The NINO study (Nosocomial Infection in VLBW infants ( 1.
Of 748 eligible infants 128 had to be excluded and of 620 study infants 116 had one or more nosocomial infection. More than 1 infection included 20 infants with EOS and LOS, 5 with EOS and viral infection, 12 with LOS and viral infection and 4 with EOS, LOS and viral infection.
Included were preterm very low birth weight (VLBW
Data were extracted from the local electronic patient management openMedocs® used at the University Hospital Graz. The local ethic committee of the Medical University of Graz ID 31-396 ex 18/19 approved the study. The study was registered at the “Deutsches Register Klinischer Studien” number DRKS00019000.
Late onset sepsis was defined as either clinical sepsis (at least 2 clinical signs and symptoms associated with elevated C-reactive protein (CRP) level above 10 mg/L or an immature-to-total neutrophil ratio >0.2 and negative blood culture, or blood culture proven sepsis – same as above and a positive blood culture with a plausible pathogen) and duration of antibiotic treatment for at least 7 days. Symptoms and signs of late-onset sepsis had to be observed after the third day of life ( > 72 h postpartum):
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temperature instability: hyperthermia >38.5 °C, hypothermia
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respiratory disorders: tachypnea >60/min, dyspnea (nasal flares, retractions, grunting), apnea
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gastrointestinal symptoms: drinking weakness, vomiting, abdominal distension
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circulatory insufficiency: tachycardia >180 bpm, bradycardia 2 sec, paleness
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metabolic acidosis, hyperglycemia or hypoglycemia
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oliguria or anuria
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neurological disorders: hyperexcitability, convulsive seizures
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septic shock, multi organ failure, disseminated intravascular coagulation
Nosocomial viral infections were defined as respiratory or gastrointestinal infections acquired during the first hospital stay. Nasopharyngeal swaps and stool cultures were done routinely in case of a symptomatic preterm infant. No invasive fungal infections were documented during the study period (a prophylactical antifungal therapy was given in all VLBW infants).
Maternal data included maternal age, mode of delivery and morbidities including preeclampsia, pregnancy-induced hypertension (PIH), HELLP syndrome (hemolysis + elevated liver enzymes + low platelet count), preterm premature rupture of membranes (PPROM) and amniotic infection syndrome (AIS).
Perinatal data included gestational age in weeks, birth weight in grams including small for gestational age (SGA)/ intrauterine growth restriction (IUGR), gender, APGAR score at 1, 5, and 10 min after birth, and multiple pregnancy (twins or triplets).
Neonatal data included respiratory distress syndrome (RDS with surfactant application), bronchopulmonary dysplasia (BPD), Ureaplasma or Mycoplasma pneumonia, patent ductus arteriosus (PDA), intra-periventricular hemorrhage (I/PVH), periventricular leukomalacia (PVL), ileus, intestinal perforation, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), neonatal abstinence syndrome (NAS), and the ventilation mode (invasive/ INSURE [intubate-surfactant-extubate] or non-invasive), duration of ventilation and duration of neonatal hospital stay.
Follow-up data included all admissions due to infectious diseases during the first 2 years of life, the number of rehospitalizations per infant, the age in months (chronological age) at time of rehospitalization and the duration of each hospital stay. The infections were subdivided into respiratory tract infection, gastrointestinal tract infection, and other infectious diseases (febrile infection without focus, febrile seizures, urinary tract infection, wound infection, roseola infantum, pharyngitis, tonsillitis, otitis media, nephrolithiasis, lymphadenitis, aphthous stomatitis, preseptal cellulitis, encephalitis, meningitis).
Neurodevelopmental outcome at two years of age corrected for prematurity was done using the German adaptation of Bayley Scales of Infant Development (BSID) II (second edition published in 2007) and the German adaption of the BSID III (published in 2014). The BSID II was used until 2015 and the BSID III thereafter. We assessed the mental development index (MDI) and physical development index (PDI) when using the BSID II, and the cognitive and motor scales when using the BSID III (the language scale was not part of the test battery at our institution, speech and language assessment using SETK-2 was conducted at the age of 2.5 years).
The reliability coefficients of subtests of the Bayley-III-scales are between r = 0.77 and r = 0.89; the reliability coefficients of the scales between r = 0.86 and r = 0.88; and the mean reliability coefficients of subtests between r = 0.68 and r = 0.83. The standardization of Bayley-III included 878 German children without any known impairment, split in 17 age groups, adding 131 Dutch infants; a total sample of 1009 children.
Some infants could not be tested due to their cognitive or motor impairment. Therefore, we introduced an additional definition of the neurodevelopmental impairment (NDI), which depended on the detailed descriptions in the medical documents at the age of 2 years corrected for prematurity [9]. The term NDI represents neurologic disability defined by one or more of the following impairments: infants with cerebral palsy with a gross motor function classification system (GMFCS) level ≥2, a BSID II or III cognitive score of
Statistical analyses were done using IBM SPSS Statistics 26. Data are presented as mean ± standard deviation (SD) or median and interquartile range for continuous variables and absolute and relative frequencies for categorical data. To identify predictors for neurodevelopmental impairment and rehospitalization uni- and multivariate logistic regression analyses were performed. Variables with a p p- values are reported for uni- and multivariate results.
Exploratory, the impact of nosocomial infections on cognitive and motor outcome, using different thresholds ( t test. Statistics
