Prospective surveillance of bacterial colonization and primary sepsis: findings of a tertiary neonatal intensive and intermediate care unit.

BACKGROUND: Preterm infants and critically ill neonates are predisposed to nosocomial infections as sepsis. Moreover, these infants acquire commensal bacteria, which might become potentially harmful. On-ward transmission of these bacteria can cause outbreaks. AIM: To report the findings of a prospective surveillance of bacterial colonization and primary sepsis in preterm infants and neonates. METHODS: The results of the surveillance of bacterial colonization of the gut and the respiratory tract, targeting meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and Gram-negative bacteria from November 2016 to March 2018 were analysed. Bacterial colonization was compared to surveillance of sepsis. FINDINGS: Six-hundred and seventy-one patients were admitted and 87.0 % (N=584) of the patients were screened; 48.3% (N=282) of the patients screened were colonized with at least one of the bacteria included in the screening; 26.2% of them (N=74) had multi-drug-resistant strains. A total of 534 bacterial isolates were found. The most frequently found species were Escherichia coli, Enterobacter cloacae, Klebsiella oxytoca and Klebsiella pneumoniae. Three MRSA but no VRE were detected. The surveillance detected a K. pneumoniae cluster involving nine patients. There were 23 blood-culture-confirmed sepsis episodes; 60.9% (N=14) were caused by staphylococci. Gram-negative bacteria (one Klebsiella aerogenes and two E. cloacae) caused three sepsis episodes which were preceded by colonization with the respective isolates. CONCLUSIONS: Surveillance of colonization provided a comprehensive overview of species and antibiotic resistance patterns. It allowed early detection of a colonization cluster. Knowledge of colonization and surveillance of sepsis is useful for guiding infection control measures and antibiotic treatment.

Heart rate, respiratory rate, apnoeas and peripheral arterial oxygen saturation in healthy term neonates during quiet sleep.

AIM: This study compiled percentiles for cardiorespiratory parameters in healthy term neonates during quiet sleep. METHODS: We enrolled 215 healthy term neonates born at Hannover Medical School, Germany, between October 2011 and March 2013. They were prospectively observed on the maternity ward at a median age of two days using six-hour recordings of pulse oximeter plethysmography, oxygen saturation, thoracic breathing movements and electrocardiogram during sleep in a supine position. We examined their heart rate, respiratory rate and oxygen saturation during quiet sleep, plus bradycardias, apnoeas lasting at least four-seconds and desaturations below 85%. RESULTS: The 3rd, 50th and 97th percentiles were calculated as follows: heart rate 87, 112 and 133 beats per minute, respiratory rate 32, 44 and 57 per minute and oxygen saturation 94, 98 and 100%. Desaturations, apnoeas and bradycardias below 80 beats per minute were common and recorded in 54%, 98% and 30% of participants. In contrast, only 7% experienced bradycardias of less than two-thirds of the baseline heart rate and 5% experienced apnoeas exceeding 15 seconds. CONCLUSION: Our results will facilitate the evidence-based valuation of cardiorespiratory parameters in term neonates and help validate the significance of cardiorespiratory events in preterm infants at discharge.

Pregnancy risk factors for very premature delivery: what role do hypertension, obesity and diabetes play?

PURPOSE: Very premature delivery is a major cause of infant morbidity and mortality. Obesity, diabetes and pregnancy hypertension are known risk factors for pregnancy complications. The study aimed to scrutinize differences of pregnancy complications in a cohort of very premature deliveries compared to a national group. METHODS: In a multicenter study performed between January 2009 and December 2010 including 1,577 very low birth weight (VLBW) infants, we compared parental reported pregnancy problems of VLBW infants with a national cohort (KIGGS). We compared reported pregnancy complications to reasons for premature delivery and neonatal outcome within the group of VLBW infants. RESULTS: While parents of the national cohort reported pregnancy-induced hypertension in 8 %, parents of VLBW infants reported this complication more frequently (27 %). Mothers of the national cohort were significantly younger (1 year), suffered less from obesity, anaemia, diabetes. Regression analysis showed that hypertension (OR = 5.11) and advanced maternal age (OR = 1.03) increased the risk for premature birth. Women with hypertension were likely to experience a clinically indicated premature delivery, had more VLBW infants with a moderate growth restriction, but less multiples and their infants had less intraventricular haemorrhages grade 3 or 4. Otherwise, neonatal outcome was correlated with gestational age but not with the pregnancy complications diabetes, hypertension or obesity. CONCLUSION: Premature birth seems to be correlated to gestational hypertension and associated problems in about » of VLBW infants. Further studies should focus on preventing and treating gestational hypertension to avoid premature delivery and associated neonatal morbidity.

