A lower motor neuron disease in takahe (Porphyrio hochstetteri) is an endoplasmic reticulum storage disease.

AIMS: To investigate the pathogenesis of a disease in takahe (Porphyrio hochstetteri) with intracytoplasmic inclusion bodies in lower motor neurons. METHODS: Four birds aged between 5 and 12 years, from three different wildlife sanctuaries in New Zealand were examined. Of these, only one had signs of spinal dysfunction in the form of paresis. Stained paraffin sections of tissues were examined by light microscopy and immunostained sections of the ventral horn of the spinal cord by confocal microscopy. Epoxy resin sections of the spinal cord from the bird with spinal dysfunction were examined by electron microscopy. RESULTS: Two types of inclusion bodies were noted, but only in motor neurons of the ventral spinal cord and brain stem. These were large globoid eosinophilic bodies up to 5 µm in diameter, and yellow/brown granular inclusions mostly at the pole of the cell. The globoid bodies stained with Luxol fast blue but not with periodic acid Schiff (PAS), or Sudan black. The granular inclusions stained with Luxol fast blue, PAS and Sudan black. Both bodies were slightly autofluorescent. On electron microscopy the globoid bodies had an even electron-dense texture and were bound by a membrane. Beneath the membrane were large numbers of small intraluminal vesicles. The smaller granular bodies were more heterogeneous, irregularly rounded and membrane-bound accumulations of granular electron-dense material, often with electron-lucent vacuoles. Others were more vesicular but contained varying amounts of electron-dense material. The large globoid bodies did not immunostain for lysosomal markers lysosomal associated protein 1 (LAMP1) or cathepsin D, so were not lysosomal. The small granular bodies stained for cathepsin D by a chromogenic method.A kindred matrix analysis showed two cases to be as closely related as first cousins, and another case was almost as closely related to one of them, but the fourth bird was unrelated to any other. CONCLUSIONS: It was concluded that this was an endoplasmic reticulum storage disease due to a specific protein misfolding within endoplasmic reticulum. It was rationalised that the two types of inclusions reflected the same aetiology, but that misfolded protein in the smaller granular bodies had entered the lysosomal system via endoplasmic reticulum autophagy. Although the cause was unclear, it most likely had a genetic aetiology or predisposition and, as such, has clinical relevance.

Online Hydrophilic Interaction Chromatography (HILIC) Enhanced Top-Down Mass Spectrometry Characterization of the SARS-CoV-2 Spike Receptor-Binding Domain.

SARS-CoV-2 cellular infection is mediated by the heavily glycosylated spike protein. Recombinant versions of the spike protein and the receptor-binding domain (RBD) are necessary for seropositivity assays and can potentially serve as vaccines against viral infection. RBD plays key roles in the spike protein's structure and function, and thus, comprehensive characterization of recombinant RBD is critically important for biopharmaceutical applications. Liquid chromatography coupled to mass spectrometry has been widely used to characterize post-translational modifications in proteins, including glycosylation. Most studies of RBDs were performed at the proteolytic peptide (bottom-up proteomics) or released glycan level because of the technical challenges in resolving highly heterogeneous glycans at the intact protein level. Herein, we evaluated several online separation techniques: (1) C2 reverse-phase liquid chromatography (RPLC), (2) capillary zone electrophoresis (CZE), and (3) acrylamide-based monolithic hydrophilic interaction chromatography (HILIC) to separate intact recombinant RBDs with varying combinations of glycosylations (glycoforms) for top-down mass spectrometry (MS). Within the conditions we explored, the HILIC method was superior to RPLC and CZE at separating RBD glycoforms, which differ significantly in neutral glycan groups. In addition, our top-down analysis readily captured unexpected modifications (e.g., cysteinylation and N-terminal sequence variation) and low abundance, heavily glycosylated proteoforms that may be missed by using glycopeptide data alone. The HILIC top-down MS platform holds great potential in resolving heterogeneous glycoproteins for facile comparison of biosimilars in quality control applications.

