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Background: Preterm infants are at risk for neurodevelopmental deficits. An association between retinopathy of prematurity (ROP) and impaired cognitive outcome has already been described. However, less is known about the impact of ROP on visual motor integration (VMI), which is a prerequisite not only for fine motor abilities but also for further school skills. Therefore, the aim of this study was to retrospectively investigate the impact of ROP on VMI at preschool age. Methods: The study was conducted at the Medical University of Vienna, including patients born between January 2009 and December 2014 with a gestational age of less than 30 weeks and/or a birth weight of less than 1,500 g. VMI was determined by Beery-Buktenica Developmental Test of Visual Motor Integration (Beery VMI) at the age of 5 years. Results: Out of 1,365 patients, 353 met inclusion criteria for this study. Two hundred sixteen of them had no ROP, while 137 had ROP (stage 1: n = 23, stage 2: n = 74, stage 3: n = 40). Mean value of the Beery VMI score was significantly lower in the ROP group compared to the No-ROP group (90 ± 16 vs. 99 ± 14; p < 0.01). By correcting for other important medical conditions, ROP still had a significant impact on Beery VMI score (p < 0.01). Particularly, lower scores were found for stage 2 (p < 0.01) and stage 3 (p < 0.01). Conclusion: Beery VMI scores were significantly lower in preterm infants with ROP stage 2 and 3 than in infants without ROP. This study shows the negative impact of ROP on VMI skills at preschool age, even after adjustment for key demographic and medical characteristics.

Providing optimal pain relief is a challenging task when caring for premature infants. The aim of this study was to compare the long-term cognitive, motor, and behavioral outcomes of preterm infants before and after the implementation of a pain and sedation protocol. In addition, we investigated whether the increased opiate administration resulting after the implementation process had an impact on these outcomes. Cognitive outcomes were evaluated using the Kaufman Assessment Battery for Children (KABC), neuromotor examinations were based on Amiel-Tison, and behavioral outcomes were assessed using the parent-reported Child Behavior Checklist (CBCL). One hundred extremely preterm infants were included in the study (control group, n = 53; intervention group, n = 47). No significant differences were found in cognitive and motor outcomes at preschool age. However, every increase in the cumulative opiate exposure for each 100 mg/kg was weakly significantly associated with a higher risk for autism spectrum features (adjusted odds ratio (aOR) = 1.822, 95% confidence interval (CI) [1.231–2.697]; P = 0.03) and withdrawn behavior (aOR = 1.822, 95% CI [1.231–2.697]; P = 0.03) at preschool age. Increased neonatal cumulative opiate exposure did not alter cognitive and motor outcomes but may represent a risk factor for autism spectrum and withdrawn behavior at preschool age.

Background: Culture-proven sepsis is the gold standard in early-onset neonatal sepsis diagnosis. Infants born ≤29 weeks gestation after preterm rupture of membranes in the years 2009–2015 were included in a retrospective cohort study performed at a level III fetal-maternal unit. The study aimed to compare culture-proven sepsis, clinical sepsis and positive laboratory biomarkers ≤72 h as predictors of mortality before discharge and the combined outcome of mortality or severe short-term morbidity (severe cerebral morbidity, bronchopulmonary dysplasia and retinopathy). Results: Of the 354 patients included, culture-proven sepsis, clinical sepsis and laboratory biomarkers were positive in 2.3%, 8.5% and 9.6%, respectively. The mortality rate was 37.5% for patients with culture-proven sepsis (3/8), 33.3% for patients with clinical sepsis (10/30) and 8.8% for patients with positive laboratory biomarkers (3/34), respectively. Mortality or severe morbidity occurred in 75.0% of patients with culture-proven sepsis (6/8), 80.0% of patients with clinical sepsis (24/30) and 44.1% of patients with positive laboratory biomarkers (15/34), respectively. Conclusion: In preterm infants after preterm rupture of membranes, clinical sepsis was almost four times more common and at least equally valuable in predicting mortality and mortality or severe morbidity compared to culture-proven sepsis.

