UNLABELLED: <p>Introduction: FIREFLEYE next 3 years of age efficacy and safety outcomes after intravitreal aflibercept 0.4 mg injection versus laser therapy for retinopathy of prematurity (ROP) in the randomized, FIREFLE...UNLABELLED: <p>Introduction: FIREFLEYE next 3 years of age efficacy and safety outcomes after intravitreal aflibercept 0.4 mg injection versus laser therapy for retinopathy of prematurity (ROP) in the randomized, FIREFLEYE trial are reported. METHODS: Children born prematurely (gestational age ≤32 weeks) or with low birth weight (≤1,500 g) were treated for ROP in FIREFLEYE. Efficacy and safety end points for this prespecified interim analysis included ROP status, unfavorable structural outcomes, disease recurrence, treatment of ROP complications, vascularization completion, visual function, adverse events, and growth outcomes. RESULTS: One hundred children were enrolled (aflibercept, 66 [128 eyes]; laser, 34 [64 eyes]). Data for the 3-year analysis were available for 90 children (aflibercept, 60; laser, 30). Most children had no ROP or unfavorable structural outcomes (aflibercept, 98.3% and 93.9% vs. laser, 96.7% and 94.1%), with no ROP reactivation after age 50 weeks. Two children (aflibercept) with re-activated disease received bilateral laser treatment prior to age 50 weeks. Most children could fix and follow a 5-cm toy (aflibercept, 96.6%; laser, 98.3% of eyes). Binocular best-corrected visual acuity (Snellen equivalent) was ≥20/200 and ≥20/40 in 97.8% and 66.7% (aflibercept) versus 100% and 47.8% (laser) of children, respectively. High myopia was present in 8.9% (aflibercept) and 24.1% (laser) of eyes. Adverse events and growth outcomes were as expected for the population. CONCLUSION: Descriptive analyses of the 3-year outcomes confirm long-term, stable disease control following aflibercept 0.4 mg treatment of severe acute-phase ROP, with age-appropriate visual function, less frequent/severe myopia compared with laser, and no ocular or systemic safety concerns. </p>.
In the article "No Short-Term Effect of Low-Dose Nicotine on Inflammation after Global Hypoxia in Newborn Piglets" [Neonatology. 2025;122:171-180; https://doi.org/10.1159/000541217] by Volstad et al., the following corre...In the article "No Short-Term Effect of Low-Dose Nicotine on Inflammation after Global Hypoxia in Newborn Piglets" [Neonatology. 2025;122:171-180; https://doi.org/10.1159/000541217] by Volstad et al., the following corrections to the legend of Table 1 should be observed.The sentence "Statistically significant differences (<0.05) are highlighted in bold" has been removed as these differences are indicated using superscript letters (a-d).Superscript letter c incorrectly read "Significant lower pH in control versus LN group (p = 0.041)" and should correctly read "Significant lower pH in control versus HN group (p = 0.041)."Superscript letter d incorrectly read "Significant lower pH in HN versus LN group (p = 0.040)" and should correctly read "Significant lower lactate in HN versus LN group (p = 0.040)."The original article has been updated to reflect the above.
UNLABELLED: <p>Introduction: The aim of this study was to correlate oxygenation index (OI) and oxygen saturation index (OSI) in congenital diaphragmatic hernia (CDH) and determine the impact of guideline changes from two...UNLABELLED: <p>Introduction: The aim of this study was to correlate oxygenation index (OI) and oxygen saturation index (OSI) in congenital diaphragmatic hernia (CDH) and determine the impact of guideline changes from two different epochs. METHODS: Retrospective analysis of 390 CDH neonates managed at University of Utah/Primary Children's Hospitals from 2003 to 2024. We performed regression analysis for paired OI and OSI values over the first week of life (2,604 pairs), comparing pre- (2003-2015) and post- (2016-2024) epoch effects of a 2016 CDH guideline. We analyzed predictive abilities for OI and OSI within and between epochs for extracorporeal membrane oxygenation (ECMO) and/or death. RESULTS: OI and OSI showed higher correlation in the post- (R2 = 0.755) vs. pre-epoch (R2 = 0.650). Between epochs analysis demonstrated lower inspired oxygen, mean airway pressure, arterial oxygen pressure, OI, and OSI in the post-epoch. ECMO use was lower in post-epoch (9.8% vs. 33%), but pre-ECMO OI and OSI were similar between epochs. Classification of severe lung dysfunction by OI >25 or OSI >12 showed similar abilities to predict ECMO and/or death. DISCUSSION: OI and OSI were highly correlated in CDH but affected by variation in CDH management. OSI classified severity of cardiopulmonary dysfunction as effectively as OI. </p>.
