Chest compressions superimposed with sustained inflation during neonatal cardiopulmonary resuscitation: are we ready for a clinical trial?

Neonates requiring cardiopulmonary resuscitation (CPR) are at risk of mortality and neurodevelopmental injury. Poor outcomes following the need for chest compressions (CCs) in the delivery room prompt the critical need for improvements in resuscitation strategies. This article explores a technique of CPR which involves CCs with sustained inflation (CC+SI). Unique features of CC+SI include (1) improved tidal volume delivery, (2) passive ventilation during compressions, (3) uninterrupted compressions and (4) improved stability of cerebral blood flow during resuscitation. CC+SI has been shown in animal studies to have improved time to return of spontaneous circulation and reduced mortality without significant increase in markers of inflammation and injury in the lung and brain, compared with standard CPR. The mechanics of CCs, rate of compressions, ventilation strategies and compression-to-ventilation ratios are detailed here. A large randomised controlled trial comparing CC+SI versus the current 3:1 compression-to-ventilation ratio is needed, given the growing evidence of its potential benefits.

Application of desirability of outcome ranking to the milking in non-vigorous infants trial.

OBJECTIVES: Neonatal trials have traditionally used binary composite short-term (such as death or bronchopulmonary dysplasia) or longer-term (such as death or severe neurodevelopmental impairment) outcomes. We applied the Desirability Of Outcome Ranking (DOOR) method to rank the overall patient outcome by best (no morbidities) to worst (death). STUDY DESIGN: Using a completed large multicenter trial (Milking In Non-Vigorous Infants [MINVI]) of umbilical cord milking (UCM) vs. early cord clamping (ECC), we applied the DOOR methodology to neonatal outcomes. Six outcomes were chosen and ranked: no interventions or NICU admission (most desirable); received initial cardiorespiratory support at birth; neonatal intensive care unit (NICU) admission for predefined criteria; mild hypoxic-ischemic encephalopathy (HIE); moderate to severe HIE; and death (least desirable). RESULTS: 1524 non-vigorous newborns born between 35 and 42 weeks' gestation had data for analysis. The DOOR distribution was different between the UCM and ECC arms, with a significantly greater probability (55.8 % [95 % CI 53.1-58.5 %; p < 0.0001]) of a randomly selected neonate having a more desirable outcome if they were in the UCM arm. DOOR probabilities of averting individual adverse outcomes such as NICU admission for predefined criteria (52.8 %; 95%CI 50.5-55.1 %) and cardiorespiratory support (54.0 %; 95%CI 51.6-56.4 %) were significantly higher among those in the UCM group. CONCLUSION: DOOR provides an overall assessment of the benefits and harms with greater insight than typical binary composite measures to clinicians and parents when evaluating an intervention. Future neonatal trials should consider the a priori use of the DOOR methodology to evaluate trial outcomes.

Parental perspectives on a trial using waived informed consent at birth.

OBJECTIVES: To determine parental perspectives in a trial with waived consent. STUDY DESIGN: Anonymous survey of birth parents with term infants who were randomized using a waiver of consent, administered after infant discharge. RESULTS: 121 (11%) survey responses were collected. Of the 121 responding parents 111 (92%) reported that this form of consent was acceptable and 116 (96%) reported feeling comfortable having another child participate in a similar study. 110 (91%) respondents reported that they both understood the information provided in the consent process and had enough time to consider participation. Four percent had a negative opinion on the study's effect on their child's health. CONCLUSIONS: Most responding parents reported both acceptability of this study design in the neonatal period and that the study had a positive effect on their child's health. Future work should investigate additional ways to involve parents and elicit feedback on varied methods of pediatric consent.

Optimizing transition: Providing oxygen during intact cord resuscitation.

Delayed clamping and cutting of the umbilical cord at birth is standard practice for management for all newborns. Preterm infants may additionally benefit from a combination of ventilation and oxygen provision during intact cord resuscitation. This review highlights both the potential benefits of such a combined approach and the need for further rigorous studies, including randomized controlled trials, of delivery room management in this population.

Curriculum and assessment tool for less invasive surfactant administration: an international Delphi consensus study.