Major contributors to hospital mortality in very-low-birth-weight infants: data of the birth year 2010 cohort of the German Neonatal Network.

The German Neonatal Network (GNN) is a prospective cohort study with the focus on long term development of very-low-birth-weight infants. It was the aim of this study to determine detailed information on causes of mortality in the GNN birth cohort 2010.Major contributors to hospital mortality were recorded by the attending neonatologists for the cohort of very-low-birth-weight (VLBW) infants born in centres of the German Neonatal Network (GNN) in 2010. The data quality was approved by on-site monitoring.2 221 VLBW infants were born in GNN centres in 2010, and death occurred in 221 infants. Male infants carried a higher risk than females (58.8% males among non-survivors vs. 51.7% among survivors, p=0.047). In 11 infants, the major contributor to death was not determined by the attending neonatologist. In 25 infants born at the limit of viability, comfort palliative care was primarily initiated and 14 infants had lethal malformations. The majority of non-survivors suffered from inflammatory diseases including sepsis- or necrotizing enterocolitis (NEC)-associated death (n=56). Respiratory pathology was a major contributor to death in 65 infants including 11 infants who died from pulmonary haemorrhage.Potentially preventable complications of preterm birth such as sepsis, NEC and pulmonary haemorrhage predominate the major contributors to mortality in the GNN 2010 cohort. In order to decrease the rate of these associated deaths, future trials should focus on prophylaxis and therapy optimization strategies for these outcomes.

Portal venous gas detected by ultrasound differentiates surgical NEC from other acquired neonatal intestinal diseases.

BACKGROUND: The definite clinical diagnosis of acquired neonatal intestinal diseases (ANID) is a challenge, usually met by applying Bell's or, more recently, Gordon's classification. Both classifications incorporate radiological pneumatosis intestinalis (PI) as a cornerstone of the NEC diagnosis. However, PI may be absent or difficult to identify by abdominal X-ray. Portal venous gas detected by ultrasound (PVG-US) has been proposed as another characteristic of NEC, but its incidence in other entities of ANID remains unknown. OBJECTIVE: To determine whether PVG-US and Gordon's classification can help to differentiate between NEC and other ANID, especially SIP. METHODS: Retrospective analysis of the data of 83 infants, who underwent laparotomy for a clinical diagnosis of ANID was performed. The results of PVG-US and other markers of ANID were compared with the operative result, defined as the gold standard for diagnosis. RESULTS: The NEC diagnosis was confirmed in 28/83 infants and PVG-US was present in 23 (82%) of those patients prior to operation. PVG-US was detected in 2 patients without NEC (one volvulus, one SIP), resulting in an 82% sensitivity and a 96% specificity. The sensitivity and specificity of radiological PI for patients with NEC was lower (75 and 91%), but the combination of PVG-US and radiological PI increased the sensitivity for NEC detection to 89%. Gordon's classification had a sensitivity of 93% and a specificity of 92% for NEC diagnosis. CONCLUSION: Screening for PVG-US and Gordon's classification are valid tools to differentiate between NEC and other ANID including SIP. Although an effect of these proposed diagnostic tools on treatment regimen and operative management has yet to be verified, the improvement in diagnosing ANID is certainly valuable.

Prenatal benzoate treatment in urea cycle defects.