The effect of automated oxygen control on clinical outcomes in preterm infants: a pre- and post-implementation cohort study.

Several studies demonstrated an increase in time spent within target range when automated oxygen control (AOC) is used. However the effect on clinical outcome remains unclear. We compared clinical outcomes of preterm infants born before and after implementation of AOC as standard of care. In a retrospective pre-post implementation cohort study of outcomes for infants of 24-29 weeks gestational age receiving respiratory support before (2012-2015) and after (2015-2018) implementation of AOC as standard of care were compared. Outcomes of interest were mortality and complications of prematurity, number of ventilation days, and length of stay in the Neonatal Intensive Care Unit (NICU). A total of 588 infants were included (293 pre- vs 295 in the post-implementation cohort), with similar gestational age (27.8 weeks pre- vs 27.6 weeks post-implementation), birth weight (1033 grams vs 1035 grams) and other baseline characteristics. Mortality and rate of prematurity complications were not different between the groups. Length of stay in NICU was not different, but duration of invasive ventilation was shorter in infants who received AOC (6.4 ± 10.1 vs 4.7 ± 8.3, p = 0.029).Conclusion: In this pre-post comparison, the implementation of AOC did not lead to a change in mortality or morbidity during admission. What is Known: • Prolonged and intermittent oxygen saturation deviations are associated with mortality and prematurity-related morbidities. • Automated oxygen controllers can increase the time spent within oxygen saturation target range. What is New: • Implementation of automated oxygen control as standard of care did not lead to a change in mortality or morbidity during admission. • In the period after implementation of automated oxygen control, there was a shift toward more non-invasive ventilation.

Lower lip squamous cell carcinoma in patients with photosensitive disorders: Analysis of cases treated at the Brazilian National Cancer Institute (INCA) from 1999 to 2012.

BACKGROUND: Lower lip squamous cell carcinoma (LLSCC) is a common malignancy of the head and neck, being mainly a consequence of a chronic exposure to ultraviolet (UV) light solar radiation. Here, we evaluated the clinicopathological profile of patients with photosensitive disorders (xeroderma pigmentosum, lupus erythematosus and albinism) that developed LLSCC. MATERIAL AND METHODS: Data from patients who had a diagnosed LLSCC with a prior xeroderma pigmentosum, lupus erythematosus or albinism diagnosis that were treated at INCA from 1999 to 2012 were collected from patients medical records (n=16). The control group was composed of 68 patients with LLSCC without a medical history of photosensitivity. The clinicopathological data of this study population were collected and the association between these variables was analyzed by Fisher's exact test. Survival curves were constructed using the Kaplan-Meier method and compared by log-rank test. All statistical analyses were performed using SPSS statistics package. RESULTS: The mean age of patients in the photosensitive and non-photosensitive groups was 42 years and 67 years, respectively (p<0.0001). A previous history of malignant diseases was more common in the photosensitive group (p=0.001). In both groups, most tumors showed a pathological stage I/II disease. Overall and cancer-specific survival were not statistically different. However, disease-free interval showed a significant difference (p=0.01) between the photosensitive and non-photosensitive patients. CONCLUSIONS: Photosensitive patients presented LLSCC at earlier age but it usually was not the primary tumor in these patients. Furthermore, a more aggressive pathological behavior was not seen when compared with tumors from non-photosensitive patients. The disease-free interval was lower in photosensitive patients, as expected.

Concentrations of calcium and 25-hydroxycholecalciferol (vitamin D3) in plasma of wild kakapo (Strigops habroptilus) living on two islands in New Zealand.

