Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

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.

Short and mid-term neonatal outcomes in high-risk infants undergoing FICare: a case control study.

BACKGROUND: FICare model has been evaluated mostly on the stable preterm infant.We have scaled the model to two implementation levels(basic/advanced),making it suitable for all high-risk neonates.We report on the short- and mid-term outcomes of infants enrolled in a pilot on FICare implementation at our NICU. METHODS: During 52 months study period,families were invited to join the program if their newborns' admission required neonatal specialized care for at least 3 weeks,and trained according to the program's curricula.Following a rigorous sequential admission order,each case(FICare group:134 < 34 weeks;52 term newborns)was matched by a contemporary control(CC:134 < 34 weeks;52 term newborns)and 2 historical controls born within the 3 years prior to FICare site implementation(HC:268 < 34 weeks;104 term newborns),cared as usual RESULTS: FICare intervention started by the end of first week of postnatal life.Rates of breastfeeding during admission and at discharge,and direct breastfeeding upon discharge were higher in FICare compared to CC and HC.Duration of intermediate care hospitalization(preterm and term cohorts)and total hospital length of stay (term cohorts)were shorter in FICare group.Use of Emergency Services after discharge was also lower in the FICare group CONCLUSIONS: Short and mid-term efficacy of FICare on health outcomes and family empowerment in a broader and highly-vulnerable neonatal population supports its generalization in complex healthcare neonatal services. IMPACT STATEMENT: Scaling the FICare model to the critically ill, unstable premature and term infant is feasible and safe. The early intervention shows similar benefits in the short- and mid-term infants' outcomes in the whole spectrum of neonatal specialized care.

Near-infrared spectroscopy monitoring of neonatal cerebrovascular reactivity: where are we now?

Cerebrovascular reactivity defines the ability of the cerebral vasculature to regulate its resistance in response to both local and systemic factors to ensure an adequate cerebral blood flow to meet the metabolic demands of the brain. The increasing adoption of near-infrared spectroscopy (NIRS) for non-invasive monitoring of cerebral oxygenation and perfusion allowed investigation of the mechanisms underlying cerebrovascular reactivity in the neonatal population, confirming important associations with pathological conditions including the development of brain injury and adverse neurodevelopmental outcomes. However, the current literature on neonatal cerebrovascular reactivity is mainly still based on small, observational studies and is characterised by methodological heterogeneity; this has hindered the routine application of NIRS-based monitoring of cerebrovascular reactivity to identify infants most at risk of brain injury. This review aims (1) to provide an updated review on neonatal cerebrovascular reactivity, assessed using NIRS; (2) to identify critical points that need to be addressed with targeted research; and (3) to propose feasibility trials in order to fill the current knowledge gaps and to possibly develop a preventive or curative approach for preterm brain injury. IMPACT: NIRS monitoring has been largely applied in neonatal research to assess cerebrovascular reactivity in response to blood pressure, PaCO2 and other biochemical or metabolic factors, providing novel insights into the pathophysiological mechanisms underlying cerebral blood flow regulation. Despite these insights, the current literature shows important pitfalls that would benefit to be addressed in a series of targeted trials, proposed in the present review, in order to translate the assessment of cerebrovascular reactivity into routine monitoring in neonatal clinical practice.

Neuromonitoring in neonatal critical care part I: neonatal encephalopathy and neonates with possible seizures.

