Management of Enteral Feeding and Application of Probiotics in Very Low Birth Weight Infants - A National Survey in German NICUs.

BACKGROUND: The advantage of breast milk feeding, and supplementation of probiotics is well known and proven. However, the lack of reliable amounts of colostrum and/or transient breast milk during the first few postnatal days might inhibit timely enteral nutrition. METHODS: The aim of this nationwide survey in German Level-1 neonatal intensive care units (NICUs) was to collect data regarding the management of feeding in the first days of life in very low birth weight infants (VLBWIs, birth weight<1500 g). In addition, we analyzed differences in the use of probiotics. An online survey was sent to all 163 Level-1 NICUs in Germany. RESULTS: 110/163 (67.5%) hospitals participated in our study. One-fifth of all participants used exclusively breast milk. The reported incidence of necrotizing enterocolitis (NEC) was lower in NICUs that exclusively used breast milk in VLBWIs (p=0.08). Two-thirds start enteral feeding independent of gestational age during the first 12 hours postnatally with either breast milk or formula. 80% of all participants checked gastric residuals routinely. The use of probiotics differs widely concerning duration and interruption during antibiotic therapy. CONCLUSION: The exclusive use of breast milk is associated with a lower incidence of NEC. The result of our survey emphasizes the paramount importance of nutrition with mother`s milk. In case of insufficient availability of mother`s milk, the use of human donor milk still appears to be superior to formula feeding. The implementation of human donor milk banks should therefore be promoted.

Possible role of SIRT1 and SIRT3 in post-translational modifications in human breast milk during the neonatal period.

We measured free and proteinic concentrations of native and modified amino acids from post-translational modifications (PTMs) and correlated them with the activity of SIRT1 and SIRT3 in the pellet and aqueous phases of human breast milk samples of ten lactating women during the neonatal period. SIRT1 and SIRT3 correlated directly with citrullination, asymmetric dimethylation and glycation of L-arginine, hydroxylation and glycation of L-lysine. SIRT1 and SIRT3 correlated inversely with the hydroxylation of L-proline. SIRT1 and SITR3 tended to correlate inversely with oxidative stress measured as malondialdehyde. Our study suggests that SIRT1 and SIRT3 may modulate PTMs in human breast milk cells.

Anatomic accuracy, physiologic characteristics, and fidelity of very low birth weight infant airway simulators.

BACKGROUND: Medical simulation training requires realistic simulators with high fidelity. This prospective multi-center study investigated anatomic precision, physiologic characteristics, and fidelity of four commercially available very low birth weight infant simulators. METHODS: We measured airway angles and distances in the simulators Premature AirwayPaul (SIMCharacters), Premature Anne (Laerdal Medical), Premie HAL S2209 (Gaumard), and Preterm Baby (Lifecast Body Simulation) using computer tomography and compared these to human cadavers of premature stillbirths. The simulators' physiologic characteristics were tested, and highly experienced experts rated their physical and functional fidelity. RESULTS: The airway angles corresponded to those of the reference cadavers in three simulators. The nasal inlet to glottis distance and the mouth aperture to glottis distance were only accurate in one simulator. All simulators had airway resistances up to 20 times higher and compliances up to 19 times lower than published reference values. Fifty-six highly experienced experts gave three simulators (Premature AirwayPaul: 5.1 ± 1.0, Premature Anne 4.9 ± 1.1, Preterm Baby 5.0 ± 1.0) good overall ratings and one simulator (Premie HAL S2209: 2.8 ± 1.0) an unfavorable rating. CONCLUSION: The simulator physiology deviated significantly from preterm infants' reference values concerning resistance and compliance, potentially promoting a wrong ventilation technique. IMPACT: Very low birth weight infant simulators showed physiological properties far deviating from corresponding patient reference values. Only ventilation with very high peak pressure achieved tidal volumes in the simulators, as aimed at in very low birth weight infants, potentially promoting a wrong ventilation technique. Compared to very low birth weight infant cadavers, most tested simulators accurately reproduced the anatomic angular relationships, but their airway dimensions were relatively too large for the represented body. The more professional experience the experts had, the lower they rated the very low birth weight infant simulators.