AIMS This preliminary study had the objectives of describing the concentrations of ionised calcium and 25-hydroxycholecalciferol (25(OH)D3) in the blood of wild kakapo (Strigops habroptilus) living on two islands in New Zealand, and to determine the effects of supplementary feeding on these blood parameters. METHODS Blood samples were obtained from 33 kakapo living on two offshore islands during routine health checks in 2015. Birds on Hauturu were sampled in May (n=5) and birds on Whenua Hou were sampled in July (n=15) and November (n=26). Of the birds sampled on Whenua Hou in November, 15 received supplementary food prior to sampling. Samples were analysed for pH, and concentrations of ionised calcium, total calcium, phosphorous, total protein, albumin, globulin, uric acid and 25(OH)D3. RESULTS Concentrations of ionised calcium did not differ between unsupplemented birds on the two islands, nor between supplemented (median 1.17 (95% CI=1.12-1.20) mmol/L) and unsupplemented (median 1.09 (95% CI=1.08-1.14) mmol/L) birds sampled in November on Whenua Hou (p>0.05), and were comparable with published normal ranges for other psittacines. Concentrations of 25(OH)D3 did not differ between unsupplemented birds on the two islands (p>0.05), but were higher in supplemented (median 8.00 (95% CI=4.76-8.45) nmol/L) than unsupplemented (median 0.00 (95% CI=-0.16-0.48) nmol/L) birds on Whenua Hou (p<0.001). All values were much lower than published ranges for healthy psittacines. There was no difference between male and female birds on Whenua Hou for any parameter measured (p>0.05). CONCLUSIONS AND CLINICAL RELEVANCE The calcium status of the kakapo in this study was comparable to other wild psittacines, however concentrations of 25(OH)D3 were much lower. The concentrations of 25(OH)D3 may be within the normal range for the species, however further data are required to confirm this. The significant increase in concentrations of 25(OH)D3 in supplementary fed birds suggests that this food was providing more of the nutrient than the wild diet at that time of year, although the effects of this are unknown. Further investigation is required into the calcium and vitamin D3 status of kakapo, across a wider range of locations, seasons and ages. This would help define normal ranges for these parameters, allow interpretation in clinically abnormal individuals, and guide the refinement of supplementary foods. This information would, therefore, assist the future conservation management of this critically endangered species.

Exerted force on the face mask in preterm infants at birth is associated with apnoea and bradycardia.

BACKGROUND: During stabilisation of preterm infants at birth, a face mask is used to provide respiratory support. However, application of these masks may activate cutaneous stretch receptors of the trigeminal nerve, causing apnoea and bradycardia. This study investigated the amount of force exerted on the face mask during non-invasive ventilation of preterm infants at birth and whether the amount of exerted force is associated with apnoea and bradycardia. METHODS: A prospective observational study was performed in preterm infants born <32 weeks of gestation who were stabilised at birth. During the first 10 minutes of respiratory support, we measured breathing and heart rate as well as the amount of force exerted on a face mask using a custom-made pressure sensor placed on top of the face mask. RESULTS: Thirty infants were included (median (IQR) gestational age(GA) 28+3 (27+0-30+0) weeks, birthweight 1104 (878-1275) grams). The median exerted force measured was 297 (198-377) grams, ranging from 0 to 1455 grams. Significantly more force was exerted on the face mask during positive pressure ventilation when compared to CPAP (410 (256-556) vs 286 (190-373) grams, p = 0.009). In a binary logistic regression model, higher forces were associated with an increased risk of apnoea (OR = 1.607 (1.556-1.661), p < 0.001) and bradycardia (OR = 1.140 (1.102-1.180), p < 0.001) during the first 10 minutes of respiratory support at birth. CONCLUSION: During mask ventilation, the median exerted force on a face mask was 297 grams with a maximum of 1455 grams. Higher exerted forces were associated apnoea and bradycardia during the first 10 minutes of respiratory support at birth.

Adverse respiratory patterns in near-term spontaneously breathing newborn lambs with elevated airway liquid volumes at birth.

