This study aimed to describe the epidemiology of vertically transmitted sepsis (VS) and nosocomial sepsis (NOS) in very low birth weight (VLBW) neonates (birth weight ≤ 1,500 g) over the past 22 years in Spain.
 This is a retrospective analysis of prospectively collected VS and NOS in neonates from 1996 to 2018 in the 44 neonatal units integrated in the Spanish Neonatal Network Grupo Castrillo.
 A total of 2,676 episodes of VS were recorded in 2,196,129 live births (LBs; 1.2/1,000 LBs) over the study period (1996-2018). The incidence declined from 2.4 to 1 to 1.2/1,000 LBs ( < 0.0001). Of the 2,676 episodes, 95.7% were early onset (≤72 hours) and 4.3% cases late onset VS. Group B streptococcus (GBS) (33.1%) and (29.3%) were the most frequently isolated pathogen. The GBS incidence declined significantly from 1.25 to 0.21/1,000 LBs ( < 0.0001). incidence showed a significant increase trend in VLBW infants ( < 0.05). The global mortality per 1000 LBs decreased from 0.21 to 0.13/1,000. A total of 7,036 episodes of NOS involving 5,493 VLBW infants were registered over 20,935 neonatal admissions (NAs) in the study period (2006-2018). The incidence was 26.2 per 100 NAs. The median postnatal age at onset was 13 days (interquartile range [IQR]: 9-23 days). Around 80% of cases occurred in infants with a central line in place. Gram positive (GP) bacteria accounted for 66.2% with as the most frequently isolated pathogen, gram negative (GN) bacteria entailed 27.4%, and fungi 6.2%. was the most common GN isolated and the most prevalent fungus. The overall mortality was 8.3%.
 The causative pathogen of neonatal sepsis may change over time and between countries, therefore a national surveillance network based on a consensus definition could be essential to provide accurate information.
· Grupo Castrillo is a Spanish network for neonatal infections surveillance.. · A neonatal sepsis definition based on epidemilogical and not only chronological criteria was established.. · Epidemiology of neonatal sepsis may change over time; therefore, a national surveillance network is essential to provide accurate information..

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