Neonatal Palliative Care for Complicated Cardiac Anomalies: A 10-Year Experience of an Interdisciplinary Program at a Large Tertiary Cardiac Center.

OBJECTIVES: To report the outcomes of a Neonatal Palliative Care (NPC) Program at a large tertiary cardiac center caring for a subset of fetuses and neonates with life-limiting cardiac diagnoses or cardiac diagnoses with medical comorbidities leading to adverse prognoses. STUDY DESIGN: The Neonatal Comfort Care Program at New York-Presbyterian Morgan Stanley Children's Hospital/Columbia University Medical Center is an interdisciplinary team that offers the option of NPC to neonates prenatally diagnosed with life-limiting conditions, including single ventricle (SV) congenital heart disease (CHD) or less severe forms of CHD complicated by multiorgan dysfunction or genetic syndromes. RESULTS: From 2008 to 2017, the Neonatal Comfort Care Program cared for 75 fetuses or neonates including 29 with isolated SV CHD, 36 with CHD and multiorgan dysfunction and/or severe genetic abnormalities, and 10 neonates with a prenatal diagnosis of isolated CHD and postnatal diagnoses of severe conditions who were initially in intensive care before transitioning to NPC because of a poor prognosis. CONCLUSIONS: At New York-Presbyterian Morgan Stanley Children's Hospital/Columbia University Medical Center, a large tertiary cardiac center, 13.5% of parents of fetuses or neonates with isolated SV CHD opted for NPC. Twenty-six of 29 newborns with SV CHD treated with NPC died. Of the remaining, 2 neonates with mixing lesions are alive at 3 and 5 years of age, and 1 neonate was initially treated with NPC and then pursued surgical palliation. These results suggest that NPC is a reasonable choice for neonates with SV CHD.

Neonatal palliative care.

PURPOSE OF REVIEW: A significant number of newborns are affected by life-limiting or life-threatening conditions. When prolongation of survival is no longer a goal, or prognosis is uncertain, a plan of care focused on the infant's comfort is essential. The aim of this article is to review the most recent and relevant literature regarding neonatal palliative care (NPC). RECENT FINDINGS: A variety of perinatal and NPC programs are described, but most programs focus exclusively on end-of-life care. Moreover, there is a great need to standardize practices and obtain follow-up quality measures.Guidelines to address infants' basic needs, to achieve a state of comfort, are proposed. A multidisciplinary team addressing the infants' medical and nonmedical needs, parental grieving process, and providers' distress is recommended. SUMMARY: NPC is a unique multidisciplinary approach for the care of newborns affected by life-limiting or complex medical conditions with uncertain prognosis. Standardized guidelines should be implemented with the goal of achieving a state of comfort for newborns throughout the course of illness. Further studies are warranted to assess whether NPC effectively promotes newborns' comfort and parents and providers' satisfaction.

Is urinary neutrophil gelatinase-associated lipocalin able to predict acute kidney injury episodes in very low birth weight infants in clinical settings?

BACKGROUND: We evaluated the potential utility of elevated urinary neutrophil gelatinase-associated lipocalin (UNGAL) concentration as a screening test for early identification of acute kidney injury (AKI) in very low birth weight (VLBW) newborns. METHODS: Urine for UNGAL analysis was collected prospectively daily until 32 wk postmenstrual age in 91 VLBW newborns, yielding 2,899 specimens. UNGAL values > 50 ng/ml were considered elevated. AKI was defined as two or more consecutive elevations in s[Cr] above the 95th percentile adjusted for gestational age and chronological age within a 48 h period. We compared UNGAL values taken during the 5 d prior to AKI onset (pre-AKI) to values taken during non-AKI days. RESULTS: Overall, 15 episodes of AKI were identified in 13 infants. UNGAL was available in 44 pre-AKI days and 969 non-AKI days. UNGAL > 50 ng/ml occurred more often in pre-AKI days than in non-AKI days (risk ratio 3.48 (1.89, 6.40)). Positive and negative likelihood ratios were 1.92 (1.52, 2.41) and 0.52 (0.34, 0.78), respectively. CONCLUSION: Although UNGAL elevation > 50 ng/ml discriminates between pre-AKI and non-AKI days, high false positive and false negative rates limit utility as a screening test in VLBW newborns.