Management of prolonged meconium evacuation in preterm infants: A survey-based analysis in German Neonatal Intensive Care Units.

AIM: Due to the functional immaturity of bowel motility, a delayed passage frequently requires evacuation of meconium in preterm infants. Often rectal enemas and oral laxatives are used to manage these bowel evacuation disorders. METHODS: An online survey was sent to all 163 high-level Neonatal Intensive Care Units (NICUs) in Germany. The participants were queried on rectal enemas, laxative therapy and outcome incidences. RESULTS: A total of 110/163 (67.5%) hospitals participated in the study. 103/110 (93.6%) participating sites applied rectal enemas in cases of delayed meconium evacuation and 63/110 (57.3%) additionally used oral laxatives. In total, 15 different solutions and 7 different application systems were used for rectal instillation. Preterm infants receiving enemas within the first 48 hours after birth were found to have a significantly lower incidence of FIP (p = 0.006). Altogether 8 different oral laxatives were utilised. CONCLUSION: Therapeutic approaches to the management of prolongated meconium evacuation differ widely among German NICUs. Our survey highlights the diversity of applied substances, means of application and differences in duration and frequency of interventions. Macrogol was commonly used in neonates as an oral laxative despite the lack of approval from the manufacturer.

Hydrolytic biotransformation of the bumetanide ester prodrug DIMAEB to bumetanide by esterases in neonatal human and rat serum and neonatal rat brain-A new treatment strategy for neonatal seizures?

OBJECTIVES: The loop diuretic bumetanide has been proposed previously as an adjunct treatment for neonatal seizures because bumetanide is thought to potentiate the action of γ-aminobutyric acid (GABA)ergic drugs such as phenobarbital by preventing abnormal intracellular accumulation of chloride and the subsequent "GABA shift." However, a clinical trial in neonates failed to demonstrate such a synergistic effect of bumetanide, most likely because this drug only poorly penetrates into the brain. This prompted us to develop lipophilic prodrugs of bumetanide, such as the N,N-dimethylaminoethyl ester of bumetanide (DIMAEB), which rapidly enter the brain where they are hydrolyzed by esterases to the parent compound, as demonstrated previously by us in adult rodents. However, it is not known whether esterase activity in neonates is sufficient to hydrolyze ester prodrugs such as DIMAEB. METHODS: In the present study, we examined whether esterases in neonatal serum of healthy term infants are capable of hydrolyzing DIMAEB to bumetanide and whether this activity is different from the serum of adults. Furthermore, to extrapolate the findings to brain tissue, we performed experiments with brain tissue and serum of neonatal and adult rats. RESULTS: Serum from 1- to 2-day-old infants was capable of hydrolyzing DIMAEB to bumetanide at a rate similar to that of serum from adult individuals. Similarly, serum and brain tissue of neonatal rats rapidly hydrolyzed DIMAEB to bumetanide. SIGNIFICANCE: These data provide a prerequisite for further evaluating the potential of bumetanide prodrugs as add-on therapy to phenobarbital and other antiseizure drugs as a new strategy for improving pharmacotherapy of neonatal seizures.

Necrotizing enterocolitis and high intestinal iron uptake due to genetic variants.