The blooming of neonatal neurocritical care over the last decade reflects substantial advances in neuromonitoring and neuroprotection. The most commonly used brain monitoring tools in the neonatal intensive care unit (NICU) are amplitude integrated EEG (aEEG), full multichannel continuous EEG (cEEG), and near-infrared spectroscopy (NIRS). While some published guidelines address individual tools, there is no consensus on consistent, efficient, and beneficial use of these modalities in common NICU scenarios. This work reviews current evidence to assist decision making for best utilization of neuromonitoring modalities in neonates with encephalopathy or with possible seizures. Neuromonitoring approaches in extremely premature and critically ill neonates are discussed separately in the companion paper. IMPACT: Neuromonitoring techniques hold promise for improving neonatal care. For neonatal encephalopathy, aEEG can assist in screening for eligibility for therapeutic hypothermia, though should not be used to exclude otherwise eligible neonates. Continuous cEEG, aEEG and NIRS through rewarming can assist in prognostication. For neonates with possible seizures, cEEG is the gold standard for detection and diagnosis. If not available, aEEG as a screening tool is superior to clinical assessment alone. The use of seizure detection algorithms can help with timely seizures detection at the bedside.

Neuromonitoring in neonatal critical care part II: extremely premature infants and critically ill neonates.

Neonatal intensive care has expanded from cardiorespiratory care to a holistic approach emphasizing brain health. To best understand and monitor brain function and physiology in the neonatal intensive care unit (NICU), the most commonly used tools are amplitude-integrated EEG, full multichannel continuous EEG, and near-infrared spectroscopy. Each of these modalities has unique characteristics and functions. While some of these tools have been the subject of expert consensus statements or guidelines, there is no overarching agreement on the optimal approach to neuromonitoring in the NICU. This work reviews current evidence to assist decision making for the best utilization of these neuromonitoring tools to promote neuroprotective care in extremely premature infants and in critically ill neonates. Neuromonitoring approaches in neonatal encephalopathy and neonates with possible seizures are discussed separately in the companion paper. IMPACT: For extremely premature infants, NIRS monitoring has a potential role in individualized brain-oriented care, and selective use of aEEG and cEEG can assist in seizure detection and prognostication. For critically ill neonates, NIRS can monitor cerebral perfusion, oxygen delivery, and extraction associated with disease processes as well as respiratory and hypodynamic management. Selective use of aEEG and cEEG is important in those with a high risk of seizures and brain injury. Continuous multimodal monitoring as well as monitoring of sleep, sleep-wake cycling, and autonomic nervous system have a promising role in neonatal neurocritical care.

Near-infrared spectroscopy for perioperative assessment and neonatal interventions.

Perioperative applications of near-infrared spectroscopy (NIRS) to monitor regional tissue oxygenation and perfusion in cardiac and noncardiac surgery are of increasing interest in neonatal care. Complex neonatal surgery can impair adequate oxygen delivery and tissue oxygen consumption and increase the risk of neurodevelopmental delay. Coupled with conventional techniques, NIRS monitoring may enable targeted hemodynamic management of the circulation in both cardiac and noncardiac surgical procedures. In this narrative review, we discuss the application of perioperative NIRS in specific neonatal interventions, including surgical intervention for congenital heart defects, definitive closure of the patent ductus arteriosus, neurological and gastrointestinal disorders, and use of extracorporeal membrane oxygenation. We identified areas for future research within disease-specific indications and offer a roadmap to aid in developing evidence-based targeted diagnostic and management strategies in neonates. IMPACT: There is growing recognition that perioperative NIRS monitoring, used in conjunction with conventional monitoring, may provide critical hemodynamic information that either complements clinical impressions or delivers novel physiologic insight into the neonatal circulatory and perfusion pathways.

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.

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.

Diagnostic and predictive value of Doppler ultrasound for evaluation of the brain circulation in preterm infants: a systematic review.

