Neonatal ventriculomegaly: Pathophysiology and management guided with cranial ultrasonography.

Neonatal ventriculomegaly often, but not always, follows intraventricular haemorrhage in infants born preterm. Serial cranial ultrasonography (CUS) is a very useful tool to evaluate the mechanism behind ventricular dilatation, to differentiate several types of cerebrospinal fluid retention, and to guide treatment. This review examines neonatal ventriculomegaly and its definition, pathophysiology, treatment, and prognosis from the perspective of CUS assessment. It also outlines the consensus statements formulated by the EurUS.Brain group, which are based on rounds of expert opinions on neonatal ventriculomegaly management, detailing the need and timing of ventricular access device placement, in the context of posthaemorrhagic ventricular dilation. The pathophysiology of neonatal ventriculomegaly is more complex than previously considered. CUS is a valuable, non-invasive tool to determine pathophysiology, intervention thresholds, and prognosis in neonates with ventriculomegaly. Given new insights into the existence of glymphatics and water circulation in the cerebrum, further research in that area may bring new treatment options.

Association between early echocardiography screening of low systemic blood flow and intraventricular hemorrhage in preterm infants: a multicenter cohort study.

OBJECTIVE: To determine whether early echocardiography screening of low systemic blood flow reduces intraventricular hemorrhage in preterm infants. STUDY DESIGN: Prospective multicenter study in preterm infants below 33 weeks of gestational age at nine neonatal units. Five units performed early echocardiography screening for low systemic blood flow and guided clinical management (exposure group) and 4 units did not (control group). Our main outcome was ≥grade II intraventricular hemorrhage or death within the first 7 days of life. The main analysis used the inverse probability of treatment weighting. RESULTS: Three hundred and thirty-two preterm infants (131 in the exposure group and 201 in the control group) were included. Exposure to early echocardiography screening was associated with a significant reduction in ≥grade II intraventricular hemorrhage or early death [odds ratio 0.285 (95% CI: 0.133-0.611); p = 0.001]. CONCLUSIONS: Early echocardiography screening for low systemic blood flow may reduce the incidence of intraventricular hemorrhage in preterm infants.

Predicting the effectiveness of drugs used for treating cardiovascular conditions in newborn infants.

BACKGROUND: Cardiovascular support (CVS) treatment failure (TF) is associated with a poor prognosis in preterm infants. METHODS: Medical charts of infants with a birth weight <1500 g who received either dopamine (Dp) or dobutamine (Db), were reviewed. Treatment response (TR) occurred if blood pressure increased >3rd centile for gestational age or superior vena cava flow was maintained >55 ml/kg/min, with decreased lactate or less negative base excess, without additional CVS. A predictive model of Dp and Db on TR was designed and the impact of TR on survival was analyzed. RESULTS: Sixty-six infants (median gestational age 27.3 weeks, median birth weight 864 g) received Dp (n = 44) or Db (n = 22). TR occurred in 59% of the cases treated with Dp and 31% with Db, p = 0.04. Machine learning identified a model that correctly labeled Db response in 90% of the cases and Dp response in 61.4%. Sixteen infants died (9% of the TR group, 39% of the TF group; p = 0.004). Brain or gut morbidity-free survival was observed in 52% vs 30% in the TR and TF groups, respectively (p = 0.08). CONCLUSIONS: New predictive models can anticipate Db but not Dp effectiveness in preterm infants. These algorithms may help the clinicians in the decision-making process. IMPACT: Failure of cardiovascular support treatment increases the risk of mortality in very low birth weight infants. A predictive model built with machine learning techniques can help anticipate treatment response to dobutamine with high accuracy. Predictive models based on artificial intelligence may guide the clinicians in the decision-making process.

Posthemorrhagic ventricular dilatation late intervention threshold and associated brain injury.