Introduction: Recent evidence indicates that respiratory distress (RD) in near-term infants is caused by elevated airway liquid (EL) volume at the beginning of air-breathing after birth. While the adverse effects EL volumes on newborn lung function are known, the effects on respiratory control and breathing patterns shortly after birth (<4 h) are unknown. We investigated the effects of EL volumes on cardiorespiratory function and breathing patterns in spontaneously breathing near-term newborn lambs in the first hours after birth. Methods: At 137-8 days gestation (2-3 days prior to delivery; term ∼147 days), sterile surgery was performed on fetal sheep (n = 17) to implant catheters and blood flow probes. At 140 days, lambs were delivered via caesarean section under spinal anaesthesia. Airway liquid volumes were adjusted to mimic the level expected following vaginal delivery (∼10 ml/kg; Controls; n = 7), or elective caesarean section (∼30 ml/kg; elevated airway liquid group; EL; n = 10). Spontaneous breathing and cardiorespiratory parameters were recorded over four hours after birth. Non-invasive respiratory support with supplemental oxygen was provided if required. Results: EL lambs required higher inspired oxygen levels (p = 0.0002), were less active (p = 0.026), fed less (p = 0.008) and had higher respiratory morbidity scores than Controls (p < 0.0001). EL lambs also displayed higher rates of breathing patterns associated with RD, such as expiratory braking and tachypnoea. These patterns were particularly evident in male EL lambs who displayed higher levels of severe respiratory morbidity (e.g., expiratory braking) than female EL lambs. Conclusion: The study demonstrates that EL volumes at birth trigger respiratory behaviour and breathing patterns that resemble clinically recognised features of RD in term infants.

Investigating the European perspective of neonatal point-of-care echocardiography in the neonatal intensive care unit--a pilot study.

UNLABELLED: Point-of-care functional neonatal echocardiography (fnECHO) is increasingly used to assess haemodynamic status or patency of the ductus arteriosus (PDA). In Australasia, 90 % of neonatal intensive care units (NICUs) practice point-of-care fnECHO. The Australian Society of Ultrasound Medicine offers a training certificate for fnECHO. In Europe, the use and indications of fnECHO and the extent of point-of-care fnECHO training and accreditation are unknown. We aimed to assess utilisation and training of fnECHO in Europe. For this, we conducted an email survey of 45 randomly chosen tertiary NICUs in 17 European countries. The recall rate was 89 % (n = 40). Neonatologists with skills in fnECHO worked in 29 NICUs (74 %), but paediatric cardiologists would routinely perform most fnECHOs. Twenty-four-hour echocardiography service was available in 31 NICUs (78 %). Indications for fnECHO included assessment of haemodynamic volume status (53 %), presence or absence of pulmonary hypertension of the neonate (55 %), indication for and effect of volume replacement therapy (58 %), PDA assessment and monitoring of PDA treatment (80 %). Teaching of fnECHO was offered to trainees in 22 NICUs (55 %). Teaching of fnECHO was provided by paediatric cardiologists (55 %) or by neonatologists (45 %). Only six (15 %) national colleges accredited fnECHO teaching courses. CONCLUSION: fnECHO is widely practiced by neonatologists across Europe for a broad range of clinical questions. However, there is a lack of formal training and accreditation of fnECHO skills. This could be addressed by designing a dedicated European fnECHO training programme and by agreeing on a common European certificate of fnECHO.

Respiratory patterns in spontaneously breathing near-term lambs delivered by caesarean section under spinal anaesthesia.

Introduction: The transition to newborn life has typically been studied in intubated and mechanically ventilated newborn lambs delivered via caesarean section (CS) under general anaesthesia. As a result, little is known of the spontaneous breathing patterns in lambs at birth, particularly those at risk of developing respiratory distress (RD). We have developed a method for delivering spontaneously breathing near-term lambs to characterise their breathing patterns in the immediate newborn period. Methods: At 137-8 days gestation (2-3 days prior to delivery; term ∼147 days), fetal lambs (n = 7) were partially exteriorised for instrumentation (insertion of catheters and flow probes) before they were returned to the uterus. At 140 days, lambs were delivered via CS under light maternal sedation and spinal anaesthesia. Lambs were physically stimulated and when continuous breathing was established, the umbilical cord was clamped. Breathing patterns were assessed by measuring intrapleural and upper-tracheal pressures during the first four hours after birth. Results: Newborn lambs display significant heterogeneity in respiratory patterns in the immediate newborn period that change with time after birth. Seven distinct breathing patterns were identified including: (i) quiet (tidal) breathing, (ii) breathing during active periods, (iii) breathing during oral feeding, (iv) tachypnoea, (v) expiratory braking manoeuvres, (vi) expiratory pauses or holding, and (vii) step changes in ventilation. Conclusions: We have described normal respiratory behaviour in newborn lambs, in order to identify respiratory behaviours that are indicative of RD in term newborn infants.