Urinary neutrophil gelatinase-associated lipocalin: potential biomarker for late-onset sepsis.

BACKGROUND: To assess the ability of urinary neutrophil gelatinase-associated lipocalin (UNGAL) to discriminate between culture-positive vs. culture-negative late-onset sepsis evaluations. METHODS: This is a prospective observational study of 136 neonates who underwent ≥1 sepsis evaluation at >72 h of age. Urine was obtained at the time of sepsis evaluation to measure UNGAL concentration. Using generalized estimating equations controlling for gender, gestational and postnatal age, acute kidney injury, and within-patient correlations, pair-wise contrasts between mean log UNGAL concentrations of infants with negative sepsis evaluations vs. culture-positive sepsis and presumed sepsis were assessed. Discrimination characteristics at several UNGAL cutoff concentrations were assessed using receiver-operating characteristic curves. RESULTS: The predicted mean log UNGAL values of culture-positive sepsis and presumed sepsis vs. negative sepsis evaluations differed significantly (P < 0.001 and P = 0.02, respectively). At a cutoff ≥ 50 ng/ml, UNGAL discriminated between culture-positive sepsis and culture-negative sepsis evaluations with sensitivity = 86%, specificity = 56%, positive predictive value = 41%, negative predictive value = 92%, and number needed to treat = 3. CONCLUSION: UNGAL is a noninvasive biomarker with high negative predictive value at the time of late-onset sepsis evaluation in neonates and could be a useful adjunct to traditional components of sepsis evaluations.

Serum creatinine concentration in very-low-birth-weight infants from birth to 34-36 wk postmenstrual age.

BACKGROUND: Serum creatinine (s[Cr]) reference ranges for very-low-birth-weight (VLBW) infants must account for physiologic changes in the first months of life. METHODS: We retrospectively identified a sample of 218 appropriate-for-gestational age (GA) VLBW infants without risk factors for renal impairment, and classified into one of three GA groups: 25-27, 28-29, and 30-33 wk. We observed three phases of s[Cr] change (initial, decline, and equilibrium), whose characteristics varied by GA group. We used mixed-effects regression models to estimate mean and upper 95th prediction interval of s[Cr] for each GA group from birth to 34-36 wk post menstrual age (PMA). RESULTS: In phase I, s[Cr] increased after birth, then returned slowly to baseline. The duration of phase I and the magnitude of s[Cr] rise decreased with increasing GA. In phase II, s[Cr] declined abruptly at a rate that increased with GA. A gradual transition to phase III, a steady-state equilibrium with similar s[Cr] among GA groups, began at approximately 34-36 wk PMA. We constructed GA group-specific nomograms depicting s[Cr] behaviour across the three phases. CONCLUSION: The reference ranges derived from a sample of infants without risk factors for renal impairment provide a context for quantitative interpretation of s[Cr] trends in VLBW infants.

Complete hydatidiform mole and live fetus in a singleton pregnancy with confined placental mosaicism and fetomaternal hemorrhage: a case report.

BACKGROUND: Coexistence of complete mole and a live fetus is uncommon (1:22,000-100,000), more so with euploidy. CASE: We present a case of a molar pregnancy with a euploid fetus who had close fetal evaluation for second trimester bleeding. The patient presented at 29 weeks' pregnancy with decreased fetal movements, a result of fetomaternal hemorrhage. She underwent cesarean section and delivered a live infant. By close follow-up and a multidisciplinary approach, the appropriate diagnosis and a favorable outcome were achieved. Both mother and the child at 5 years of age are doing well. CONCLUSION: Detailed anatomic and molecular studies demonstrated a complete mole resulting from confined placental mosaicism, with molar tissue showing a single paternal allele at 8/8 informative loci, all shared with the fetus, thus this coexistent molar pregnancy was not that of a separate conceptus.

Respiratory outcomes of neonates born after previable premature rupture of membranes and treated with gentle ventilation.

