Practical approaches for supporting informed consent in neonatal clinical trials.

The survival and health of preterm and critically ill infants have markedly improved over the past 50 years, supported by well-conducted neonatal research. However, newborn research is difficult to undertake for many reasons, and obtaining informed consent for research in this population presents several unique ethical and logistical challenges. In this article, we explore methods to facilitate the consent process, including the role of checklists to support meaningful informed consent for neonatal clinical trials. CONCLUSION: The authors provide practical guidance on the design and implementation of an effective consent checklist tailored for use in neonatal clinical research.

Sustained inflation improves initial lung aeration in newborn rabbits with a diaphragmatic hernia.

BACKGROUND: Infants with a congenital diaphragmatic hernia (DH) have underdeveloped lungs and require mechanical ventilation after birth, but the optimal approach is unknown. We hypothesised that sustained inflation (SI) increases lung aeration in newborn kittens with a DH. METHODS: In pregnant New Zealand white rabbits, a left-sided DH was induced in two fetal kittens per doe at 24-days gestation (term = 32 days); litter mates acted as controls. DH and control kittens were delivered by caesarean section at 30 days, intubated and mechanically ventilated (7-10 min) with either an SI followed by intermittent positive pressure ventilation (IPPV) or IPPV throughout. The rate and uniformity of lung aeration was measured using phase-contrast X-ray imaging. RESULTS: Lung weights in DH kittens were ~57% of controls. An SI increased the rate and uniformity of lung aeration in DH kittens, compared to IPPV, and increased dynamic lung compliance in both control and DH kittens. However, this effect of the SI was lost when ventilation changed to IPPV. CONCLUSION: While an SI improved the rate and uniformity of lung aeration in both DH and control kittens, greater consideration of the post-SI ventilation strategy is required to sustain this benefit. IMPACT: Compared to intermittent positive pressure ventilation (IPPV), an initial sustained inflation (SI) increased the rate and uniformity of lung aeration after birth. However, this initial benefit is rapidly lost following the switch to IPPV. The optimal approach for ventilating CDH infants at birth is unknown. While an SI improves lung aeration in immature lungs, its effect on the hypoplastic lung is unknown. This study has shown that an SI greatly improves lung aeration in the hypoplastic lung. This study will guide future studies examining whether an SI can improve lung aeration in infants with a CDH.

Correction: Prediction of mortality in very low birth weight neonates in Spain.

[This corrects the article DOI: 10.1371/journal.pone.0235794.].

Effect of prenatal diaphragmatic hernia on pulmonary arterial morphology.

Congenital diaphragmatic hernia (CDH) is a major cause of severe lung hypoplasia and pulmonary hypertension in the newborn. While the pulmonary hypertension is thought to result from abnormal vascular development and arterial vasoreactivity, the anatomical changes in vascular development are unclear. We have examined the 3D structure of the pulmonary arterial tree in rabbits with a surgically induced diaphragmatic hernia (DH). Fetal rabbits (n = 6) had a left-sided DH created at gestational day 23 (GD23), delivered at GD30, and briefly ventilated; sham-operated litter mates (n = 5) acted as controls. At postmortem the pulmonary arteries were filled with a radio-opaque resin before the lungs were scanned using computed tomography (CT). The 3D reconstructed images were analyzed based on vascular branching hierarchy using the software Avizo 2020.2. DH significantly reduced median number of arteries (2,579 (8440) versus 576 (442), p = .017), artery numbers per arterial generation, mean total arterial volume (43.5 ± 8.4 vs. 19.9 ± 3.1 µl, p = .020) and mean total arterial cross-sectional area (82.5 ± 2.3 vs. 28.2 ± 6.2 mm2 , p =.036). Mean arterial radius was increased in DH kittens between the eighth and sixth branching generation and mean arterial length between the sixth and 28th branching generation. A DH in kittens resulted in threefold reduction in pulmonary arterial cross-sectional area, primarily due to reduced arterial branching. Thus, the reduction in arterial cross-sectional area could be a major contributor to pulmonary hypertension infants with CDH.

Perinatal predictors of clinical instability at birth in late-preterm and term infants.