BackgroundIntestinal iron is a nutritional compound, which is essential for enteric microbiota. We evaluated the hypothesis that polymorphisms, which are known modifiers of intestinal iron uptake in adults, are associated with necrotizing enterocolitis (NEC) in preterm infants.MethodsPreterm infants (birth weight below 1,500 g) were studied. Single-nucleotide polymorphisms with known effects on serum iron levels (rs1800562, rs1799945, and rs855791) were determined using PCR. The effects of polymorphisms on NEC surgery were tested by Mendelian randomization. Outcome data were compared with χ2-test, Fisher's exact test, t-test, and Cochran-Armitage test for trend and multiple logistic regression analysis.ResultsComplete genotyping data were available for 11,166 infants. High serum iron levels due to rs855791 genotype were associated with a significantly reduced risk of NEC surgery (odds ratio (OR) 0.265; 95% confidence interval (CI) 0.11-0.65; adjusted P=0.011). Carriers of the rs855791 A-allele not receiving prophylactic probiotics had a higher risk of NEC surgery (OR 1.12, 95% CI 1.08-1.70, nominal P=0.002). Prophylactic treatment with probiotics was associated with a reduced risk of NEC surgery in carriers of the rs855791 A-Allele. No differences were found with regard to other short- or long-term outcome data.ConclusionPolymorphisms inducing lower intestinal iron uptake like the rs855791 A-allele might be an underestimated risk factor for NEC.

Comprehensive analysis of the L-arginine/L-homoarginine/nitric oxide pathway in preterm neonates: potential roles for homoarginine and asymmetric dimethylarginine in foetal growth.

L-Arginine (Arg) and L-homoarginine (hArg) are precursors of nitric oxide (NO), a signalling molecule with multiple important roles in human organism. In the circulation of adults, high concentrations of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) and low concentrations of hArg emerged as cardiovascular risk factors. Yet, the importance of the Arg/hArg/NO pathway, especially of hArg and ADMA, in preterm neonates is little understood. We comprehensively investigated the Arg/hArg/NO pathway in 106 healthy preterm infants (51 boys, 55 girls) aged between 23 + 6 and 36 + 1 gestational weeks. Babies were divided into two groups: group I consisted of 31 babies with a gestational age of 23 + 6 - 29 + 6 weeks; group II comprised 75 children with a gestational age of 30 + 0 - 36 + 1 weeks. Plasma and urine concentrations of ADMA, SDMA, hArg, Arg, dimethylamine (DMA) which is the major urinary ADMA metabolite, as well as of nitrite and nitrate, the major NO metabolites, were determined by GC-MS and GC-MS/MS methods. ADMA and hArg plasma levels, but not the hArg/ADMA molar ratio, were significantly higher in group II than in group I: 895 ± 166 nM vs. 774 ± 164 nM (P = 0.001) for ADMA and 0.56 ± 0.04 µM vs. 0.48 ± 0.08 µM (P = 0.010) for hArg. There was no statistical difference between the groups with regard to urinary ADMA (12.2 ± 4.6 vs 12.8 ± 3.6 µmol/mmol creatinine; P = 0.61) and urinary SDMA. Urinary hArg, ADMA, SDMA correlated tightly with each other. Urinary excretion of DMA was slightly higher in group I compared to group II: 282 ± 44 vs. 247 ± 35 µmol/mmol creatinine (P = 0.004). The DMA/ADMA molar ratio in urine was tendentiously higher in neonates of group I compared to group II: 27 ± 13 vs. 20 ± 5 (P = 0.065). There were no differences between the groups with respect to Arg in plasma and to nitrite and nitrate in plasma and urine. In preterm neonates, ADMA and hArg biosynthesis increases with gestational age without remarkable changes in the hArg/ADMA ratio or NO biosynthesis. Our study suggests that ADMA and hArg are involved in foetal growth.

Parents' Prenatal, Onward, and Postdischarge Experiences in Case of Extreme Prematurity: When to Set the Course for a Trusting Relationship between Parents and Medical Staff.

