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.).

Altered sleep and inflammation are related to outcomes in neonatal encephalopathy.

AIM: Immune dysregulation and delayed onset of sleep wake cycling (SWC) are associated with worse outcome in neonatal encephalopathy (NE), however the association between sleep and immune dysfunction in NE remains unclear. Aimed to evaluate association of sleep and systemic inflammation with outcomes in NE. METHODS: Amplitude-integrated electroencephalography (aEEG) recordings were collected on infants undergoing therapeutic hypothermia (TH). Duration to onset of (SWC) and sleep quality (SQ) were examined. Blood samples collected during the first 2 days of life. Thirteen pro- and anti-inflammatory serum cytokines were quantified. Adverse outcome defined as death or abnormal MRI brain. RESULTS: Earlier onset of SWC and better SQ had less adverse outcomes. SQ provided better prognostic value and showed better interobserver agreement compared to duration to SWC. Better SQ associated with lower cytokines EPO and interleukin (IL)-1ß. In infants with unfavourable outcome, shorter duration to SWC was associated with higher EPO and better SQ was associated with lower TNF-α. CONCLUSION: Earlier onset of SWC or better SQ showed less systemic inflammation and fewer adverse outcomes. SQ during TH provided better prognostic information than time of onset of SWC. Modulation of circadian rhythm in infants with NE may have an immunomodulatory role, leading to improved outcomes.

Capnometry during neonatal transport-Mini review.

AIM: The aim of this review was to give an overview of available data on end-tidal CO2 (etCO2 ) monitoring, also called capnometry, during neonatal transport. METHODS: Pubmed/MEDLINE database was searched using research question (capno* OR etCO2 OR detCO2 OR (['end tidal' OR 'end-tidal'] AND [CO2 OR 'carbon dioxide']) AND (neonat* OR infant* OR newborn*) AND transport*). All articles relevant to the topic were reviewed and summarised. RESULTS: The lack of studies relevant to neonatal transport prompted us to extend the search to capnometry in a neonatal intensive care setting. The published studies are showing conflicting results. The different study populations, technologies used to measure etCO2 , types of etCO2 sampling and the diverse sites of blood gas tests make the data unsuitable for systematic comparison. CONCLUSION: Further research to obtain more data on capnometry during neonatal transport will be necessary to define precisely under what circumstances can end-tidal monitoring of CO2 be reliably used in neonates during transport and also how to interpret the measured values.

Relationship Between Postnatal Pulmonary Arterial Pressure and Altered Diastolic Function in Neonates with Down Syndrome.

OBJECTIVE: To assess the influence of diastolic dysfunction on the evolution of pulmonary hypertension in neonates with Down Syndrome over the early newborn period. STUDY DESIGN: This was a prospective observational cohort study. Echocardiography was performed three times over the first week of life in both Down syndrome and control cohorts. Measurements of pulmonary arterial pressure in addition to left ventricular (LV) and right ventricular systolic and diastolic function were collected. RESULTS: Seventy babies with Down syndrome and 60 control infants were enrolled. Forty-eight of the infants with Down syndrome (69%) were born with congenital heart disease (CHD). Echocardiography surrogates of pulmonary hypertension and myocardial function remained significantly impaired in the Down syndrome group in comparison with control infants (all P < .01). In the Down syndrome group, LV early diastolic strain rate was independently associated with measures of pulmonary hypertension while controlling for gestational age, cesarean delivery, and the presence of CHD (P < .01). CONCLUSIONS: Intrinsic LV diastolic impairment is directly associated with higher indices of pulmonary hypertension in infants with Down syndrome and may be a contributing factor to its evolution.

HK1 haemolytic anaemia in association with a neurological phenotype and co-existing CEP290 Meckel-Gruber in a Romani family.

HK1 deficient Haemolytic Anaemia in association with a Neurological Phenotype & co-existing Meckel-Gruber due to CEP290 in a Romani family.

The Possible Protective Role of Bilirubin on Oxidative Stress Related Morbidity in Preterm Infants.