To identify characteristics associated with delivery room clinical instability in at-risk infants. Prospective cohort study. Two perinatal centres in Melbourne, Australia. Infants born at ≥ 35+0 weeks' gestation with a first-line paediatric doctor requested to attend. Clinical instability defined as any one of heart rate < 100 beats per minute for ≥ 20 s in the first 10 min after birth, maximum fraction of inspired oxygen of ≥ 0.70 in the first 10 min after birth, 5-min Apgar score of < 7, intubated in the delivery room or admitted to the neonatal unit for respiratory support. Four hundred and seventy-three infants were included. The median (IQR) gestational age at birth was 39+4 (38+4-40+4) weeks. Eighty (17%) infants met the criteria for clinical instability. Independent risk factors for clinical instability were labour without oxytocin administration, presence of a medical pregnancy complication, difficult extraction at birth and unplanned caesarean section in labour. Decision tree analysis determined that infants at highest risk were those whose mothers did not receive oxytocin during labour (25% risk). Infants at lowest risk were those whose mothers received oxytocin during labour and did not have a medical pregnancy complication (7% risk). CONCLUSIONS: We identified characteristics associated with clinical instability that may be useful in alerting less experienced clinicians to call for senior assistance early. The decision trees provide intuitive visual aids but require prospective validation. WHAT IS KNOWN: • First-line clinicians attending at-risk births may need to call senior colleagues for assistance depending on the infant's condition. • Delays in effectively supporting a compromised infant at birth is an important cause of neonatal morbidity and infant-mother separation. WHAT IS NEW: • This study identifies risk factors for delivery room clinical instability in at-risk infants born at ≥ 35+0 weeks' gestation. • The decision trees presented provide intuitive visual tools to aid in determining the need for senior paediatric presence.

Respiratory function monitoring during neonatal resuscitation: A systematic review.

Aim: Positive pressure ventilation via a facemask is critical in neonatal resuscitation, but frequently results in mask leak, obstruction, and inadequate respiratory support. This systematic review aimed to determine whether the display of respiratory function monitoring improved resuscitation or clinical outcomes. Methods: Randomized controlled trials comparing outcomes when respiratory function monitoring was displayed versus not displayed for newborns requiring positive pressure ventilation at birth were selected and from databases (last search August 2022), and assessed for risk of bias using Cochrane Risk of Bias Tools for randomized control trials. The study was registered in the Prospective Register of Systematic Reviews. Grading of Recommendations, Assessment, Development and Evaluations was used to assess the certainty of evidence. Treatment recommendations were approved by the Neonatal Life Support Task Force of the International Liaison Committee on Resuscitation. Results reported primary and secondary outcomes and included resuscitation and clinical outcomes. Results: Of 2294 unique articles assessed for eligibility, three randomized controlled trials were included (observational studies excluded) (n = 443 patients). For predefined resuscitation and clinical outcomes, these studies either did not report the primary outcome (time to heart rate ≥ 100 bpm from birth), had differing reporting methods (achieving desired tidal volumes, significant mask leak) or did not find significant differences (intubation rate, air leaks, death before hospital discharge, severe intraventricular hemorrhage, chronic lung disease). Limitations included limited sample size for critical outcomes, inconsistent definitions amongst studies and unreported long-term outcomes. Conclusion: Although respiratory function monitoring has been utilized in clinical care, there is currently insufficient evidence to suggest its benefit for newborn infants receiving respiratory support for resuscitation at birth. Registration: PROSPERO CRD42021278169 (registered November 27, 2021). Funding: The International Liaison Committee on Resuscitation provided support that included access to software platforms and teleconferencing.

Evaluating Clinical Outcomes and Physiological Perspectives in Studies Investigating Respiratory Support for Babies Born at Term With or at Risk of Transient Tachypnea: A Narrative Review.

Respiratory distress in the first few hours of life is a growing disease burden in otherwise healthy babies born at term (>37 weeks gestation). Babies born by cesarean section without labor (i.e., elective cesarean section) are at greater risk of developing respiratory distress due to elevated airway liquid volumes at birth. These babies are commonly diagnosed with transient tachypnea of the newborn (TTN) and historically treatments have mostly focused on enhancing airway liquid clearance pharmacologically or restricting fluid intake with limited success. Alternatively, a number of clinical studies have investigated the potential benefits of respiratory support in newborns with or at risk of TTN, but there is considerable heterogeneity in study designs and outcome measures. A literature search identified eight clinical studies investigating use of respiratory support on outcomes related to TTN in babies born at term. Study demographics including gestational age, mode of birth, antenatal corticosteroid exposure, TTN diagnosis, timing of intervention (prophylactic/interventional), respiratory support (type/interface/device/pressure), and study outcomes were compared. This narrative review provides an overview of factors within and between studies assessing respiratory support for preventing and/or treating TTN. In addition, we discuss the physiological understanding of how respiratory support aids lung function in newborns with elevated airway liquid volumes at birth. However, many questions remain regarding the timing of onset, pressure delivered, device/interface used and duration, and weaning of support. Future studies are required to address these gaps in knowledge to provide evidenced based recommendations for management of newborns with or at risk of TTN.

