Umbilical artery eucapnic pH to assess fetal well-being.

BACKGROUND: Umbilical artery gas results help obstetricians assess fetal well-being during labor and guide screening decisions on eligibility for therapeutic hypothermia (ie, whole-body or head cooling). The accuracy of results, especially for the base deficit on arterial cord gas analysis, in predicting brain injury is questioned. A novel biomarker specifically calculated for fetal acid-base physiology and response to asphyxia-neonatal eucapnic pH as a marker of neonatal metabolic acidosis-has the potential to be an accurate predictor of hypoxic-ischemic encephalopathy. OBJECTIVE: We aimed to compare false-negative rates of hypoxic-ischemic encephalopathy for umbilical artery pH, base deficit, and neonatal eucapnic pH in assessing fetal acid-base balance as a marker of fetal well-being and predicting acute brain injury. STUDY DESIGN: This is a retrospective single-center cohort study of newborns ≥ 35 weeks of gestation diagnosed with hypoxic-ischemic encephalopathy. We compared false-negative rates for any grade of hypoxic-ischemic encephalopathy using unilateral paired chi-square statistical analysis based on cutoff values for umbilical artery pH ≤7.00, base deficit ≥16 mmol/L, base deficit ≥12 mmol/L and neonatal eucapnic pH ≤7.14. We performed an analysis of variance between umbilical artery pH, base deficit, and neonatal eucapnic pH for each hypoxic-ischemic encephalopathy grade. RESULTS: We included 113 newborns. False-negative rate for hypoxic-ischemic encephalopathy was significantly higher for base deficit <16 mmol/L (n=78/113; 69.0%) than <12 mmol/L (n=46/113; 40.7%), pH >7.00 (n=41/113; 36.3%), or neonatal eucpanic pH >7.14 (n=35/113; 31.0%) (P<.0001). All true-positive cases were identified using only umbilical artery pH and neonatal eucapnic pH. Base deficit ≥16 or ≥12 mmol/L did not add any value in identifying newborns with hypoxic-ischemic encephalopathy when using umbilical artery pH and neonatal eucapnic pH. No association emerged between any marker and hypoxic-ischemic encephalopathy severity grading. CONCLUSION: Our findings support the accuracy of neonatal eucapnic pH to assess fetal well-being during labor and to improve predictive performance for acute brain injury. Neonatal eucpanic pH, in addition to umbilical artery pH, may be a viable alternative in identifying newborns at risk for hypoxic-ischemic encephalopathy.

Is it time to end the use of base deficit for fetal well-being assessment?

Authors have expressed reservations regarding the use of base deficit measured in umbilical artery blood samples to assess fetal well-being during the course of labor and to predict neonatal neurologic morbidity. Despite its integration into clinical practice for more than 50 years, obstetricians and maternal-fetal medicine specialists may not realize that this marker has significant limitations in accurately identifying neonatal metabolic acidosis as a proxy for fetal well-being. In brief, there are 2 large families of base deficit, namely whole blood and extracellular fluid. Both rely on equations that use normal adult acid-base characteristics (pH 7.40 and partial CO2 pressure of 40 mm Hg) that overlook the specificity of the normal in utero acid-base status of pH 7.27 and partial CO2 pressure of 54 mm Hg. In addition, it ignores the unique characteristic of the in utero fetal response to acute hypoxia. The dependence on placental circulation for CO2 elimination may lead to extremely high values (up to 130 to 150 mm Hg) during hypoxic events, a phenomenon that is absent in adults with acute metabolic acidosis who can hyperventilate. The dispute over if to include a correction for high partial CO2 pressure in the bicarbonate estimation, as presented in the Great Trans-Atlantic Debates, remains unresolved. The key constants computed for adult acid-base physiology in the current base deficit algorithms, without accounting for the impact of high partial CO2 pressure or other fetal characteristics of buffering capacity (eg, differences in body water content composition, plasma protein, and hemoglobin attributes), may lead to an overestimation of metabolic acidosis, especially in newborns who are experiencing hypercarbia during the early stages of the hypoxic response. These unrecognized limitations impact the base deficit results and may mislead clinicians on fetal well-being assessments when discussing the management of fetal heart rate monitoring and neonatal outcomes. Based on our arguments, we believe that it is prudent to consider an alternative to base deficit for drawing conclusions regarding fetal well-being during the course of birth management. We propose a marker specifically related to the newborn acid-base physiology--the neonatal eucapnic pH correction. This marker can be added to arterial cord blood gas analysis, and we have described how to interpret it as a marker of neonatal metabolic acidosis.