BACKGROUND: Training and assessment of operator competence for the less invasive surfactant administration (LISA) procedure vary. This study aimed to obtain international expert consensus on LISA training (LISA curriculum (LISA-CUR)) and assessment (LISA assessment tool (LISA-AT)). METHODS: From February to July 2022, an international three-round Delphi process gathered opinions from LISA experts (researchers, curriculum developers, and clinical educators) on a list of items to be included in a LISA-CUR and LISA-AT (Round 1). The experts rated the importance of each item (Round 2). Items supported by more than 80% consensus were included. All experts were asked to approve or reject the final LISA-CUR and LISA-AT (Round 3). RESULTS: A total of 153 experts from 14 countries participated in Round 1, and the response rate for Rounds 2 and 3 was >80%. Round 1 identified 44 items for LISA-CUR and 22 for LISA-AT. Round 2 excluded 15 items for the LISA-CUR and 7 items for the LISA-AT. Round 3 resulted in a strong consensus (99-100%) for the final 29 items for the LISA-CUR and 15 items for the LISA-AT. CONCLUSIONS: This Delphi process established an international consensus on a training curriculum and content evidence for the assessment of LISA competence. IMPACT: This international consensus-based expert statement provides content on a curriculum for the less invasive surfactant administration procedure (LISA-CUR) that may be partnered with existing evidence-based strategies to optimize and standardize LISA training in the future. This international consensus-based expert statement also provides content on an assessment tool for the LISA procedure (LISA-AT) that can help to evaluate competence in LISA operators. The proposed LISA-AT enables standardized, continuous feedback and assessment until achieving proficiency.

Cardiac and cerebral hemodynamics with umbilical cord milking compared with early cord clamping: A randomized cluster crossover trial.

OBJECTIVE: A large, randomized cluster cross-over trial (N = 1730) comparing intact umbilical cord milking (UCM) to early cord clamping (ECC) in non-vigorous near-term/term newborns demonstrated a reduction in cardiorespiratory interventions at birth and less moderate to severe hypoxic ischemic encephalopathy. We evaluated changes in cerebral tissue oxygenation (StO2), pulse oximetry (SpO2), pulse rate and fraction of inspired oxygen (FiO2) during the first 10 min of life in a subset of infants enrolled in the parent trial. STUDY DESIGN: Infants enrolled in the Milking in Non-Vigorous Infants trial that had StO2 monitoring at birth were included in the sub-study conducted at 3 hospitals the US and Canada. A near-infrared spectroscopy sensor, pulse oximeter and electrocardiogram electrodes were placed. Pulse rate, StO2, SpO2, and FiO2 were collected for the first 10 min after birth. Longitudinal models were used to compare effects of UCM and ECC. RESULTS: Thirty-four infants had StO2 data. Fifteen of these infants received UCM and 19 had ECC. Infants receiving UCM had similar heart rates, SpO2, and StO2 values, but were exposed to less FiO2 over the first 10 min of life than infants with ECC (0.26 ± 0.12 vs. 0.81 ± 0.05 at 10 min). CONCLUSION: Non-vigorous term/near term infants who received UCM at birth required lower FiO2 after delivery when compared to infants who umbilical cords were clamped soon after birth while achieving similar peripheral and cerebral oxygenation. Cord milking may be a potential option for placental transfusion in non-vigorous near term/term infants when delayed cord clamping cannot be performed.

Umbilical cord milking in nonvigorous infants: a cluster-randomized crossover trial.

BACKGROUND: Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits. OBJECTIVE: We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks' gestation. STUDY DESIGN: This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks' gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept. RESULTS: Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41-1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33-0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33-0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24-0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62-1.06), or a serious adverse event composite of death before discharge. CONCLUSION: Among nonvigorous infants born at 35 to 42 weeks' gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping.

Transcutaneous bilirubin levels in extremely preterm infants less than 30 weeks gestation.

OBJECTIVE: The primary objective of this study was to determine the relationship between transcutaneous bilirubin (TcB) levels and total serum bilirubin (TSB) levels in extremely preterm infants. STUDY DESIGN: We conducted a prospective multicenter study of extremely preterm infants less than 30 weeks gestation in California. Difference between paired TcB and TSB values were compared based on gestational age, birth weight, maternal race/ethnicity, chronological age as well as during and after phototherapy. RESULTS: TSB values ranged from 0 to 12.6 mg/dl and the TcB values ranged from 0 to 14.2 mg/dl. TSB was predicted with a high degree of accuracy at TSB = 2.37 + 0.54 (TcB) with r = 0.786. There was good correlation across gestational age, birth weight, race/ethnic, chronological age subgroups as well as during and after phototherapy. CONCLUSION: Our study supports the use of TcB as a screening tool for monitoring jaundice in extremely preterm infants.