OBJECTIVE: We aim to describe neonatal respiratory outcomes following previable preterm premature rupture of membranes(PPROM) when gentle ventilation is utilized. We also report maternal morbidity and mortality. STUDY DESIGN: This is a retrospective single-center cohort study of infants delivered between 2016 and 2020 that included infants born at ≥23 weeks without major congenital anomaly after a pregnancy complicated with PPROM before 23 weeks gestation. Statistical analysis utilized unpaired Student's t-test or Mann-Whitney U-test when appropriate. RESULTS: 35 infants from 33 pregnancies were included. 91.4% of infants survived until discharge and 12.1% developed Bronchopulmonary Dysplasia (BPD). Those who developed BPD had significantly lower amniotic fluid levels prior to delivery (p < 0.05). There was no significant maternal morbidity or mortality in this cohort. CONCLUSION: This cohort had high survival and low rates of respiratory morbidities. This suggests the use of gentle ventilation might be the optimal strategy for patients born after previable PPROM.

Evaluation of learning transfer after a perinatal/neonatal palliative care virtual training course.

Background: The success of a training can be determined by the degree of learning transfer. To address a gap in educational offerings during the pandemic, an interdisciplinary team developed and offered a 3-day virtual course, called Next Level Perinatal Palliative Care Training. Objective: This study aimed to evaluate the transfer of learning and practice from a virtual training course on perinatal/neonatal palliative care (PNPC) by a range of clinicians. Study design: A descriptive prospective survey design was used to collect data at two time points, immediately following the training course and 6 months later. Frequency and descriptive statistics were used to measure the implementation of PNPC quality indicators, self-reported competence, and clinical facilitators and barriers. A t-test was used to compare participants' anticipated learning transfer to actual learning transfer. Two open-ended items assessed benefits and drawbacks of virtual training. Results: At course completion, participants anticipated opportunities to implement PNPC strategies with means of 84-87, and at the 6-month mark, the reported implementation had means ranging from 71 to 77. At 6 months post training, participants reported feeling competent/highly competent in each variable with frequency scores of 89%-98%. The opportunity to learn key concepts of PNPC and refresh skill sets ranked as the top facilitators, while the top barriers were the lack of opportunity to use PNPC principles and the lack of funding. Conclusion: Learning transfer after a virtual training course of PNPC proved to be successful, with a high rate of self-reported actual implementation and competence at 6 months after the training.

Propranolol Therapy for Congenital Chylothorax.

Congenital chylothorax is a rare and often severe anomaly without well-established medical therapies. Previously, propranolol use in patients with lymphatic malformations and secondary chylothorax was associated with improvement in clinical signs. We hypothesized that propranolol treatment would be beneficial for severe congenital chylothorax. We reviewed medical records of neonates born from 2015 to 2019 at our tertiary center with a prenatal diagnosis of congenital chylothorax for whom either prenatal or postnatal propranolol therapy was initiated. Inclusion was limited to fetuses diagnosed with severe congenital chylothorax without significant genetic, infectious, or cardiac anomalies, and who underwent prenatal interventions to mitigate consequences of the condition. Propranolol was administered orally to pregnant women at 20 mg 4 times daily and increased to a maximum dose of 40 mg 4 times daily, or to infants at 0.3 mg/kg/d and increased to 1 to 2 mg/kg/d. Primary outcomes were the time course of resolution of ultrasonographical, clinical, and/or radiologic signs of chylothorax after treatment with propranolol. Four neonates met the inclusion criteria. In 2 cases, prenatal initiation of propranolol led to resolution of the chylothoraxes before delivery (38 and 32 days after treatment) on a dose of 40 mg/day 4 times daily. Neonates had a normal postnatal course. Postnatal propranolol was initiated in 2 neonates with respiratory failure when chylothoraces were refractory to standard management. Stabilization and improvement of their pleural effusion was observed by imaging at 29 and 13 days after initiation of propranolol. There were no significant maternal or neonatal complications from prenatal or postnatal propranolol use. Propranolol may be efficacious in treating severe fetal congenital chylothorax.

International Standards for Pediatric Palliative Care: From IMPaCCT to GO-PPaCS.