Time to improve documentation of neonatal resuscitation: a narrative review.

A complete, objective and systematic documentation of delivery room resuscitation is important for research, for quality improvement, for teaching and as a reference for postresuscitation care. However, documentation during neonatal resuscitation is usually paper-based, retrospective, inaccurate and unreliable. In this narrative review, we discuss the strengths and pitfalls of current documentation methods in neonatal resuscitation, as well as the challenges of introducing new or emerging technologies in this field. In particular, we discuss innovations in electronic and automated medical records, video recording and Smartphones and Tablet Apps. Given the lack of a consensus standard, we finally propose a list of items that should be part of any neonatal resuscitation documentation method.

Higher CPAP levels improve functional residual capacity at birth in preterm rabbits.

BACKGROUND: Preterm infants are commonly supported with 4-8 cm H2O continuous positive airway pressures (CPAP), although higher CPAP levels may improve functional residual capacity (FRC). METHODS: Preterm rabbits delivered at 29/32 days (~26-28 weeks human) gestation received 0, 5, 8, 12, 15 cm H2O of CPAP or variable CPAP of 15 to 5 or 15 to 8 cm H2O (decreasing ~2 cm H2O/min) for up to 10 min after birth. RESULTS: FRC was lower in the 0 (6.8 (1.0-11.2) mL/kg) and 5 (10.1 (1.1-16.8) mL/kg) compared to the 15 (18.8 (10.9-22.4) mL/kg) cm H2O groups (p = 0.003). Fewer kittens achieved FRC > 15 mL/kg in the 0 (20%), compared to 8 (36%), 12 (60%) and 15 (73%) cm H2O groups (p = 0.008). While breathing rates were not different (p = 0.096), apnoea tended to occur more often with CPAP < 8 cm H2O (p = 0.185). CPAP belly and lung bulging rates were similar whereas pneumothoraces were rare. Lowering CPAP from 15 to 5, but not 15 to 8 cm H2O, decreased FRC and breathing rates. CONCLUSION: In all, 15 cm H2O of CPAP improved lung aeration and reduced apnoea, but did not increase the risk of lung over-expansion, pneumothorax or CPAP belly immediately after birth. FRC and breathing rates were maintained when CPAP was decreased to 8 cm H2O. IMPACT: Although preterm infants are commonly supported with 4-8 cm H2O CPAP at birth, preclinical studies have shown that higher PEEP levels improve lung aeration. In this study, CPAP levels of 15 cm H2O improved lung aeration and reduced apnoea in preterm rabbit kittens immediately after birth. In all, 15 cm H2O CPAP did not increase the risk of lung over-expansion (indicated by bulging between the ribs), pneumothorax, or CPAP belly. These results can be used when designing future studies on CPAP strategies for preterm infants in the delivery room.

Sustained Inflation Versus Intermittent Positive Pressure Ventilation for Preterm Infants at Birth: Respiratory Function and Vital Sign Measurements.

OBJECTIVE: To characterize respiratory function monitor (RFM) measurements of sustained inflations and intermittent positive pressure ventilation (IPPV) delivered noninvasively to infants in the Sustained Aeration of Infant Lungs (SAIL) trial and to compare vital sign measurements between treatment arms. STUDY DESIGN: We analyzed RFM data from SAIL participants at 5 trial sites. We assessed tidal volumes, rates of airway obstruction, and mask leak among infants allocated to sustained inflations and IPPV, and we compared pulse rate and oxygen saturation measurements between treatment groups. RESULTS: Among 70 SAIL participants (36 sustained inflations, 34 IPPV) with RFM measurements, 40 (57%) were spontaneously breathing prior to the randomized intervention. The median expiratory tidal volume of sustained inflations administered was 5.3 mL/kg (IQR 1.1-9.2). Significant mask leak occurred in 15% and airway obstruction occurred during 17% of sustained inflations. Among 34 control infants, the median expiratory tidal volume of IPPV inflations was 4.3 mL/kg (IQR 1.3-6.6). Mask leak was present in 3%, and airway obstruction was present in 17% of IPPV inflations. There were no significant differences in pulse rate or oxygen saturation measurements between groups at any point during resuscitation. CONCLUSION: Expiratory tidal volumes of sustained inflations and IPPV inflations administered in the SAIL trial were highly variable in both treatment arms. Vital sign values were similar between groups throughout resuscitation. Sustained inflation as operationalized in the SAIL trial was not superior to IPPV to promote lung aeration after birth in this study subgroup. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02139800.