OBJECTIVE: In patients with severe urea cycle defects (UCD) metabolic decompensation with hyperammonaemia typically occurs during the first days of life resulting in severe neurological damage or death. Benzoate can eliminate nitrogen independent of the urea cycle. Usually, benzoate is started soon after birth, but prenatal administration might improve metabolic stability. DESIGN: Two fetuses with a prenatal diagnosis of UCD (female: citrullinaemia; male: ornithine transcarbamylase deficiency) were loaded with benzoate prenatally via the placenta by infusing their mothers with benzoate. Benzoate concentrations were measured in umbilical cord blood and the blood of the mothers and their newborns. RESULTS: Therapeutic concentrations of benzoate were found in umbilical cord blood and in the children's blood. Thus, benzoate transfer across the placenta was demonstrated. Plasma ammonia and glutamine levels in the postnatal period were within the normal range. CONCLUSIONS: Benzoate infusion of the mother shortly before birth is safe and results in therapeutic levels of benzoate in umbilical cord blood.

Developmental changes of oxalate excretion in enterally fed preterm infants.

To further substantiate gestational age-related changes in oxalate excretion, we studied urinary oxalate excretion in 66 preterm infants born at 23.4-34.7 weeks of gestation. Spot urine of 66 preterm infants was analysed by ion chromatography as soon as they were completely orally fed with enriched breast milk and/or special preterm milk formula (days 7 to 57 of postnatal life). Infants with evidence of renal, gastrointestinal, muscular or metabolic disease were not included. Newborns on parenteral nutrition were excluded. Oxalate/creatinine ratios (Ox/Cr) decreased with gestational age (three age groups: group 1, 23 0/7-28 0/7; group 2, 28 1/7-32 0/7; and group 3, 32 1/7-35 0/7 weeks of gestation). The mean Ox/Cr was highest in group 1 (398.2 mmol/mol +/- 116.8; n = 21). Differences between groups 1 + 3 were statistically significant; p = 0.001; those between groups 1 + 2 and between groups 2 + 3 were not. Ox/Cr correlated inversely with gestational and maturational age (r = -0.41, p = 0.001; r = -0.33, p = 0.007) and positively with postnatal age (r = 0.32, p = 0.008). It correlated inversely with birth weight as well as actual weight at sample collection (r = -0.46 and -0.44, p < 0.001). Ox/Cr was significantly linked to energy and carbohydrate intake (r = 0.3 and 0.4, p = 0.03 and 0.001). These results were independent of sex. In the present study we show that urinary oxalate excretion in preterm infants depends on gestational age.

Evaluation of portal venous gas detected by ultrasound examination for diagnosis of necrotising enterocolitis.

BACKGROUND: Early diagnosis of necrotising enterocolitis (NEC) is difficult but essential for timely therapy. The diagnostic hallmarks and specific radiological signs for NEC are pneumatosis intestinalis (PI) and portal venous gas (PVG), but PVG in abdominal ultrasound (PVG-US) has been proposed as an effective tool in the diagnosis of NEC as well. OBJECTIVE: To prospectively assess the value of PVG-US for the diagnosis of NEC. METHODS: The study screened 352 neonates for PVG-US (n = 796 routine examinations) and performed 48 additional screenings in 34/352 neonates with suspected (stage I, n = 28) or definite NEC (stage > or =II, n = 20). Sensitivity and specificity of PVG-US for detection of NEC were computed by using NEC stage > or =II as the reference standard. RESULTS: PVG-US was only present in cases of suspected or definite NEC. The study observed PVG-US in 4/28 NEC stage I and in 9/20 NEC stage > or =II episodes corresponding to a 86% specificity and a 45% sensitivity for diagnosis of NEC stage > or =II. However, 7/20 patients with NEC stage > or =II showed intraoperative findings other than NEC and another 3/20 infants presented with radiologically unspecific intestinal dilatation. None of these 10 infants had detectable PVG-US. Thus, with application of specific radiological signs the sensitivity of PVG-US for diagnosis of NEC stage > or =II increased to 90%. CONCLUSION: Screening for PVG-US is a useful, easy and quick bedside test with a high specificity for NEC. Moreover, these results question the value of the Walsh criteria in the diagnosis of NEC.

Therapeutic lung puncture for diffuse unilateral pulmonary interstitial emphysema in preterm infants.