Time to achieve desired fraction of inspired oxygen using a T-piece ventilator during resuscitation of preterm infants at birth.

AIM: To determine the time between adjustment of FiO2 at the oxygen blender and the desired FiO2 reaching the preterm infant during respiratory support at birth. METHODS: This observational study was performed using a Neopuff™ T-piece Resuscitator attached to either a test lung (during initial bench tests) or a face mask during the stabilization of infants at birth. FiO2 was titrated following resuscitation guidelines. The duration for the desired FiO2 to reach either the test lung or face mask was recorded, both with and without leakage. A respiratory function monitor was used to record FiO2 and amount of leak. RESULTS: In bench tests, the median (IQR) time taken to achieve a desired FiO2 was 34.2 (21.8-69.1) s. This duration was positively associated with the desired FiO2 difference, the direction of titration (upwards) and the occurrence of no leak (R2 0.863, F 65.016, p < 0.001). During stabilization of infants (median (IQR) gestational age 29+0 (28+2-30+0) weeks, birthweight 1290 (1240-1488) g), the duration (19.0 (0.0-57.0) s) required to reach a desired FiO2 was less, but still evident. In 27/55 (49%) titrations, the desired FiO2 was not achieved before the FiO2 levels were again changed. CONCLUSION: There is a clear delay before a desired FiO2 is achieved at the distal end of the T-piece resuscitator. This delay is clinically relevant as this delay could easily lead to over- and under titration of oxygen, which might result in an increased risk for both hypoxia and hyperoxia.

Inter-twin hemoglobin difference at birth in uncomplicated monochorionic twins in relation to the size of the placental anastomoses.

OBJECTIVE: To evaluate the relation between Hb levels and the size of the placental anastomoses. METHODS: We performed a retrospective review of all uncomplicated MC twins delivered vaginally at our center from 2002 to 2017. Hb levels at birth and on day 2 were retrieved. All MC placentas were routinely injected with colored dye and high-resolution pictures were taken for computer-based analysis. We measured the size of arterio-arterial (AA) and veno-venous (VV) anastomoses as well as the total venous size, defined as the sum of the diameter of first generation of placental veins within 5 cm of each cord insertion. We assessed the relation between Hb levels and placental angioarchitecture. RESULTS: A total of 170 MC twin pairs were analyzed. Median Hb level in twin 1 was significantly lower than that in twin 2 both at birth (16.0 versus 17.4 g/dl, P = 0.02) and on day 2 (14.6 versus 18.1 g/dl, P = 0.000000188). Inter-twin Hb difference on day 2 was positively correlated with the size of AA anastomoses (Spearman r = 0.25, 95% CI 0.04-0.43, P = 0.0161). The diameter of AA anastomoses was positively related to the total size of veins connecting to AA anastomoses in the placental territory of twin 2 (Spearman r = 0.55, 95% CI 0.41-0.66, P = 0.0001). DISCUSSION: MC twins with larger AA anastomoses have higher Hb differences at birth. Higher Hb levels in second born twins may partly be due to increased placento-fetal transfusion through larger placental vessels.

The effect of implementing an automated oxygen control on oxygen saturation in preterm infants.