Increased end-expiratory pressures improve lung function in near-term newborn rabbits with elevated airway liquid volume at birth.

Approximately 53% of near-term newborns admitted to intensive care experience respiratory distress. These newborns are commonly delivered by cesarean section and have elevated airway liquid volumes at birth, which can cause respiratory morbidity. We investigated the effect of providing respiratory support with a positive end-expiratory pressure (PEEP) of 8 cmH2O on lung function in newborn rabbit kittens with elevated airway liquid volumes at birth. Near-term rabbits (30 days; term = 32 days) with airway liquid volumes that corresponded to vaginal delivery (∼7 mL/kg, control, n = 11) or cesarean section [∼37 mL/kg; elevated liquid (EL), n = 11] were mechanically ventilated (tidal volume = 8 mL/kg). The PEEP was changed after lung aeration from 0 to 8 to 0 cmH2O (control, n = 6; EL, n = 6), and in a separate group of kittens, PEEP was changed after lung aeration from 8 to 0 to 8 cmH2O (control, n = 5; EL, n = 5). Lung function (ventilator parameters, compliance, lung gas volumes, and distribution of gas within the lung) was evaluated using plethysmography and synchrotron-based phase-contrast X-ray imaging. EL kittens initially receiving 0 cmH2O PEEP had reduced functional residual capacities and lung compliance, requiring higher inflation pressures to aerate the lung compared with control kittens. Commencing ventilation with 8 cmH2O PEEP mitigated the adverse effects of EL, increasing lung compliance, functional residual capacity, and the uniformity and distribution of lung aeration, but did not normalize aeration of the distal airways. Respiratory support with PEEP supports lung function in near-term newborn rabbits with elevated airway liquid volumes at birth who are at a greater risk of suffering respiratory distress.NEW & NOTEWORTHY Term babies born by cesarean section have elevated airway liquid volumes, which predisposes them to respiratory distress. Treatments targeting molecular mechanisms to clear lung liquid are ineffective for term newborn respiratory distress. We showed that respiratory support with an end-expiratory pressure supports lung function in near-term rabbits with elevated airway liquid volumes at birth. This study provides further physiological understanding of lung function in newborns with elevated airway liquid volumes at risk of respiratory distress.

Respiratory support after delayed cord clamping: a prospective cohort study of at-risk births at ≥35+0 weeks gestation.

OBJECTIVE: To identify risk factors associated with delivery room respiratory support in at-risk infants who are initially vigorous and received delayed cord clamping (DCC). DESIGN: Prospective cohort study. SETTING: Two perinatal centres in Melbourne, Australia. PATIENTS: At-risk infants born at ≥35+0 weeks gestation with a paediatric doctor in attendance who were initially vigorous and received DCC for >60 s. MAIN OUTCOME MEASURES: Delivery room respiratory support defined as facemask positive pressure ventilation, continuous positive airway pressure and/or supplemental oxygen within 10 min of birth. RESULTS: Two hundred and ninety-eight infants born at a median (IQR) gestational age of 39+3 (38+2-40+2) weeks were included. Cord clamping occurred at a median (IQR) of 128 (123-145) s. Forty-four (15%) infants received respiratory support at a median of 214 (IQR 156-326) s after birth. Neonatal unit admission for respiratory distress occurred in 32% of infants receiving delivery room respiratory support vs 1% of infants who did not receive delivery room respiratory support (p<0.001). Risk factors independently associated with delivery room respiratory support were average heart rate (HR) at 90-120 s after birth (determined using three-lead ECG), mode of birth and time to establish regular cries. Decision tree analysis identified that infants at highest risk had an average HR of <165 beats per minute at 90-120 s after birth following caesarean section (risk of 39%). Infants with an average HR of ≥165 beats per minute at 90-120 s after birth were at low risk (5%). CONCLUSIONS: We present a clinical decision pathway for at-risk infants who may benefit from close observation following DCC. Our findings provide a novel perspective of HR beyond the traditional threshold of 100 beats per minute.

