CPAP Versus NIPPV Postextubation in Preterm Neonates: A Comparative-Effectiveness Study.

BACKGROUND AND OBJECTIVES: Nasal intermittent positive pressure ventilation (NIPPV) has been shown to be superior to nasal continuous positive airway pressure (CPAP) postextubation in preterm neonates. However, studies have not permitted high CPAP pressures or rescue with other modes. We hypothesized that if CPAP pressures >8 cmH2O and rescue with other modes were permitted, CPAP would be noninferior to NIPPV. METHODS: We conducted a pragmatic, comparative-effectiveness, noninferiority study utilizing network-based real-world data from 22 Canadian NICUs. Centers self-selected CPAP or NIPPV as their standard postextubation mode for preterm neonates <29 weeks' gestation. The primary outcome was failure of the initial mode ≤72 hours. Secondary outcomes included failure ≤7 days, and reintubation ≤72 hours and ≤7 days. Groups were compared using a noninferiority adjusted risk-difference (aRD) margin of 0.05, and margin of no difference. RESULTS: A total of 843 infants extubated to CPAP and 974 extubated to NIPPV were included. CPAP was not noninferior (and inferior) to NIPPV for failure of the initial mode ≤72 hours (33.0% vs 26.3%; aRD 0.07 [0.03 to 0.12], Pnoninferiority(NI) = .86), and ≤7 days (40.7% vs 35.8%; aRD 0.09 [0.05 to 0.13], PNI = 0.97). However, CPAP was noninferior (and equivalent) to NIPPV for reintubation ≤72 hours (13.2% vs 16.1%; aRD 0.01 [-0.05 to 0.02], PNI < .01), and noninferior (and superior) for reintubation ≤7 days (16.4% vs 22.8%; aRD -0.04 [-0.07 to -0.001], PNI < .01). CONCLUSIONS: CPAP was not noninferior to NIPPV for failure ≤72 hours postextubation; however, it was noninferior to NIPPV for reintubation ≤72 hours and ≤7 days. This suggests CPAP may be a reasonable initial postextubation mode if alternate rescue strategies are available.

High inter-rater reliability between physicians and nurses utilising modified Downes' scores in preterm respiratory distress.

AIM: To assess the inter-rater reliability of modified Downes' scores assigned by physicians and nurses in the Ethiopian Neonatal Network and to calculate the concordance of score-based treatment for preterm infants with respiratory distress. METHODS: We included preterm infants admitted from June 2020 to July 2021 to four tertiary neonatal intensive care units (NICUs) of the Ethiopian Neonatal Network that presented with respiratory distress. We calculated the kappa statistic to determine the nurse and physician correlation for each component of the modified Downes' score and total score on admission and evaluated the concordance of scores above and below the treatment threshold of 4. RESULTS: Of the 1151 eligible infants admitted, 817 infants (71%) had scores reported concurrently and independently by nurse and physician. The kappa statistic for modified Downes' score components ranged from 0.88 to 0.92 and was 0.89 for the total score. There was 98% concordance for score-based treatment. CONCLUSION: Incorporation of the modified Downes' score on admission for preterm infants with respiratory distress was feasible in tertiary NICUs in Ethiopia. The kappa statistics showed near-perfect agreement between nurse and physician assessments, translating to a very high degree of concordance in score-based treatment recommendations. These results highlight an opportunity for task-shifting assessments and empowering nurses.

Timing of Systemic Steroids and Neurodevelopmental Outcomes in Infants < 29 Weeks Gestation

Objective: To determine the association between postnatal age (PNA) at first administration of systemic postnatal steroids (sPNS) for bronchopulmonary dysplasia (BPD) and mortality or significant neurodevelopmental impairment (sNDI) at 18−24 months corrected age (CA) in infants < 29 weeks' gestation. Methods: Data from the Canadian Neonatal Network and Canadian Neonatal Follow-up Network databases were used to conduct this retrospective cohort study. Infants exposed to sPNS for BPD after the 1st week of age were included and categorized into 8 groups based on the postnatal week of the exposure. The primary outcome was a composite of mortality or sNDI. A multivariable logistic regression model adjusting for potential confounders was used to determine the association between the sPNS and ND outcomes. Results: Of the 10,448 eligible infants, follow-up data were available for 6200 (59.3%) infants. The proportion of infants at first sPNS administration was: 8%, 17.5%, 23.1%, 18.7%, 12.6%, 8.3%, 5.8%, and 6% in the 2nd, 3rd, 4th, 5th, 6th, 7th, 8−9th, and ≥10th week of PNA respectively. No significant association between the timing of sPNS administration and the composite outcome of mortality or sNDI was observed. The odds of sNDI and Bayley-III motor composite < 70 increased by 1.5% (95% CI 0.4, 2.9%) and 2.6% (95% CI 0.9, 4.4%), respectively, with each one-week delay in the age of initiation of sPNS. Conclusions: No significant association was observed between the composite outcome of mortality or sNDI and PNA of sPNS. Among survivors, each week's delay in initiation of sPNS may increase the odds of sNDI and motor delay.

Relative effectiveness and safety of pharmacotherapeutic agents for patent ductus arteriosus (PDA) in preterm infants: a protocol for a multicentre comparative effectiveness study (CANRxPDA).