OBJECTIVE: To systematically assess white matter injury (WMI) in preterm infants with posthemorrhagic ventricular dilatation (PHVD) using a high-threshold intervention strategy. STUDY DESIGN: This retrospective analysis included 85 preterm infants (≤34 weeks of gestation) with grade 2-3 germinal matrix-intraventricular hemorrhage. Cranial ultrasound (cUS) scans were assessed for WMI and ventricular width and shape. Forty-eight infants developed PHVD, 21 of whom (intervention group) underwent cerebrospinal fluid drainage according to a predefined threshold (ventricular index ≥p97+4 mm or anterior horn width >10 mm, and the presence of frontal horn ballooning). The other 27 infants underwent a conservative approach (non-intervention group). The two PHVD groups were compared regarding ventricular width at two stages: the worst cUS for the non-intervention group (scans showing the largest ventricular measurements) versus pre-intervention cUS in the intervention group, and at term equivalent age. WMI was classified as normal/mild, moderate and severe. RESULTS: The intervention group showed significantly larger ventricular index, anterior horn width and thalamo-occipital diameter than the non-intervention group at the two timepoints. Moderate and severe WMI were more frequent in the infants with PHVD (p<0.001), regardless of management (intervention or conservative management). There was a linear relationship between the severity of PHVD and WMI (p<0.001). CONCLUSIONS: Preterm infants with PHVD who undergo a high-threshold intervention strategy associate an increased risk of WMI.

Predictive Model of Early Spontaneous Ductus Arteriosus Closure Based on Neonatologist Performed Echocardiography in Preterm Infants.

Background: Patent ductus arteriosus (PDA) treatment remains controversial. Modeling on the predictive capacity of early spontaneous PDA closure would help in decision-making. Aim: To design a predictive model of early spontaneous PDA closure. Methods: As part of a trial to assess efficacy and safety of two ibuprofen treatment schemes for PDA, infants below 29 weeks' gestation were scanned between 18 and 72 h of birth, and serially if indicated. PDA treatment was decided based on echocardiography signs of lung overflow or systemic hypoperfusion and clinical criteria. A PDA score that included the echocardiographic parameters significantly associated with treatment prescription was retrospectively applied. Perinatal variables and screening score were included in a backwards elimination model to predict early spontaneous closure. Results: Among 87 eligible infants (27 weeks' gestation; age at screening 45 h), 21 received ibuprofen at 69 h of life [screening score = 7 (IQR = 5-8.5); score at treatment = 9 (IQR = 8-9)], while 42 infants had conservative management, [screening score = 1 (IQR = 0-4)]. Twenty four infants were excluded (ibuprofen contraindication, declined consent or incomplete echocardiography). Screening score showed an AUC = 0.93 to predict early spontaneous PDA closure, [cut-off value = 4.5 (sensitivity = 0.90, specificity = 0.86)]. The predictive model for early spontaneous PDA closure followed the equation: Log (p/1-p) = -28.41 + 1.23* gestational age -0.87* PDA screening score. Conclusions: A predictive model of early spontaneous PDA closure that includes gestational age and the screening PDA score is proposed to help clinicians in the decision- making for PDA treatment. In addition, this model could be used in future intervention trials aimed to prevent PDA related morbidities to improve the eligibility criteria.

Randomised trial of dobutamine versus placebo for low superior vena cava flow in preterm infants: Long-term neurodevelopmental outcome.

AIM: Although circulatory impairment during the transitional circulation associates morbidity and mortality, its treatment remains controversial. In a pilot trial on circulatory impairment defined as low superior vena cava (SVC) flow, dobutamine (Db) versus placebo (PL) showed a trend towards improved short-term outcomes. The purpose of this study was to report on the long-term outcome of the infants who were observed for SVC flow patterns. METHODS: Among the 126 infants <31 weeks of gestation prospectively scanned from birth, 28 presented low SVC flow within the first 24 h after birth and received Db (n = 16) or PL (n = 12). Follow-up of survivors included motor assessment and Bayley Scales II or III at 2 years, and the Reynolds Intellectual Assessment Scale at 6 years. Neurodevelopmental impairment (NDI) was defined as: cerebral palsy (Gross Motor Function Classification System ≥ level 2), or a cognitive function score < -2 standard deviations; or moderate or severe hearing or visual impairment. Db group, PL group and normal-flow group were compared. RESULTS: Eighteen infants died (Db: 5; PL: 2; normal flow group: 11, P = 0.1). Follow-up in survivors was accomplished in 80% and 55% of the cohort at 2 years and 6 years, respectively. No significant difference in the combined outcome (mortality or NDI) was found between the groups (42% Db, 36% PL, 30% normal flow group). CONCLUSIONS: This exploratory analysis did not show any differences in the long-term outcome of infants according to SVC flow patterns or its treatment early after birth.