Maternal bleeding complications and neonatal outcomes following early versus delayed umbilical cord clamping in cesarean deliveries for very low birthweight infants.

OBJECTIVE: Determine effect of at least 60 s delayed cord clamping (DCC) on postpartum hemorrhage and maternal estimated blood loss (EBL) in very low birth weight (VLBW) cesarean deliveries when compared to early cord clamping (ECC). STUDY DESIGN: Retrospective study of VLBW infants at birth. Maternal pre- and post-operative hemoglobin, EBL, and neonatal outcomes were collected. RESULTS: In total, 620 VLBW infants (DCC = 166, ECC = 454) born to 545 mothers (DCC = 155, ECC = 390) were included. Maternal PPH between DCC was 8% versus ECC was 10% p = 0.52. There were no differences in estimated blood loss or rate of maternal blood transfusion between groups. The post-operative hemoglobin was lower in infants receiving ECC compared to DCC (10.4 [9.4-11.5] versus 10.8 [10.1-11.9] g/dl, p = 0.01). In comparing pre-operative to post-operative hemoglobin there was no difference between DCC and ECC (-1.2 [-2.0 to -0.3] versus -1.2 [-2.1 to -0.6] g/dl, p = 0.46). CONCLUSION: DCC of at least 60 s did not increase maternal bleeding complications during VLBW cesarean delivery. To our knowledge, this retrospective study is the largest sample size to date of preterm cesarean deliveries to support maternal safety regarding bleeding complications after delayed cord clamping.

Use of Pulse Oximetry Pulsatility Index Screening for Critical Congenital Heart Disease.

OBJECTIVE: This study aimed to compare oximetry data (pre- and postductal oxygen saturation [SpO2], pre- and postductal pulsatility index [PI]) in healthy newborns (≥35 weeks' gestational age) to infants who have critical congenital heart disease (CCHD). STUDY DESIGN: This is a retrospective analysis of data obtained from electronic medical records, recorded as part of routine pulse oximetry screening (POS) for CCHD in infants born between the years 2013 and 2020. Testing was performed at 24 ± 2 hours of life. Data were analyzed to detect differences in pre- and postductal SpO2 and pre- and postductal PI in healthy newborns compared with infants who have CCHD. Newborns were excluded from analysis if they: (1) had a prenatal diagnosis of CCHD in the medical record, (2) had previously been admitted to the neonatal intensive care unit, or (3) had failed POS but were found no CCHD by diagnostic echocardiography. RESULTS: A total of 88,754 healthy newborns had received POS between the years 2013 and 2020. Of the 88,736 newborn records available for analysis,18 newborns were diagnosed with CCHD. Eight were identified by POS before discharge and 10 were diagnosed after discharge. Infants diagnosed with CCHD by POS had lower pre- and postductal SpO2 compared with normal infants. Their postductal PI was significantly lower. Infants who had CCHD that was not identified by POS had similar pre- and postductal SpO2 values, but their postductal PI was lower. Using a postductal PI cutoff of 1.21 had a receiver operating curve of area under the curve 0.77 (95% confidence interval: 0.672, 0.869) with 74% sensitivity and 61% specificity. CONCLUSION: In our large cohort of infants born in San Diego County, the postductal PI is lower in infants with CCHD. Given that PI is routinely displayed on every pulse oximeter and the high morbidity of missed CCHD, PI should be incorporated into routine CCHD screening. KEY POINTS: · Postductal PI is lower in newborn who presented later with congenital heart disease.. · Postductal PI cut-off of 1.21 may help practitioners determine if a newborn is at risk for CCHD.. · This large cohort study demonstrates that a low PI can detect additional CCHD cases..

A newborn's "life line" - A review of umbilical cord management strategies.

Literature supporting various umbilical management strategies have increased substantially over the past decade. Delayed cord clamping and umbilical cord milking are increasing embraced by obstetricians and neonatologists, and multiple international governing bodies now endorse these practices. This review summarizes the benefits and limitations of the different umbilical cord management strategies for term, near-term, and preterm neonates. Additional studies are underway to elucidate the safety profile of these practices, long term outcomes, and variations within these strategies that could potentially augment the benefits.