CONTEXT: Since the publication of the IMPaCCT project in 2007, much effort has been made to develop new approaches to pediatric palliative care (PPC). Fifteen years later, it is time to redefine the standards in PPC. OBJECTIVES: An international group of experts in PPC has revised the standards in PPC through the GO-PPaCS project (Global Overview - PPC Standards). The goal was to update the PPC standards considering the specificity of different settings, resources, and emerging challenges. The present document is intended to reach all people directly or indirectly involved in PPC. METHODS: A literature review in MEDLINE was conducted to expand on the fundamental points and current standards on PPC and to cover an international setting. The literature search (updated on the 15th of April 2021) was carried out using different combinations of keywords and focusing on papers published in English over the past 5 years (2016-2020), but older articles were considered when relevant. The consensus on the fundamental points, standards of care and paper contents was reached by open discussion. RESULTS: Fundamental points were defined regarding the definition of PPC, eligibility criteria and the magnitude of the need for PPC, while standards were redefined for the following six areas: 1) clinical, developmental, psychological, social, ethical and spiritual needs; 2) end-of-life care; 3) care models and settings of care; 4) PPC in humanitarian emergencies; 5) care tools; and 6) education and training for healthcare providers. CONCLUSION: The present document, developed with the contribution of an international group of experts from different countries, experiences and models of care, provides fundamental points and standards for a wider implementation of PPC worldwide.

Implementation of Quality Indicators of Perinatal/Neonatal Palliative Care One-Year Following Formal Training.

Objective: The aim of this study was to measure implementation of quality indicators (QIs) of Perinatal/Neonatal Palliative Care (PNPC) as reported by participants following a one-year training course. Study Design: A cross-sectional survey mixed-method design was used to obtain data from an interdisciplinary team of professionals one year after attending a PNPC training course. A questionnaire with 32 QIs queried participants about self-reported implementation of PNPC and that of their colleagues. Descriptive and frequency data were analyzed to measure the implementation of PNPC QIs. Qualitative data were examined using content analysis. Results: Response rate was 34 of 76 (44.7%). Half of the QIs are implemented in clinical settings by course attendees more than 90% of the time, and 15 QIs are implemented between 70 and 89.9%. Colleagues within the same healthcare system applied palliative care practices less frequently than those who attended the training course. When asked if quality indicators were "always" implemented by colleagues, the average difference in scores was 36% lower. Qualitative analyses resulted in three themes that addressed changes in clinical practice, and four themes that summarized barriers in practice. Conclusion: There is high frequency of implementation of QIs by professionals who attended an evidence based PNPC training course. PNPC is implemented by the colleagues of attendees, but with less frequency. Attending evidence-based education increases clinicians' opportunities to translate quality PNPC care into clinical settings.

Urinary neutrophil gelatinase-associated lipocalin is a promising biomarker for late onset culture-positive sepsis in very low birth weight infants.

Need for the early identification of sepsis in very low birth weight (VLBW) infants has led to the search for reliable biomarkers. This study aims to determine whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) rises in culture-positive sepsis and, if so, is elevated at the time sepsis is suspected. This is a prospective study of 91 VLBW infants whose urine was collected daily for uNGAL analysis. In 65 episodes of suspected sepsis, four groups were identified: a) culture-positive sepsis; b) single culture positive for Staphylococcus epidermidis; c) and d) negative culture with antibiotic treatment for >or=7 d and <7 d, respectively. Daily means of uNGAL of each group were estimated for comparison. Mean uNGAL in group A (179 ng/mL) was significantly elevated on the day blood culture was drawn (day 0) compared with the mean of healthy VLBW infants (6.5 ng/mL), and to the means in groups B, C, and D (p<0.05). In group A, mean uNGAL was significantly elevated on day 0 and daily for 5 days when compared with that of the day before culture (p<0.05 to <0.005). uNGAL shows promise as an early marker for culture-positive sepsis in VLBW infants.

The clinical utility of urinary neutrophil gelatinase-associated lipocalin in the neonatal ICU.