BACKGROUND: Pulmonary interstitial emphysema (PIE) represents a severe complication of respiratory distress syndrome and can dramatically impair the ventilation of premature infants. OBJECTIVES: We report three mechanically ventilated premature infants with severe diffuse, unilateral PIE not responding to conventional treatment, whose clinical condition improved dramatically following an ipsilateral pneumothorax. RESULTS: In the first two patients, the pneumothoraces occurred spontaneously. In the third patient, the ipsilateral lung was punctured with a pigtail catheter to create and - subsequently drain - a pneumothorax. Thereafter, mechanical ventilation could be discontinued within 3 days in all infants. CONCLUSIONS: Lung puncture with consecutive tension release of the overinflated lung by drainage is a therapeutic option for premature infants suffering from diffuse PIE in whom other conservative measures fail. It may be considered before proceeding to surgical measures in order to preserve potentially functional lung tissue.

Detection of hyperoxaemia in neonates: data from three new pulse oximeters.

AIM: To determine the sensitivity and specificity of three newly developed pulse oximeters in the detection of hyperoxaemia, defined as an arterial partial pressure of oxygen (PaO(2)) of > 80 mm Hg. METHODS: SpO(2) readings from three oximeters (Agilent Viridia (AgV), Masimo SET (MaS), Nellcor Oxismart (NeO)) were documented in 56 infants (median gestational age at birth 35.5 weeks, range 24-41) whenever an arterial blood gas was taken for clinical purposes. Blood samples were analysed within one minute in a Radiometer ABL 505 blood gas analyser and OSM3 co-oximeter. RESULTS: Between 280 and 291 blood gases were analysed for each instrument; 105-112 showed a PaO(2) > 80 mm Hg. At an upper alarm limit of 95%, the three instruments detected hyperoxaemia with 93-95% sensitivity. Specificity at this alarm level ranged from 26 to 45%. The mean (SD) difference between arterial oxygen saturation and SpO(2) (bias) was -0.25 (2.5)% for AgV, -0.06 (2.5)% for MaS, and -0.91 (2.6)% for NeO (p < 0.01, NeO v AgV and MaS). CONCLUSION: These instruments detected hyperoxaemia with sufficient sensitivity at an upper alarm limit of 95%, but showed differences in their specificity, which was probably related to differences in measurement bias.

Patient with trisomy 6 mosaicism.

Trisomy 6 and trisomy 6 mosaicism were found in chorionic villi cell culture and short term incubation in a prenatal diagnosis at 12 weeks of gestation in a pregnancy with a growth retarded fetus showing nuchal translucency. The child was born in the 25th gestational week with a number of malformations including heart defects, deep-set ears, cleft right hand, cutaneous syndactylies, and overlapping toes of irregular shape and length. Trisomy 6 was not found in peripheral blood lymphocytes but was confirmed in umbilical cord fibroblasts. Currently, at the age of 2-3/4 years, the development of the child is relatively normal despite considerable growth delay. At the age of two years, she developed a papular erythema clinically suggestive of epidermal nevi. Cytogenetic analysis of fibroblast cultures derived from skin from a right hand finger and the inguinal area confirmed the presence of a trisomy 6 mosaicism. This is the first observation of a liveborn with trisomy 6 mosaicism.

Skin-to-skin (kangaroo) care, respiratory control, and thermoregulation.

AIM: To demonstrate that skin-to-skin care (SSC) has no detrimental effects on the frequency of episodes of bradycardia and/or hypoxemia. METHODS: Twenty-two spontaneously breathing preterm infants (median gestational age at birth, 29 weeks [range, 24-31 weeks]; age at study, 26 days [range, 7-72 days]; weight at study, 1310 g [range, 725-1890 g]) had three 2-hour recordings of breathing movements, nasal airflow, heart rate, and oxygen saturation as measured by pulse oximetry (SpO(2)) before, during, and after SSC. Rectal temperature was obtained every 2 hours. Recordings were analyzed for baseline heart and respiratory rates, bradycardia (heart rate < two thirds of baseline), and hypoxemia (SpO(2) < or =80%), as well as for breathing pattern (regular vs non-regular). RESULTS: Baseline heart rate and respiratory rate increased during SSC (P <.01), as did the combined frequency of bradycardia and hypoxemia (from 1.5/h [0-8] before to 2.8/h [0-15] during SSC; P<.05). Rectal temperature increased from 36.9 degrees C (36.2 degrees -37.4 degrees C) to 37.3 degrees C (36.6 degrees -38.6 degrees C; P <.01). The proportion of regular breathing pattern decreased from 14% (2%-28%) to 7% (3%-26%) with SSC (P<.01). CONCLUSION: SSC was associated with a significant increase in the combined frequency of bradycardia and hypoxemia and with less regular breathing. These changes were unexpected and may have been related to heat stress. Body temperature, heart rate, and oxygenation should be monitored during SSC.