The NICU Antibiotics and Outcomes (NANO) trial: a randomized multicenter clinical trial assessing empiric antibiotics and clinical outcomes in newborn preterm infants.

BACKGROUND: Early-onset sepsis is an important cause of neonatal morbidity and mortality in the preterm population. Infants perceived to be at increased risk for early-onset sepsis are often treated empirically with broad-spectrum antibiotics while awaiting confirmatory blood cultures, despite an overall incidence of early-onset sepsis of 2-3% among extremely-low-birthweight (ELBW) infants. Recent observational studies associate perinatal antibiotic use with an increased incidence of necrotizing enterocolitis, late-onset sepsis, and mortality among ELBW infants. Given currently available data and variability in clinical practice, we designed a prospective multi-institutional randomized controlled trial to determine the safety of early antibiotic use in ELBW infants. METHODS: The NICU Antibiotics and Outcomes (NANO) trial is a multicenter, double-blinded, randomized controlled trial. A sample of 802 ELBW preterm infants will undergo web-based stratified block randomization to receive empiric antibiotics (EA; ampicillin and gentamicin) or placebo during routine evaluation for early-onset sepsis. Participating sites will use preexisting institutional protocols for antibiotic dosage and duration. Infants born at participating sites with a gestational age of 29 weeks or less are eligible for enrollment. Exclusion criteria include maternal intrauterine infection, hemodynamic or respiratory instability, delivery by caesarean section for maternal indications without labor or prolonged rupture of membranes, and prior administration of antibiotics. The primary outcome is the composite incidence of necrotizing enterocolitis, late-onset sepsis, or death during participants' index hospitalization. Maternal and infant samples will be collected longitudinally and assessed for differences in microbiome composition and diversity. DISCUSSION: The NANO trial is designed to compare the rate of adverse outcomes of EA use at birth versus placebo in ELBW preterm infants. If EA at birth worsens clinical outcomes, then the results of the trial may help providers decrease antibiotic utilization in the NICU and subsequently decrease the incidence of complications associated with early antibiotic use in ELBW infants. If we instead find that EA improve outcomes, then the trial will validate a longstanding clinical practice that has not previously been supported by high-quality data. Future studies will assess long-term clinical and microbial outcomes in infants who received empiric antibiotics following delivery. TRIAL REGISTRATION: Trial registration data: June 25, 2019  NCT03997266 .

Variations in umbilical cord clamping practices in the United States: a national survey of neonatologists.

OBJECTIVE: Since the first publication of the American College of Obstetricians and Gynecologists committee opinion in 2012, and following the update in 2017, multiple institutions in the United States (US) adopted the practice of delayed cord clamping (DCC) and/or umbilical cord milking (UCM) in preterm and term infants. However, there have been variations reported in practices with regard to method of placental transfusion, timing of cord clamping and gestational age thresholds. Furthermore, the optimal cord clamping practice in situations of depressed infants needing resuscitation or in higher-risk delivery situations, such as placental abruption, intrauterine growth restriction, multiple gestation, chorioamnionitis, maternal human immunodeficiency virus syndrome/hepatitis or maternal general anesthesia is often debated. An evaluation of these variations and exploration of associated factors was needed to optimally target opportunities for improvement and streamline research activities. The objective of this survey, specifically aimed at neonatologists working in the US was to identify and describe current cord clamping practices and evaluate factors associated with variations. STUDY DESIGN: The survey was distributed electronically to the US neonatologists in August 2019 with a reminder email sent in October 2019. Clinicians were primarily identified from Perinatal Section of AAP, with reminders also sent through various organizations including California Association of Neonatologists, Pediatrix and Envision national groups. Descriptive variables of interest included years of experience practicing neonatology, affiliation with a teaching institution, level of the neonatal intensive care unit (NICU) and practicing region of the US. Questions on variations in cord management practices included information about center specific guideline/protocol, cord clamping practices, gestational age threshold of placental transfusion, performance of UCM and practice in higher-risk delivery situations. RESULTS: The response rate was 14.8%. Among 517 neonatologists whom responded, majority (85.5%) of the practices had a guideline and performed (81.7%) DCC in all gestational ages. The cord clamping practice was predominantly DCC and it was categorized as reporting clamping times <60 s in 46.6% and ≥60 s in 48.7% of responses. A significant association was detected between time of delay in cord clamping and region of practice. The Northeast region was more likely to clamp the cord in <60 s than other regions in the US. More than half of the providers responded not performing any UCM (57.3%) in their practice. Significant associations were detected between performance of UCM and all queried demographic variables independently. Clinicians with >20 years of experience were more likely from institutions performing UCM compared to the providers with fewer years of experience. However, teaching hospitals were less likely to perform UCM compared to non-teaching hospitals. Similarly, practices with level IV NICUs were less likely to perform UCM compared to practices with level III units. Hospitals in the Midwest region of US were less likely to perform UCM compared to hospitals in the Western region. Significant variations were also noticed for not providing placental transfusion in higher-risk deliveries. Demographic and professional factors were noted to be associated with these differences. CONCLUSION: Although the majority of practices have a guideline/protocol and are performing DCC in all gestational ages, there are variations noted with regard to timing, method, and performance in higher-risk deliveries. Demographic and professional factors play an important role in these variations. Future research needs to focus on the modifiable factors to optimize the procedure and impact of DCC.