INTRODUCTION: Very and extremely preterm infants frequently have brain injury-related long-term neurodevelopmental problems. Altered perfusion, for example, seen in the context of a hemodynamically significant patent ductus arteriosus (PDA), has been linked to injury of the immature brain. However, a direct relation with outcome has not been reviewed systematically. METHODS: A systematic review was conducted to provide an overview of the value of different cerebral arterial blood flow parameters assessed by Doppler ultrasound, in relation to brain injury, to predict long-term neurodevelopmental outcome in preterm infants. RESULTS: In total, 23 studies were included. Because of heterogeneity of studies, a meta-analysis of results was not possible. All included studies on resistance index (RI) showed significantly higher values in subjects with a hemodynamically significant PDA. However, absolute differences in RI values were small. Studies using Doppler parameters to predict brain injury and long-term neurodevelopmental outcome were inconsistent. DISCUSSION: There is no clear evidence to support the routine determination of RI or other Doppler parameters in the cerebral arteries to predict brain injury and long-term neurodevelopmental outcome in the preterm infant. However, there is evidence that elevated RI can point to the presence of a hemodynamically significant PDA.

No neurodevelopmental benefit of cerebral oximetry in the first randomised trial (SafeBoosC II) in preterm infants during the first days of life.

AIM: Cerebral hypoxia has been associated with neurodevelopmental impairment. We studied whether reducing cerebral hypoxia in extremely preterm infants during the first 72 hours of life affected neurological outcomes at two years of corrected age. METHODS: In 2012-2013, the phase II randomised Safeguarding the Brains of our smallest Children trial compared visible cerebral near-infrared spectroscopy (NIRS) monitoring in an intervention group and blinded NIRS monitoring in a control group. Cerebral hypoxia was significantly reduced in the intervention group. We followed up 115 survivors from eight European centres at two years of corrected age, by conducting a medical examination and assessing their neurodevelopment with the Bayley Scales of Infant and Toddler Development, Second or Third Edition, and the parental Ages and Stages Questionnaire (ASQ). RESULTS: There were no differences between the intervention (n = 65) and control (n = 50) groups with regard to the mean mental developmental index (89.6 ± 19.5 versus 88.4 ± 14.7, p = 0.77), ASQ score (215 ± 58 versus 213 ± 58, p = 0.88) and the number of children with moderate-to-severe neurodevelopmental impairment (10 versus six, p = 0.58). CONCLUSION: Cerebral NIRS monitoring was not associated with long-term benefits or harm with regard to neurodevelopmental outcome at two years of corrected age.

New developments in cerebral blood flow autoregulation analysis in preterm infants: a mechanistic approach.

BACKGROUND: Impaired autoregulation capacity implies that changes in cerebral perfusion follow changes in blood pressure; however, no analytical method has explored such a signal causality relationship in infants. We sought to develop a method to assess cerebral autoregulation from a mechanistic point of view and explored the predictive capacity of the method to classify infants at risk for adverse outcomes. METHODS: The partial directed coherence (PDC) method, which considers synchronicity and directionality of signal dependence across frequencies, was used to analyze the relationship between spontaneous changes in mean arterial pressure (MAP) and the cerebral tissue oxygenation index (TOI). PDCMAP>>TOI indicated that changes in TOI were induced by MAP changes, and PDCTOI>>MAP indicated the opposite. RESULTS: The PDCMAP>>TOI and PDCTOI>>MAP values differed. PDCMAP>>TOI adjusted by gestational age predicted low superior vena cava flow (≤41 ml/kg per min), with an area under the receiver operating characteristic curve of 0.72 (95% CI: 0.63-0.81; P < 0.001), whereas PDCTOI>>MAP did not. The adjusted pPDCMAP>>TOI (the average value per patient) predicted severe intracranial hemorrhage and mortality. CONCLUSION: PDCMAP>>TOI allows for a noninvasive physiological interpretation of the pressure autoregulation process in neonates. PDCMAP>>TOI is a good classifier for infants at risk of brain hypoperfusion and adverse outcomes.

Brain injury in the international multicenter randomized SafeBoosC phase II feasibility trial: cranial ultrasound and magnetic resonance imaging assessments.

