Iatrogenic severe hyperglycemia due to parenteral administration of glucose in children - a case series.

BACKGROUND: Iatrogenic severe hyperglycemia (ISH) caused by glucose-containing i.v. solution is a potentially fatal treatment error. The objective of this study was to investigate the causes, circumstances, course of disease, and complications of ISH > 300 mg/dl (16.7 mmol/l) in neonates and children. METHODS: We emailed a survey to 105 neonatal and pediatric intensive care units in Germany, Austria, and Switzerland, asking to retrospectively report cases of ISH. RESULTS: We received 11 reports about premature infants to children. Four patients (36%) had poor outcome: 2 died and 2 suffered persistent sequelae. The highest observed blood glucose was at median 983 mg/dl (54.6 mmol/l) (range 594-2240 mg/dl; 33.0-124.3 mmol/l) and median time to normoglycemia was 7 h (range 2-23). Blood glucose was higher and time to normoglycemia longer in patients with poor outcome. Invasive therapy was required in 73% (mechanical ventilation) and 50% (vasopressor therapy) of patients, respectively. Administration of insulin did not differ between outcome groups. Patients with poor outcome showed coma (100% vs. 40%) and seizures (75% vs. 29%) more frequently than those with good outcome. CONCLUSIONS: ISH is a severe condition with high morbidity and mortality. Further research to amplify the understanding of this condition is needed, but focus should largely be held on its prevention.

Vancomycin-induced ototoxicity in very-low-birthweight infants.

BACKGROUND: Vancomycin is an extensively used anti-infective drug in neonatal ICUs. However, exposure-toxicity relationships have not been clearly defined. OBJECTIVES: To evaluate the risk profile for hearing deficits in vancomycin-exposed very-low-birthweight infants (VLBWI). METHODS: In a large cohort study of the German Neonatal Network (GNN; n = 16 967 VLBWI) we assessed the association of vancomycin treatment and pathological hearing tests at discharge and at 5 year follow-up. We performed audits on vancomycin exposure, drug levels, dose adjustments and exposure to other ototoxic drugs in a subgroup of 1042 vancomycin-treated VLBWI. RESULTS: In the GNN cohort, 28% (n = 4739) were exposed to IV vancomycin therapy. In multivariable logistic regression analysis, vancomycin exposure proved to be independently associated with pathological hearing test at discharge (OR 1.18, 95% CI 1.03-1.34, P = 0.016). Among vancomycin-treated infants, a cumulative vancomycin dose above the upper quartile (>314 mg/kg bodyweight) was associated with pathological hearing test at discharge (OR 2.1, 95% CI 1.21-3.64, P = 0.009), whereas a vancomycin cumulative dose below the upper quartile was associated with a reduced risk of pathological tone audiometry results at 5 years of age (OR 0.29, 95% CI 0.1-0.8, P = 0.02, n = 147). CONCLUSIONS: Vancomycin exposure in VLBWI is associated with an increased, dose-dependent risk of pathological hearing test results at discharge and at 5 years of age. Prospective studies on long-term hearing impairment are needed.

Active perinatal care of preterm infants in the German Neonatal Network.

OBJECTIVE: To determine if survival rates of preterm infants receiving active perinatal care improve over time. DESIGN: The German Neonatal Network is a cohort study of preterm infants with birth weight <1500 g. All eligible infants receiving active perinatal care are registered. We analysed data of patients discharged between 2011 and 2016. SETTING: 43 German level III neonatal intensive care units (NICUs). PATIENTS: 8222 preterm infants with a gestational age between 22/0 and 28/6 weeks who received active perinatal care. INTERVENTIONS: Participating NICUs were grouped according to their specific survival rate from 2011 to 2013 to high (percentile >P75), intermediate (P25-P75) and low (

Preterm prelabor rupture of membranes and outcome of very-low-birth-weight infants in the German Neonatal Network.

OBJECTIVE: It was the aim of our study to evaluate the independent effect of preterm prelabor rupture of membranes (PPROM) as a cause of preterm delivery on mortality during primary hospital stay and significant morbidities in very-low-birth-weight (VLBW) infants < 32 weeks of gestation. DESIGN: Observational, epidemiological study design. SETTING: Population-based cohort, German Neonatal Network (GNN). POPULATION: 6102 VLBW infants were enrolled in GNN from 2009-2012, n=4120 fulfilled criteria for primary analysis (< 32 gestational weeks, no pre-eclampsia, HELLP (highly elevated liver enzymes and low platelets syndrome) or placental abruption as cause of preterm birth). METHODS: Multivariable logistic regression analyses included PPROM as potential risk factors for adverse outcomes and well established items such as gestational age in weeks, birth weight, antenatal steroids, center, inborn delivery, multiple birth, gender and being small-for-gestational-age. RESULTS: PPROM as cause of preterm delivery had no independent effect on the risk of early-onset sepsis, clinical sepsis and blood-culture proven sepsis, while gestational age proved to be the most important contributor to sepsis risk. The diagnosis of PPROM was associated with an increased risk for bronchopulmonary dysplasia (BPD; OR: 1.25, 95% CI: 1.02-1.55, p=0.03) but not with other major outcomes. CONCLUSIONS: The diagnosis of PPROM per se is not associated with adverse outcome in VLBW infants < 32 weeks apart from a moderately increased risk for BPD. Randomized controlled trials with primary neonatal outcomes are needed to determine which subgroup of VLBW infants benefit from expectant or intentional management of PPROM.

FUT 2 polymorphism and outcome in very-low-birth-weight infants.