Eucapnic pH coupled with arterial cord pH improves hypoxic-ischemic encephalopathy prediction.

OBJECTIVE: To consider the classical use of "pH < 7.0 and/or a base deficiency ≥12 mmol/L" as markers of the risk of neonatal hypoxic-ischemic encephalopathy (HIE), recalling various criticisms of the use of these markers in favor of that of neonatal eucapnic pH, which appears to be a better marker of this risk. METHODS: Fifty-five cases of acidemia with pH < 7.00 were collected from a cohort from the Nice University Hospital with eight cases of HIE. We compared the receiver operating characteristics curves established from the positive likelihood ratio (+LR) for each case of: umbilical cord artery pH (pHa), neonatal eucapnic pH (pH euc-n) in isolation (not matched to pHa), and matched pHa to its own pH euc-n. RESULTS: The areas under the curve (AUC) are identical for pHa and pH euc-n, but AUC for the matched pair pHa-pH euc-n appears superior but non-significant because of the small number in our cohort. However, using the bootstrap method, the partial AUC for a sensitivity greater than 75% indicates the significant superiority (P < 0.01) of the matched pair pHa-pH euc-n approach. CONCLUSION: The originality of this study lies in the use of two methodologic approaches: (1) standardized partial analysis of the AUCs of the pHa curve and that of pHa matched to its own pH euc-n, and (2) bootstrap statistical technique, that allowed us to conclude (P < 0.01) that the combined use of pH measured at the cord coupled with its eucapnic correction is better for diagnosing metabolic acidosis and best predicting the risk of HIE.

Development of a Bedside Tool to Predict the Diagnosis of Cerebral Palsy in Term-Born Neonates.

Importance: Cerebral palsy (CP) is the most common abnormality of motor development and causes lifelong impairment. Early diagnosis and therapy can improve outcomes, but early identification of infants at risk remains challenging. Objective: To develop a CP prognostic tool that can be applied to all term neonates to identify those at increased risk of developing CP. Design, Setting, and Participants: This case-control study used data from the Canadian Cerebral Palsy Registry (data collected from January 2003 to December 2019) for children with CP and the Alberta Pregnancy Outcomes and Nutrition study (mothers enrolled from May 2009 to September 2012; data extracted in 2020) for controls. There were 2771 children with CP and 2131 controls evaluated; 941 and 144, respectively, were removed for gestational age less than 37 weeks at birth, 565 with CP removed for incomplete data, and 2 controls removed for a diagnosis of CP. Data were analyzed from April to August 2022. Exposures: Potential risk factors were selected a priori based on the literature, including maternal, intrapartum, and infant characteristics. Main Outcomes and Measures: Diagnosis of CP, defined as a disorder of motor function due to a nonprogressive brain abnormality before age 1 year and classified by Gross Motor Function Classification System levels I to V. Results: Of 3250 included individuals, 1752 (53.9%) were male, and the median (IQR) gestational age at birth was 39 (38-40) weeks. Encephalopathy was present in 335 of 1184 infants with CP (28%) and 0 controls. The final prediction model included 12 variables and correctly classified 75% of infants, with a sensitivity of 56% (95% CI, 52-60) and specificity of 82% (95% CI, 81-84). The C statistic was 0.74 (95% CI, 71-76). Risk factors were found to be additive. A proposed threshold for screening is probability greater than 0.3, with a sensitivity of 65% (95% CI, 61-68) and specificity of 71% (95% CI, 69-73). The prognostic tool identified 2.4-fold more children with CP than would have presented with encephalopathy (odds ratio, 13.8; 95% CI, 8.87-22.65; P < .001). Conclusions and Relevance: In this case-control study, a prognostic model using 12 clinical variables improved the prediction of CP compared with clinical presentation with encephalopathy. This tool can be applied to all term newborns to help select infants for closer surveillance or further diagnostic tests, which could improve outcomes through early intervention.