PURPOSE OF REVIEW: Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been identified as an early marker of acute kidney injury (AKI) in pediatric and adult populations. The aim of this review is to provide the most recent and relevant knowledge about the use of uNGAL as an early marker of renal failure and, possibly, of other morbid conditions in full-term and very low birth weight infants. RECENT FINDINGS: A recently provided reference range for uNGAL in very low birth weight infants shows that normative values for this population are similar to those of older children and adults. Increased production of uNGAL is associated with AKI in young children undergoing cardiac bypass. uNGAL is acutely produced in critically ill newborns with or without AKI. SUMMARY: Further studies to confirm uNGAL's potential to predict AKI in cardiac and noncardiac populations of newborns are required prior to utilizing this promising biomarker in clinical practice. The finding of markedly elevated uNGAL levels in critically ill newborns with normal renal function strongly suggests that uNGAL may have a role in the detection of nonrenal morbid conditions such as sepsis.

The Neonatal Comfort Care Program: Origin and Growth Over 10 Years.

The objective of perinatal palliative care is to provide holistic and comprehensive health care services to women who are anticipating the birth of a neonate diagnosed prenatally with a life-limiting condition and to continue supportive interventions for the mother and neonate after the birth. The nature of pregnancy, with two patients requiring medical care, requires clinicians from different specialties to engage with one another, the patient, and her chosen family members. Following birth, additional skill sets to treat the medical and comfort needs of the neonate, as well as the psychoemotional and medical needs of the mother, are required. An interdisciplinary team is necessary to assist families throughout the pregnancy and postnatal journey, and coordination of such care is an integral component of palliative care services. The number of palliative care programs is increasing, but little is written about the origins of such programs, their subsequent growth, and how transitions of care occur within the programs. In this publication, we will present data garnered from interdisciplinary team members of a single organization, the Neonatal Comfort Care Program at Columbia University Irving Medical Center, and how they provide care for families throughout the pregnancy and postnatal trajectory. We will address the origin and growth of the program, the development of the interdisciplinary team, and the strategies used for high-quality communication and their respective impact on care continuity. We will also provide specific recommendations from data gathered from team members, examine the role of formal and informal education, and identify barriers and future opportunities.

Assessment of Healthcare Professionals' Self-Perceived Competence in Perinatal/Neonatal Palliative Care After a 3-Day Training Course.

Background: Perinatal/neonatal palliative care (PNPC) offers a plan of care for improving the quality of life of infants when the prolongation of life is no longer the goal of care. The number of PNPC programs has increased in recent years, but training for clinicians has not kept pace. Therefore, an interdisciplinary team developed a 3-day intensive PNPC training course for physicians, nurses, and other healthcare professionals at Columbia University Irving Medical Center (CUIMC). Objective: The aim of this study was to assess the efficacy of a PNPC training course in improving the self-reported competence of participants. Study Design: A cross-sectional survey design was used to obtain data from 88 healthcare professionals who attended the PNPC training course. Data was collected using a validated questionnaire. The questionnaire included 32 items that queried participants about their self-assessed competence using a forced 1-4 Likert scale. The 32 items, which served as the outcome variables, were clustered into the eight domains of palliative care. The survey was administered through a web-based tool at the beginning and the conclusion of the course. Results: Results from two-sample t-tests comparing pre-test and post-test self-assessed competence were statistically significant for each item across disciplines. Additional analysis revealed that after participation in the training course, the statistically significant differences between physicians' and nurses' pre-course self-reported competence disappeared. Conclusion: The development of an evidence-based curriculum improved the self-reported competence of participants across disciplines, filled a specific gap in nurses' self-reported competence and addressed a global training need.

Patterns of Urinary Neutrophil Gelatinase-Associated Lipocalin and Acute Kidney Injury in Neonates Receiving Cardiopulmonary Bypass.