OBJECTIVE: To evaluate the effect of implementing automated oxygen control as routine care in maintaining oxygen saturation (SpO2) within target range in preterm infants. METHODS: Infants <30 weeks gestation in Leiden University Medical Centre before and after the implementation of automated oxygen control were compared. The percentage of time spent with SpO2 within and outside the target range (90-95%) was calculated. SpO2 values were collected every minute and included for analysis when infants received extra oxygen. RESULTS: In a period of 9 months, 42 preterm infants (21 manual, 21 automated) were studied. In the automated period, the median (IQR) time spent with SpO2 within target range increased (manual vs automated: 48.4 (41.5-56.4)% vs 61.9 (48.5-72.3)%; p<0.01) and time SpO2 >95% decreased (41.9 (30.6-49.4)% vs 19.3 (11.5-24.5)%; p<0.001). The time SpO2<90% increased (8.6 (7.2-11.7)% vs 15.1 (14.0-21.1)%; p<0.0001), while SpO2<80% was similar (1.1 (0.4-1.7)% vs 0.9 (0.5-2.1)%; ns). CONCLUSIONS: During oxygen therapy, preterm infants spent more time within the SpO2 target range after implementation of automated oxygen control, with a significant reduction in hyperoxaemia, but not hypoxaemia.

Early-Onset Thrombocytopenia in Small-For-Gestational-Age Neonates: A Retrospective Cohort Study.

Thrombocytopenia is a common finding in small for gestational age (SGA) neonates and is thought to result from a unique pathophysiologic mechanism related to chronic intrauterine hypoxia. Our objective was to estimate the incidence and severity of early-onset thrombocytopenia in SGA neonates, and to identify risk factors for thrombocytopenia. We performed a retrospective cohort study of all consecutive SGA neonates admitted to our ward and a control group of appropriate for gestational age (AGA) neonates matched for gestational age at birth. Main outcome measures were incidence and severity of thrombocytopenia, hematological and clinical risk factors for thrombocytopenia, and bleeding. A total of 330 SGA and 330 AGA neonates were included, with a mean gestational age at birth of 32.9 ± 4 weeks. Thrombocytopenia (<150x10(9)/L) was found in 53% (176/329) of SGA neonates and 20% (66/330) of AGA neonates (relative risk (RR) 2.7, 95% confidence interval (CI) [2.1, 3.4]). Severe thrombocytopenia (21-50x10(9)/L) occurred in 25 neonates (8%) in the SGA and 2 neonates (1%) in the AGA group (RR 12.5, 95% CI [3.0, 52.5]). Platelet counts <20x10(9)/L were not recorded. Within the SGA group, lower gestational age at birth (p = <0.01) and erythroblastosis (p<0.01) were independently associated with a decrease in platelet count. Platelet count was positively correlated with birth weight centiles. In conclusion, early-onset thrombocytopenia is present in over 50% of SGA neonates and occurs 2.7 times as often as in AGA neonates. Thrombocytopenia is seldom severe and is independently associated with lower gestational age at birth and erythroblastosis.

Umbilical blood flow patterns directly after birth before delayed cord clamping.

BACKGROUND: Delayed umbilical cord clamping (DCC) affects the cardiopulmonary transition and blood volume in neonates immediately after birth. However, little is known of blood flow in the umbilical vessels immediately after birth during DCC. The objective is to describe the duration and patterns of blood flow through the umbilical vessels during DCC. METHODS: Arterial and venous umbilical blood flow was measured during DCC using Doppler ultrasound in uncomplicated term vaginal deliveries. Immediately after birth, the probe was placed in the middle of the umbilical cord, pattern and duration of flow in vein and arteries were evaluated until cord clamping. RESULTS: Thirty infants were studied. Venous flow: In 10% no flow was present, in 57% flow stopped at 4:34 (3:03-7:31) (median (IQR) min:sec) after birth, before the cord was clamped. In 33%, flow continued until cord clamping at 5:13 (2:56-9:15) min:sec. Initially, venous flow was intermittent, increasing markedly during large breaths or stopping and reversing during crying, but then became continuous. Arterial flow: In 17% no flow was present, in 40% flow stopped at 4:22 (2:29-7:17) min:sec, while cord pulsations were still palpable. In 43% flow continued until the cord was clamped at 5:16 (3:32-10:10) min:sec. Arterial flow was pulsatile, unidirectional towards placenta or bidirectional to/from placenta. In 40% flow became continuous towards placenta later on. CONCLUSIONS: During delayed umbilical cord clamping, venous and arterial umbilical flow occurs for longer than previously described. Net placental transfusion is probably the result of several factors of which breathing could play a major role. Umbilical flow is unrelated to cessation of pulsations.