Assessing shared decision making during antenatal consultations regarding extreme prematurity.

OBJECTIVE: To assess whether antenatal decisions regarding the neonatal care at birth for extremely preterm infants are more likely to be made when using shared decision-making (SDM)-style consultations compared to standard consultations. STUDY DESIGN: In 2015, we implemented a clinical practice guideline promoting SDM use within antenatal consultations in our single-centre university-based perinatal unit. We conducted a prospective cohort study with a retrospective chart review based on data collected from all pregnant women presenting to obstetrical triage between 22 + 0 and 25 + 6 weeks gestation between September 2015 and June 2018. RESULT: Two-hundred-and-seventeen cases presented; 137 received antenatal consultations with 82 (60%) being SDM-style. Decisions were frequently made (88%; 120/137) after the consultations, with no significant difference between consultation style (RR 1.08, 95% CI [0.95-1.26], p = 0.28). CONCLUSION: The provision of either an SDM-style or a standard antenatal consultation seemed to comparably facilitate the reaching of a care decision.

Vulnerabilities in clinician-parent exchanges and the cascade of communication traps: a review.

This review considers parent-clinician interactions that are associated with vulnerabilities in communication and what we refer to as 'communication traps'. Communication traps are defined by high-stress situations with affect-laden subject matter that can lead to progressively dysfunctional communications/exchanges that are avoidable. While this framework was developed in neonatology, it can be applied to other clinical practices.Communication competencies in paediatrics require the rapid development of a therapeutic alliance between parents and clinicians to ensure the provision of best care to their infants. In order to facilitate parent-clinician communication, our framework focuses clinicians' attention on the affective, behavioural and cognitive (ABC) cues that are indicative of real, apparent or potential communication traps. Strategies are provided to slow down clinicians' responses to more effectively consider ABC cues that suggest if patients/parents have failed to engage or disengage from a situation. This framework is illustrated by presenting a narrative synthesised from a number of experiences that clinicians have encountered. This review identifies key decision points in the communication process that, if left unaddressed, can cascade into communication traps which may be difficult to escape.Using results from communication studies and psychological research, our framework was developed to identify key decision points for ABC cues that can be used to prevent falling into communication traps.

Maternal High-Dose DHA Supplementation and Neurodevelopment at 18-22 Months of Preterm Children.

OBJECTIVES: To determine whether maternal supplementation with high-dose docosahexaenoic acid (DHA) in breastfed, very preterm neonates improves neurodevelopmental outcomes at 18 to 22 months' corrected age (CA). METHODS: Planned follow-up of a randomized, double-blind, placebo-controlled, multicenter trial to compare neurodevelopmental outcomes in breastfed, preterm neonates born before 29 weeks' gestational age (GA). Lactating mothers were randomized to receive either DHA-rich algae oil or a placebo within 72 hours of delivery until 36 weeks' postmenstrual age. Neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development third edition (Bayley-III) at 18 to 22 months' CA. Planned subgroup analyses were conducted for GA (<27 vs ≥27 weeks' gestation) and sex. RESULTS: Among the 528 children enrolled, 457 (86.6%) had outcomes available at 18 to 22 months' CA (DHA, N = 234, placebo, N = 223). The mean differences in Bayley-III between children in the DHA and placebo groups were -0.07 (95% confidence interval [CI] -3.23 to 3.10, P = .97) for cognitive score, 2.36 (95% CI -1.14 to 5.87, P = .19) for language score, and 1.10 (95% CI -2.01 to 4.20, P = .49) for motor score. The association between treatment and the Bayley-III language score was modified by GA at birth (interaction P = .07). Neonates born <27 weeks' gestation exposed to DHA performed better on the Bayley-III language score, compared with the placebo group (mean difference 5.06, 95% CI 0.08-10.03, P = .05). There was no interaction between treatment group and sex. CONCLUSIONS: Maternal DHA supplementation did not improve neurodevelopmental outcomes at 18 to 22 months' CA in breastfed, preterm neonates, but subgroup analyses suggested a potential benefit for language in preterm neonates born before 27 weeks' GA.