Elevated urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts acute kidney injury (AKI) in children following cardiopulmonary bypass (CPB) during cardiac surgery, but little is known about uNGAL's predictive ability in neonates in this setting. We sought to determine the relationship between AKI and post-CPB uNGAL in neonates in the first 72 post-operative hours. METHODS: Urine samples for uNGAL analysis were collected at preoperative baseline and serially post-operatively from 76 neonates undergoing CPB. Mixed-effects regression models and logistic models assessed associations between uNGAL and AKI (controlling for sex, gestational age, CPB time, surgical complexity, and age at surgery). Receiver-operator curves were applied to define optimal uNGAL cut-off values for AKI diagnosis. RESULTS: Between 0 and 4 h post-operatively, uNGAL values did not differ between neonates with and without AKI. After 4 h until 16 h post-operatively, significant time-wise separation occurred between uNGAL values of neonates with AKI and those without AKI. Odds ratios at each time point significantly exceeded unity, peaking at 10 h post-operatively (3.48 (1.58, 8.71)). Between 4 and 16 h post-operatively, uNGAL discriminated AKI from no-AKI, with a sensitivity of 0.63 (0.49, 0.75) and a specificity of 0.68 (0.62, 0.74) at a cut-off value of 100 ng/mL. CONCLUSION: After 4 h until 16 h post-operatively, elevated uNGAL is associated with AKI in neonates receiving CPB during cardiac surgery; however, this relationship is more complex than in older children.

Reference values of urinary neutrophil gelatinase-associated lipocalin in very low birth weight infants.

In very low birth weight (VLBW) infants, acute renal impairment (ARI) is common, but there is no consensus about criteria for its diagnosis. Neutrophil gelatinase-associated lipocalin (NGAL) is an early and sensitive indicator of renal impairment in experimental animals, children, and adults. Urinary NGAL (UNGAL) is detectable in VLBW infants; however, there is no reference range in this population. The objective of this study is to define the reference range for UNGAL in VLBW infants with no risk factors for acute renal impairment. UNGAL concentration was determined in urine samples collected from day of life (DOL) 4 through DOL 30 in 50 newborns with uncomplicated clinical courses, selected from a total of 145 prospectively enrolled appropriate for gestational age inborn VLBW premature infants. The birth weight and gestational age ranges were 790-1490 g and 26-33 wk, respectively. The median, 95th and 99th percentiles, and range of pooled UNGAL values were 5 ng/mL, 50 ng/mL, 120 ng/mL, and 2-150 ng/mL, respectively. Greater variability and higher quantile levels of UNGAL were observed in females versus males. In conclusion, a reference range for UNGAL in VLBW infants, similar to that in children and adults, has been established.

Neonatal hepatic mesenchymal hamartoma causing cardiac failure and disseminated intravascular coagulopathy.

Even with advance prenatal diagnostic tools, differentiating among specific types of hepatic masses continues to challenge many physicians. Here, we report a neonate with life-threatening hepatic mass, cardiac failure, and disseminated intravascular coagulopathy, which clinically resembled hepatic hemangioma. A hepatic mesenchymal hamartoma was detected by postmortem pathology.

Reference range of urinary neutrophil gelatinase-associated lipocalin in very low-birth-weight infants: preliminary data.

We sought to determine the reference range for urinary neutrophil gelatinase-associated lipocalin (UNGAL) in very low-birth-weight (VLBW) infants with uncomplicated clinical courses. Samples of urine from 53 VLBW infants between 3 and 28 days of life were prospectively collected weekly for measurement of UNGAL. A subset of 22 infants with uncomplicated medical courses without risk factors for renal impairment was selected for study. Mean +/- standard deviation and range for birth weight and gestational age of study infants were 1156 +/- 191, 790 to 1440 g and 29 +/- 2, 27 to 33 weeks, respectively. The 95th and 99th percentiles for UNGAL concentration from this group of infants were 25 ng/mL and 75 ng/mL, respectively. Bootstrapped mean 95th and 99th percentile values and their standard errors and 95 percent confidence intervals in ng/mL were 33.1 +/- 13.0 (7.7, 58.6) and 67.5 +/- 15.1 (37.9, 97.1), respectively. These values fall within the adult reference range. UNGAL values were stable across the ranges of gestational and postnatal age of the study infants. A preliminary reference range for UNGAL in VLBW infants has been established. Further investigation with more frequent urine collections in a larger population of VLBW infants that includes those with birth weights < 750 g and gestational ages < 27 weeks is necessary to confirm this reference range.

Phenotypic Variation between Monochorionic Diamniotic Twins with Coffin-Siris Syndrome.

The first known documented case of monochorionic-diamniotic twins with Coffin-Siris syndrome is described in this study. This case is notable because of the phenotypic differences between infants despite having identical genomes and causative variants. Also unique to this case is the clinical influence of early diagnosis using precision medicine techniques.