Time to desaturation in preterm infants undergoing endotracheal intubation.

BACKGROUND: Neonatal endotracheal intubation is often associated with physiological instability. The Neonatal Resuscitation Program recommends a time-based limit (30 s) for intubation attempts in the delivery room, but there are limited physiological data to support recommendations in the neonatal intensive care unit (NICU). We aimed to determine the time to desaturation after ceasing spontaneous or assisted breathing in preterm infants undergoing elective endotracheal intubation in the NICU. METHODS: Observational study at The Royal Women's Hospital, Melbourne. A secondary analysis was performed of video recordings of neonates ≤32 weeks' postmenstrual age undergoing elective intubation. Infants received premedication including atropine, a sedative and muscle relaxant. Apnoeic oxygenation time (AOT) was defined as the time from the last positive pressure or spontaneous breath until desaturation (SpO2 <90%). RESULTS: Seventy-eight infants were included. The median (IQR) gestational age at birth was 27 (26-29) weeks and birth weight 946 (773-1216) g. All but five neonates desaturated to SpO2 <90% (73/78, 94%). The median (IQR) AOT was 22 (14-32) s. The median (IQR) time from ceasing positive pressure ventilation to desaturation <80% was 35 (24-44) s and to desaturation <60% was 56 (42-68) s. No episodes of bradycardia were seen. CONCLUSIONS: This is the first study to report AOT in preterm infants. During intubation of preterm infants in the NICU, desaturation occurs quickly after cessation of positive pressure ventilation. These data are important for the development of clinical guidelines for neonatal intubation. TRIAL REGISTRATION NUMBER: ACTRN12614000709640.

Neonatal videolaryngoscopy as a teaching aid: the trainees' perspective.

INTRODUCTION: Neonatal intubation is a challenging skill to acquire. A randomised controlled trial (RCT) found junior trainees had higher intubation success rates if their supervisor shared their airway view on a videolaryngoscope screen compared with intubations where the supervisor could not see the videolaryngoscope screen. The intubations in the trial were supervised by a group of experienced neonatologists who developed an intubation teaching package that aimed to be informative, consistent and supportive. We surveyed the trainees to assess their experiences of the intubation attempts. METHODS: Trainees participating in the RCT completed questionnaires anonymously after each intubation attempt. Questionnaires used 5-point Likert scales and free comment sections. Quantitative analysis was performed using descriptive statistics. In a qualitative analysis, free comments were coded to identify central recurring themes. RESULTS: Two hundred and six questionnaires were completed by 36 trainees. The majority reported that the guidance received during intubation was helpful, the postprocedure feedback was educational and their confidence levels were increased. Trainees appreciated a controlled environment and calm, consistent guidance. They found intubations in the delivery room, those involving unstable infants, large audiences and parental presence more stressful. Responses were positive whether the videolaryngoscope screen was visible or covered, emphasising the importance of consistent guidance. Overall, 16% of intubations were reported as intimidating. CONCLUSION: The shared airway view offered by videolaryngoscopy was well received. In addition, taking measures to control the setting, with standardised guidance and feedback, improved confidence and created a more positive learning experience.

Documentation during neonatal resuscitation: a systematic review.

OBJECTIVE: Accurate documentation in healthcare is necessary for ethical, legal, research and quality improvement purposes. In this review, we aimed to evaluate the accuracy of methods of documentation of delivery room resuscitations. METHODS: A systematic literature search in MEDLINE was conducted to identify original studies that reported the quality of documentation records during newborn resuscitation in the delivery room. Data extracted from the studies included population characteristics, methodology, documentation protocols, use of gold standard and main results (initial assessment of heart rate and peripheral oxygen saturation, respiratory support and supplementary oxygen). RESULTS: In total, 197 records were screened after initial database search, of which seven studies met the inclusion criteria and were finally included in this review. Four studies were chart reviews and three studies compared conventional documentation methods with video recording. Only one study tested an intervention to improve documentation. Documentation was often inaccurate and important resuscitation events and interventions were poorly recorded. Lack of uniformity among studies preclude pooled analysis, but it seems that complex or advanced procedures were more accurately reported than basic interventions. CONCLUSIONS: There is little literature regarding accuracy of documentation during neonatal resuscitation, but current quality of documentation seems to be unsatisfactory. There is a need for consensus guidelines and innovative solutions in newborn resuscitation documentation.