Outcomes of infants with hypoxic-ischemic encephalopathy during COVID-19 pandemic lockdown in Canada: a cohort study.

PURPOSE: To evaluate change in the severity of hypoxic-ischemic encephalopathy (HIE) and associated morbidities between pre- and during COVID-19 pandemic periods in Canada. METHODS: We conducted a retrospective cohort study extracting the data from level-3 NICUs participating in Canadian Neonatal Network (CNN). The primary outcome was a composite of death in the first week after birth and/or stage 3 HIE (Sarnat and Sarnat). Secondary outcomes included rate and severity of HIE among admitted neonates, overall mortality, brain injury on magnetic resonance imaging (MRI), neonates requiring resuscitation, organ dysfunction, and therapeutic hypothermia (TH) usage. We included 1591 neonates with gestational age ≥ 36 weeks with HIE during the specified periods: pandemic cohort from April 1st to December 31st of 2020; pre-pandemic cohort between April 1st and December 31st of 2017, 2018, and 2019. We calculated the odds ratio (OR) and confidence intervals (CI). RESULTS: We observed no significant difference in the primary outcome (15% vs. 16%; OR 1.08; 95%CI 0.78-1.48), mortality in the first week after birth (6% vs. 6%; OR 1.10, 95%CI 0.69-1.75), neonates requiring resuscitation, organ dysfunction, TH usage, or rate of brain injury. In the ad hoc analysis, per 1000 live births, there was an increase in the rate of infants with HIE and TH use. CONCLUSIONS: Severity of HIE, associated morbidities, and mortality were not significantly different during the pandemic lockdown compared to a pre-pandemic period in Canada. Anticipated risks and difficulties in accessing healthcare have not increased the mortality and morbidities in neonates with HIE in Canada.

Antimicrobial utilization in very-low-birth-weight infants: association with probiotic use.

OBJECTIVE: To examine the association between probiotic use and antimicrobial utilization. STUDY DESIGN: We retrospectively evaluated very-low-birth-weight (VLBW) infants admitted to tertiary neonatal intensive care units in Canada between 2014 and 2019. Our outcome was antimicrobial utilization rate (AUR) defined as number of days of antimicrobial exposure per 1000 patient-days. RESULT: Of 16,223 eligible infants, 7279 (45%) received probiotics. Probiotic use rate increased from 10% in 2014 to 68% in 2019. The AUR was significantly lower in infants who received probiotics vs those who did not (107 vs 129 per 1000 patient-days, aRR = 0.89, 95% CI [0.81, 0.98]). Among 13,305 infants without culture-proven sepsis or necrotizing enterocolitis ≥Stage 2, 5931 (45%) received probiotics. Median AUR was significantly lower in the probiotic vs the no-probiotic group (78 vs 97 per 1000 patient-days, aRR = 0.85, 95% CI [0.74, 0.97]). CONCLUSION: Probiotic use was associated with a significant reduction in AUR among VLBW infants.

Evaluating parental perceptions of written handbooks provided during shared decision making with parents anticipating extremely preterm birth.