Perinatal Outcomes of Subjects Enrolled in a Multicenter Trial with a Waiver of Antenatal Consent.

OBJECTIVE: This study aimed to determine whether outcomes differed between infants enrolled in the PREMOD2 trial and those otherwise eligible but not enrolled, and whether the use of waiver effected these differences. STUDY DESIGN: The multicenter PREMOD2 (PREmature infants receiving Milking Or Delayed cord clamping) trial was approved for waiver of antenatal consent by six of the nine sites institutional review boards, while three sites exclusively used antenatal consent. Every randomized subject delivered at a site with a waiver of consent was approached for postnatal consent to allow for data collection. Four of those six sites IRBs required the study team to attempt antenatal consent when possible. Three sites exclusively used antenatal consent. RESULTS: Enrolled subjects had higher Apgar scores, less use of positive pressure ventilation, a lower rate of bronchopulmonary dysplasia, and a less frequent occurrence of the combined outcome of severe intraventricular hemorrhage or death. A significantly greater number of infants were enrolled at sites with an option of waiver of consent (66 vs. 26%, risk ratio = 2.54, p < 0.001). At sites with an option of either approaching families before delivery or after delivery with a waiver of antenatal consent, those approached prior to delivery refused consent 40% (range 15-74% across six sites) of the time. CONCLUSION: PREMOD2 trial demonstrated analytical validity limitations because of the variable mix of antenatal consent and waiver of consent. A waiver of antenatal consent for minimal risk interventional trials conducted during the intrapartum period will be more successful in enrolling a representative sample of low and high-risk infants if investigators are able to enroll all eligible subjects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03019367. KEY POINTS: · Waiver of consent is when informed consent cannot be obtained prior to delivery.. · Cord milking is a procedure in which blood is pushed (stripped) two to four times towards the newborn.. · Delayed clamping means the umbilical cord is not clamped immediately after birth..

A Pilot Randomized Trial of Heart Rate Monitoring Using Conventional Versus a New Electrocardiogram Algorithm during Neonatal Resuscitation at Birth.

Current guidelines support the use of a cardiac monitor during neonatal resuscitation. Infants born preterm randomized to a novel electrocardiogram algorithm displayed a heart rate sooner than the conventional electrocardiogram algorithm. Although resuscitation outcomes were not different, the availability of an earlier heart rate may benefit neonatal providers during high-risk resuscitations. TRIAL REGISTRATION: ClinicalTrials.govNCT04587934.

Delayed cord clamping in healthy term infants: More harm or good?

It is recommended to delay cord clamping in healthy term infants for at least 60- and 180-s in high- and limited-resource environments, as delayed cord clamping lowers the incidence of anemia and iron deficiency and improves neurodevelopment. There are improvements in hemodynamic parameters such as peripheral arterial oxygen saturation, heart rate, cardiac output, and cerebral oxygenation. Historically, delayed cord clamping caused a higher rate of hyperbilirubinemia and phototherapy, but more recent evidence suggests this may no longer be the case. In limited-resource environments delayed cord clamping may reduce anemia and iron deficiency potentially improving neurodevelopmental outcomes. The use of delayed cord clamping in newborn infants with intrauterine growth restriction or monochorionic twins is limited and further evidence is needed before it can be formally recommended.

Association between early cerebral oxygenation and neurodevelopmental impairment or death in premature infants.

