Feasibility of Umbilical Cord Blood Collection in Neonates at Risk of Brain Damage-A Step Toward Autologous Cell Therapy for a High-risk Population.

Evidence for umbilical cord blood (UCB) cell therapies as a potential intervention for neurological diseases is emerging. To date, most existing trials worked with allogenic cells, as the collection of autologous UCB from high-risk patients is challenging. In obstetric emergencies the collection cannot be planned. In preterm infants, late cord clamping and anatomic conditions may reduce the availability. The aim of the present study was to assess the feasibility of UCB collection in neonates at increased risk of brain damage. Infants from four high-risk groups were included: newborns with perinatal hypoxemia, gestational age (GA) ≤30 + 0 weeks and/or birthweight <1,500 g, intrauterine growth restriction (IUGR), or monochorionic twins with twin-to-twin transfusion syndrome (TTTS). Feasibility of collection, quantity and quality of obtained UCB [total nucleated cell count (TNC), volume, sterility, and cell viability], and neonatal outcome were assessed. UCB collection was successful in 141 of 177 enrolled patients (hypoxemia n = 10; GA ≤30 + 0 weeks n = 54; IUGR n = 71; TTTS n = 6). Twenty-six cases were missed. The amount of missed cases per month declined over the time. Volume of collected UCB ranged widely (median: 24.5 ml, range: 5.0-102 ml) and contained a median of 0.77 × 108 TNC (range: 0.01-13.0 × 108). TNC and UCB volume correlated significantly with GA. A total of 10.7% (19/177) of included neonates developed brain lesions. To conclude, collection of UCB in neonates at high risk of brain damage is feasible with a multidisciplinary approach and intensive training. High prevalence of brain damage makes UCB collection worthwhile. Collected autologous UCB from mature neonates harbors a sufficient cell count for potential therapy. However, quality and quantity of obtained UCB are critical for potential therapy in preterm infants. Therefore, for extremely preterm infants alternative cell sources such as UCB tissue should be investigated for autologous treatment options because of the low yield of UCB.

Differential impact of flow and mouth leak on oropharyngeal humidification during high-flow nasal cannula: a neonatal bench study.

BACKGROUND: Heated humidification is paramount during neonatal high-flow nasal cannula (HFNC) therapy. However, there is little knowledge about the influence of flow rate and mouth leak on oropharyngeal humidification and temperature. METHODS: The effect of the Optiflow HFNC on oropharyngeal gas conditioning was investigated at flow rates of 4, 6 and 8 L min-1 with and without mouth leak in a bench model simulating physiological oropharyngeal air conditions during spontaneous breathing. Temperature and absolute humidity (AH) were measured using a digital thermo-hygrosensor. RESULTS: Without mouth leak, oropharyngeal temperature and AH increased significantly with increasing flow (P < 0.001). Mouth leak did not affect this increase up to 6 L min-1, but at 8 L min-1, temperature and AH plateaued, and the effect of mouth leak became statistically significant (P < 0.001). CONCLUSIONS: Mouth leak during HFNC had a negative impact on oropharyngeal gas conditioning when high flows were applied. However, temperature and AH always remained clinically acceptable.

Relationship between computerized wheeze detection and lung function parameters in young infants.

OBJECTIVE: Computerized respiratory sound analysis (CORSA) has been validated in the assessment of wheeze in infants, but it is unknown whether automatically detected wheeze is associated with impaired lung function. This study investigated the relationship between wheeze detection and conventional lung function testing (LFT) parameters. METHODS: CORSA was performed using the PulmoTrack® monitor in 110 infants, of median (interquartile range) postmenstrual age 50 (46-56) weeks and median body weight 4,810 (3,980-5,900) g, recovering from neonatal intensive care. In the same session, LFT was performed, including tidal breathing measurements, occlusion tests, body plethysmography, forced expiratory flow by rapid thoracoabdominal compression, sulfur hexafluoride (SF6 ) multiple breath washout (MBW), and capillary blood gas analysis. Infants were classified as wheezers or non-wheezers using predefined cut-off values for the duration of inspiratory and expiratory wheeze. RESULTS: Wheezing was detected in 72 (65%) infants, with 43 (39%) having inspiratory and 53 (48%) having expiratory wheezing. Endotracheal mechanical ventilation in the neonatal period for > 24 hr was associated with inspiratory wheeze (P = 0.009). Airway resistance was increased in both inspiratory (P = 0.02) and expiratory (P = 0.004) wheezers and correlated with the duration of expiratory wheeze (r = 0.394, P < 0.001). Expiratory wheezers showed a significant increase in respiratory resistance (P = 0.001), time constant (0.012), and functional residual capacity using SF6 MBW (P = 0.019). There was no association between wheezing and forced expiratory flow or blood gases. CONCLUSION: CORSA can help identify neonates and young infants with subclinical airway obstruction and may prove useful in the follow-up of high-risk infants.