OBJECTIVE: To explore parental perceptions of written handbooks provided to them during antenatal counseling for anticipated extremely preterm birth. STUDY DESIGN: This study involved a prospective convenience sample of parents anticipating delivery between 22 weeks + 0 days and 25 weeks + 6 days gestation. The antenatal counseling involved a shared decision-making process. In-person interviews were conducted using a semi-structured interview guide to gather feedback about new parent handbooks developed to support decision making. The questions during the semi-structured interview targeted seven main themes: overall impression, timing, graphs/tables, formatting, imagery, ease of use and understanding, and content. The interviews followed an antenatal consultation and provision of the appropriate handbook(s) by a neonatologist. Interviews were transcribed verbatim and thematic analysis of the data was completed. RESULTS: Eleven parents were interviewed. All parents described the provision of the handbook(s) following the consultation with a neonatologist as the ideal time. All parents considered a visual representation of the data to be invaluable. Parents considered the handbooks easy to understand and straightforward. Some parents were satisfied with simple information, which helped them feel less overwhelmed; others felt the depth of information was insufficient. Parents preferred a paper copy to electronic. Reactions to the photo of an infant receiving intensive care varied; some parents felt frightened, others felt comforted. CONCLUSION: Overall, parents positively evaluated the handbooks, supporting their utility for parents anticipating extremely preterm birth. Concrete suggestions for improvement were made; the handbooks will be modified accordingly. Parents at other perinatal centers may benefit from receiving such handbooks.

Medications to manage infant pain, distress and end-of-life symptoms in the immediate postpartum period.

INTRODUCTION: Perinatal palliative care (PnPC) is a growing field where healthcare providers from multiple disciplines are supporting families and providing holistic care for their babies with life-limiting illnesses. It is important to have an approach that includes the standardized management of end-of-life symptoms that are anticipated around the time of birth. AREAS COVERED: A need was identified to develop medication orders for the initial pharmacological management of symptoms at end-of-life for infants with life-limiting conditions intended for use outside of an intensive care setting. The choice of medications was based on a review of the literature, discussion with content experts and guided by their ease of use, accessibility and noninvasive route of delivery. The recommendations can be used as a guide for the initial management of common symptoms encountered in perinatal palliative care. EXPERT OPINION: There are studies looking at many qualitative aspects of perinatal palliative care including perceptions of care, decision-making, and bereavement; however, few specifically focus on symptom management in the delivery room and postpartum ward settings. There is a need for standardization of the medical management of infants born with life-limiting conditions whose parents choose to pursue palliative care.

Pandemic planning: Developing a triage framework for Neonatal Intensive Care Unit.

Although the Covid-19 pandemic has not had a direct impact on neonates so far, it has raised concerns about resource distribution and showed that planning is required before the next crisis or pandemic. Resource allocation must consider unique Neonatal Intensive Care Unit (NICU) attributes, including physical space and equipment that may not be transferable to older populations, unique skills of NICU staff, inherent uncertainty in prognosis both antenatally and postnatally, possible biases against neonates, and the future pandemic disease's possible impact on neonates. We identified the need for a validated Neonatal Severity of Illness Prognostic Score to guide triage decisions. Based on this score, triage decisions are the responsibility of an informed triage team not involved in direct patient care. Support for the distress experienced by parents and staff is needed. This paper presents essential considerations in developing a practical framework for resources and triage in the NICU before, during and after a pandemic.

Protocol for a multicenter, double-blind, randomized, placebo-controlled phase III trial of the inhaled ß2-adrenergic receptor agonist salbutamol for transient tachypnea of the newborn (the REFSAL trial).