OBJECTIVES: This article aims to investigate the impact of prenatal counseling on subsequent parents' experiences during in-patient care of their infant(s) and whether feelings of parents with deceased infants are different in principle. STUDY DESIGN: A questionnaire was sent to 99 families with a child born less than 26 weeks' gestational age at Medical School Hanover 2000-2008. Statistical analysis was performed using Fisher exact t test and chi-square tests in IBM SPSS Statistics for Windows, Version 20.0. RESULTS: Response rate was 73%. Parents with solely surviving children significantly more often answered the questionnaire (p < 0.001). Regardless of the infants' outcome, parents who felt well involved in prenatal decision making significantly more often also felt adequately involved in postnatal treatment of their child (p = 0.006) and would again decide on life-sustaining treatment of an extremely premature infant (p = 0.007). Furthermore, they were significantly less dubious about the treatment of their baby (p = 0.013) than parents not feeling sufficiently involved. Significantly fewer parents with only surviving child(ren) decided to have another baby later than parents with at least one deceased child (p = 0.004). CONCLUSION: This study stresses the impact of prenatal counseling and shows that, regardless of outcome, the course of a trusting relationship between parents and health care team is already set before birth.

Impact of Introducing PROMPT on Permanent Brachial Plexus Injury and Tears III°/IV° in Shoulder Dystocia: The Hanover Cohort Study.

Objective: To test the hypothesis that PROMPT reduces permanent brachial plexus palsy and perineal tears. Design: A prospective/retrospective cohort study. Setting. Hanover Medical School, Germany. Population/Sample. A self-selected population. Methods: The training period is from November 9th, 2017, until December 31st, 2019; control: January 1st, 2004, until November 8th, 2017. Main Outcome Measures. Shoulder dystocia, nonpermanent and permanent brachial plexus injuries (BPIs), perineal tears III°/IV°, manual manoeuvres, and asphyxia. Results: There was a total of 22,640 births, and shoulder dystocia increased from 48/18,031 (0.27%) to 23/4,609 (0.50%) ((p=0.017), OR: 1.88, 95% CI: (1.14; 3.09)), whereas BPIs decreased from 7/48 (14.6%) to 1/23 (4.3%) (p=0.261). There was 1/7 (14.2%) of permanent BPI before and 0/1 (0%) case after. Perinatal asphyxia increased from 3/48 (6.3%) to 4/23 (17.4%) (p=0.23). However, adverse outcomes after one year were zero. McRoberts' manoeuvre increased from 37/48 (77.1%) to 23/23 (100%) ((p=0.013), OR: 1.62, 95% CI: (1.33; 1.98)), and internal rotation manoeuvres and manual extraction of the posterior arm from 6/48 (12.5%) to 5/23 (21.7%) (p=0.319). Episiotomies decreased from 5,267/18,031 (29.2%) to 836/4,609 (18.1%) ((p < 0.001), OR: 0.54, 95% CI: (0.49, 0.58)), whereas perineal tears III°/IV° associated with shoulder dystocia increased from 1/48 (2.1%) to 1/23 (4.8%) (p=0.546). Vaginal operative deliveries remained constant (6.5% vs. 7%). Conclusions: PROMPT significantly improves the management of shoulder dystocia and decreases permanent brachial plexus injuries but not perineal tears III°/IV°.

Growth and Duration of Inflammation Determine Short- and Long-Term Outcome in Very-Low-Birth-Weight Infants Requiring Abdominal Surgery.

Necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP) and meconium-related ileus (MI) requiring surgical intervention are associated with a high risk of severe short- and long-term complications in very-low-birth-weight (VLBW) infants including poor growth, cholestasis and neurodevelopmental impairment. This retrospective study aimed to identify risk factors for such complications in a cohort of 55 VLBW preterm infants requiring surgery with enterostomy creation due to NEC, SIP or MI. Long-term follow-up was available for 43 (78%) infants. Multiple regression analyses revealed that the duration of inflammation and longitudinal growth determined the risk of cholestasis and neurodevelopmental outcome at 2 years corrected age independent of the aetiology of the intestinal complication. Direct bilirubin increased by 4.9 µmol/L (95%CI 0.26-9.5), 1.4 µmol/L (95%CI 0.6-2.2) and 0.8 µmol/L (95%CI 0.22-1.13) with every day of elevated (Interleukin-6) IL-6, (C-reactive protein) CrP and parenteral nutrition. The mental development index at 2 years corrected age decreased by 3.8 (95%CI -7.3--0.36), 0.4 (95%CI 0.07-0.80) and 0.3 (95%CI 0.08-0.57) with every day of elevated IL-6 and every 1 point decrease in weight percentile at discharge and 2 years. These data stress the importance of optimal timing for the initial surgery in order to prevent prolonged inflammation and an early reversal of the enterostomy in case of poor growth or insufficient enteral nutrition.