[Osteomyelitis in children: sometimes hard to recognize]. / Osteomyelitis bij kinderen: soms moeilijk te herkennen.

In a 15-year-old girl with pain in the right lower abdomen and a 9-year-old boy with pain in the left thigh, an elevated sedimentation rate and C-reactive protein were reason to suspect osteomyelitis. Although no abnormalities could be seen on X-rays, skeletal scintigraphy revealed pathology in Liv-v and the sacroiliac joint, respectively. In the girl, Staphylococcus aureus was cultivated from material obtained by puncture and biopsy. After treatment with antibiotics, rest and gradual mobilisation, the girl retained a scoliosis; the boy was cured without residual complaints or abnormalities. Osteomyelitis of the spine and sacroiliac joint are rare disorders in children. The subtle and non-specific symptoms sometimes make the diagnosis difficult. Conventional X-ray is the primary radiological investigation. Bone scintigraphy (99mTc-oxidronate) is useful in the initial evaluation of children with suspected osteomyelitis. It is sensitive, relatively inexpensive, often does not require sedation and can detect multiple foci of disease. MRI is also highly sensitive and more specific than bone scintigraphy, but it cannot be used as a screening technique when the site of pathology is unclear. MRI is useful when the bone scintigram is inconclusive and in complicated cases for better anatomic details.

Auditing documentation on delivery room management using video and physiological recordings.

OBJECTIVE: Neonatal resuscitation is often retrospectively documented, which can lead to inaccuracy and incomplete recording of delivery room management. In this study, we assessed the accuracy and completeness of neonatal resuscitation documentation in our neonatal intensive care unit. METHODS: Recordings of physiological parameters and video data were performed in the delivery room and used to deduct the clinical condition of the infant, the interventions done and their effect on the infant's condition. The data from the recordings were compared with the documentation on neonatal stabilisation in the medical records (paper or digital). RESULTS: Recordings of 54 infants were compared with the documentation in their medical records. In 93% of the medical records delivery room management was documented. The clinical condition of the infant at birth was documented in 76% and 1 min Apgar scores in 98%. Respiratory support was correctly documented in 83%, heart rate in 37% and oxygen saturation in 13%. In 57% use of supplemental oxygen and its indication were correctly reported. Seven infants were intubated and this was correctly documented in 57%. Apgar scores were compared between the recordings and the medical records. At 1 min, 5 min and 10 min after birth the Apgar score, given by the researcher using the recordings, was similar to the scores in the medical records in 33%, 44% and 53%, respectively. CONCLUSIONS: Accurate and complete documentation of neonatal resuscitation continues to be a challenge. Recordings of physiological parameters and video imaging can improve documentation by providing detailed information.

The risk for hyperoxaemia after apnoea, bradycardia and hypoxaemia in preterm infants.

OBJECTIVE: To investigate the occurrence and duration of oxygen saturation (SpO2) ≥95%, after extra oxygen for apnoea, bradycardia, cyanosis (ABC), and the relation with the duration of bradycardia and/or SpO2 ≤80%. METHODS: All preterm infants <32 weeks' gestation supported with nasal continuous positive airway pressure (nCPAP) admitted to our centre were eligible for the study. We retrospectively identified all episodes of ABCs. In ABCs where oxygen supply was increased, duration and severity of bradycardia (<80 bpm), SpO2 ≤80%, SpO2 ≥95% and their correlation were investigated. RESULTS: In 56 infants, 257 ABCs occurred where oxygen supply was increased. SpO2 ≥95% occurred after 79% (202/257) of the ABCs, duration of extra oxygen supply was longer in ABCs with SpO2 ≥95% than without SpO2 ≥95% (median (IQR) 20 (8-80) vs 2 (2-3) min; p<0.001)). The duration of SpO2 ≥95% was longer than bradycardia and SpO2 ≤80% (median (IQR) 13 (4-30) vs 1 (1-1) vs 2 (1-2) min; p<0.001). SpO2 ≥95% lasted longer when infants were in ambient air than when oxygen was given before the ABC occurred (median (IQR)15 (5-38) min vs 6 (3-24) min; p<0.01). CONCLUSIONS: In preterm infants supported with nCPAP in the neonatal intensive care unit (NICU), SpO2 ≥95% frequently occurred when oxygen was increased for ABCs and lasted longer than the bradycardia and SpO2 ≤80%.