Background: Transient tachypnea of the newborn (TTN), which results from inadequate absorption of fetal lung fluid, is the most common cause of neonatal respiratory distress. Stimulation of ß-adrenergic receptors enhances alveolar fluid absorption. Therefore, the ß2-adrenergic receptor agonist salbutamol has been proposed as a treatment for TTN. This study aims to evaluate the efficacy and safety of salbutamol as supportive pharmacotherapy together with non-invasive nasal continuous positive airway pressure (NIV/nCPAP) for the prevention of persistent pulmonary hypertension of the newborn (PPHN) in infants with TTN. Methods and analysis: This multicenter, double-blind, phase III trial will include infants with a gestational age between 32 and 42 weeks who are affected by respiratory disorders and treated in eight neonatal intensive care units in Poland. A total of 608 infants within 24 h after birth will be enrolled and randomly assigned (1:1) to receive nebulized salbutamol with NIV or placebo (nebulized 0.9% NaCl) with NIV. The primary outcome is the percentage of infants with TTN who develop PPHN. The secondary outcomes are the severity of respiratory distress (assessed with the modified TTN Silverman score), frequency of need for intubation, duration of NIV and hospitalization, acid-base balance (blood pH, partial pressure of O2 and CO2, and base excess), and blood serum ionogram for Na+, K+, and Ca2+. Discussion: The Respiratory Failure with Salbutamol (REFSAL) study will be the first clinical trial to evaluate the efficacy and safety of salbutamol in the prevention of persistent pulmonary hypertension in newborns with tachypnea, and will improve short term outcomes. If successful, the study will demonstrate the feasibility of early intervention with NIV/nCPAP together with nebulized salbutamol in the management of TTN. Ethics and dissemination: The study protocol was approved by the Bioethics Committee of the Medical University of Warsaw, Warsaw, Poland on November 16, 2020 (decision number KB/190/2020). All procedures will follow the principles of the Declaration of Helsinki. The results of the study will be submitted for knowledge translation in peer-reviewed journals and presented at national and international pediatric society conferences. Clinical Trial Registration: It is registered at ClinicalTrials.gov NCT05527704, EudraCT 2020-003913-36; Protocol version 5.0 from 04/01/2022.

Extremely low gestational age infants: Developing a multidisciplinary care bundle.

BACKGROUND: Clinical experience in managing extremely low gestational age infants, particularly those born <24 weeks' gestation, is limited in Canada. Our goal was to develop a bedside care bundle for infants born <26 weeks' gestation, with special considerations for infants of <24 weeks, to harmonize and improve quality of care. METHODS: We created a multidisciplinary working group with experience in caring for preterm infants, searched the literature from 2000 to 2019 to identify best practices for the care of extremely preterm infants and consulted colleagues across Canada and internationally. Iterative improvements were made following the Plan-Do-Study-Act methodology. RESULTS: A care bundle, created in October 2015, was divided into three time periods: initial resuscitation/stabilization, the first 72 hours and days 4 to 7, with each period subdivided in 8 to 12 care themes. Revisions and practice changes were implemented to improve skin integrity, admission temperature, timing of initiation of feeds, reliability of transcutaneous CO2 monitoring and ventilation. Of 127 infants <26 weeks admitted between implementation and end of 2019, 78 survived to discharge (61%). CONCLUSION: It will be important to determine, with ongoing auditing and further evaluation, whether our care bundle led to improvements of short- and long-term outcomes in this population. Our experience may be useful to others caring for extremely low gestational age infants.

Parents' Views to Strengthen Partnerships in Newborn Intensive Care.

Background: Parental involvement in their newborn's neonatal intensive care reduces stress and helps with the parent-child attachment, transition to home, and future development. However, parents' perspectives are not often sought or considered when adapting family-centered care in neonatal intensive care units (NICUs). Aim: To identify what parents believe helps or hinders their involvement in their newborn's care when admitted to our Level 3B NICU. Methods: Between August and October 2018, nine mothers and one father were interviewed during three 60- to 90-min audiotaped focus groups using a semi-structured interview tool. From the content analysis of the verbatims, three reviewers identified key themes that affected how involved parents could be in their newborn's care. Results: Parents provided examples of factors that facilitated or restricted their involvement. The analysis identified themes: (1) parent-staff interactions, (2) supportive/trustworthy healthcare professionals, (3) consistency in care and caring staff, (4) family, couple, and peer support, (5) newborn status, (6) resources and education for parents, (7) the NICU environment, and (8) academic and research participation. Conclusion: We identified a conceptual framework to allow our NICU team to prioritize working strategies to strengthen parental involvement in newborn care. In addition to implementing ways to involve parents, we need to address parents' satisfaction with their participation. These findings may help other investigators explore parents' expectations toward their NICU experience.