To evaluate the effect of bilirubin levels in the first week of life on the frequency of oxidative-stress related morbidity.We included all preterm infants with a gestational age less than 32 weeks. The mean total serum bilirubin of the first week of life was measured and compared between infants with and without oxidative stress related morbidity.A total of 116 preterm infants were included. Univariate analysis showed that mean ± SD TSB levels were statistically significantly lower in infants with chronic lung disease (95 ± 31.4micromole/l vs 119 ± 31micromole/l, p = 0.019), necrotizing enterocolitis (94.4 ± 29micromole/l vs 118 ± 31micromole/l p = 0.044) and patent ductus arteriosus (104 ± 33micromole/l vs 120 ± 30micromole/l p = 0.018). However, when adjusted for gestational age, there were no longer statistically significant differences observed.Elevated bilirubin levels in the first week of life are not protective against the oxidative stress related morbidity in very preterm infants.

Cerebral oxygen saturation and autoregulation during hypotension in extremely preterm infants.

BACKGROUND: The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO2) and autoregulatory capacity (CAR) remains unknown. METHODS: Prospective cohort study of blinded rScO2 measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO2, mean arterial blood pressure, duration of cerebral hypoxia, and transfer function (TF) gain inversely proportional to CAR, were compared between hypotensive infants randomized to receive dopamine or placebo and between hypotensive and non-hypotensive infants, and related to early intraventricular hemorrhage or death. RESULTS: In 89 potentially eligible HIP trial patients with rScO2 measurements, the duration of cerebral hypoxia was significantly higher in 36 hypotensive compared to 53 non-hypotensive infants. In 29/36 hypotensive infants (mean GA 25 weeks, 69% males) receiving the study drug, no significant difference in rScO2 was observed after dopamine (n = 13) compared to placebo (n = 16). Duration of cerebral hypoxia was associated with early intraventricular hemorrhage or death.  Calculated TF gain (n = 49/89) was significantly higher reflecting decreased CAR in 16 hypotensive compared to 33 non-hypotensive infants. CONCLUSIONS: Dopamine had no effect on rScO2 compared to placebo in hypotensive infants. Hypotension and cerebral hypoxia are associated with early intraventricular hemorrhage or death. IMPACT: Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation. Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants. Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants. Since systematic treatment of hypotension may not be associated with better outcomes, the diagnosis of cerebral hypoxia in hypotensive extremely preterm infants might guide treatment.

Pathogenesis of necrotising enterocolitis: The impact of the altered gut microbiota and antibiotic exposure in preterm infants.

Necrotising enterocolitis (NEC) is a devastating condition with high morbidity and mortality seen predominately in preterm infants. Multiple factors are associated with the pathogenesis of NEC. The widespread use of antibiotics in the neonatal intensive care unit might play a role in the pathogenesis of NEC in preterm infants. This review provides a summary on the intestinal microbiota in preterm infants with a focus on how antibiotic exposure may reduce the biodiversity of the intestinal microbiota and may predispose preterm infants to NEC. CONCLUSION: Prolonged antibiotic therapy has been suggested as a risk factor for the development of NEC in preterm infants.

Are antibiotics a risk factor for the development of necrotizing enterocolitis-case-control retrospective study.

Previous studies have identified numerous risk factors associated with necrotizing enterocolitis (NEC) in very low birth weight (VLBW; birth weight less than 1500 g) infants. One of the potential pathophysiological contributors could be antibiotic therapy. Our aim was to explore the association between antibiotic exposure and NEC in VLBW infants. We designed a retrospective 1:2 case-control cohort study in a level III neonatal intensive care unit. Our study group composed of VLBW infants born between January 2012 and December 2014 with a diagnosis of NEC stage IIA or greater (Bell's modified criteria). Our intent was to match every case in the study group to two controls. Our primary outcome was an association between antibiotic exposure and NEC. Twenty-two cases of NEC were matched to 32 controls. The infants who developed NEC were exposed to a statistically significantly more frequent number of antibiotic courses and to more days on any antibiotic prior to the development of NEC. There were significant differences between cases and controls with respect to the duration of exposure to gentamicin and meropenem specifically.Conclusion: The data from our study demonstrate that prolonged exposure to antibiotic therapy is associated with an increased risk of NEC among VLBW infants. Furthermore, gentamicin and meropenem, but not other antibiotics, had a significant association with the incidence of NEC. What is known: • Early antibiotic exposure is a risk factor for the development of necrotising enterocolitis (NEC) in very low birth weight infants • Prolonged initial empirical antibiotic course for ≥ 5 days, despite sterile blood culture, is associated with an increased risk of developing NEC What is new: • The cumulative total number of days of antibiotic exposure is associated with an increased risk of developing NEC • Gentamicin and meropenem, but not other antibiotics, had a significant association with the incidence of NEC in our study.

