Inadequate Timing Limits the Benefit of Antenatal Corticosteroids on Neonatal Outcome: Retrospective Analysis of a High-Risk Cohort of Preterm Infants in a Tertiary Center in Germany

Abstract

Introduction A common problem in the treatment of threatened preterm birth is the timing and the unrestricted use of antenatal corticosteroids (ACS). This study was performed to evaluate the independent effects of the distinct timing of antenatal corticosteroids on neonatal outcome parameters in a cohort of very low (VLBW; 1000 – 1500 g) and extreme low birth weight infants (ELBW; < 1000 g). We hypothesize that a prolonged ACS-to-delivery interval leads to an increase in respiratory complications.

Materials and Methods Main data source was the prospectively collected single center data for the German nosocomial infection surveillance system (KISS) between 2015 and 2018. Multivariate regression analysis was performed to determine independent effects of the ACS-to-delivery interval on the need for ventilation, surfactant or the occurrence of bronchopulmonary dysplasia, neonatal sepsis or necrotizing enterocolitis. Subgroup analysis was performed for ELBW and VLBW neonates.

Results A total of 239 neonates were included. We demonstrate a significantly increased risk of respiratory distress characterized by the need for ventilation (OR 1.045; CI 1.011 – 1.080) and surfactant administration (OR 1.050, CI 1.018 – 1.083) depending on the ACS-to-delivery interval irrespective of other confounders. Every additional day between ACS and delivery increased the risk for ventilation by 4.5% and for surfactant administration by 5%. Subgroup analysis revealed significant differences of respiratory complications in VLBW infants.

Conclusions Our data strongly support the deliberate use and timing of antenatal corticosteroids in pregnancies with threatened preterm birth versus a liberal strategy. When given more than 7 days before birth, each day between application and delivery increases is relevant concerning major effects on the infant. Especially VLBW preterm neonates benefit from optimal timing.

Zusammenfassung

Introduction Die uneingeschränkte Gabe von antenatalen Kortikosteroiden (ACS) und der Zeitpunkt dieser Gabe stellen ein verbreitetes Problem in der Behandlung drohender Frühgeburten dar. Ziel dieser Studie war es, die unabhängige Wirkung pränataler Gaben von Kortikosteroiden zu unterschiedlichen Zeitpunkten auf die neonatalen Outcome-Parameter in einer Gruppe von Neugeborenen mit sehr niedrigem (very-low-birthweight, VLBW; 1000 – 1500 g) bzw. extrem niedrigem Geburtsgewicht (extremely-low-birthweight, ELBW; < 1000 g) zu evaluieren. Wir stellten die Hypothese auf, dass ein langer Intervall zwischen ACS-Gabe und Geburt zu einem Ansteig der Atemwegskomplikationen führt.

Material und Methoden Die Hauptdatenquelle waren prospektive monozentrische Daten, die für das deutsche Überwachungssystem für nosokomiale Infektionen (KISS) in einem einzigen Zentrum zwischen 2015 und 2018 gesammelt wurden. Es wurde eine multivariate Regressionsanalyse durchgeführt, um die unabhängige Wirkung des Intervalls zwischen ACS-Gabe und Geburt auf den Bedarf nach künstlicher Beatmung bzw. einer Surfactant-Therapie sowie das Auftreten einer bronchopulmonalen Dysplasie, einer neonatalen Sepsis oder einer nekrotisierenden Enterokolitis zu bestimmen. Es wurden Untergruppenanalysen für die Gruppen der ELBW- und der VLBW-Neugeborenen durchgeführt.

Ergebnisse Insgesamt wurden 239 Neugeborenen in die Studie aufgenommen. Wir fanden ein signifikant höheres Risiko für ein Atemnotsyndrom, das durch die Notwendigkeit einer mechanischen Beatmung (OR 1,045; KI 1,011 – 1,080) bzw. einer Surfactant-Gabe (OR 1,050, KI 1,018 – 1,083) gekennzeichnet war. Ungeachtet anderer Störfaktoren hing das Risiko von der Dauer des Intervalls zwischen ACS-Gabe und Geburt ab. Jeder zusätzliche Tag zwischen ACS-Gabe und Geburt erhöhte das Risiko für eine mechanische Beatmung um 4,5% und für eine Surfactant-Therapie um 5%. Die Untergruppenanalyse zeigte signifikante Unterschiede in den Atemwegskomplikationen bei VLBW-Neugeborenen.

Schlussfolgerungen Unsere Daten unterstreichen die Bedeutung, die ein bewusster Einsatz und das richtigen Timing von ACS-Gaben bei Schwangerschaften mit drohender Frühgeburt anstatt einer liberalen Strategie hat. Wenn die ACS-Gabe mehr als 7 Tage vor der Geburt erfolgt, kann jeder zusätzliche Tag zwischen ACS-Gabe und Geburt wichtige Auswirkungen auf das Neugeborene haben. Besonders VLBW-Frühgeborene profitieren von einem optimalen Timing.

Key words

antenatal corticosteroids - preterm birth - VLWB - perinatal outcome - respiratory distress syndrome

Schlüsselwörter

antenatale Kortikosteroide - Frühgeburt - VLWB - perinatales Outcome - Atemnotsyndrom des Frühgeborenen

Publication History

Received: 03 May 2021

Accepted after revision: 22 August 2021

Article published online:
03 March 2022

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