Coached, Coordinated, Enhanced Neonatal Transition (CCENT): protocol for a multicentre pragmatic randomised controlled trial of transition-to-home support for parents of high-risk infants.

INTRODUCTION: Having an infant admitted to the neonatal intensive care unit (NICU) is associated with increased parental stress, anxiety and depression. Enhanced support for parents may decrease parental stress and improve subsequent parent and child outcomes. The Coached, Coordinated, Enhanced Neonatal Transition (CCENT) programme is a novel bundled intervention of psychosocial support delivered by a nurse navigator that includes Acceptance and Commitment Therapy-based coaching, care coordination and anticipatory education for parents of high-risk infants in the NICU through the first year at home. The primary objective is to evaluate the impact of the intervention on parent stress at 12 months. METHODS AND ANALYSIS: This is a multicentre pragmatic randomised controlled superiority trial with 1:1 allocation to the CCENT model versus control (standard neonatal follow-up). Parents of high-risk infants (n=236) will be recruited from seven NICUs across three Canadian provinces. Intervention participants are assigned a nurse navigator who will provide the intervention for 12 months. Outcomes are measured at baseline, 6 weeks, 4, 12 and 18 months. The primary outcome measure is the total score of the Parenting Stress Index Fourth Edition Short Form at 12 months. Secondary outcomes include parental mental health, empowerment and health-related quality of life for calculation of quality-adjusted life years (QALYs). A cost-effectiveness analysis will examine the incremental cost of CCENT versus usual care per QALY gained. Qualitative interviews will explore parent and healthcare provider experiences with the intervention. ETHICS AND DISSEMINATION: Research ethics approval was obtained from Clinical Trials Ontario, Children's Hospital of Eastern Ontario Research Ethics Board (REB), The Hospital for Sick Children REB, UBC Children's and Women's REB and McGill University Health Centre REB. Results will be shared with Canadian level III NICUs, neonatal follow-up programmes and academic forums. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03350243).

Risk factors for re-hospitalization following neonatal discharge of extremely preterm infants in Canada.

OBJECTIVE: Survivors of extremely preterm birth are at risk of re-hospitalization but risk factors in the Canadian population are unknown. Our objective is to identify neonatal, sociodemographic, and geographic characteristics that predict re-hospitalization in Canadian extremely preterm neonates. METHODS: This is a retrospective analysis of a prospective observational cohort study that included preterm infants born 22 to 28 weeks' gestational age from April 1, 2009 to September 30, 2011 and seen at 18 to 24 months corrected gestational age in a Canadian Neonatal Follow-Up Network clinic. Characteristics of infants re-hospitalized versus not re-hospitalized are compared. The potential neonatal, sociodemographic, and geographic factors with significant association in the univariate analysis are included in a multivariate model. RESULTS: From a total of 2,275 preterm infants born at 22 to 28 weeks gestation included, 838 (36.8%) were re-hospitalized at least once. There were significant disparities between Canadian provincial regions, ranging from 25.9% to 49.4%. In the multivariate logistic regression analysis, factors associated with an increased risk for re-hospitalization were region of residence, male sex, bronchopulmonary dysplasia, necrotizing enterocolitis, prolonged neonatal intensive care unit (NICU) stay, ethnicity, Indigenous ethnicity, and sibling(s) in the home. CONCLUSION: Various neonatal, sociodemographic, and geographic factors predict re-hospitalization of extremely preterm infants born in Canada. The risk factors of re-hospitalization provide insights to help health care leaders explore potential preventative approaches to improve child health and reduce health care system costs.

Umbilical artery base deficit/excess: sailing blindly in a thick fog.

Assessing the wellbeing of newborns at birth with base deficit (BD)/base excess(BE) is well anchored in clinicians' practice. However, clinicians may not fully understand the concepts behind BD and the concerns regarding the validity of BD results provided by the hospital laboratory. These concerns are linked to the inconsistencies between the equations to calculate BD, and that these equations do not consider the aspects of acid-base physiology at birth. Additionally, the evidence-based supporting BD threshold in the literature to help physicians in making decisions is rather insufficient. These considerations support the need to review practice guidelines that use BD to guide decisions and bring to an end to clinicians to sail blindly in a thick fog.