Background International guidelines recommend the use of item based scales for the assessment of pain and sedation. In our previous study, the implementation of the Neonatal Pain Agitation and Sedation Scale (N-PASS), and the associated systematic assessment and treatment of pain and sedation reduced pain and over-sedation in our intervention group, but lead to a significant increase of individual opiate exposure. This increased opiate exposure was not associated with impaired motor and mental development at one year of age. As one-year follow-up is not necessarily representative for future outcomes, we retested our sample at three years of age. Methods Fifty-three patients after (intervention group) and 61 before implementation (control group) of the N-PASS and the Vienna Protocol for the Management of Neonatal Pain and Sedation (VPNPS), were compared for motor, mental and behavioural development at three-years follow-up using the Bayley Scales of Infant Development. Results Cumulative opiate exposure was not associated with mental (p = .31) and motor (p = .20) problems when controlling for other important medical conditions, but was associated to lower behavioural scores (p = .007). No statistically significant differences were found with regard to mental (p = .65), psychomotor (p = .12) and behavioural (p = .61) development before and after the implementation of the N-PASS and the VPNPS. Conclusion Implementing a neonatal pain and sedation protocol increased opiate exposure without affecting neurodevelopmental outcome at three-years of age.

Background: Methicillin-susceptible Staphylococcus aureus (MSSA) is a major contributor to infectious episodes of very low birth weight infants (VLBWI), resulting in significant morbidity and mortality. Objective: To examine the efficacy and safety of surveillance cultures and the decolonization of MSSA-colonized VLBWI. Methods: VLBWI admitted to our neonatal wards in 2011-2016 were retrospectively analyzed. Rates of MSSA-attributable infections were compared before and after the implementation of active surveillance cultures and the decolonization of MSSA-colonized patients. The mupirocin susceptibility of isolated MSSA strains was routinely tested. Results: A total of 1,056 VLBWI were included in the study, 552 in the pre-intervention period and 504 in the post-intervention period. The implementation of surveillance cultures and decolonization of colonized patients resulted in a 50% reduction of incidence rates per 1,000 patient-days of MSSA-attributable infections (1.63 [95% CI 1.12-2.31] vs. 0.83 [95% CI 0.47-1.35], p = 0.024). No adverse effects were observed from application of the decolonization protocol with mupirocin and octenidin. No mupirocin-resistant MSSA strains were detected during the study period. Conclusion: Implementation of an active surveillance and decolonization protocol resulted in a reduction of MSSA-attributable infections in VLBWI.

Pentoxifylline (PTX) is a candidate adjuvant medication for the treatment of sepsis and necrotizing enterocolitis in preterm infants. There is only limited data on safety and compatibility with other commonly used intravenous medications. This retrospective single-center study of 198 preterm infants (September 2012-September 2018) was performed at a level IV neonatal intensive care unit. Electronic data of all preterm infants who received pentoxifylline for sepsis or necrotizing were extracted from routine databases. We analyzed a total of 1081 PTX treatment days from 217 treatment episodes in 198 preterm infants (mean gestational age 27 weeks; mean birth weight 1060 g). At a mean daily dose of 28 mg/kg, no clinically relevant side effects were observed. PTX therapy was not associated with clinically significant changes of blood biochemistry and hematology parameters. Concomitant infusion of PTX with other common NICU medications was well tolerated, and there was no evidence of incompatibility.Conclusion: Intravenous PTX is compatible with standard NICU drugs and well tolerated in critically ill preterm infants. What is Know: •Currently, there are no evidence-based adjuvant medications available that target the harmful inflammatory host response in neonatal sepsis or necrotizing enterocolitis. •Pentoxifylline (PTX) is a candidate adjuvant medication for the treatment of sepsis and necrotizing enterocolitis in preterm infants; however, safety data are rare and PTX is currently used off-label. What is New: •Here we report on our experience in the pragmatic routine use of PTX as adjuvant therapy in 198 preterm infants with sepsis or NEC. •Concomitant infusion of PTX with other common NICU medications was well tolerated, and there was no evidence of incompatibility. No clinically relevant side effects were observed.