Banked preterm versus banked term human milk to promote growth and development in very low birth weight infants.

BACKGROUND: Human milk banking has been available in many countries for the last three decades. The milk provided from milk banking is predominantly term breast milk, but some milk banks provide preterm breast milk. There are a number of differences between donor term and donor preterm human milk. OBJECTIVES: To determine the effect of banked donor preterm milk compared with banked donor term milk regarding growth and developmental outcomes in very low birth weight infants (infants weighing less than 1500 grams). SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 7), MEDLINE via PubMed (1966 to 23 October 2018), Embase (1980 to 23 October 2018), and CINAHL (1982 to 23 October 2018). We also searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing banked donor preterm milk with banked donor term milk regarding growth and developmental outcomes in very low birth weight infants DATA COLLECTION AND ANALYSIS: We planned to perform assessment of methodology regarding blinding of randomisation, intervention and outcome measurements as well as completeness of follow-up. We planned to evaluate treatment effect using a fixed-effect model using relative risk (RR), relative risk reduction, risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) or the number needed to treat for an additional harmful outcome (NNTH) for categorical data; and using mean, standard deviation and weighted mean difference (WMD) for continuous data. We planned to use the GRADE approach to assess the quality of evidence. MAIN RESULTS: No studies met the inclusion criteria. AUTHORS' CONCLUSIONS: We found no evidence to support or refute the effect of banked donor preterm milk compared to banked term milk regarding growth and developmental outcomes in very low birth weight infants.

Noninvasive continuous cardiac output and cerebral perfusion monitoring in term infants with neonatal encephalopathy: assessment of feasibility and reliability.

BackgroundNoninvasive hemodynamic monitoring of infants with neonatal encephalopathy (NE) undergoing therapeutic hypothermia (TH) would be a potentially useful clinical tool. We aimed to assess the feasibility and reliability of noninvasive cardiac output monitoring (NICOM) and near-infrared spectroscopy (NIRS) in this cohort.MethodsNICOM and NIRS were commenced to measure cardiac output (CO), systemic vascular resistance (SVR), blood pressure (BP), and cerebral regional oxygen saturations (SctO2) during TH and rewarming. NICOM measures of CO were also compared with simultaneous echocardiography-derived CO (echo-CO).ResultsTwenty infants with a median gestation of 40 weeks were enrolled. There was a strong correlation between NICOM- and echo-CO (r2=0.79, P<0.001). NICOM-CO was systematically lower than echo-CO with a bias of 27% (limits of agreement 3-51%). NICOM illustrated lower CO during TH, which increased during rewarming. SctO2 increased over the first 30 h of TH and stayed high for the remainder of the study. There was a rise in SVR over the first 30 h of TH and a decrease during rewarming (all P<0.05).ConclusionsNoninvasive hemodynamic assessment of infants with NE is feasible and illustrates potentially important changes. Larger studies are needed to assess the clinical applicability of those methods in this cohort.

A review of superior vena cava flow measurement in the neonate by functional echocardiography.

Neonatologists have begun using superior vena cava flow as assessed by functional echocardiography to facilitate real-time decision-making on cardiovascular care. This review aims to describe the basis of the technique, summarise the evidence for its use and compare the technique to existing clinical, biochemical and radiological techniques for assessing neonatal circulatory status. CONCLUSION: Although echocardiographic measurements of superior vena cava flow, like other measures of perfusion, are not perfect, their noninvasive nature and ability to facilitate real-time decision-making means that at present, they remain the best available methodology of monitoring central perfusion in the neonatal population.

Thyroid function testing in neonates born to women with hypothyroidism.