Prediction of mortality in very low birth weight neonates in Spain.

OBJECTIVE: Predictive models for preterm infant mortality have been developed internationally, albeit not valid for all populations. This study aimed to develop and validate different mortality predictive models, using Spanish data, to be applicable to centers with similar morbidity and mortality. METHODS: Infants born alive, admitted to NICU (BW<1500 g or GA<30 w), and registered in the SEN1500 database, were included. There were two time periods; development of the predictive models (2009-2012) and validation (2013-2015). Three models were produced; prenatal (1), first 24 hours of life (2), and whilst admitted (3). For the statistical analysis, hospital mortality was the dependent variable. Significant variables were used in multivariable regression models. Specificity, sensitivity, accuracy, and area under the curve (AUC), for all models, were calculated. RESULTS: Out of 14953 included newborns, 2015 died; 373 (18.5%) in their first 24 hours, 1315 (65.3%) during the first month, and 327 (16.2%) thereafter, before discharge. In the development stage, mortality prediction AUC was 0.834 (95% CI: 0.822-0.846) (p<0.001) in model 1 and 0.872 (95% CI: 0.860-0.884) (p<0.001) in model 2. Model 3's AUC was 0.989 (95% CI: 0.983-0.996) (p<0.001) and 0.942 (95% CI: 0.929-0.956) (p<0.001) during the 0-30 and >30 days of life, respectively. During validation, models 1 and 2 showed moderate concordance, whilst that of model 3 was good. CONCLUSION: Using dynamic models to predict individual mortality can improve outcome estimations. Development of models in the prenatal period, first 24 hours, and during hospital admission, cover key stages of mortality prediction in preterm infants.

Predicción de mortalidad en recién nacidos prematuros. Revisión sistemática actualizada / Prediction of mortality in premature neonates. An updated systematic review

INTRODUCCIÓN: La prematuridad extrema se asocia a altas tasas de mortalidad. Para profesionales y familias, es prioritario establecer de forma individualizada las probabilidades de muerte en diferentes momentos. El objetivo de este estudio es efectuar una revisión sistemática de modelos predictivos de mortalidad en prematuros publicados recientemente. MÉTODOS: Doble búsqueda de artículos publicados en PubMed sobre modelos predictivos de muerte en prematuros. Población estudiada: prematuros con edad gestacional ≤ 30 semanas o peso al nacer ≤ 1.500 g. Inclusión: trabajos publicados con nuevos modelos desde junio del 2010 hasta julio del 2019, tras revisión sistemática de Medlock (2011). Se valoran: población, características de modelos, variables utilizadas, medidas de funcionamiento y validación. RESULTADOS: De 7.744 referencias (primera búsqueda) y 1.435 (segunda búsqueda), se seleccionaron 31 trabajos, incluyéndose al final 8 nuevos modelos. Cinco modelos (62,5%) se desarrollaron en América del Norte y 2 (25%) en Europa. Un modelo secuencial (Ambalavanan) permite realizar predicciones de muerte al nacer, 7, 28 días de vida y 36 semanas posmenstruales. Análisis de regresión logística múltiple en el 87,5% de modelos. La discriminación poblacional se midió por odds ratio (75%) y área bajo la curva (50%). La «validación» se ha realizado en 5 modelos (interna). Tres modelos disponen de acceso online. No hay modelos predictivos validados en España. CONCLUSIONES: La toma de decisiones basada en modelos predictivos permite una mayor individualización de la atención dada a un niño prematuro y una mejor utilización de recursos. Es necesario desarrollar modelos de predicción de mortalidad en prematuros de España