Randomized Trial on Echocardiography-Guided Ductus Arteriosus Treatment to Reduce Necrotizing Enterocolitis.

OBJECTIVE: Patent ductus arteriosus (PDA) approach remains controversial. We aim to evaluate whether echocardiography-guided (EchoG) PDA closure (to reduce drug exposure) and 24-h continuous ibuprofen infusion (24 h-IB) (to reduce peak concentration), compared with EchoG PDA closure plus conventional bolus (bolus-IB), reduces severe bowel adverse event rate in preterm infants with hemodynamically significant (hs) PDA. STUDY DESIGN: The study design is a multicenter, blinded, randomized controlled trial. Infants with <28 weeks of gestation underwent routine echocardiographic assessment (18-72 h of birth); infants with 28-33 weeks were screened only in cases where PDA was clinically suspected. HsPDA was considered if ductal diameter >1.5 mm and indicators of pulmonary overflow, systemic hypoperfusion, or both were present. Pharmacodynamic effect of CYP450 genotypes was also analyzed. RESULTS: One hundred forty-six infants [median gestational age 26 (25-28) weeks; median birth weight 881 (704-1,100) g] were randomized to 24 h-IB (n = 70) or bolus-IB (n = 76) study group at 86 (58-140) h from birth. Groups were comparable regarding perinatal and neonatal clinical data, but higher prevalence of male sex in the bolus-IB group was found. Neither severe bowel adverse event rate [10% (24 h-IB) and 2.6% (bolus-IB), p = 0.1] nor ductal closure rate was different between the study groups. Postnatal age and peripheral SaO2 at treatment start and pulmonary hemorrhage were associated with severe bowel events, independent of treatment group allocation. CYP2C8 genetic polymorphisms were associated with ibuprofen efficacy (p = 0.03). CONCLUSIONS: Ibuprofen intravenous continuous infusion compared with bolus infusion in preterm infants with hsPDA shows similar rates of success and does not reduce the prevalence of severe bowel events.

Pharmacokinetic study (phase I-II) of a new dobutamine formulation in preterm infants immediately after birth.

BACKGROUND: Dobutamine is particularly suited to treatment of haemodynamic insufficiency caused by increased peripheral vascular resistance and myocardial dysfunction in the preterm infant. Knowledge of the elimination half-life is essential to estimate the steady state when its efficacy/safety can be evaluated. METHODS: Analysis of pharmacokinetic data in ten preterm newborns treated with a new neonatal formulation of dobutamine (IMP) after screening for haemodynamic insufficiency within the first 72 h from birth. Blood samples were withdrawn at the end of IMP infusion and at a random time after the end of infusion (5 min, 15 min, 45 min, 2 h and 6 h). IMP concentration in each sample was measured by ultra-high performance liquid chromatography with electrochemical detection. RESULTS: Median duration of IMP infusion was 37.7 h (IQR 21.2). Calculated IMP half-life ranged between 3.06 and 36.1 min (median 10.6 min), leading to a time to reach the steady-state concentration between 15 min and >2 h. Adverse events were not related to IMP. CONCLUSIONS: The wide variability in dobutamine metabolism in preterm infants requires awareness about the risk of under- or overtreatment. A delay of up to 3 h might be required before drawing blood samples to evaluate the effective dose. IMPACT: Small trials suggest dobutamine as the optimal drug in the preterm infant with haemodynamic insufficiency after birth. Age-related differences in drug pharmacokinetics may result in suboptimal treatments. The lack of formal studies in preterms results in inadequate data on efficacy and safety. This study provides data on the variability of the elimination half-life of dobutamine in the very preterm infant during transitional circulation. There is a wide variation in the time to reach the plasma concentration corresponding to steady state, the moment when its efficacy/safety can be reliably evaluated. This information is crucial for planning future trials on cardiovascular support.