Our aim was to assess the utility of serum thyroxine and thyroid stimulating hormone performed at 10-14 days of life in diagnosing congenital hypothyroidism (CH) in babies born to mothers with hypothyroidism. This was a retrospective study of all babies born in a tertiary referral centre for neonatology over a 12-month period. Infants who had thyroid function testing (TFT) checked at 10-14 days of life because of maternal hypothyroidism during the period of study were included. The results of the newborn bloodspot and day 10-14 TFT were recorded along with whether or not patients were subsequently treated. Of the 319 patients included in the study, only two patients were found to have CH and in both cases the newborn blood spot had been abnormal. CONCLUSION: No extra cases of CH were detected from the thyroid test at 10-14 days and this practice should be discontinued due to the robust nature of existing newborn screening programmes. What is Known: • Congenital hypothyroidism(CH) is the commonest preventable cause of childhood intellectual impairment. • Family history of hypothyroidism has been implicated as a risk factor for CH. • CH has formed part of newborn screening since the 1970s. What is New: • There is no research recommending thyroid function testing at 10-14 days of life to detect CH in neonates born to mothers with hypothyroidism. • Thyroid function testing at 10-14 days of life does not improve diagnostic yield for CH in babies born to mothers with hypothyroidism. • Newborn blood spot remains the mainstay for accurate and timely diagnosis of CH.

Is routine transvaginal cervical length measurement cost-effective in a population where the risk of spontaneous preterm birth is low?

INTRODUCTION: A recent meta-analysis has suggested that routine measurement of the cervical length should be performed in conjunction with the anomaly scan to identify a group of women at increased risk of preterm delivery. We decided to investigate whether this recommendation is justifiable in a population where the risk of preterm birth is low. MATERIAL AND METHODS: We reviewed 12 years of obstetric data from the Coombe Women and Infants University Hospital. Relative risks of adverse outcomes from the randomized controlled trial were applied and we extrapolated the possible numbers of women requiring intervention. We then used published neonatal data to estimate the cost of neonatal care and estimated the costs of providing the service. RESULTS: Over 12 years from 2000 until 2011, there were 94 646 singleton deliveries, 1776 happening before 34 weeks. Spontaneous onset occurred in 882 (49.7%) of this group. These 882 births were studied. If we apply the figures from a randomized controlled trial, 1609 women (1.7% from our total population) would be expected to have a cervical length 15 mm. If we gave vaginal progesterone to all women with a sonographically short cervix, we would reduce the delivery rate before 34 weeks by 27.7%. The annual costs of providing the service were estimated to be €109 249 and the cost of immediate neonatal care was estimated to be €380 514. CONCLUSION: Given the implications associated with preterm delivery, routine measurement of cervical length at the time of the anomaly scan may be justifiable from a cost point of view in a population where the risk of preterm birth is low.

Serial N-terminal pro-brain natriuretic peptide measurement as a predictor of significant patent ductus arteriosus in preterm infants beyond the first week of life.

UNLABELLED: The aim of the study was to assess the role of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration as a predictor of patent ductus arteriosus (PDA) in very low birth weight infants beyond the first week of life. This was a prospective observational study; newborns with a birth weight < 1500 g were eligible for enrolment. Enrolled infants were screened by echocardiography on day seven of life for the presence of a PDA. This was paired with a blood sample for NT-proBNP level. Echocardiography and NT-proBNP levels were repeated at weekly intervals. The primary outcome was correlation between PDA and NT-proBNP level and between measurements of PDA significance and NT-proBNP. Sixty-nine neonates were enrolled following parental consent. The mean birth weight was 1119 ± 257 g and mean gestational age was 28.6 ± 2.6 weeks. Median NT-proBNP level on day seven was 11469 ng/l in infants with a PDA vs. 898 ng/l in infants without a PDA (p < 0.0001). There was a statistically significant correlation between PDA diameter and NT-proBNP level on day seven, day 14 and day 21. CONCLUSION: NT-proBNP concentration is significantly increased in infants with a PDA and correlates well with PDA diameter in the first three weeks of life.

Prophylactic Oropharyngeal Surfactant for Preterm Newborns at Birth: A Randomized Clinical Trial.