INTRODUCTION: Congenital erythropoietic porphyria (CEP), especially neonatal-onset CEP, is a rare autosomal recessive disorder with an estimated incidence of one in one million. It is caused by UROS gene variants and may...INTRODUCTION: Congenital erythropoietic porphyria (CEP), especially neonatal-onset CEP, is a rare autosomal recessive disorder with an estimated incidence of one in one million. It is caused by UROS gene variants and may mimic severe systemic conditions, delaying diagnosis. CASE PRESENTATION: We report a male neonate born with asphyxia, hepatosplenomegaly, cytopenia, and multiorgan dysfunction, initially suspected to have familial hemophagocytic lymphohistiocytosis. Targeted panels for familial hemophagocytic lymphohistiocytosis and autoinflammatory disorders were negative. Red urine and photosensitive blistering lesions were observed. Rapid trio whole genome sequencing identified a homozygous NM_000375.3 (UROS):c.562G>T (p.Gly188Trp) variant previously reported only in compound heterozygous patients and classified as pathogenic in ClinVar (RCV000003959). Subsequent biochemical testing confirmed markedly elevated porphyrin levels, establishing a diagnosis of CEP. CONCLUSION: This case highlights the diagnostic challenges of neonatal CEP, where systemic illness may obscure the classical signs. This underscores the value of a genomics-first approach in critically ill neonates.
UNLABELLED: <p>Introduction: There is a paucity of data with regards to benefits and harms associated with deferred cord clamping (DCC) in triplets. The objective was to compare outcomes of triplets following exposure to...UNLABELLED: <p>Introduction: There is a paucity of data with regards to benefits and harms associated with deferred cord clamping (DCC) in triplets. The objective was to compare outcomes of triplets following exposure to DCC in a national cohort admitted to the NICU in Canada with a gestational age of <33 weeks. METHODS: We conducted a retrospective, population-representative, cohort study of triplets born before 33 weeks of gestation in a Canadian NICU. DCC was defined as cord clamping conducted after 30 s of the birth of the neonate. Our primary outcome was survival without neurological injury or late-onset sepsis, and individual outcomes of neonatal survival, severe neurological injury, and late-onset sepsis. We utilized the target trial emulation technique to analyze data considering discordant exposure, discordant outcomes, and the correlated nature of outcomes within the triplet set. RESULTS: Of the 226 sets of triplets included in the study, 100 sets had all 3 received DCC, 22 had 2/3 received DCC, 32 had 1/3 received DCC, and 72 had none received DCC for a total of 376 neonates who received DCC and 302 did not receive DCC. There was no association of benefit or harm between DCC and any of the outcomes studied in any of the analyses. Univariate comparison of outcomes indicated higher receipt of inotropes and higher length of stay among those who did not receive DCC compared to other groups. CONCLUSION: In this retrospective cohort study, DCC was not associated with benefit or harm in very preterm triplets. </p>.
