Neonatal Sepsis Episodes and Retinopathy of Prematurity in Very Preterm Infants
Authors: Glaser Kirsten , Härtel Christoph , Klingenberg Claus , Herting Egbert , Fortmann Mats I. , Speer Christian P. , Stensvold Hans J. , Huncikova Zuzana , Rønnestad Arild E. , Nentwich Martin M. , Stahl Andreas , Dammann Olaf , Göpel Wolfgang , Faust Kirstin , Müller Dirk , Thome Ulrich , Guthmann Florian , von der Wense Axel , Wieg Christian , Weller Ursula , Höhn Thomas , Olbertz Dirk , Felderhoff-Müser Ursula , Rossi Rainer , Teig Norbert , Heitmann Friedhelm , Heckmann Matthias , Schmidtke Susanne , Bohnhorst Bettina , Kribs Angela , Vochem Matthias , Wellmann Sven , Möller Jens , Eichhorn Joachim , Wintgens Jürgen , Böttger Ralf , Flügel Markus , Hubert Mechthild , Dördelmann Michael , Hillebrand Georg , Roll Claudia , Jensen Reinhard , Rüdiger Mario , Humberg Alexander , Longardt Ann Carolin , Schäfer Stefan , Schaible Thomas , Franz Axel , Hensel Kay , Kunzmann Steffen , Schmidt Esther , Orlikowsky Thorsten , Gerleve Hubert , Depping Nico , Haase Roland , Hoppenz Marc , Vilser Daniel , Küster Helmut , Fuchs Hans , Körner Thorsten , Brune Thomas , Müller Andreas , Urlichs Florian , Berghäuser Martin , Proquitté Hans , Morhart Patrick , Lindner Wolfgang , Schlösser Rolf , Schneider Welfhard , Schroth Michael , Rieger-Fackeldey Esther , Dohle Frank , Bauer Jaqueline , Völkl Thomas , Brevis Nunez Francisco , Welsch Michael , Krüger Marcus ,   German Neonatal Network, the Norwegian Neonatal Network Investigators, and the Infection, Inflammation, Immunology and Immunisation section of the European Society for Paediatric Research
Published: July 2024

Importance

Retinopathy of prematurity (ROP) is a major morbidity of preterm infants causing visual impairment, including blindness, for which timely treatment is vital and prevention is key. Increasing evidence suggests that exposure to neonatal sepsis contributes to ROP development.

Objective

To investigate the association between neonatal sepsis and ROP in 2 large-scale cohorts of preterm infants born at less than 29 weeks’ gestation.

Design, Setting, and Participants

This retrospective cohort study was conducted using data from the German Neonatal Network (GNN) and Norwegian Neonatal Network (NNN). The GNN involves 68 and the NNN includes 21 level III neonatal intensive care units. Participants were infants born at a gestation of 22 weeks and 0 days to 28 weeks and 6 days and enrolled in the GNN between January 1, 2009, and December 31, 2022, and NNN between January 1, 2009, and December 31, 2018. Data were analyzed from February through September 2023.

Exposure

Single or multiple episodes of culture-proven sepsis.

Main Outcomes and Measures

Any ROP and treatment-warranted ROP.

Results

Among 12 794 infants in the GNN (6043 female [47.2%] and 6751 male [52.8%]; mean [SD] gestational age, 26.4 [1.5] weeks) and 1844 infants in the NNN (866 female [47.0%] and 978 male [53.0%]; mean [SD] gestational age, 25.6 [1.5] weeks), the mean (SD) birth weight was 848 (229) g and 807 (215) g, respectively. Any ROP was present in 6370 infants (49.8%) in GNN and 620 infants (33.6%) in NNN, and treatment-warranted ROP was present in 840 infants (6.6%) in GNN and 140 infants (7.6%) in NNN. In both cohorts, there were increasing rates of treatment-warranted ROP with each sepsis episode (no sepsis: 572 of 10 658 infants [5.4%] in GNN and 85 of 1492 infants (5.7%) in NNN; 1 episode: 190 of 1738 infants in GNN [10.9%] and 29 of 293 infants [9.9%] in NNN; 2 episodes: 53 of 314 infants in GNN [16.9%] and 13 of 49 infants [26.5%] in NNN; 3 episodes: 25 of 84 infants [29.8%] in GNN and 3 of 10 infants [30.0%] in NNN). After adjusting for multiple confounders in the GNN dataset, the number of sepsis episodes was associated with ROP and treatment-warranted ROP compared with 0 episodes (1 episode: adjusted odds ratio [aOR], 1.44 [95% CI, 1.27-1.63]; P &amp;lt; .001 and OR, 1.60 [95% CI, 1.31-1.96]; P &amp;lt; .001, respectively; 2 episodes: OR, 1.81 [95% CI, 1.35-2.42]; P &amp;lt; .001 and OR, 2.38 [95% CI, 1.68-3.37]; P &amp;lt; .001, respectively; 3 episodes: OR, 4.39 [95% CI, 2.19-8.78]; P &amp;lt; .001 and OR, 3.88 [95% CI, 2.29-6.55]; P &amp;lt; .001, respectively). These associations were confirmed for any ROP by propensity score matching (for example, the aOR with propensity score matching was 1.76 [95% CI, 1.54-2.02]; P &amp;lt; .001 for 1 episode vs 0 episodes and 1.58 [95% CI, 1.12-2.22]; P = .007 for 3 episodes vs 0 or 1 episode). In the NNN dataset, surgical NEC was associated with treatment-warranted ROP (multivariable analysis: aOR, 3.37 [95% CI, 1.78-6.37]; P &amp;lt; .001).

Conclusions and Relevance

This study found that in the large-scale GNN cohort, recurrent culture-proven sepsis was associated with ROP and treatment-warranted ROP in infants born at less than 29 weeks.