BACKGROUND: Abnormal cerebral perfusion during the first days of life in preterm infants is associated with higher grades of intraventricular hemorrhages and lower developmental score. In SafeBoosC II, we obtained a significant reduction of cerebral hypoxia by monitoring cerebral oxygenation in combination with a treatment guideline. Here, we describe (i) difference in brain injury between groups, (ii) feasibility of serial cranial ultrasound (cUS) and magnetic resonance imaging (MRI), (iii) local and central cUS assessment. METHODS: Hundred and sixty-six extremely preterm infants were included. cUS was scheduled for day 1, 4, 7, 14, and 35 and at term-equivalent age (TEA). cUS was assessed locally (unblinded) and centrally (blinded). MRI at TEA was assessed centrally (blinded). Brain injury classification: no, mild/moderate, or severe. RESULTS: Severe brain injury did not differ significantly between groups: cUS (experimental 10/80, control 18/77, P = 0.32) and MRI (5/46 vs. 3/38, P = 0.72). Kappa values for local and central readers were moderate-to-good for severe and poor-to-moderate for mild/moderate injuries. At TEA, cUS and MRI were assessed in 72 and 64%, respectively. CONCLUSION: There was no difference in severe brain injury between groups. Acquiring cUS and MRI according the standard operating procedures must be improved for future trials. Whether monitoring cerebral oxygenation during the first 72 h of life prevents brain injury should be evaluated in larger multicenter trials.

The SafeBoosC II randomized trial: treatment guided by near-infrared spectroscopy reduces cerebral hypoxia without changing early biomarkers of brain injury.

BACKGROUND: The SafeBoosC phase II multicentre randomized clinical trial investigated the benefits and harms of monitoring cerebral oxygenation by near-infrared spectroscopy (NIRS) combined with an evidence-based treatment guideline vs. no NIRS data and treatment as usual in the control group during the first 72 h of life. The trial demonstrated a significant reduction in the burden of cerebral hypoxia in the experimental group. We now report the blindly assessed and analyzed treatment effects on electroencephalographic (EEG) outcomes (burst rate and spectral edge frequency 95% (SEF95)) and blood biomarkers of brain injury (S100ß, brain fatty acid-binding protein, and neuroketal). METHODS: One hundred and sixty-six extremely preterm infants were randomized to either experimental or control group. EEG was recorded at 64 h of age and blood samples were collected at 6 and 64 h of age. RESULTS: One hundred and thirty-three EEGs were evaluated. The two groups did not differ regarding burst rates (experimental 7.2 vs. control 7.7 burst/min) or SEF95 (experimental 18.1 vs. control 18.0 Hz). The two groups did not differ regarding blood S100ß, brain fatty acid-binding protein, and neuroketal concentrations at 6 and 64 h (n = 123 participants). CONCLUSION: Treatment guided by NIRS reduced the cerebral burden of hypoxia without affecting EEG or the selected blood biomarkers.

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.

Specific IgA, But Not IgG, in Human Milk From COVID-19-Infected Mothers Neutralizes SARS-CoV-2.

This study highlights the importance of human milk in providing anti-severe acute respiratory syndrome coronavirus 2 immunity to newborns. The highest protective activity of human milk against COVID-19 was found in colostrum from infected mothers. Neutralizing activity was associated with high levels of specific IgA. Depletion of IgA, but not IgG, from milk samples completely abolished the ability of human milk to neutralize severe acute respiratory syndrome coronavirus 2.

EUROPEAN ASSOCIATION OF PERINATAL MEDICINE (EAPM) EUROPEAN MIDWIVES ASSOCIATION (EMA) Joint position statement: Caesarean delivery rates at a country level should be in the 15-20 % range.