Aim This study compared the short-term and neurodevelopmental outcomes of extremely preterm infants before and after the implementation of a protocol to manage neonatal pain and sedation. Methods Our study cohort comprised 140 extremely preterm infants from two neonatal intensive care units. We retrospectively analysed opiate exposure, time on mechanical ventilation, inotropic support, nutritional aspects and growth 12 months before (controls) vs 12 months after (intervention) the implementation of the Vienna Protocol for Neonatal Pain and Sedation. Infants were evaluated at the corrected age of 12 months using the Bayley Scales of Infant Development - Second Edition. Results After the protocol was implemented, the cumulative opiate dose increased from a baseline of 15 mg/kg ± 41 to 89 mg/kg ± 228 morphine equivalents. Time on mechanical ventilation, inotropic support, length of parenteral nutrition, growth, length of stay and in-hospital morbidity were similar before and after the implementation, with no differences between the groups in mental, motor and behavioural development at the one-year follow-up. However, opiate exposure was a possible risk factor for lower behaviour rating scores (estimate = -0.04; p = 0.006). [Correction added on 23 February 2016, after online publication: In the preceding sentences, the cumulative opiate dose as well as the estimate value for the behavioral rating scale were previously incorrect and have been amended in this current version.] Conclusion Implementing a neonatal pain and sedation protocol increased opiate exposure, but had no effect on the in-hospital and neurodevelopmental outcomes of extremely preterm infants.

Background Symptoms at suspicion of necrotizing enterocolitis (NEC) are often nonspecific and several biomarkers have been evaluated for their discriminative power to both diagnose and predict the course from NEC suspicion to complicated disease requiring surgical intervention. Thus, we aimed to assess the utility of interleukin-6 (IL-6) to predict surgical intervention in infants suffering from NEC and, furthermore, to discriminate infants with starting NEC or late-onset sepsis (LOS). Methods IL-6 serum levels at disease onset were retrospectively analyzed in 24 infants suffering from NEC as well as 16 neonates with LOS. Results IL-6 serum levels at disease onset were significantly higher in infants suffering from NEC necessitating surgical intervention in the disease course compared to infants with medical NEC (5000 [785–5000] vs. 370 [78–4716] pg/ml, p = 0.0008) as well as gram-positive LOS (5000 [785–5000] vs. 84 [12–269] pg/ml, p = 0.0001). Infants suffering from gram-negative LOS exhibited elevated IL-6 serum levels at disease onset comparable to infants with surgical NEC (5000 [1919–5000] vs. 5000 [785–5000] pg/ml, p = 1.00). Conclusion The proinflammatory cytokine IL-6 appears to be a promising marker to distinguish surgical NEC from medical NEC at the onset of disease but cannot discriminate between surgical NEC and gram-negative LOS. Level of evidence II

Little is known about the side effects of micafungin in extremely low birth weight infants. In a retrospective single-center study, 19 extremely low birth weight infants were analyzed for micafungin efficacy and safety. At a mean±standard deviation daily dosage of 7.5 ± 2.0 mg/kg, no clinically relevant side effects were observed. A significant increase of liver enzymes was reversible after treatment.

Methicillin-susceptible Staphylococcus aureus (MSSA) is a major contributor to infectious episodes of very low birth weight infants (VLBWI), resulting in significant morbidity and mortality.To examine the efficacy and safety of surveillance cultures and the decolonization of MSSA-colonized VLBWI.VLBWI admitted to our neonatal wards in 2011-2016 were retrospectively analyzed. Rates of MSSA-attributable infections were compared before and after the implementation of active surveillance cultures and the decolonization of MSSA-colonized patients. The mupirocin susceptibility of isolated MSSA strains was routinely tested.A total of 1,056 VLBWI were included in the study, 552 in the pre-intervention period and 504 in the post-intervention period. The implementation of surveillance cultures and decolonization of colonized patients resulted in a 50% reduction of incidence rates per 1,000 patient-days of MSSA-attributable infections (1.63 [95% CI 1.12-2.31] vs. 0.83 [95% CI 0.47-1.35], p = 0.024). No adverse effects were observed from application of the decolonization protocol with mupirocin and octenidin. No mupirocin-resistant MSSA strains were detected during the study period.Implementation of an active surveillance and decolonization protocol resulted in a reduction of MSSA-attributable infections in VLBWI.