INTRODUCTION: Patent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in preterm infants and evidence regarding the best treatment approach is lacking. Currently available medical options to treat a PDA include indomethacin, ibuprofen or acetaminophen. Wide variation exists in PDA treatment practices across Canada. In view of this large practice variation across Canadian neonatal intensive care units (NICUs), we plan to conduct a comparative effectiveness study of the different pharmacotherapeutic agents used to treat the PDA in preterm infants. METHODS AND ANALYSIS: A multicentre prospective observational comparative-effectiveness research study of extremely preterm infants born <29 weeks gestational age with an echocardiography confirmed PDA will be conducted. All participating sites will self-select and adhere to one of the following primary pharmacotherapy protocols for all preterm babies who are deemed to require treatment.Standard dose ibuprofen (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals) irrespective of postnatal age (oral/intravenous).Adjustable dose ibuprofen (oral/intravenous) (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals if treated within the first 7 days after birth. Higher doses of ibuprofen up to 20 mg/kg followed by two doses of 10 mg/kg at 24 hours intervals if treated after the postnatal age cut-off for lower dose as per the local centre policy).Acetaminophen (oral/intravenous) (15 mg/kg every 6 hours) for 3-7 days.Intravenous indomethacin (0.1-0.3 mg/kg intravenous every 12-24 hours for a total of three doses). OUTCOMES: The primary outcome is failure of primary pharmacotherapy (defined as need for further medical and/or surgical/interventional treatment following an initial course of pharmacotherapy). The secondary outcomes include components of the primary outcome as well as clinical outcomes related to response to treatment or adverse effects of treatment. SITES AND SAMPLE SIZE: The study will be conducted in 22 NICUs across Canada with an anticipated enrollment of 1350 extremely preterm infants over 3 years. ANALYSIS: To examine the relative effectiveness of the four treatment strategies, the primary outcome will be compared pairwise between the treatment groups using χ2 test. Secondary outcomes will be compared pairwise between the treatment groups using χ2 test, Student's t-test or Wilcoxon rank sum test as appropriate. To further examine differences in the primary and secondary outcomes between the four groups, multiple logistic or linear regression models will be applied for each outcome on the treatment groups, adjusted for potential confounders using generalised estimating equations to account for within-unit-clustering. As a sensitivity analysis, the difference in the primary and secondary outcomes between the treatment groups will also be examined using propensity score method with inverse probability weighting approach. ETHICS AND DISSEMINATION: The study has been approved by the IWK Research Ethics Board (#1025627) as well as the respective institutional review boards of the participating centres. TRIAL REGISTRATION NUMBER: NCT04347720.

Assessment of renal circulation in small for gestational age and appropriate for gestational age term newborns: a prospective study.

PURPOSE: To compare selected parameters of renal circulation between small for gestational age (SGA) and appropriate for gestational age (AGA) newborns. METHODS: Fifty-two SGA and 100 AGA term newborns were examined. The size of the kidneys were measured, and renal blood flow in the central and intraparenchymal renal arteries were assessed via Doppler sonography. Peak systolic velocity (PSV), end diastolic velocity (EDV), mean blood flow velocity (V mean), resistance index (RI), and pulsatility index (PI) were determined and compared between the groups. RESULTS: No statistically significant differences in the velocity parameters were found between SGA and AGA infants in central renal arteries. Slightly higher RIs and PIs were seen in AGA newborns (RI, 0.76 +/- 0.13 versus 0.78 +/- 0.06 [p < 0.05]; PI, 1.65 +/- 0.54 versus 1.84 +/- 0.46 [p < 0.05]). There were statistically significant differences between the groups in all measured parameters in intraparenchymal arteries (RI, 0.57 +/- 0.11 versus 0.63 +/- 0.05 [p < 0.001]; PI, 0.89 +/- 0.26 versus 1.09 +/- 0.16 [p < 0.001]) except PSV (7.11 +/- 1.55 versus 7.14 +/- 0.81 cm/s [p > 0.05]). CONCLUSION: Based on our findings, we suggest that renal circulation is not negatively influenced by intrauterine growth restriction in SGA neonates compared with AGA newborns.

Comparison of Doppler parameters of central versus intraparenchymal renal arteries in physiologically normal newborns.

BACKGROUND: Changes in renal arterial Doppler flow may identify parenchymal disease, but in newborns knowledge of normal physiological parameters is a prerequisite for correct interpretation. OBJECTIVE: To evaluate renal blood flow in healthy newborns by means of Doppler US. MATERIALS AND METHODS: On the fourth day of life we examined 100 normal term newborn infants (200 kidneys). Blood flow in the central renal arteries was compared with that in the intraparenchymal arteries. Maximum systolic velocity ( V(max)), end-diastolic velocity ( V(ed)), mean flow velocity ( V(mean)), resistive index (RI) and pulsatility index (PI) were assessed. RESULTS: All parameters were significantly higher in the central renal arteries than in the intraparenchymal arteries (RI 0.78+/-0.07 vs 0.62+/-0.05, P<0.0001; PI 1.84+/-0.52 vs 1.09+/-0.18, P<0.0001). CONCLUSIONS: Physiological data are presented that are necessary for the correct interpretation of neonatal Doppler US.