Cranial ultrasound findings in preterm germinal matrix haemorrhage, sequelae and outcome.

Germinal matrix-intraventricular haemorrhage (GMH-IVH), periventricular haemorrhagic infarction (PHI) and its complication, post-haemorrhagic ventricular dilatation (PHVD), are still common neonatal morbidities in preterm infants that are highly associated with adverse neurodevelopmental outcome. Typical cranial ultrasound (CUS) findings of GMH-IVH, PHI and PHVD, their anatomical substrates and underlying mechanisms are discussed in this paper. Furthermore, we propose a detailed descriptive classification of GMH-IVH and PHI that may improve quality of CUS reporting and prediction of outcome in infants suffering from GMH-IVH/PHI.

Ecografía a pie de cama: ¿es el momento de incluirla en la formación del pediatra? / Point-of-care ultrasound: Is it time to include it in the paediatric specialist training program?

La ecografía a pie de cama (EPC) se ha convertido en los últimos años en una herramienta imprescindible para la práctica clínica. La EPC debe entenderse como una extensión de la exploración física habitual que, sin sustituirla, la complementa y la enriquece. La EPC permite al clínico responder preguntas concretas sobre el diagnóstico, entender mejor la fisiopatología, orientar el tratamiento o realizar procedimientos invasivos con mayor seguridad. A pesar de su integración en muchos centros y en las diferentes subespecialidades pediátricas, no disponemos de recomendaciones específicas que establezcan los objetivos formativos en las distintas áreas de capacitación, la metodología de entrenamiento o la certificación de competencias en pediatría. Estos elementos son imprescindibles para que la EPC pueda implementarse en la práctica diaria con garantías de eficiencia y seguridad. Este artículo aborda las principales aplicaciones de la EPC en pediatría mediante una revisión no sistemática por parte de expertos en diferentes áreas de la práctica clínica en España. Además, se discute acerca de la falta de planes formativos a nivel estatal, contando con la aportación de la experiencia de Estados Unidos. En vista de la situación actual de la EPC, en nuestra opinión es urgente que se establezcan recomendaciones basadas en la evidencia para el entrenamiento en EPC que sirvan como base para el desarrollo de planes formativos y la integración de la EPC en el programa formativo de la especialidad

Point-of-care ultrasound (POCUS) has become an essential tool for clinical practice in recent years. It should be considered as an extension of the standard physical examination, which complements and enriches it without substituting it. POCUS enables the physician to answer specific clinical questions about the diagnosis, to understand better the pathophysiological context, to orientate the treatment, and to perform invasive procedures more safely. Despite its current use in many centres, and in most paediatric sub-specialties, there are currently no specific recommendations addressing educational aims in the different training areas, as well as methodology practice and the certification process in paediatrics. These ingredients are essential for POCUS implementation in daily practice, with a quality guarantee in terms of efficiency and safety. Several POCUS experts in different paediatric medicine environments performed a non-systematic review addressing the main paediatric POCUS applications in paediatrics. The lack of educational programs in POCUS in Spain is also discussed, and the experience in the United States of America in this topic is provided. Considering the current situation of POCUS in paediatrics, we strongly believe that it is urgent to establish evidence-based recommendations for POCUS training that should be the base to develop educational programs and to include POCUS in the paediatric residency training

[Point-of-care ultrasound: Is it time to include it in the paediatric specialist training program?] / Ecografía a pie de cama: ¿es el momento de incluirla en la formación del pediatra?

