“As suggested by others, the exact timing of deferred cord clamping may be less important than allowing infants to establish respiration with an intact cord,” they added. Future studies are needed to better establish the value of cord clamping and its optimal timing. [Arch Dis Child Fetal Neonatal Ed 2015;100:F355-360]