Procalcitonin and valuable clinical symptoms in the early detection of neonatal late-onset bacterial infection.

AIM: To evaluate which clinical symptoms indicate proven neonatal bacterial infection (NBI) and whether measuring procalcitonin aside from C-reactive protein and interleukin 6 improves sensitivity and specificity in diagnosis. METHODS: In a prospective observational study, clinical symptoms and procalcitonin, C-reactive protein and interleukin 6 were simultaneously determined from the 4th day of life in 170 preterm and term neonates at the first time of suspicion of NBI. Proven NBI was defined as a positive culture of otherwise sterile body fluids or radiologically verified pneumonia in combination with elevated inflammatory markers. RESULTS: Fifty-eight (34%) patients were diagnosed with proven late-onset NBI. In case of proven NBI, odds ratio and 95% confidence intervals were 2.64 (1.06-6.54) for arterial hypotension, 5.16 (2.55-10.43) for feeding intolerance and 9.18 (4.10-20.59) for prolonged capillary refill. Sensitivity of combined determination of C-reactive protein (>10 mg/L) and interleukin 6 (>100 pg/mL) was 91.4%, specificity 80.4%, positive predictive value 70.7% and negative predictive value 94.7%. The additional determination of procalcitonin (>0.7 ng/mL) resulted in 98.3%, 65.2%, 58.8% and 98.6%, respectively. CONCLUSION: Arterial hypotension, feeding intolerance and especially prolonged capillary refill indicate proven neonatal late-onset bacterial infection, even at the time of first suspicion. Additional measurement of procalcitonin does indeed improve sensitivity to nearly 100%, but is linked to a decline in specificity. Nevertheless, in the high-risk neonatal population, additional procalcitonin measurement can be recommended because all infants with NBI have to be identified.

Dead space washout by intentional leakage flow during conventional ventilation of premature infants-an experimental study.

OBJECTIVE: Invasive mechanical ventilation poses a strong risk factor for the development of chronic lung disease in preterm infants. A reduction of the dead space as part of the total breathing volume would reduce the ventilation effort and thereby lower the risk of ventilator-induced lung injuries. In this experimental study, we compared the efficacy of mechanical dead space washout via uncontrolled and controlled leakage flow in their ability to eliminate CO2 during conventional ventilation in preterm infants. METHODS: Three frequently used neonatal ventilators, operating under standard conventional ventilating parameters, were individually connected to a test lung. To maintain a constant physiological end-expiratory pCO2 level during ventilation, the test lung was continuously flooded with CO2 . A side port in the area of the connector between the endotracheal tube and the flow sensor allowed breathing gas to escape passively or in a second experimental setup, regulated by a pump. Measurements of end-expiratory pCO2 were taken in both experiments and compared to end-expiratory pCO2 levels of ventilation without active dead space leakage. RESULTS: Following dead space washout, a significant reduction of end-expiratory pCO2 was attained. Under conditions of uncontrolled leakage, the mean decrease was 14.1% while controlled leakage saw a mean reduction of 16.1%. CONCLUSION: Washout of dead space by way of leakage flow is an effective method to reduce end-expiratory pCO2 . Both controlled and uncontrolled leakage provide comparable results, but precise regulation of leakage allows for a more stable ventilation by preventing uncontrolled loss of tidal volume during inspiration.