Point-of-care ultrasound (POCUS) has become an essential tool for clinical practice in recent years. It should be considered as an extension of the standard physical examination, which complements and enriches it without substituting it. POCUS enables the physician to answer specific clinical questions about the diagnosis, to understand better the pathophysiological context, to orientate the treatment, and to perform invasive procedures more safely. Despite its current use in many centres, and in most paediatric sub-specialties, there are currently no specific recommendations addressing educational aims in the different training areas, as well as methodology practice and the certification process in paediatrics. These ingredients are essential for POCUS implementation in daily practice, with a quality guarantee in terms of efficiency and safety. Several POCUS experts in different paediatric medicine environments performed a non-systematic review addressing the main paediatric POCUS applications in paediatrics. The lack of educational programs in POCUS in Spain is also discussed, and the experience in the United States of America in this topic is provided. Considering the current situation of POCUS in paediatrics, we strongly believe that it is urgent to establish evidence-based recommendations for POCUS training that should be the base to develop educational programs and to include POCUS in the paediatric residency training.

Childhood Neurodevelopmental Outcome in Low Birth Weight Infants With Post-ligation Cardiac Syndrome After Ductus Arteriosus Closure.

BACKGROUND: Post-ligation cardiac syndrome (PLCS) is a common complication of patent ductus arteriosus (PDA) surgical closure in low birth weight infants. It has been associated with mortality, but there is a lack of information about the neurodevelopmental outcome of the survivors. We aimed to explore the prevalence of PLCS and to assess whether this clinical condition is a risk factor for adverse outcome, (moderate or severe neurodevelopmental disabilities). METHODS: We retrospectively reviewed the medical charts of all the infants < 30 weeks of gestation who underwent ductus arteriosus ligation at our unit between 2005 and 2009. RESULTS: During the study period, 39 preterm infants [mean gestational age 26.4 (2) weeks] underwent surgical closure of the PDA at a mean postnatal age of 25.3 (2.3) days. Twenty six percent of the study population developed PLCS. Five infants died and the follow-up was accomplished in 24 infants (70% of the survivors) at a mean age of 5.3 (1.5) years (range 2-9 years). Neurodevelopmental impairment was observed in 6 in the PLCS group (75%) and in 6 infants in the no PLCS group (37%), p = 0.08]. Multiple regression analyses showed that the best fitting model for predicting adverse outcome included PLCS and low birth weight, p = 0.018. CONCLUSION: Preterm infants undergoing surgical closure of PDA who fulfill the criteria of PLCS according to this study seem to have a tendency toward higher risk of long-term neurodevelopmental impairment. Prospective clinical trials reporting long-term follow-up data should be designed to confirm the hypotheses generated in this pilot study.

Validity of Biomarkers of Early Circulatory Impairment to Predict Outcome: A Retrospective Analysis.

Objectives: The definition of circulatory impairment in the premature infant is controversial. Current research suggests overdiagnosis and overtreatment. We aimed to analyse which biomarkers move clinicians to initiate cardiovascular treatment (CVT). The prognostic capacity for adverse outcome (death and/or moderate-severe brain damage by cranial ultrasound at term equivalent) of these biomarkers was evaluated. Study Design: Retrospective data analysis from preterm infants enrolled in a placebo-controlled trial on dobutamine for low superior vena cava (SVC) flow, who showed normal SVC flow within the first 24 h (not randomized). Five positive biomarkers were considered: MABP < gestational age (GA)-1 mmHg; MABP < GA-5 mmHg; lactate > 4 mmol/L; BE < -9 mmol/L; SVC flow <51 ml/kg/min. Results: Ninety eight infants formed the study cohort. Thirty six received CVT (2-95 h). Logistic regression models adjusted for gestational age showed a positive association between CVT and the risk of death or moderate-severe abnormal cranial ultrasound at term equivalent [(OR 5.2, 95%CI: 1.8-15.1) p = 0.002]. MABP < GA-1 mmHg and lactate > 4 mmol/L were the most prevalent biomarkers at start of treatment. Low BE, high serum lactate and low SVC flow at first echocardiography showed a trend toward being associated with adverse outcome, although not statistically significant. Conclusions: Low blood pressure and high lactate are the most prevalent biomarkers used for CVT prescription. Lactic acidosis and low SVC flow early after birth showed a trend toward being associated with adverse outcome. These findings support using a combination of biomarkers for inclusion in a placebo-controlled trial on CVT during transitional circulation.