AIM We evaluated the incidence of arterial catheterisation and analysed the risk factors and the extent and outcome of ischaemic complications in neonates. METHODS This was a retrospective cohort study of 1506 neonates admitted to two, ten-bed neonatal intensive care units (NICUs) at the Medical University of Vienna, Austria, between 1 January 2011 and 31 December 2014. Medical charts, daily reports and photo documentation were reviewed for arterial catheterisation and ischaemic complications. Patients with severe ischaemic complications were followed up to evaluate extremity function, scaring and cosmetic results. RESULTS There were 542 arterial catheterisations in 485 patients, including 275 born below 28 weeks, which resulted in severe complications in 19 of 485 (4%) patients. Three died before follow-up. Patients with complications had a significantly lower birthweight, lower postmenstrual age and higher rates of intracranial haemorrhage, retinopathy of prematurity and necrotising enterocolitis. They had also undergone multiple arterial catheterisations more often, needed longer inotropic support and had longer NICU stays than patients without complications. Extremity function was unimpaired in ten of 16 patients with severe ischaemic complications. CONCLUSION Severe ischaemic complications in neonates following arterial catheterisation were rare events, but could cause devastating damage. Most patients didn't show impaired extremity function at follow-up.

BackgroundParenteral nutrition associated cholestasis (PNAC) is a frequently observed pathology in extremely low birth weight (ELBW) infants. Its pathogenesis is determined by the composition and duration of parenteral nutrition (PN) as well as the tolerance of enteral feeds (EF). “Aggressive” nutrition is increasingly used in ELBW infants to improve postnatal growth. Little is known about the effect of “aggressive” nutrition on the incidence of PNAC. We analyzed the influence of implementing an “aggressive” nutritional regimen on the incidence of PNAC and growth in a cohort of ELBW infants.MethodsELBW infants were nourished using a “conservative” (2005–6;n= 77) or “aggressive” (2007–9;n= 85) nutritional regimen that differed in the composition of PN after birth as well as the composition and timing of advancement of EFs. We analyzed the incidence of PNAC (conjugated bilirubin > 1.5 mg/dl (25 µmol/l)) corrected for confounders of cholestasis (i.e., NEC and/or gastrointestinal surgery, sepsis, birth weight, Z-score of birth weight, time on PN and male sex), growth until discharge (as the most important secondary outcome) and neonatal morbidities.ResultsThe incidence of PNAC was significantly lower during the period of “aggressive” vs. “conservative “nutrition (27% vs. 46%,P< 0.05; adjusted OR 0.275 [0.116–0.651],P< 0.01). Body weight (+411g), head circumference (+1 cm) and length (+1 cm) at discharge were significantly higher. Extra-uterine growth failure (defined as a Z-score difference from birth to discharge lower than −1) was significantly reduced for body weight (85% vs. 35%), head circumference (77% vs. 45%) and length (85% vs. 65%) (P< 0.05). The body mass index (BMI) at discharge was significantly higher (11.1 vs. 12.4) using “aggressive” nutrition and growth became more proportionate with significantly less infants being discharged below the 10th BMI percentile (44% vs. 9%), while the percentage of infants discharged over the 90th BMI percentile (3% vs. 5%) did not significantly increase.Discussion“Aggressive” nutrition of ELBW infants was associated with a significant decrease of PNAC and marked improvement of postnatal growth.