Comparisons between umbilical cord biomarkers for newborn hypoxic-ischemic encephalopathy.

BACKGROUND: Cord blood umbilical artery (Ua) pH, base deficit (BD), and pH eucapnic Blickstein/Green-50 may mislead clinicians to identify newborns at risk for hypoxic-ischemic encephalopathy. Neonatal eucapnic pH (pH euc-n Racinet-54) may be a comprehensive alternative. The goal of the study is to compare the predictive performance of these four biomarkers for the combined primary outcome of hypoxic-ischemic encephalopathy/death. METHODS: This retrospective cohort study includes newborns ≥35 weeks gestational age. Receiver operating characteristics curves analysis was performed for Ua cord pH, BD, pH euc-n Racinet-54, and pH eucapnic Blickstein/Green-50 for the global cohort and for two subgroups of newborns with Ua cord pH ≤ 7.15. Cutoff values were derived for all four markers. RESULTS: From the original cohort of 61,037 newborns born between 1 January 2007 and 31 December 2016, we excluded cases with major congenital malformations and missing/incomplete data. The global cohort includes 51,286 newborns and 60 newborns afflicted with hypoxic-ischemic encephalopathy (HIE)/death. The area under the curves (AUC) derived from the global cohort were comparable between Ua cord pH (0.95; 95%CI = 0.94-0.95), BD (0.93; 95%CI = 0.93-0.93), pH euc-n Racinet-54 (0.93; 95% CI = 0.93-0.93), and lower for pH Blickstein/Green-50 (0.78; 95% CI = 0.77-0.78) (p < .05). Within newborn with severe acidemia (pH ≤ 7.00) and moderate acidemia (7.00 ≤ pH ≤ 7.15), pH euc-n Racinet-54 had the largest AUC and best positive likelihood ratios especially for sensitivity ≥ 0.80 to minimize false negative cases. CONCLUSION: In this large retrospective study, predictive performance for Ua cord pH, BD, and pH euc-n Racinet-54 are comparable when applied to the global group. For newborns with Ua cord pH ≤ 7.00 and Ua cord 7.00 ≤ pH ≤ 7.15, pH euc-n Racinet-54 appears better to identify those with HIE/death, especially when the target is sensitivity > 80%. Prospective studies will confirm if pH euc-n Racinet-54 is a better alternative to Ua cord pH and BD to evaluate newborn acid-base physiology.

Umbilical artery carbon dioxide decreases the risk for hypoxic-ischaemic encephalopathy.

AIM: An accurate biomarker for metabolic acidosis at birth is needed. Our aims were to investigate the link between umbilical artery pCO2 and the risk for hypoxic-ischaemic encephalopathy (HIE) and to compare false-negative screen results in newborn infants with HIE using three umbilical artery blood gas biomarkers. METHODS: From a cohort of newborn infants ≥35 weeks born in Ottawa, Canada, between January 2007 and December 2016, we highlighted those with HIE or who died. We compared the umbilical artery pCO2 for matched pH >mean versus matched pH ≤mean. We compared false-negative rates for three umbilical artery biomarkers-pH <7.0, base deficit ≥16 mmol/L and neonatal eucapnic pH ≤7.14. RESULTS: This study included 51 286 newborn infants, 51% male and a mean gestational age of 38.9 ± 1.5 weeks. The rate for HIE or death with umbilical artery pCO2 for matched pH >mean was 22%, compared to 78% for matched pH ≤mean. In 60 HIE or deaths, the false-negative rate for umbilical artery neonatal eucapnic pH ≤7.14 was 8%; compared to 31% for pH <7.00 and 36% for base deficit ≥16 mmol/L. CONCLUSION: The rate of HIE or death is lower in newborn infants with higher pCO2 . Using neonatal eucapnic pH decreases the risk of missing newborn infants with HIE.