Nasal high-frequency oscillation ventilation in neonates: a survey in five European countries.

UNLABELLED: Nasal high-frequency oscillation ventilation (nHFOV) is a non-invasive ventilation mode that applies an oscillatory pressure waveform to the airways using a nasal interface. nHFOV has been shown to facilitate carbon dioxide expiration, but little is known about its use in neonates. In a questionnaire-based survey, we assessed nHFOV use in neonatal intensive care units (NICUs) in Austria, Switzerland, Germany, the Netherlands, and Sweden. Questions included indications for nHFOV, equipment used, ventilator settings, and observed side effects. Of the clinical directors of 186 NICUs contacted, 172 (92 %) participated. Among those responding, 30/172 (17 %) used nHFOV, most frequently in premature infants <1500 g (27/30) for the indication nasal continuous positive airway pressure (nCPAP) failure (27/30). Binasal prongs (22/30) were the most common interfaces. The median (range) mean airway pressure when starting nHFOV was 8 (6-12) cm H2O, and the maximum mean airway pressure was 10 (7-18) cm H2O. The nHFOV frequency was 10 (6-13) Hz. Abdominal distension (11/30), upper airway obstruction due to secretions (8/30), and highly viscous secretions (7/30) were the most common nHFOV side effects. CONCLUSION: In a number of European NICUs, clinicians use nHFOV. The present survey identified differences in nHFOV equipment, indications, and settings. Controlled clinical trials are needed to investigate the efficacy and side effects of nHFOV in neonates.

Influence of nose and mouth leaks on peripheral oxygen saturation during continuous positive airway pressure in neonates.

BACKGROUND: Nose and mouth leaks impair effective pressure transmission during neonatal continuous positive airway pressure (CPAP), but little is known about how these leaks affect physiological parameters. This study investigated the influence of nose leaks and spontaneous mouth opening on peripheral oxygen saturation (SpO2) and respiratory rate (RR) using nasopharyngeal CPAP. METHODS: In 32 neonates with a gestational age of 30 (24-38) weeks and a birth weight of 1435 (710-2730) g, SpO2 and RR measurements were taken with and without occlusion of the contralateral nostril in a randomized cross-over trial in 1-minute intervals over a 10-minute period during each condition. Mouth opening and newborn activity were documented. RESULTS: SpO2 with open nostril was comparable to that with occluded nostril [93 (78.5-99.5)% vs. 94 (80-100)%, P=0.20]. RR decreased from 51 (26-82)/min to 48 (32-85)/min (P=0.027). In infants with an SpO2 ≤ 93% during open nostril (n=17), SpO2 increased after nostril occlusion [91 (80-96)% vs. 89.5 (78.5-93)%, P=0.036]. The mouth was open in 78.5% of measurements with open nostril, and in 87.4% of measurements after nostril occlusion (P=0.005). No significant influence of mouth opening or closure on SpO2 or RR was detected. CONCLUSIONS: In neonates on unilateral nasopharyngeal CPAP with an SpO2 ≤ 93%, occlusion of the contralateral nostril significantly increased SpO2 and reduced RR. The beneficial physiological effects further support using binasal prongs to minimize nose leaks in this population. Future studies should investigate the beneficial effects of reducing mouth leaks when applying CPAP to these infants.