While cesarean deliveries performed for health indications can save lives, unnecessary cesareans cause unjustifiable health risks for the mother, newborn, and for future pregnancies. Previous recommendations for cesarean delivery rates at a country level in the 10-15% range are currently unrealistic, and the proposed concept that striving to achieve specific rates is not important has resulted in a confusing message reaching healthcare professionals and the public. It is important to have a clear understanding of when cesarean delivery rates are deviating from internationally acceptable ranges, to trigger the implementation of healthcare policies needed to correct this problem. Based on currently existing scientific evidence, we recommend that cesarean delivery rates at a country level should be in the 15-20% range. This advice is based on the demonstration of decreased maternal and neonatal mortalities when national cesarean delivery rates rise to circa 15%, but values exceeding 20% are not associated with further benefits. It is also based on real-world experiences from northern European countries, where cesarean delivery rates in the 15-20% range are associated with some of the best maternal and perinatal quality indicators in the world. With the increase in cesarean delivery rates projected for the coming years, experience in provision of intrapartum care may come under threat in many hospitals, and recovering from this situation is likely to be a major challenge. Professional and scientific societies, together with healthcare authorities and governments need to prioritize actions to reverse the upward trend in cesarean delivery rates observed in many countries, and to strive to achieve values as close as possible to the recommended range.

Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery.

BACKGROUND: Inodilators are routinely used in cardiovascular surgery with cardiopulmonary bypass (CPB). Information regarding safety and tolerability of the novel molecule, levosimendan (LEVO), in newborns is anecdotal; no pharmacokinetic data in this population are available. METHODS: This was a phase I, randomized, and blinded study. Neonates undergoing surgical repair for congenital heart defects received stepwise dose increases of milrinone (MR; 0.5-1 µg/kg/min, n = 9) or LEVO (0.1-0.2 µg/kg/min, n = 11) as an i.v. continuous infusion, starting before CPB. Infants had continuous, time-locked, physiological, and near-infrared spectroscopy (NIRS) (cerebral and peripheral) recordings during the first 24 h, and at 48 and 96 h postsurgery. Serial biochemistry and pharmacokinetic studies were performed. RESULTS: During the first 24 h postsurgery, patients showed time-related, group-independent increased cerebral tissue oxygenation and decreased diastolic blood pressure; in addition, group-dependent differences in heart rate and peripheral perfusion were found. Early postsurgery, MR-treated infants showed lower pH, higher glycemia, and higher inotrope score. The groups differed in cerebral NIRS-derived variables from 24 to 96 h. Study drug withdrawal at 96 h was more frequent with LEVO. LEVO intermediate metabolites were detected in plasma at day 14 after surgery. CONCLUSION: LEVO is well tolerated in critically ill neonates. LEVO may have advantages over MR in terms of the dosing regimen.

Surveillance of Viral Respiratory Infections in the Neonatal Intensive Care Unit-Evolution in the Last 5 Years.

Viral respiratory infections (VRIs) in very low birthweight infants can be associated with high rates of morbidity. The COVID-19 pandemic has exerted a strong impact on viral circulation. The purpose of this study is to report on VRIs during NICU admission in infants below 32 weeks' gestation and compare data collected between the pre-and post-COVID-19 pandemic periods. A prospective surveillance study was conducted at a tertiary NICU between April 2016 and June 2022. The COVID-19 post-pandemic period was established as being from March 2020 onwards. Respiratory virus detection was performed by real-time multiplex PCR assays in nasopharyngeal aspirates (NPAs). A total of 366 infants were enrolled. There were no statistical differences between periods regarding infants' birth weight, gestational age, gender distribution, or rates of bronchopulmonary dysplasia. Among the 1589 NPA collected during the pre-COVID-19 period, 8.9% were positive, and among the 1147 NPA collected during the post-pandemic period, only 3% were positive (p < 0.005). The type of viruses detected did not differ according to the study period (pre-COVID19 vs. post-COVID-19): rhinovirus (49.5% vs. 37.5%), adenovirus (22.6% vs. 25%), and human coronavirus (12.9% vs. 16.7%). SARS-CoV-2 was only detected in one patient. In conclusion, the viral profile causing VRI during the pre-COVID-19 and post-COVID-19 era was similar. However, the total number of VRI dropped significantly, most probably due to the global increase in infection prevention measures.