Effect of Cerebral Oximetry-Guided Treatment on Brain Injury in Preterm Infants as Assessed by Magnetic Resonance Imaging at Term Equivalent Age: An Ancillary SafeBoosC-III Study.

INTRODUCTION: The SafeBoosC-III trial investigated the effect of cerebral oximetry-guided treatment in the first 72 h after birth on mortality and severe brain injury diagnosed by cranial ultrasound in extremely preterm infants (EPIs). This ancillary study evaluated the effect of cerebral oximetry on global brain injury as assessed by magnetic resonance imaging (MRI) at term equivalent age (TEA). METHODS: MRI scans were obtained between 36 and 44.9 weeks PMA. The Kidokoro score was independently evaluated by two blinded assessors. The intervention effect was assessed using the nonparametric Wilcoxon rank sum test for median difference and 95% Hodges-Lehmann (HL) confidence intervals (CIs). The intraclass correlation coefficient (ICC) was used to assess the agreement between the assessors. RESULTS: A total of 210 patients from 8 centers were included, of whom 121 underwent MRI at TEA (75.6% of alive patients): 57 in the cerebral oximetry group and 64 in the usual care group. There was an excellent correlation between the assessors for the Kidokoro score (ICC agreement: 0.93, 95% CI: 0.91-0.95). The results showed no significant differences between the cerebral oximetry group (median 2, interquartile range [IQR]: 1-4) and the usual care group (median 3, IQR: 1-4; median difference -1 to 0, 95% HLCI: -1 to 0; p value 0.1196). CONCLUSIONS: In EPI, the use of cerebral oximetry-guided treatment did not lead to significant alterations in brain injury, as determined by MRI at TEA. The strong correlation between the assessors highlights the potential of the Kidokoro score in multicenter trials.

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

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

An Artificial Placenta Experimental System in Sheep: Critical Issues for Successful Transition and Survival up to One Week.

OBJECTIVE: To describe the development of an artificial placenta (AP) system in sheep with learning curve and main bottlenecks to allow survival up to one week. METHODS: A total of 28 fetal sheep were transferred to an AP system at 110-115 days of gestation. The survival goal in the AP system was increased progressively in three consecutive study groups: 1-3 h (n = 8), 4-24 h (n = 10) and 48-168 h (n = 10). Duration of cannulation procedure, technical complications, pH, lactate, extracorporeal circulation (EC) circuit flows, fetal heart rate, and outcomes across experiments were compared. RESULTS: There was a progressive reduction in cannulation complications (75%, 50% and 0%, p = 0.004), improvement in initial pH (7.20 ± 0.06, 7.31 ± 0.04 and 7.33 ± 0.02, p = 0.161), and increment in the rate of experiments reaching survival goal (25%, 70% and 80%, p = 0.045). In the first two groups, cannulation accidents, air bubbles in the extracorporeal circuit, and thrombotic complications were the most common cause of AP system failure. CONCLUSIONS: Achieving a reproducible experimental setting for an AP system is extremely challenging, time- and effort-consuming, and requires a highly multidisciplinary team. As a result of the learning curve, we achieved reproducible transition and survival up to 7 days. Extended survival requires improving instrumentation with custom-designed devices.

Extremely Preterm Infant Admissions Within the SafeBoosC-III Consortium During the COVID-19 Lockdown.

Objective: To evaluate if the number of admitted extremely preterm (EP) infants (born before 28 weeks of gestational age) differed in the neonatal intensive care units (NICUs) of the SafeBoosC-III consortium during the global lockdown when compared to the corresponding time period in 2019. Design: This is a retrospective, observational study. Forty-six out of 79 NICUs (58%) from 17 countries participated. Principal investigators were asked to report the following information: (1) Total number of EP infant admissions to their NICU in the 3 months where the lockdown restrictions were most rigorous during the first phase of the COVID-19 pandemic, (2) Similar EP infant admissions in the corresponding 3 months of 2019, (3) the level of local restrictions during the lockdown period, and (4) the local impact of the COVID-19 lockdown on the everyday life of a pregnant woman. Results: The number of EP infant admissions during the first wave of the COVID-19 pandemic was 428 compared to 457 in the corresponding 3 months in 2019 (-6.6%, 95% CI -18.2 to +7.1%, p = 0.33). There were no statistically significant differences within individual geographic regions and no significant association between the level of lockdown restrictions and difference in the number of EP infant admissions. A post-hoc analysis based on data from the 46 NICUs found a decrease of 10.3%in the total number of NICU admissions (n = 7,499 in 2020 vs. n = 8,362 in 2019). Conclusion: This ad hoc study did not confirm previous reports of a major reduction in the number of extremely pretermbirths during the first phase of the COVID-19 pandemic. Clinical Trial Registration: ClinicalTrial.gov, identifier: NCT04527601 (registered August 26, 2020), https://clinicaltrials.gov/ct2/show/NCT04527601.