Cardiovascular Drug Therapy for Human Newborn: Review of Pharmacodynamic Data.

BACKGROUND: Circulatory failure in preterm and term newborn infants is commonly treated with inotropes or vasoactive medications. In this structured literature review, the available data on pharmacodynamic effects of the inotropes adrenaline, dobutamine, dopamine, levosimendan, milrinone, noradrenaline, and the vasoactive drugs vasopressin and hydrocortisone are presented. METHODS: Structured searches were conducted to identify relevant articles according to pre-defined inclusion criteria which were human clinical trials published after 2000. RESULTS: Out of 101 identified eligible studies only 22 studies met the criteria for evidence based practice guidelines level I to IV. The most prevalent pharmacodynamic effects were increase in blood pressure and/or heart rate, which were also the most frequently studied circulatory parameters. CONCLUSION: This review demonstrates the need for further systematic studies on all reviewed drugs with incorporation of novel non-invasive biomarkers in this vulnerable patient group, for more timely and appropriate treatment for clinical efficacy.

Reliability in cerebellar size assessment by 2D cranial ultrasonography in neonates.

BACKGROUND: Cerebellar size appears to be correlated with the long-term outcome of preterm infants. Two-dimensional cranial ultrasonography (2D-cUS) is the first-line, routine tool to characterize newborn cerebral structures. Information regarding the accuracy of 2D-cUS for assessing cerebellar size is scarce. OBJECTIVES: To assess the reliability of cerebellar size using 2D-cUS. METHODS: Fifty infants were prospectively scanned for a variety of clinical indications. The scans were stored and then independently analyzed offline by two observers. The transverse cerebellar diameter coronally from the anterior and mastoid fontanels (TCD-AF and TCD-MF, respectively); the midsagittal cerebellar vermis height and the anterior-posterior diameter from the AF; and the width and height of the fourth ventricle coronally from the MF view were measured. Interobserver variability was assessed using the intraclass correlation (ICC) with 95% confidence interval (CI) for each of the paired measures. RESULTS: A total 294 images were included in the analysis. The interobserver ICCs were TCD-AF = 0.85 (0.76-0.91), TCD-MF = 0.9 (0.83-0.94), vermis height = 0.79 (0.66-0.88), anterior-posterior vermis diameter = 0.71 (0.5-0.84), width of the fourth ventricle = 0.72 (0.33-0.9), height of the fourth ventricle = 0.86 (0.7-0.92). The ICC for the TCD comparing the AF and the MF approach was ≥0.9 for both observers. CONCLUSIONS: The reliability of the offline 2D-cUS cerebellar size assessments is good, and TCD-MF is the most consistent measure. Further studies should address the predictive value for the neurodevelopmental outcome of serial cerebellar size assessments by 2D-cUS for preterm infants.

The SafeBoosC phase II clinical trial: an analysis of the interventions related with the oximeter readings.

BACKGROUND: The SafeBoosC phase II randomised clinical trial recently demonstrated the benefits of a combination of cerebral regional tissue oxygen saturation (rStO2) by near-infrared spectroscopy (NIRS) and a treatment guideline to reduce the oxygen imbalance in extremely preterm infants. AIMS: To analyse rStO2-alarm-related clinical decisions and their heterogeneity in the NIRS experimental group (NIRS monitoring visible) and their impact on rStO2 and SpO2. METHODS: Continuous data from NIRS devices and the alarms (area under the curve of the rStO2 out of range had accumulated 0.2%h during 10 min), clinical data at discrete time points and interventions prompted by the alarms were recorded. RESULTS: Sixty-seven infants had data that fulfilled the requirements for this analysis. 1107 alarm episodes were analysed. The alarm triggered a treatment guideline intervention in 25% of the cases; the type of intervention chosen varied among clinical sites. More than 55% of alarms were not followed by an intervention ('No action'); additionally, in 5% of alarms the rStO2 value apparently was considered non-reliable and the sensor was repositioned. The percentage of unresolved alarms at 30 min after 'No action' almost doubled the treatment guideline intervention (p<0.001). Changes in peripheral oxygen saturation (SpO2), were observed only after treatment guideline interventions. CONCLUSIONS: This study shows that 25% of rStO2 alarms were followed by a clinical intervention determined by the treatment guideline. However, the rStO2 and SpO2 returned to normal ranges after the intervention, supporting the notion that decisions taken by the clinicians were appropriate. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov NCT01590316.