Importance: Preterm newborns at risk of respiratory distress syndrome are supported with continuous positive airway pressure (CPAP). Many newborns worsen despite CPAP and are intubated for surfactant administration, an effective therapy for treatment of respiratory distress syndrome. Endotracheal intubation is associated with adverse effects. Pharyngeal administration of surfactant to preterm animals and humans has been reported as an alternative. Objective: To assess whether giving prophylactic oropharyngeal surfactant to preterm newborns at birth would reduce the rate of intubation for respiratory failure. Design, Setting, and Participants: This unblinded, parallel-group randomized clinical trial (Prophylactic Oropharyngeal Surfactant for Preterm Infants [POPART]) was conducted from December 17, 2017, to September 11, 2020, at 9 tertiary neonatal intensive care units in 6 European countries. Newborns born before 29 weeks of gestation without severe congenital anomalies, for whom intensive care was planned, were eligible for inclusion. The data were analyzed from July 27, 2022, to June 20, 2023. Intervention: Newborns were randomly assigned to receive oropharyngeal surfactant at birth in addition to CPAP or CPAP alone. Randomization was stratified by center and gestational age (GA). Main Outcomes and Measures: The primary outcome was intubation in the delivery room for bradycardia and/or apnea or in the neonatal intensive care unit for prespecified respiratory failure criteria within 120 hours of birth. Caregivers were not masked to group assignment. Results: Among 251 participants (mean [SD] GA, 26 [1.5] weeks) who were well matched at study entry, 126 (69 [54.8%] male) with a mean (SD) birth weight of 858 (261) grams were assigned to the oropharyngeal surfactant group, and 125 (63 [50.4%] male) with a mean (SD) birth weight of 829 (253) grams were assigned to the control group. The proportion of newborns intubated within 120 hours was not different between the groups (80 [63.5%) in the oropharyngeal surfactant group and 81 [64.8%] in the control group; relative risk, 0.98 [95% CI, 0.81-1.18]). More newborns assigned to the oropharyngeal surfactant group were diagnosed with and treated for pneumothorax (21 [16.6%] vs 8 [6.4%]; P = .04). Conclusions and Relevance: This randomized clinical trial found that administration of prophylactic oropharyngeal surfactant to newborns born before 29 weeks' GA did not reduce the rate of intubation in the first 120 hours of life. These findings suggest that administration of surfactant into the oropharynx immediately after birth in addition to CPAP should not be routinely used. Trial Registration: EudraCT: 2016-004198-41.

The NOFLO trial: low-flow nasal prongs therapy in weaning nasal continuous positive airway pressure in preterm infants.

OBJECTIVE: To determine if low-flow nasal prongs therapy with room air, compared with no treatment, facilitates weaning from nasal continuous positive airway pressure (NCPAP) in very low birth weight (VLBW, birth weight <1500 g) infants. STUDY DESIGN: VLBW infants who received respiratory support for ≥ 48 hours and who were stable on NCPAP for 24 hours were eligible for inclusion in this multicenter, randomized controlled trial. On stopping NCPAP, infants were randomized to receive 1 L/min air via nasal prongs or to spontaneous breathing in room air. The primary outcome measure was failure to wean. Secondary outcome measures included length of time to failure and change in heart rate, respiratory rate, oxygen saturation, and respiratory distress score. RESULTS: Seventy-eight infants were randomized: 39 to nasal prongs and 39 to spontaneous breathing. The groups were similar at birth and at randomization. Sixteen infants (41%) in the nasal prongs group failed the weaning process compared with 12 infants (31%) in the spontaneous breathing group (OR 1.57, 95% CI 0.56 to 4.43, P = .48). There were no significant differences between the groups in secondary outcomes. CONCLUSIONS: In this study, we did not demonstrate a benefit of low-flow room air via nasal prongs to wean VLBW infants from NCPAP.

Thresholds for surfactant use in preterm neonates: a network meta-analysis.

OBJECTIVE: To perform a network meta-analysis of randomised controlled trials of different surfactant treatment strategies for respiratory distress syndrome (RDS) to assess if a certain fraction of inspired oxygen (FiO2) is optimal for selective surfactant therapy. DESIGN: Systematic review and network meta-analysis using Bayesian analysis of randomised trials of prophylactic versus selective surfactant for RDS. SETTING: Cochrane Central Register of Controlled Trials, MEDLINE, Embase and Science Citation Index Expanded. PATIENTS: Randomised trials including infants under 32 weeks of gestational age. INTERVENTIONS: Intratracheal surfactant, irrespective of type or dose. MAIN OUTCOME MEASURES: Our primary outcome was neonatal mortality, compared between groups treated with selective surfactant therapy at different thresholds of FiO2. Secondary outcomes included respiratory morbidity and major complications of prematurity. RESULTS: Of 4643 identified references, 14 studies involving 5298 participants were included. We found no statistically significant differences between 30%, 40% and 50% FiO2 thresholds. A sensitivity analysis of infants treated in the era of high antenatal steroid use and nasal continuous positive airway pressure as initial mode of respiratory support showed no difference in mortality, RDS or intraventricular haemorrhage alone but suggested an increase in the combined outcome of major morbidities in the 60% threshold. CONCLUSION: Our results do not show a clear benefit of surfactant treatment at any threshold of FiO2. The 60% threshold was suggestive of increased morbidity. There was no advantage seen with prophylactic treatment. Randomised trials of different thresholds for surfactant delivery are urgently needed to guide clinicians and provide robust evidence. PROSPERO REGISTRATION NUMBER: CRD42020166620.