Background: One third of all preterm births are due to preterm premature rupture of membranes (pPROM). An accurate prognostic evaluation after admission to the neonatal intensive care unit is necessary. Objective: The aim of this study was to identify prognostic factors within the first hour of life for mortality, short-term pulmonary morbidity, chronic lung disease (CLD) and severe cerebral morbidity in very low birth weight (VLBW) infants after pPROM. Methods: This retrospective study included 300 infants with pPROM who fit the study criteria and were derived from a cohort of 1,435 VLBW infants. A total of 17 obstetric and neonatal factors were evaluated by univariate and multivariate analysis. Results: Gestational age at birth and 5-min Apgar score correlated significantly with all 4 outcomes. The results of the first blood gas analysis correlated with 3 outcomes and the first mean arterial pressure with 2 outcomes. Anhydramnios and a lower number of courses of antenatal steroids correlated with higher mortality, and preterm labor correlated with CLD. The multivariate analysis revealed gestational age, 5-min Apgar score, the results of the first blood gas analysis, the first mean arterial pressure and anhydramnios to be significant predictors. The positive predictive value ranged from 20 to 81%, and the negative predictive value ranged from 79 to 92%. Conclusion: Gestational age at birth and parameters reflecting postnatal adaptation were the most precise factors for assessment of the prognosis of VLBW infants after pPROM within the first hour of life. Apart from anhydramnios, obstetric factors did not predict neonatal outcome. At 1 h of age, our models of perinatal risk factors were more effective in predicting a favorable outcome than an adverse outcome.

Expectations and requirements concerning the identification and surveillance of healthcare-associated infections (HAIs) are increasing, calling for differentiated automated approaches. In an attempt to bridge the "definition swamp" of these infections and serve the needs of different users, we improved the monitoring of nosocomial infections (MONI) software to create better surveillance reports according to consented national and international definitions, as well as produce infection overviews on complex clinical matters including alerts for the clinician's ward and bedside work. MONI contains and processes surveillance definitions for intensive-care-unit-acquired infections from the European Centre for Disease Prevention and Control, Sweden, as well as the Centers for Disease Control and Prevention, USA. The latest release of MONI also includes KISS criteria of the German National Reference Center for Surveillance of Nosocomial Infections. In addition to these "classic" surveillance criteria, clinical alert criteria--which are similar but not identical to the surveillance criteria--were established together with intensivists. This is an important step to support both infection control and clinical personnel; and--last but not least--to foster co-evolution of the two groups of definitions: surveillance and alerts.

Aim The study investigated early postnatal vital signs in very low birthweight (VLBW) infants who later developed patent ductus arteriosus (PDA). We hypothesised that the early postnatal course of vital signs and blood gas variables might differ between infants whose PDA closed spontaneously, those who responded to ibuprofen and those who later required PDA ligation. Methods We analysed computerised records of VLBW infants born

OBJECTIVE: To evaluate the implementation of a neonatal pain and sedation protocol at 2 ICUs. METHODS: The intervention started with the evaluation of local practice, problems, and staff satisfaction. We then developed and implemented the Vienna Protocol for Neonatal Pain and Sedation. The protocol included well-defined strategies for both nonpharmacologic and pharmacologic interventions based on regular assessment of a translated version of the Neonatal Pain Agitation and Sedation Scale and titration of analgesic and sedative therapy according to aim scores. Health care staff was trained in the assessment by using a video-based tutorial and bedside teaching. In addition, we performed reevaluation, retraining, and random quality checks. Frequency and quality of assessments, pharmacologic therapy, duration of mechanical ventilation, and outcome were compared between baseline (12 months before implementation) and 12 months after implementation. RESULTS: Cumulative median (interquartile range) opiate dose (baseline dose of 1.4 [0.5–5.9] mg/kg versus intervention group dose of 2.7 [0.4–57] mg/kg morphine equivalents; P = .002), pharmacologic interventions per episode of continuous sedation/analgesia (4 [2–10] vs 6 [2–13]; P = .005), and overall staff satisfaction (physicians: 31% vs 89%; P < .001; nurses: 17% vs 55%; P < .001) increased after implementation. Time on mechanical ventilation, length of stay at the ICU, and adverse outcomes were similar before and after implementation. CONCLUSIONS: Implementation of a neonatal pain and sedation protocol at 2 ICUs resulted in an increase in opiate prescription, pharmacologic interventions, and staff satisfaction without affecting time on mechanical ventilation, length of intensive care stay, and adverse outcomes.