INTRODUCTION: Extreme prematurity is associated with high mortality rates. The probability of death at different points in time is a priority for professionals and parents, and needs to be established on an individual basis. The aim of this study is to carry out a systematic review of predictive models of mortality in premature infants that have been published recently. METHODS: A double search was performed for article published in PubMed on models predicting mortality in premature neonates. The population studied were premature neonates with a gestational age of ≤ 30 weeks and / or a weight at birth of ≤ 1500g. Works published with new models from June 2010 to July 2019 after a systematic review by Medlock (2011) were included. An assessment was made of the population, characteristics of the model, variables used, measurements of functioning, and validation. RESULTS: Of the 7744 references (1st search) and 1435 (2nd search) found, 31 works were selected, with 8 new models finally being included. Five models (62.5%) were developed in North America and 2 (25%) in Europe. A sequential model (Ambalavanan) enables predictions of mortality to be made at birth, 7, 28 days of life, and 36 weeks post-menstrual. A multiple logistic regression analysis was performed on 87.5% of the models. The population discrimination was measured using Odds Ratio (75%) and the area under the curve (50%). "Internal Validation" had been carried out on 5 models. Three models can be accessed on-line. There are no predictive models validated in Spain. CONCLUSIONS: The making of decisions based on predictive models can lead to the care given to the premature infant being more individualised and with a better use of resources. Predictive models of mortality in premature neonates in Spain need to be developed

[Prediction of mortality in premature neonates. An updated systematic review]. / Predicción de mortalidad en recién nacidos prematuros. Revisión sistemática actualizada.

INTRODUCTION: Extreme prematurity is associated with high mortality rates. The probability of death at different points in time is a priority for professionals and parents, and needs to be established on an individual basis. The aim of this study is to carry out a systematic review of predictive models of mortality in premature infants that have been published recently. METHODS: A double search was performed for article published in PubMed on models predicting mortality in premature neonates. The population studied were premature neonates with a gestational age of ≤30 weeks and / or a weight at birth of ≤1500g. Works published with new models from June 2010 to July 2019 after a systematic review by Medlock (2011) were included. An assessment was made of the population, characteristics of the model, variables used, measurements of functioning, and validation. RESULTS: Of the 7744 references (1st search) and 1435 (2nd search) found, 31 works were selected, with 8 new models finally being included. Five models (62.5%) were developed in North America and 2 (25%) in Europe. A sequential model (Ambalavanan) enables predictions of mortality to be made at birth, 7, 28 days of life, and 36 weeks post-menstrual. A multiple logistic regression analysis was performed on 87.5% of the models. The population discrimination was measured using Odds Ratio (75%) and the area under the curve (50%). "Internal Validation" had been carried out on 5 models. Three models can be accessed on-line. There are no predictive models validated in Spain. CONCLUSIONS: The making of decisions based on predictive models can lead to the care given to the premature infant being more individualised and with a better use of resources. Predictive models of mortality in premature neonates in Spain need to be developed.

Tidal volumes at birth as predictor for adverse outcome in congenital diaphragmatic hernia.

OBJECTIVE: To assess the predictive value of tidal volume (Vt) of spontaneous breaths at birth in infants with congenital diaphragmatic hernia (CDH). DESIGN: Prospective study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: Thirty infants with antenatally diagnosed CDH born at Hospital Sant Joan de Déu in Barcelona from September 2013 to September 2015. INTERVENTIONS: Spontaneous breaths and inflations given in the first 10 min after intubation at birth were recorded using respiratory function monitor. Only expired Vt of uninterrupted spontaneous breaths was included for analysis. Receiver operating characteristics (ROC) analysis was performed and the area under the curve (AUC) was estimated to assess the predictive accuracy of Vt. MAIN OUTCOME MEASURES: Mortality before hospital discharge and chronic lung disease (CLD) at day 28 of life. RESULTS: There were 1.233 uninterrupted spontaneous breaths measured, and the overall mean Vt was 2.8±2.1 mL/kg. A lower Vt was found in infants who died (n=14) compared with survivors (n=16) (1.7±1.6 vs 3.7±2.1 mL/kg; p=0.008). Vt was lower in infants who died during admission or had CLD (n=20) compared with survivors without CLD (n=10) (2.0±1.7 vs 4.3±2.2 mL/kg; p=0.004). ROC analysis showed that Vt ≤2.2 mL/kg predicted mortality with 79% sensitivity and 81% specificity (AUC=0.77, p=0.013). Vt ≤3.4 mL/kg was a good predictor of death or CLD (AUC=0.80, p=0.008) with 85% sensitivity and 70% specificity. CONCLUSION: Vt of spontaneous breaths measured immediately after birth is associated with mortality and CLD. Vt seems to be a reliable predictor but is not an independent predictor after adjustment for observed/expected lung to head ratio and liver position.