Page 122 - Physiological based CPAP for preterm infants at birth Tessa Martherus

Chapter 5
To record SpO2 and heart rate, a Radical-7 Masimo SET pulse oximeter probe (Masimo Corporation, CA, USA) was placed around the infant’s right wrist. The Teledyne Oxygen Analyser AX300-I (Teledyne Analytical Instruments, CA, USA) inserted into the inspiratory limb of the NeopuffTM circuit measured fraction of inspired oxygen (FiO2), while the disposable Avea Varflex Flow transducer (Carefusion, CA, USA) connected between the NeopuffTM and the facemask measured flows and pressures. Signals were collected by the New Life BOX Neo-RDS (Applied Biosignals, Weener, Germany) and saved by Polybench software (Applied Biosignals, Weener, Germany). Pulmochart software (Applied Biosignals, Weener, Germany) allowed a breath-by-breath analysis to calculate breathing parameters, corrected for birth weight.
The primary outcomes were feasibility and SpO2 in the first 5 min after birth. Feasibility was explored by evaluating resuscitations on protocol adherence and via post-trial evaluations with neonatologists. Physiological outcomes included SpO2, FiO2, SpO2/FiO2 ratio, heart rate, duration of hypoxia (SpO2 <25th percentile of Dawson’s target ranges (27)) and bradycardia (heart rate <100 bpm) during the first 5 and 10 min after birth. Respiratory effort parameters included breathing rate, inter-breath interval variability, minute volume, inspired tidal volume and the use of iPPV and caffeine. The infant’s overall stability was reflected by Apgar scores and time until stabilization (defined as above). Short-term outcomes included intubation <24 hours, pneumothorax <5 days, surfactant administration, intraventricular hemorrhages (IVH), spontaneous intestinal perforations and death before NICU discharge. Collected demographical characteristics were gestational age, birth weight, gender, mode of delivery, time of cord clamping, 1 min Apgar score, antenatal corticosteroids (full course defined as two doses administered at least 24 hours, but at a maximum of two weeks prior to delivery), complications during pregnancy and maternal medication use.
The sample size calculation is based on infants who were born in the LUMC, participated in DR studies (11, 28) and received 5-8 cmH2O CPAP. Infants (n=78) achieved a SpO2 of 59% ± 13 in the first 5 min after birth. An increase to 72% was considered to be clinically relevant and for this a sample size of 32 infants would be required (α=0.05, power (1–β)=0.8, 2-sided). Because we randomized per pregnancy and our study population is enriched with twin pregnancies (with the LUMC being the national referral centre for complicated twin pregnancies), an additional number of infants needed to be included to prevent loss of power. In February 2019, 28.5% infants included in the MONitoR trial (29) were twins and showed an intra-class correlation of 0.586 for SpO2. Therefore, our sample size required an additional 16.7% (0.285*0.586*100). Anticipating 10% drop-outs due to technical errors or study withdraw, a sample size of 21 infants per group was anticipated.
Statistical analysis was performed using SPSS software version 25.0 (IBM, Chicago, Illinois, 2021). Outcomes were analysed per group considering the number of included infants, despite stratification criteria. Data were presented as median (IQR) or number (%). P-values <0.05 were considered statistically significant.
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