Cardiovascular and cerebrovascular effects of caffeine maintenance in preterm infants during the transitional period

Roberta Parladori; Topun Austin; Peter Smielewski; Marek Czosnyka; Vittoria Paoletti; Francesca Vitali; Luigi Corvaglia; Silvia Martini

doi:10.1038/s41390-024-03194-4

Cardiovascular and cerebrovascular effects of caffeine maintenance in preterm infants during the transitional period

Pediatr Res. 2024 May 22. doi: 10.1038/s41390-024-03194-4. Online ahead of print.

Authors

Affiliations

¹ Neonatal Intensive Care Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
² Neonatal Intensive Care Unit, The Rosie Hospital, Cambridge University Hospitals, Cambridge, United Kingdom.
³ Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom.
⁴ Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
⁵ Neonatal Intensive Care Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. silvia.martini9@unibo.it.
⁶ Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. silvia.martini9@unibo.it.

^# Contributed equally.

PMID: 38778228
DOI: 10.1038/s41390-024-03194-4

Abstract

Background and aim: Caffeine is routinely used for the prophylaxis of prematurity-related apnoeas. We aimed to evaluate the effect of caffeine maintenance on cardiovascular and cerebrovascular haemodynamics using a non-invasive multimodal monitoring in preterm infants during the transitional period.

Methods: Infants <32 weeks' gestational age (GA) were enrolled in this observational prospective study. The following parameters were recorded before and after the administration of caffeine citrate 5 mg/kg using near-infrared spectroscopy, pulse oximetry and electrical velocimetry: heart rate, cardiac output, stroke volume, cardiac contractility, systemic vascular resistance (SVR), perfusion index, peripheral and cerebral oxygenation, cerebral fractional oxygen extraction, correlation index between cerebral oxygenation and heart rate (TOHRx, marker of cerebrovascular reactivity). Multilevel mixed-effects linear models were used to assess the impact of caffeine and of relevant clinical covariates on each parameter.

Results: Seventy-seven infants (mean GA 29.3 ± 2.5 weeks, mean birthweight 1148 ± 353 g) were included. Caffeine administration was associated with increased SVR (B = 0.623, p = 0.004) and more negative TOHRx values (B = -0.036, p = 0.022), which suggest improved cerebrovascular reactivity.

Conclusions: Caffeine administration at maintenance dosage during postnatal transition is associated with increased systemic vascular tone and improved cerebrovascular reactivity. A possible role for caffeine-mediated inhibition of adenosine receptors may be hypothesized.

Impact: This study provides a thorough and comprehensive overview of multiple cerebrovascular and cardiovascular parameters, monitored non-invasively by combining near-infrared spectroscopy, electrical velocimetry and pulse oximetry, before and after the administration of caffeine at maintenance dosage in preterm infants during postnatal transition. Caffeine was associated with an improvement in cerebrovascular reactivity and with a slight but significant increase in systemic vascular resistance, with no additional effects on other cardiovascular and cerebrovascular parameters. Our results support the safety of caffeine treatment even during a phase at risk for haemodynamic instability such as postnatal transition and suggest potential beneficial effects on cerebral haemodynamics.