[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.

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.

Amplitude Integrated Electroencephalogram as a Prognostic Tool in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review.

INTRODUCTION: Perinatal management and prognostic value of clinical evaluation and diagnostic tools have changed with the generalization of therapeutic hypothermia (TH) in infants with hypoxic-ischemic encephalopathy (HIE). AIM: to ascertain the prognostic value of amplitude integrated electroencephalogram (aEEG) in neonates with HIE considering hours of life and treatment with TH. METHODS: A systematic review was performed. Inclusion criteria were studies including data of neonates with HIE, treated or not with TH, monitored with aEEG and with neurodevelopmental follow-up of at least 12 months. The period of bibliographic search was until February 2016. No language restrictions were initially applied. Consulted databases were MEDLINE, Scopus, CINHAL and the Spanish language databases GuiaSalud and Bravo. Article selection was performed by two independent reviewers. Quality for each individual paper selected was evaluated using QUADAS-2. Review Manager (RevMan) version 5.3 software was used. Forest plots were constructed to graphically show sensitivity and specificity for all included studies, separating patients treated or not with hypothermia. Summary statistics were estimated using bivariate models and random effects approaches with the R package MADA from summary ROC curves. Meta-regression was used to estimate heterogeneity and trends. RESULTS: from the 403 articles initially identified, 17 were finally included and critically reviewed. In infants not treated with hypothermia the maximum reliability of an abnormal aEEG background to predict death or moderate/severe disability was at 36 hours of life, when a positive post-test probability of 97.90% was achieved (95%CI 88.40 to 99.40%). Positive likelihood ratio (+LR) at these hours of life was 26.60 (95%CI 4.40 to 94.90) and negative likelihood ratio (-LR) was 0.23 (95%CI 0.10 to 0.44). A high predictive value was already present at 6 hours of life in this group of patients, with a positive post-test probability of 88.20% (95%CI 79.80 to 93%) and a +LR of 4.34 (95%CI 2.31 to 7.73). In patients treated with TH the maximum predictive reliability was achieved at 72 hours of life (post-test probability of 95.70%, 95%CI 84.40 to 98.50%). +LR at this age was 24.30 (95%CI 5.89 to 71.30) and-LR was 0.40 (95%CI 0.25 to 0.57). Predictive value of aEEG at 6 hours of life was low in these patients (59.10%, 95%CI 55.70 to 63%). CONCLUSION: This study confirms that aEEG´s background activity, as recorded during the first 72 hours after birth, has a strong predictive value in infants with HIE treated or not with TH. Predictive values of traces throughout the following 72 hours are a helpful guide when considering and counselling parents about the foreseeable long-term neurological outcome.

Changes in Parenteral Nutrition During the First Week of Life Influence Early but Not Late Postnatal Growth in Very Low-Birth-Weight Infants.

BACKGROUND AND AIMS: Postnatal growth restriction remains a serious problem in very low-birth-weight infants. Enhanced parenteral supply of nutrients as soon as possible after birth is one of the strategies addressed to avoid extrauterine growth restriction. We aimed to analyze changes in growth patterns and in clinical outcomes in our unit after a change in our parenteral nutrition (PN) protocol. METHODS: We collected data from 2 time periods, comprising the 2 years before (period I) and the 2 years after (period II) the change of protocol. We included 142 very low-birth-weight infants ≤32 weeks of gestation with a birth weight ≤1500 g. Data regarding nutrition intakes (parenteral and enteral) in the first week of life, growth during admission, and clinical outcomes were retrieved from clinical charts. RESULTS: Babies in period II received a higher nutrition supply during the first week of life, but no further differences were found after this period. Weight at 14 days of life was significantly higher in period II but not at day 28 of life or discharge. CONCLUSIONS: In our population, an enhanced PN regimen for very low-birth-weight infants led to a better growth at 14 days of life. However, this positive effect had disappeared at day 28 of life. Strategies to improve nutrient supply once the preterm baby is stable and on full enteral feeds should be implemented and analyzed.