Unidentified gestational infection with Toxoplasma gondii may lead to fetal infection with severe complications later in childhood. Because diagnosis of maternal infection solely depends on serology, routine tests with high sensitivity and specificity are required. In this study, the new Roche Elecsys Toxo IgG and IgM immunoassay was compared with Sabin-Feldman dye test and immunosorbent agglutination assay-IgM as reference test. Serum samples were analyzed from 927 pregnant women, including 100 negative, 706 chronic, and 121 acute infections. The combination of both Elecsys IgG and IgM assays demonstrated high sensitivity and specificity of 97.1% and 100.0%, respectively, and a positive and negative predictive value of 100.0% and 81.3%, respectively. The Elecsys assay is a useful tool as a first-line screening method to detect gestational infections. However, if gestational infection is assumed, confirmatory testing by a reference laboratory might be necessary to discriminate between pre- and postconceptional infection to start antiparasitic treatment to avoid mother-to-fetus transmission and severe sequelae.

Objective The neonatal regional tertiary care center of the University of Vienna (VC) has been a member of the Vermont Oxford Neonatal Network (VONN) since 1994. During the period 1994--2002, important differences between the VC and the VONN in both pre- and postnatal management and in late morbidities such as chronic lung disease (CLD) and severe retinopathy of prematurity (ROP) were observed. We hypothesize that stabilization of very-low-birth-weight (VLBW) infants on nasal continuous positive airway pressure (NCPAP) immediately after birth, combined with a restrictive use of artificial ventilation, might be responsible for lower rates of CLD and ROP. Patients and methods Obstetric and neonatal data for all 1299 VLBW infants (401-1500 g) from the VC were compared with corresponding data for the 201,167 VLBW infants from the VONN for the period 1994--2002 with regard to respiratory management and patient outcome. Morbidity criteria were in accordance with VONN definitions. Results The percentage range for treatment and morbidity criteria for the VC and VONN are related to differences among various years within the observation period. Infants were stabilized at birth on NCPAP in 45-86% of cases in the VC vs. 37-63% in the VONN, the rate of mechanical ventilation was 40-59% vs. 66-74%, and use of surfactant was 31-50% vs. 55-64%. CLD was diagnosed in 14-32% of cases in the VC vs. 27-39% in the VONN, discharge on supplemental oxygen took place in 2-4% vs. 12-17% of cases and ROP (stages III and IV) was found in 1-10% vs. 8-12%. Conclusion The association of lower rates of CLD and ROP in the VC compared to the VONN might be related to differences in early respiratory management of VLBW infants at high risk of development of respiratory distress syndrome. This needs to be confirmed in a large multicenter trial.

Background and objectives We retrospectively compared short-term and neurodevelopmental outcome of very low birth weight infants (VLBWI) before (n = 84) and after implementation (n = 69) of a protocol for the management of neonatal pain and sedation. Methods Opiate exposure, time on mechanical ventilation, inotropic support, details on nutritional aspects, and growth were compared between baseline and after protocol implementation. Infants were evaluated at 12 months corrected age using standardised neurologic examination and Bayley Scales of Infant Development-II. Results Cumulative mean ± SD opiate dose (baseline dose of 14 ± 39 mg/kg vs. intervention group dose of 84 ± 222 mg/kg morphine equivalents; p Conclusions Implementation of a neonatal pain and sedation protocol results in an increase in opiate prescription without affecting short-term outcome and neurodevelopmental performance of VLBWI at 12 months corrected age.

Summary Premature infants are at substantial risk for suffering from perinatal white matter injury. Though the gut microbiota has been implicated in early-life development, a detailed understanding of the gut-microbiota-immune-brain axis in premature neonates is lacking. Here, we profiled the gut microbiota, immunological, and neurophysiological development of 60 extremely premature infants, which received standard hospital care including antibiotics and probiotics. We found that maturation of electrocortical activity is suppressed in infants with severe brain damage. This is accompanied by elevated γδ T cell levels and increased T cell secretion of vascular endothelial growth factor and reduced secretion of neuroprotectants. Notably, Klebsiella overgrowth in the gut is highly predictive for brain damage and is associated with a pro-inflammatory immunological tone. These results suggest that aberrant development of the gut-microbiota-immune-brain axis may drive or exacerbate brain injury in extremely premature neonates and represents a promising target for novel intervention strategies.