OBJECTIVE: To assess the relationship between cerebral oxygenation in the first 72 h of life and neurodevelopmental impairment (NDI) at 2 years corrected age in former premature infants. STUDY DESIGN: Prospective observational cohort study of 127 infants <32 weeks GA at birth with cerebral oxygenation monitoring using NIRS in the first 72 h of life. RESULTS: Using a threshold cutoff for cerebral hypoxia, infants with NDI or death had increased duration of hypoxia (4 vs 2.3%, p = 0.001), which was more pronounced in the 23-27 week subgroup (7.6 vs 3.2%, p < 0.001). Individual generalized estimating equations to adjust for repeated measures were modeled in this subgroup for the physiologic parameters including StO2. StO2 < 67% was a predictor for death or NDI (OR 2.75, 95% CI 1.006, 7.5132, p = 0.049). CONCLUSION: An increased duration of cerebral hypoxia is associated with NDI or death in infants born <32 weeks GA.

Multicentre, randomised trial of preterm infants receiving caffeine and less invasive surfactant administration compared with caffeine and early continuous positive airway pressure (CaLI trial): study protocol.

INTRODUCTION: Respiratory distress syndrome (RDS) or surfactant deficiency occurs primarily in premature infants resulting in composite outcomes of death or bronchopulmonary dysplasia. Initial management strategies for preterm infants with RDS includes early initiation of continuous positive airway pressure (CPAP) and titration of fractional inspired oxygen (FiO2), and may include the use of less invasive surfactant administration (LISA) to avoid the need for mechanical ventilation. In order to optimise success of non-invasive support, the use of early caffeine therapy may be critical to the success of LISA. The objective of our trial is to evaluate whether infants that receive early caffeine, CPAP and surfactant via the LISA method compared with infants that receive caffeine and CPAP alone, have a decreased need for invasive mechanical ventilation in the first 72 hours of life. METHODS AND ANALYSIS: CaLI is an unblinded multicentre, randomised controlled, trial of 180 preterm infants (24+0-29+6 weeks corrected GA). Criteria for intubation/treatment failure will follow guidelines for the management of RDS, including: (1) CPAP level of 6-8 cmH20 and FiO2 >0.40 required to maintain saturations 90%-95% for 2 hours after randomisation; (2) a pH of 7.15 or less or a paCO2 >65 mm Hg on any (2) blood gases (arterial/capillary/or venous) at least 2 hours after randomisation and in the first 72 hours of life; (3) continued apnoea/bradycardia/desaturation events despite nasal intermittent minute ventilation mode of ventilation. Infants will be randomised by 1 hour of life and caffeine/LISA treatments administered by 2 hour of life. Caffeine will be administered prior to surfactant in the LISA arm and before 2 hours of life in the control arm. ETHICS AND DISSEMINATION: Chiesi Farmaceutici, S.p.A is the sponsor of CaLI. Ethical approval has been obtained. Results will be submitted for publication in peer reviewed journals. TRIAL REGISTRATION NUMBER: www.Clinicaltrials.gov: NCT04209946; Pre-results.

Early experience with the Micro Plug Set for preterm patent ductus arteriosus closure.

OBJECTIVES: We intend to describe early experience using a new, commercially available Micro Plug Set for preterm neonate and infant transcatheter patent ductus arteriosus (PDA) occlusion. BACKGROUND: Transcatheter PDA occlusion in premature neonates and small infants is safe and effective. The procedure is early in its evolution. METHODS: Procedural and short-term outcomes of preterm neonates and infants undergoing transcatheter PDA occlusion with a new, commercially available device were reviewed. RESULTS: Eight preterm neonates and infants born at median 27 weeks gestation (23-36 weeks) underwent transcatheter PDA device closure with the Micro Plug Set. The device is short (2.5 mm) with a range of diameters (3, 4, 5, 6 mm) and delivered through a microcatheter. Procedures were performed at median 41 days of age (12-88 days) and at 1690 g (760-3,310 g). Transvenous PDA device occlusion was performed with fluoroscopic and echocardiography guidance. All procedures were successful with complete PDA occlusion. There were no procedural or short-term adverse events. CONCLUSIONS: Preterm neonate and infant transcatheter PDA device closure with a new, commercially available short and microcatheter delivered device (Micro Plug Set) was safe and effective in a small, early series of patients.