[Epidemiology and treatment of retinopathy of prematurity. The Hannover data in the Retina.net ROP registry from 2001-2017]. / Epidemiologie und Therapie der behandlungsbedürftigen Frühgeborenenretinopathie. Die Hannoveraner Daten im Retina.net ROP-Register von 2001 bis 2017.

BACKGROUND: The Retina.net ROP registry documents data of preterm infants developing stages of retinopathy of prematurity (ROP) that need ROP treatment. The aim of this analysis was to investigate data regarding epidemiology, therapy and changes over time (15 years) in a single participating center (Hannover Medical School, MHH). METHODS: Analysis of data of infants treated for ROP at a single center over time (birth 2001-2016, ROP treatment in 2002-2017). RESULTS: Overall, 65 infants were treated (23 female). In 11 infants (16.9%) ROP screening was conducted externally and infants were transferred to the MHH for ROP treatment. Between 2006 and 2016, incidence of ROP requiring treatment among infants screened for the development of ROP was 4.1%. Mean gestational age was 25.7 weeks (standard deviation, SD 1.8), mean birth weight 763 g (SD 235), postmenstrual age at treatment 38.2 weeks (SD 3.2), postnatal age 12.4 weeks (SD 3.2). There was no significant change in parameters over time. ROP zone II, stage 3+ was most frequently treated (57 eyes of 31 infants). 58 infants were treated with laser (114 eyes), 7 infants were treated with anti-VEGF (bevacizumab, bilateral, 14 eyes) from 2014 onwards. Retreatment due to recurrence of ROP was necessary in one infant after initial laser coagulation. Infants with ROP requiring treatment often presented with neonatal comorbidities, ventilation in more than 90%, bronchopulmonary dysplasia, and received transfusions. CONCLUSION: This is the first monocentric analysis over 15 years originating from the Retina.net ROP registry. In this cohort we see a change in ROP therapy from laser coagulation to anti-VEGF (bevacizumab) from 2014 onwards, demographic data and treatment parameters remained relatively stable over time.

Epidemiology and infection control of Methicillin-resistant Staphylococcus aureus in a German tertiary neonatal intensive and intermediate care unit: A retrospective study (2013-2020).

In preterm and term infants who require intermediate or intensive care Methicillin-resistant Staphylococcus aureus (MRSA) infection can lead to significant morbidity. In this study MRSA colonization and infection were assessed in a mixed tertiary neonatal intensive and intermediate care unit in Germany over an 8-year period (2013-2020). We investigated patient-related factors, associated with nosocomial MRSA acquisition, and we discuss our infection control concept for MRSA. Of 3488 patients treated during the study period, 24 were MRSA positive patients, corresponding to 26 patient hospital stays. The incidence was 0.7 MRSA patients per 100 patients. The incidence density was 0.4 MRSA patient hospital stays per 1000 patient days. Twelve patients (50%) acquired MRSA in the hospital. One patient developed a hospital acquired MRSA bloodstream infection 9 days after birth (i.e., 0.03% of all patients on the ward during the study period). A total of 122 patients had to be screened to detect one MRSA positive patient. In a logistic regression model, the use of 3rd generation intravenous cephalosporin (cefotaxim) was associated with nosocomial MRSA acquisition compared with matched control patients who did not acquire MRSA. In sum, the burden of MRSA colonization and infection in the ward was low during the study period. A comprehensive infection control concept that included microbiologic colonization screening, prospective infection surveillance together with isolation and emphasis on basic hygiene measures is essential to handle MRSA in this specialized setting.

Cardiorespiratory Events Following the Second Routine Immunization in Preterm Infants: Risk Assessment and Monitoring Recommendations.