Pulse oximeters' reliability in detecting hypoxemia and bradycardia: comparison between a conventional and two new generation oximeters.

OBJECTIVE: Pulse oximeters are increasingly used for patient monitoring; however, they are traditionally very prone to motion artifact. Newly developed instruments have lower false alarm rates. We wanted to know whether this is achieved at the expense of an increased proportion of false negative alarms such as missed or delayed identification of hypoxemia and/or bradycardia. DESIGN: Observational study. SETTING: Neonatal intensive care unit. PATIENTS: A total of 17 unsedated preterm infants (median gestational age at birth, 25 wks; range, 24-30 wks). INTERVENTION: Long-term recordings of transcutaneous partial pressure of oxygen (P(Tc)O2), heart rate, pulse oximeter saturation (SpO2), and pulse rate from a conventional oximeter and two new generation oximeters. MEASUREMENTS: Recordings were analyzed for episodes with P(Tc)O2 <40 torr or with heart rate <80 beats/min for >5 secs. Hypoxemia was considered identified if SpO2 had fallen to <85% within 2 mins of P(Tc)O2 reaching 40 torr, and bradycardia was considered identified if pulse rate had fallen to <80 beats/min within 2 mins of the heart rate reaching this threshold. MAIN RESULTS: A total of 202 falls in P(Tc)O2 to <40 torr occurred; 174 (86%) were identified by all three oximeters. Of the remaining episodes, manual analysis of red and infrared absorption signals confirmed that SpO2 had indeed been <85% for > or =10 secs in 11 episodes; therefore, these episodes should have been identified by all three oximeters. None of these had been missed by the conventional oximeter, but 10 (5.4% of the total) were missed by one of the new generation instruments (Nellcor), and one (0.5%) was missed by the other (Masimo). Of 54 bradycardias, only 14 were identified by all three oximeters; 17 (32%) were missed by the conventional, 37 (69%) by the Nellcor, and 4 (7%) by the Masimo instrument. CONCLUSION: One of the two new generation instruments investigated in this study missed 5.4% of hypoxemic episodes and 69% of bradycardias. It thus appears that this instrument's reduced false alarm rate is achieved at the expense of an unreliable and/or delayed identification of hypoxemia and bradycardia. The other instrument identified both conditions equally as or more reliably than a conventional pulse oximeter.

False alarms in very low birthweight infants: comparison between three intensive care monitoring systems.

UNLABELLED: Monitor alarms are a major burden on both patients and staff in intensive care units. We compared alarm rates from three different monitor systems (Hewlett Packard (HP), Kontron Instruments (KI), Marquette-Hellige (MH)) in a tertiary neonatal intensive care unit. Monitors were used in random order on three consecutive days over 8 h each in 16 preterm infants (median gestational age at birth 29 wk (range 24-34), age at study 18 d (8-53), weight at study 1,160g (595-1,430)). Alarms were classified as true or false using flow sheets based on continuous observation of both the patient and related parameters. There was one alarm every 9 min of monitoring. The median number of true alarms did not differ significantly between systems, being 28 per 8 h (range 9-87) for HP, 26 (3-81) for KI, and 30 (5-135) for MH. The median number of false alarms differed widely, with the HP system generating 32 (7-77) such alarms per 8 h, compared to 8 (0-19) for KI and 15 (2-32) for MH (p < 0.01 HP vs KI and MH, p < 0.05 KI vs MH). These differences between systems were mainly due to differences in pulse oximeter and transcutaneous PO2 monitor alarm rates. CONCLUSIONS: In conclusion, this study shows marked differences between both parameters and manufacturers in the frequency with which false alarms occur. It may provide a basis from which reductions in alarm rates can be sought.

