Late-onset Sepsis in Preterm Infants Can Be Detected Preclinically by Fecal Volatile Organic Compound Analysis: A Prospective, Multicenter Cohort Study.

Background: The intestinal microbiota has increasingly been considered to play a role in the etiology of late-onset sepsis (LOS). We hypothesize that early alterations in fecal volatile organic compounds (VOCs), reflecting intestinal microbiota composition and function, allow for discrimination between infants developing LOS and controls in a preclinical stage. Methods: In 9 neonatal intensive care units in the Netherlands and Belgium, fecal samples of preterm infants born at a gestational age ≤30 weeks were collected daily, up to the postnatal age of 28 days. Fecal VOC were measured by high-field asymmetric waveform ion mobility spectrometry (FAIMS). VOC profiles of LOS infants, up to 3 days prior to clinical LOS onset, were compared with profiles from matched controls. Results: In total, 843 preterm born infants (gestational age ≤30 weeks) were included. From 127 LOS cases and 127 matched controls, fecal samples were analyzed by means of FAIMS. Fecal VOCs allowed for preclinical discrimination between LOS and control infants. Focusing on individual pathogens, fecal VOCs differed significantly between LOS cases and controls at all predefined time points. Highest accuracy rates were obtained for sepsis caused by Escherichia coli, followed by sepsis caused by Staphylococcus aureus and Staphylococcus epidermidis. Conclusions: Fecal VOC analysis allowed for preclinical discrimination between infants developing LOS and matched controls. Early detection of LOS may provide clinicians a window of opportunity for timely initiation of individualized therapeutic strategies aimed at prevention of sepsis, possibly improving LOS-related morbidity and mortality.

Risk Factors for Necrotizing Enterocolitis: A Prospective Multicenter Case-Control Study.

BACKGROUND: The identification of independent clinical risk factors for necrotizing enterocolitis (NEC) may contribute to early selection of infants at risk, allowing for the development of targeted strategies aimed at the prevention of NEC. OBJECTIVE: The objective of this study was to identify independent risk factors contributing to the development of NEC in a large multicenter cohort. METHODS: This prospective cohort study was performed in 9 neonatal intensive care units. Infants born at a gestational age ≤30 weeks were included. Demographic and clinical data were collected daily until day 28 postnatally. Factors predictive of the development of NEC were identified using univariate and multivariable analyses in a 1: 5 matched case-control cohort. RESULTS: In total, 843 infants (56 NEC cases) were included in this study. In the case-control cohort, univariate analysis identified sepsis prior to the onset of NEC and formula feeding to be associated with an increased risk of developing NEC, whereas the administration of antibiotics directly postpartum was inversely associated with NEC. In a multivariable logistic regression model, enteral feeding type and the number of days parenterally fed remained statistically significantly associated with NEC, whereas the administration of antibiotics directly after birth was associated with a lower risk of developing NEC. CONCLUSIONS: Formula feeding and prolonged (duration of) parenteral feeding were associated with an increased risk of NEC. Contrary to expectations, the initiation of treatment with antibiotics within 24 h after birth was inversely associated with NEC.

NEOnatal Central-venous Line Observational study on Thrombosis (NEOCLOT): evaluation of a national guideline on management of neonatal catheter-related thrombosis.

BACKGROUND: In critically ill (preterm) neonates, central venous catheters (CVCs) are increasingly used for administration of medication or parenteral nutrition. A serious complication, however, is the development of catheter-related thrombosis (CVC-thrombosis), which may resolve by itself or cause severe complications. Due to lack of evidence, management of neonatal CVC-thrombosis varies among neonatal intensive care units (NICUs). In the Netherlands an expert-based national management guideline has been developed which is implemented in all 10 NICUs in 2014. METHODS: The NEOCLOT study is a multicentre prospective observational cohort study, including 150 preterm and term infants (0-6 months) admitted to one of the 10 NICUs, developing CVC-thrombosis. Patient characteristics, thrombosis characteristics, risk factors, treatment strategies and outcome measures will be collected in a web-based database. Management of CVC-thrombosis will be performed as recommended in the protocol. Violations of the protocol will be noted. Primary outcome measures are a composite efficacy outcome consisting of death due to CVC-thrombosis and recurrent thrombosis, and a safety outcome consisting of the incidence of major bleedings during therapy. Secondary outcomes include individual components of primary efficacy outcome, clinically relevant non-major and minor bleedings and the frequency of risk factors, protocol variations, residual thrombosis and post thrombotic syndrome. DISCUSSION: The NEOCLOT study will evaluate the efficacy and safety of the new, national, neonatal CVC-thrombosis guideline. Furthermore, risk factors as well as long-term consequences of CVC-thrombosis will be analysed. TRIAL REGISTRATION: Trial registration: Nederlands Trial Register NTR4336 . Registered 24 December 2013.

Cholesterol synthesis and de novo lipogenesis in premature infants determined by mass isotopomer distribution analysis.

Premature infants change from placental supply of mainly carbohydrates to an enteral supply of mainly lipids earlier in their development than term infants. The metabolic consequences hereof are not known but might have long-lasting health effects. In fact, knowledge of lipid metabolism in premature infants is very limited. We have quantified de novo lipogenesis and cholesterogenesis on d 3 of life in seven premature infants (birth weight, 1319 +/- 417 g; gestational age, 30 +/- 2 wk). For comparison, five healthy adult subjects were also studied. All subjects received a 12-h [1-(13)C] acetate infusion, followed by mass isotopomer distribution analysis (MIDA) on lipoprotein-palmitate and plasma unesterified cholesterol. The fraction of lipoprotein-palmitate synthesized at the end of the infusion period was 5.4 +/- 3.9% in infants, which was in the same range as found in adult subjects on a normal diet, suggesting that hepatic de novo lipogenesis is not a major contributor to fat accumulation in these premature neonates. The fractional contribution of newly synthesized cholesterol to plasma unesterified cholesterol was 7.4 +/- 1.3% after a 12-h infusion. The calculated rate of endogenous cholesterol synthesis was 31 +/- 7 mg/kg/d, a value approximately three times higher than that found in adult subjects (10 +/- 6 mg/kg/d). These results indicate that the cholesterol-synthesizing machinery is well developed in premature infants.