Machine Learning Detects Intraventricular Haemorrhage in Extremely Preterm Infants.

OBJECTIVE: To test the potential utility of applying machine learning methods to regional cerebral (rcSO2) and peripheral oxygen saturation (SpO2) signals to detect brain injury in extremely preterm infants. STUDY DESIGN: A subset of infants enrolled in the Management of Hypotension in Preterm infants (HIP) trial were analysed (n = 46). All eligible infants were <28 weeks' gestational age and had continuous rcSO2 measurements performed over the first 72 h and cranial ultrasounds performed during the first week after birth. SpO2 data were available for 32 infants. The rcSO2 and SpO2 signals were preprocessed, and prolonged relative desaturations (PRDs; data-driven desaturation in the 2-to-15-min range) were extracted. Numerous quantitative features were extracted from the biosignals before and after the exclusion of the PRDs within the signals. PRDs were also evaluated as a stand-alone feature. A machine learning model was used to detect brain injury (intraventricular haemorrhage-IVH grade II-IV) using a leave-one-out cross-validation approach. RESULTS: The area under the receiver operating characteristic curve (AUC) for the PRD rcSO2 was 0.846 (95% CI: 0.720-0.948), outperforming the rcSO2 threshold approach (AUC 0.593 95% CI 0.399-0.775). Neither the clinical model nor any of the SpO2 models were significantly associated with brain injury. CONCLUSION: There was a significant association between the data-driven definition of PRDs in rcSO2 and brain injury. Automated analysis of PRDs of the cerebral NIRS signal in extremely preterm infants may aid in better prediction of IVH compared with a threshold-based approach. Further investigation of the definition of the extracted PRDs and an understanding of the physiology underlying these events are required.

Serial Assessment of Cardiac Function and Pulmonary Hemodynamics in Infants With Down Syndrome.

BACKGROUND: There is a dearth of longitudinal data describing the evolution of cardiopulmonary hemodynamics in infants with Down syndrome (DS) beyond infancy. We hypothesized that babies with DS, independent of the presence of congenital heart disease (CHD), demonstrate biventricular systolic and diastolic impairment and sustained elevation of pulmonary pressures compared with controls over the first 2 years of age. METHODS: This was a prospective observational cohort study of 70 infants with DS (48 with CHD and 22 without CHD) and 60 controls carried out in 3 tertiary neonatal intensive care units in Dublin, Ireland. Infants with DS with and without CHD and non-DS controls underwent serial echocardiograms at birth, 6 months, 1 year, and 2 years of age to assess biventricular systolic and diastolic function using deformation analysis. Pulmonary vascular resistance was assessed using pulmonary artery acceleration time and left ventricular (LV) eccentricity index. RESULTS: Infants with DS exhibited smaller LV (birth: 27 ± 4 vs 31 ± 2 mm, P < .01; 2 years: 43 ± 5 vs 48 ± 4 mm, P < .01) and right ventricular (birth: 28 ± 3 vs 31 ± 2 mm, P < .01; 2 years: 40 ± 4 vs 44 ± 3 mm, P < .01) lengths and lower LV (birth: -19% ± 3% vs -22% ± 2%, P < .01; 2 years: -24% ± 2% vs -26% ± 2%, P < .01) and right ventricular (birth: -19% ± 4% vs -22% ± 3%, P < .01; 2 years: -29% ± 6% vs -33% ± 4%, P < .01) systolic strain over the 2-year period. Pulmonary artery acceleration time was lower in the DS group throughout the study period (birth: 44 ± 10 vs 62 ± 14 ms, P < .01; 2 years 71 ± 12 vs 83 ± 11 ms, P < .01). No differences were observed between DS infants with and without CHD (all P > .05). CONCLUSIONS: Infants with DS exhibit impaired maturational changes in myocardial function and pulmonary vascular resistance. Such novel findings provide valuable insights into the pathophysiology affecting cardiorespiratory morbidity in this population.