Effect of doxapram on episodes of apnoea, bradycardia and hypoxaemia in preterm infants.

AIM: To study the effect of doxapram on the frequency of apnoea, bradycardia and hypoxaemia. METHODS: Fifteen infants, median gestational age at birth 27 weeks (range 24-30), age at study 27 days (12-60), with >/=6 episodes of bradycardia or hypoxaemia/6 h despite serum caffeine levels in the therapeutic range, received doxapram either intravenously (0.5-2 mg/kg/h) or orally (2-8 mg/kg every 2 h). Six-hour recordings of pulse oximeter saturation (S(P)O(2)), pulse waveforms, ECG, breathing movements and nasal airflow were performed immediately before as well as 1, 3 and 6 days after onset of treatment. Recordings were analysed for apnoea (>/=4 s), bradycardia (heart rate < 2/3 of baseline) and hypoxaemia (S(P)O(2)

Necrotising enterocolitis: is there a relationship to specific pathogens?

UNLABELLED: Outbreaks of necrotising enterocolitis (NEC) have often been related to specific pathogens such as Enterobacteriaceae. This relationship, however, remains uncertain because of the retrospective nature of the studies addressing this issue. We performed a prospective study to investigate whether there is indeed an association between NEC and specific pathogens. Between April 1993 and March 1997, stools of neonates of < 36 weeks admitted to our neonatal unit were investigated for bacteria in weekly intervals. Clinical and bacteriological data from each infant who developed NEC were compared with those from two control infants matched for gestational age and date of admission. Eighteen infants developed 19 episodes of NEC (clinical signs + air in portal vein); 8 of these had laparotomy; two died. Occurrences of NEC were homogeneously distributed over the 4-year study period. The only significant differences in the clinical course prior to NEC were a more severe stage of respiratory distress syndrome [median 2 (0-4) vs. 0 (0-3), P < 0.05] and a higher proportion of infants who had only been formula fed (63 vs. 32%, P < 0.05) in the cases. Within the last week prior to NEC, potentially pathogenic bacteria were identified in stools of all cases and 79% of controls (P < 0.05). However, there was no significant difference in the occurrence of specific pathogens or groups of pathogens in cases compared with controls. CONCLUSION: Although gut colonisation with potential pathogens appeared to be a prerequisite for the development of NEC, there were no specific bacteria associated with this disease if data from infants with NEC were compared with those from time- and gestational age-matched controls.

Prenatal diagnosis of congenital alveolar proteinosis (surfactant protein B deficiency).

We report on the DNA-based prenatal diagnosis of congenital pulmonary alveolar proteinosis in a family in which alveolar proteinosis was associated with surfactant protein B (SP-B) deficiency. The parents had lost an eight-week-old female child due to this fatal disorder. The affected child was homozygous and both parents were heterozygous for a frame-shift mutation in codon 121 of the surfactant protein B gene (SFTP3-gene). Chorionic villus sampling (CVS) was performed in two subsequent pregnancies. DNA analysis revealed homozygosity for the codon 121 mutation in the first fetus, and the pregnancy was terminated. Homozygosity for the parental wild-type alleles was detected in the following prenatal diagnosis, and a healthy child has been born. DNA-based prenatal diagnosis of congenital alveolar proteinosis is simple, fast and reliable, and can be performed much earlier in pregnancy than any other method, e.g. the direct measurement of SP-B in amniotic fluid. In families with a term infant who dies of unexplained respiratory failure, genetic testing of the parents should be evaluated, since the presence of the codon 121 mutation enables prenatal diagnosis in later pregnancies.

[Bart syndrome--separate entity or a variant of epidermolysis bullosa?]. / Das Bart-Syndrom--Eigene Entität oder Variante einer Epidermolysis bullosa?

Bart syndrome was described first by Bart in 1966; it represents the combination of congenital epidermolysis bullosa, congenital localized absence of skin affecting the extremities and shedding or dystrophy of nails. This syndrome may be of clinical relevance because of its more favourable prognosis in comparison with other forms of epidermolysis bullosa. We report two patients with Bart syndrome and focus on the question, if this syndrome represents a distinct entity or a variant of epidermolysis bullosa.