Leak during manual neonatal ventilation and its effect on the delivered pressures and volumes: an in vitro study.

BACKGROUND: Mask leak is a frequent problem during manual ventilation. Our aim was to investigate the effect of predefined leaks on delivered peak inflation pressure (PIP), positive end-expiratory pressure (PEEP) and tidal volume (V(t)) when using different neonatal manual ventilation devices. METHODS: A neonatal-lung model was ventilated at different respiratory rates (RRs, 40, 60, 80/min) using a mechanically operated self-inflating bag (SIB) and a manually operated T-piece resuscitator (PIP = 20 cm H(2)O, PEEP = 5 cm H(2)O). Four open tubes of different lengths, which produced up to 90% leak, were consecutively attached between the ventilation device and the lung model. A pneumotachograph was used to measure pressures, flow and volume. RESULTS: With increasing leak (0-90%) PIP and PEEP decreased significantly (p < 0.001) for both devices. Using the SIB, the mean ± SD PIP fell from 20.1 ± 0.3 to 15.9 ± 7 cm H(2)O and PEEP fell from 5.0 ± 0 to 0.3 ± 0.5 cm H(2)O, leading to an increased pressure difference (Δp); V(t) increased from 8.8 ± 0.7 to 11.1 ± 0.8 ml (p < 0.001). With increasing RRs, the leak-dependent changes were significantly lower (p < 0.001). Using the T-piece resuscitator, PIP dropped independent of RRs from 20.3 ± 0.5 to 18.5 ± 0.6 cm H(2)O and PEEP from 5.1 ± 0.4 to 4.0 ± 0 cm H(2)O, while Δp and V(t) did not differ significantly. CONCLUSION: The decrease in PIP and PEEP with increasing leak is RR dependent and distinctly higher when using an SIB compared to a T-piece device. In contrast to V(t) delivered with the SIB, V(t) delivered by the T-piece resuscitator was nearly constant even for leaks up to 90%.

Changes in respiratory support of preterm infants in the last decade: are we improving?

BACKGROUND: Ventilator-induced lung injury has been recognized as a major contributing factor for bronchopulmonary dysplasia (BPD) in preterm infants. In the last decade, focus has shifted towards a more gentle respiratory approach. AIM: To evaluate whether guideline changes in respiratory management in the delivery room and the unit improved the incidence of BPD in very preterm infants. METHODS: Three cohorts of infants <30 weeks of gestation, born at the Leiden University Medical Center in the Netherlands in 1996-1997 (cohort '96), 2003-2004 (cohort '03) and 2008-2009 (cohort '08), were compared retrospectively. The major change was increasing use of continuous positive airway pressure in time, and monitoring the tidal volume during mechanical ventilation in cohort '08. The primary outcome was BPD at 36 weeks. RESULTS: The incidence of BPD did not change from 47% in cohort '96 to 55% in cohort '03 (n.s.), but decreased significantly to 37% in cohort '08 (cohort '96 vs. '08 and cohort '03 vs. '08: p < 0.01). We observed the same effect when only moderate and severe BPD were counted with 27% in cohort '96, 31% in cohort '03 and 14% in '08 (cohort '96 vs. '03: p = n.s., cohort '96 vs. '08: p < 0.01, cohort '03 vs. '08: p < 0.05). The mortality rate was not significantly different between the three cohorts. CONCLUSION: The incidence of BPD in our cohort of preterm infants has decreased during the last decade and could be due to the changes in respiratory management.