BACKGROUND: To determine whether the secretor gene fucosyltransferase (FUT)2 polymorphism G428A is predictive for adverse outcomes in a large cohort of very-low-birth weight (VLBW) infants. METHODS: We prospectively enrolled 2,406 VLBW infants from the population-based multicenter cohort of the German Neonatal network cohort (2009-2011). The secretor genotype (rs601338) was assessed from DNA samples extracted from buccal swabs. Primary study outcomes were clinical sepsis, blood-culture confirmed sepsis, intracerebral hemorrhage (ICH), necrotizing enterocolitis (NEC) or focal intestinal perforation requiring surgery, and death. RESULTS: Based on the assumption of a recessive genetic model, AA individuals had a higher incidence of ICH (AA: 19.0% vs. GG/AG: 14.9%, P = 0.04) which was not significant in the additive genetic model (multivariable logistic regression analysis; allele carriers: 365 cases, 1,685 controls; OR: 1.2; 95% CI: 0.99-1.4; P = 0.06). Other outcomes were not influenced by FUT2 genotype in either genetic model. CONCLUSION: This large-scale multicenter study did not confirm previously reported associations between FUT2 genotype and adverse outcomes in preterm infants.

Risk for late-onset blood-culture proven sepsis in very-low-birth weight infants born small for gestational age: a large multicenter study from the German Neonatal Network.

BACKGROUND: It was the aim of this study to assess whether very-low-birth-weight (VLBW) infants born small for gestational age (SGA; birth weight less than 10th percentile) are at increased risk for late-onset sepsis. METHODS: This was a prospective, multicenter study of the German Neonatal Network including VLBW infants from 23 to < 32 weeks post menstrual age born 2009-2011. Outcomes were compared between VLBW infants born SGA (birth weight less than tenth percentile according to gestational age and gender) and non-SGA infants. The main outcome measure was at least 1 episode of late-onset sepsis defined as blood-culture-confirmed clinical sepsis occurring at ≥ 72 hours of age. RESULTS: 5886 VLBW infants were included. In SGA infants (n = 692), an increased incidence of late-onset sepsis was noted compared with non-SGA infants (20.1% vs. 14.3 %, P < 0.001). This difference was only observed among infants with a gestational age of 27 to < 32 weeks and attributed to sepsis episodes with coagulase-negative staphylococci (12.8% vs. 8.3%, P < 0.001). Different treatment modalities (eg more frequent use of central venous lines) and longer duration of invasive therapies (parenteral nutrition, mechanical ventilation, hospitalization) may account for the increased sepsis risk with coagulase-negative staphylococci in our SGA cohort. In a multivariate logistic regression analysis, higher gestational age [per week; odds ratio (OR): 0.75, 95% confidence interval (CI): 0.72-0.78, P< 0.0001], treatment with antenatal steroids (OR: 0.7, 95% CI: 0.53-0.92, P = 0.01), German descendance (OR: 0.76, 95% CI: 0.63-0.91, P = 0.003) and prophylaxis with glycopeptide antibiotics (OR: 0.64, 95% CI: 0.47-0.87, P = 0.005) were shown to be protective against late-onset sepsis. In contrast, longer duration of parenteral nutrition (per day; OR: 1.016, 95% CI: 1.011-1.021, P < 0.0001) and SGA were found to be risk factors (OR: 1.31, 95% CI: 1.02-1.68, P= 0.03). CONCLUSIONS: SGA contributes to the risk of late-onset sepsis in VLBW infants. Future studies are needed to investigate the underlying pathophysiology to guide individualized preventive measures in this vulnerable subgroup.

Epidemic microclusters of blood-culture proven sepsis in very-low-birth weight infants: experience of the German Neonatal Network.

INTRODUCTION: We evaluated blood culture-proven sepsis episodes occurring in microclusters in very-low-birth-weight infants born in the German Neonatal Network (GNN) during 2009-2010. METHODS: Thirty-seven centers participated in GNN; 23 centers enrolled ≥50 VLBW infants in the study period. Data quality was approved by on-site monitoring. Microclusters of sepsis were defined as occurrence of at least two blood-culture proven sepsis events in different patients of one center within 3 months with the same bacterial species. For microcluster analysis, we selected sepsis episodes with typically cross-transmitted bacteria of high clinical significance including gram-negative rods and Enterococcus spp. RESULTS: In our cohort, 12/2110 (0.6%) infants were documented with an early-onset sepsis and 235 late-onset sepsis episodes (≥72 h of age) occurred in 203/2110 (9.6%) VLBW infants. In 182/235 (77.4%) late-onset sepsis episodes gram-positive bacteria were documented, while coagulase negative staphylococci were found to be the most predominant pathogens (48.5%, 95%CI: 42.01-55.01). Candida spp. and gram-negative bacilli caused 10/235 (4.3%, 95%CI: 1.68% -6.83%) and 43/235 (18.5%) late-onset sepsis episodes, respectively. Eleven microclusters of blood-culture proven sepsis were detected in 7 hospitals involving a total 26 infants. 16/26 cluster patients suffered from Klebsiella spp. sepsis. The median time interval between the first patient's Klebsiella spp. sepsis and cluster cases was 14.1 days (interquartile range: 1-27 days). First patients in the cluster, their linked cases and sporadic sepsis events did not show significant differences in short term outcome parameters. DISCUSSION: Microclusters of infection are an important phenomenon for late-onset sepsis. Most gram-negative cluster infections occur within 30 days after the first patient was diagnosed and Klebsiella spp. play a major role. It is essential to monitor epidemic microclusters of sepsis in surveillance networks to adapt clinical practice, inform policy and further improve quality of care.