Due to frequent cardiorespiratory events (CREs) in response to the first routine immunization (rIM), current guidelines recommend readmitting and monitoring extremely preterm infants after the second rIM, though evidence on CREs in response to the second rIM is weak. In a prospective observational study, preterm infants with an increase in CREs after the first rIM were monitored for CREs before and after the second rIM. Seventy-one infants with a median gestational age of 26.4 weeks and a median weight of 820 g at birth were investigated at a median postnatal age of 94 days. All but seven infants showed an increase in CREs after the second rIM. The frequency of hypoxemias (p < 0.0001), apneas (p = 0.0003) and cardiorespiratory events requiring tactile stimulation (CRE-ts) (p = 0.0034) increased significantly. The 25 infants (35%) presenting with CRE-ts were significantly more likely to have been continuously hospitalized since birth (p = 0.001) and to receive analeptic therapy at the first rIM (p = 0.002) or some kind of respiratory support at the first (p = 0.005) and second rIM (p < 0.0001). At a postmenstruational age of 43.5 weeks, CRE-ts ceased. Our data support the recommendation to monitor infants who fulfil the above-mentioned criteria during the second rIM up to a postmenstruational age of 44 weeks.

Analysis of Sirtuin 1 and Sirtuin 3 at Enzyme and Protein Levels in Human Breast Milk during the Neonatal Period.

Breast feeding is regarded as the preferred nutrition modality for children during the first few months of life. It not only furthers growth and development but also is supposed to impact later life. The first 1000 days are regarded as a critical window for development, even beyond infancy. The physiological basis underlying this beneficial effect is not clear. Sirtuins are important regulatory proteins of metabolism and are supposed to play a critical role in ageing and longevity as well as in diseases. In the present study, we developed novel methods to assay sirtuin 1 and sirtuin 3 at enzyme activity (via fluorometry) and protein levels (by Western blot) in the aqueous phase and in the cell pellet of human breast milk and assessed the impact of ongoing lactation during the neonatal period. Sirtuin activities in the aqueous phase were negatively correlated with the duration of lactation in the neonatal period. There was no correlation of sirtuin activities in the cell pellet with the duration of lactation. The amounts of sirtuin 1 and sirtuin 3 measured by Western blot were negatively correlated with the lactation period.

Detection of Serratia marcescens in neonatal intensive care units requires a rapid and comprehensive infection control response starting with the very first case.

Background: Serratia marcescens is a well-known and challenging pathogen in neonatal intensive care units. It is responsible for severe infections and can cause nosocomial outbreaks. Methods: We present the infection control response to a Serratia marcescens cluster which occurred in a tertiary neonatal intensive care unit. Results and conclusions: The presented comprehensive and decisive hygiene management response starting with the very first case aims especially at early detection and immediate interruption of nosocomial transmission. Frequent and sensitive microbiological screening, rigorous spatial isolation of colonized infants, and reinforcing adherence to hand hygiene are essential in this response, which comprises eight measures. It prevented a full-blown outbreak.

Detection of Breathing Movements of Preterm Neonates by Recording Their Abdominal Movements with a Time-of-Flight Camera.

In order to deliver an aerosolized drug in a breath-triggered manner, the initiation of the patient's inspiration needs to be detected. The best-known systems monitoring breathing patterns are based on flow sensors. However, due to their large dead space volume, flow sensors are not advisable for monitoring the breathing of (preterm) neonates. Newly-developed respiratory sensors, especially when contact-based (invasive), can be tested on (preterm) neonates only with great effort due to clinical and ethical hurdles. Therefore, a physiological model is highly desirable to validate these sensors. For developing such a system, abdominal movement data of (preterm) neonates are required. We recorded time sequences of five preterm neonates' abdominal movements with a time-of-flight camera and successfully extracted various breathing patterns and respiratory parameters. Several characteristic breathing patterns, such as forced breathing, sighing, apnea and crying, were identified from the movement data. Respiratory parameters, such as duration of inspiration and expiration, as well as respiratory rate and breathing movement over time, were also extracted. This work demonstrated that respiratory parameters of preterm neonates can be determined without contact. Therefore, such a system can be used for breathing detection to provide a trigger signal for breath-triggered drug release systems. Furthermore, based on the recorded data, a physiological abdominal movement model of preterm neonates can now be developed.