Multimodal Monitoring of Hemodynamics in Neonates With Extremely Low Gestational Age: A Randomized Clinical Trial

Abstract

Importance: Evaluation and treatment of transitional circulation in neonates with extremely low gestational age (ELGA) varies greatly across centers.

Objective: To determine whether multimodal hemodynamic monitoring in neonates with ELGA during the transitional period (first 72 hours of life) will improve cardiorespiratory-kidney health by decreasing vasoactive-ventilation-renal (VVR) score at 7 days.

Design, setting, and participants: This unmasked, 2-arm randomized clinical trial included neonates born at a gestational age of 230 to 286 weeks and admitted to a neonatal unit in Canada. Patients were enrolled from February 15, 2019, to December 31, 2021, with follow-up completed in April 2022.

Interventions: Neonates in the multimodal arm received early targeted neonatal echocardiography at 18 to 24 and 66 to 72 hours of life and cerebral near-infrared spectroscopy (NIRS) for the first 72 hours. A study guideline incorporating clinical-biochemical and cerebral near-infrared spectroscopy data was used for hemodynamic consultation in the multimodal arm. Neonates in the standard arm received hemodynamic assessment using clinical-biochemical data.

Main outcome and measures: The primary outcome was VVR score at 7 days. The VVR score incorporates measures of inotrope use, ventilation support, and kidney function to reflect cardiorespiratory-kidney health, with possible scores ranging from 0 to 69.62 at 7 days; higher scores indicate worse cardiorespiratory-kidney health.

Results: Primary analysis included 132 neonates with ELGA (68 in the multimodal arm and 64 in the standard arm) with mean (SD) gestational age of 26.4 (1.5) weeks (75 [56.8%] male). The mean (SD) VVR score at 7 days was 16.5 (15.4) in the multimodal arm and 18.9 (20.2) in the standard arm (P = .45). A day 7 peak VVR score greater than 53 (>95th percentile for VVR in the entire cohort) was seen only in the standard arm (7 of 63 [11.1%] vs 0 in the multimodal arm; P = .005) and was associated with a composite outcome of death or severe intraventricular hemorrhage (odds ratio [OR], 12.37; 95% CI, 1.92-79.63; P = .001) and bronchopulmonary dysplasia (BPD) (6 of 6 [100%] vs 55 of 116 [47.4%]; P = .01). Incidence of BPD was lower in the multimodal arm (26 of 63 [41.3%] vs 36 of 61 [59.0%]; P = .04). Logistic regression showed that VVR score at 7 days in the top quartile (adjusted OR [AOR], 11.40; 95% CI, 2.04-63.67), late sepsis (AOR, 65.24; 95% CI, 5.70-748.18), and patent ductus arteriosus treatment after 72 hours of life vs early or no treatment needed (AOR, 7.20; 95% CI, 1.60-32.41) were associated with BPD.

Conclusions and relevance: In this study of neonates with ELGA, multimodal hemodynamic assessment was not associated with decreased VVR scores at 7 days. However, this approach led to lower incidence of VVR associated with severe adverse outcomes and lower BPD incidence, suggesting further investigation is needed.

Trial registration: ClinicalTrials.gov Identifier: NCT03841929.

Figure 1.. Consort Flow Diagram

Of 165 randomized participants, 132 were included in the primary analysis as randomized consented participants. NIRS indicates near-infrared spectroscopy.

Figure 2.. Line Plots Comparing Mean Vasoactive-Ventilation-Renal (VVR) Scores During the First 72 Hours and at Day 7

Possible VVR scores range from 0 to 140.40 at baseline, 0 to 78.44 at 72 hours, and 0 to 69.60 at 7 days, with higher scores indicating worse cardiorespiratory-kidney health. The mean VVR scores were lower in multimodal arm compared with standard arm. Error bars indicate 95% CIs.