Randomized, Placebo-Controlled Trial of Dobutamine for Low Superior Vena Cava Flow in Infants.

OBJECTIVE: To gather information for a future confirmatory trial of dobutamine (DB) for circulatory impairment (ie, low superior vena cava [SVC] flow). STUDY DESIGN: A total of 127 infants born at < 31 weeks gestational age were serially scanned from birth to 96 hours after birth. The infants were randomly assigned to 2 groups and were treated with DB (stepwise dose increase, 5-10-15-20 µg/kg/min) or placebo if they had an SVC flow < 41 mL/kg/min within the first 24 hours after birth. The primary outcome measures were the achievement and maintenance of an SVC flow ≥ 41 mL/kg/min. Secondary outcome measures were the short-term evolution of clinical and biochemical variables, near-infrared spectroscopy, cranial Doppler ultrasound, and clinical outcomes. RESULTS: SVC flow increased throughout the first 96 hours for the entire cohort. All of the randomized infants (n = 28) except 2 achieved and maintained an SVC flow ≥ 41 mL/kg/min after intervention; however, the infants treated with DB (n = 16) showed a higher heart rate and improved base excess compared with those treated with placebo (n = 12). Low SVC flow was associated with low gestational age (P = .02) and poor condition at birth (P = .02). Low SVC flow significantly increased the risk of severe ischemic events (OR, 13; 95% CI, 2.4-69.2; P < .01). CONCLUSION: This exploratory trial demonstrates a tendency toward improved short-term clinical and biochemical perfusion variable outcomes in infants with low SVC flow treated with DB. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01605279) and the European Clinical Trials Database (EurodraCT 2009-010901-35).

New time-frequency method for cerebral autoregulation in newborns: predictive capacity for clinical outcomes.

OBJECTIVE: To describe an alternative analysis in the frequency-domain of the temporal relationship between 2 biological signals and evaluate the method's predictive capacity for classifying infants at risk for an adverse outcome. STUDY DESIGN: We studied 54 infants (mean gestational age 27 weeks) with invasive mean arterial blood pressure monitoring. The bivariate autoregressive spectral coherence (BiAR-COH) method and the spectral coherence methods were used to analyze the relationship between spontaneous changes in mean arterial blood pressure and the near-infrared tissue oxygenation index. RESULTS: The mean postnatal age at the beginning and end of the autoregulation study was 6.0 (3.0) and 29.0 (7.5) hours, respectively. The BiAR-COH was superior to the spectral coherence in predicting low superior vena cava (SVC) flow (≤ 41 mL/kg per minute), with an area under the receiver operating characteristic curve of 0.84 (95% CI, 0.77-0.90; P < .001). The BiAR-COH threshold for identifying low SVC flow was 0.577, with 0.8 sensitivity and 0.76 specificity. After adjusting for the repeated measures effect (multiple epochs) in a given patient, the averaged BiAR-COH per patient and averaged COH per patient were calculated as the average value per patient. The pBiAR-COH (but not the pCOH) was associated with intraventricular hemorrhage grades 3 and 4 and predicted mortality. CONCLUSIONS: The BiAR-COH classifier identifies low SVC flow infants who are at risk for brain hypoperfusion. The BiAR-COH is superior to frequency domain methods in predicting adverse outcomes in infants.