INTRODUCTION: Morbidities of prematurity are often analyzed as if their epidemiology is shared, but this assumption may mask key differences in morbidity risk. This study assesses the association between three birth size...INTRODUCTION: Morbidities of prematurity are often analyzed as if their epidemiology is shared, but this assumption may mask key differences in morbidity risk. This study assesses the association between three birth size metrics and development of chronic lung disease (CLD), severe retinopathy of prematurity (sROP), severe intraventricular hemorrhage (sIVH), and severe necrotizing enterocolitis (sNEC) when stratified by gestational age (GA) with morbidity-specific GA ranges and covariates. METHODS: For each morbidity, data from the Pediatrix Clinical Data Warehouse (2013-2018) were included for GAs with at least 1% morbidity. Birth weight, length, and head circumference were classified as small (SGA), appropriate (AGA), or large for GA (LGA) using the Olsen curves. Odds ratios and 95% confidence intervals (AGA as referent) for each morbidity by GA were calculated using logistic regression, adjusting for morbidity-specific adjustors. RESULTS: SGA weight increased the odds of CLD (OR: 1.6-2.9) and sROP (OR: 1.7-3.6) for most GAs and sNEC (OR: 1.6-1.8) in at least half of the GAs but not sIVH at any GA. LGA weight decreased the odds of CLD in some GAs and increased the odds of sIVH only at 27 weeks GA, but was not associated with sROP or sNEC at any GA. Results were similar for length and head circumference. CONCLUSION: CLD, sROP, sNEC, and sIVH are associated with GA, birth size, and covariates differently. CLD and sROP were consistently associated with size classification and GA, while sNEC demonstrated variability in its association. However, sIVH was rarely associated with birth size in this sample.
UNLABELLED: <p>Introduction: The aim of the study was to analyze for which reasons the certainty of evidence was downgraded in neonatal Cochrane reviews. METHODS: We performed a systematic meta-epidemiological review for...UNLABELLED: <p>Introduction: The aim of the study was to analyze for which reasons the certainty of evidence was downgraded in neonatal Cochrane reviews. METHODS: We performed a systematic meta-epidemiological review for Cochrane Neonatal reviews published in 2022-2024. The search was performed in January 2025, and all reviews were screened by two authors. We extracted the information from the summary of findings tables. As the main outcome, we compared the reasons for downgrading across evidence-certainty categories. Secondary outcomes included the analysis of null effects and comparison of confidence interval width. Chi2 was used to analyze the categorized variables. RESULTS: We included 54 reviews with 467 outcomes of which evidence certainty was rated very low (35%), low (43%), moderate (20%), and high (2%). Imprecision and risk of bias were the most frequent reasons for downgrading certainty of evidence (p < 0.001). Outcomes with effect estimates including the null were more often downgraded for imprecision, whereas outcomes without null effects were more often downgraded for risk of bias. A strong association was observed between certainty level and null effects: very low certainty evidence most often included the null effect, followed sequentially by low, moderate, and high certainty evidence (p < 0.001). Among dichotomous outcomes, wide confidence intervals were the predominant driver of imprecision, with CI width clearly associated both with certainty categories and with the frequency of downgrading due to imprecision. DISCUSSION: The neonatal evidence was mainly limited due to imprecision and risk of bias. This indicates that larger scale high-quality studies in various neonatal topics are still greatly warranted. </p>.
INTRODUCTION: Quantitative lung ultrasound (LUS) predicts bronchopulmonary dysplasia (BPD), but variability in BPD definitions raises concerns about its predictive consistency. We hypothesized that predictive accuracy of...INTRODUCTION: Quantitative lung ultrasound (LUS) predicts bronchopulmonary dysplasia (BPD), but variability in BPD definitions raises concerns about its predictive consistency. We hypothesized that predictive accuracy of LUS would remain stable regardless of the definition applied. METHODS: In this prospective, multicenter cohort study, preterm infants ≤30 weeks of gestation underwent extended LUS (eLUS, adj-eLUS) aeration score at days 10, 21, and 28. BPD was assessed at 36 weeks of postmenstrual age using Jobe and Bancalari (2001), NICHD (2018), and Jensen (2019) definitions. Receiver operating characteristic (ROC) analysis compared predictive performance (areas under ROC curve [AUC]) across definitions. RESULTS: Among 337 infants (mean gestational age: 27 weeks, mean birth weight: 941 g), BPD incidence ranged from 22.8 to 25.8% depending on definition. AUCs for BPD prediction ranged between 0.732 and 0.832. The mean difference (ΔAUC) between definitions was minimal (≈0.02, 95% confidence interval: 0.01-0.03) and nonsignificant at all time points. CONCLUSIONS: Quantitative LUS reliably predicts BPD regardless of its definition, and this support its use in early respiratory care and monitoring.
INTRODUCTION: Spontaneous ductal closure is common in preterm populations; however, a subset of infants develops a hemodynamically significant PDA (hsPDA), which has been associated with adverse outcomes. The objective w...INTRODUCTION: Spontaneous ductal closure is common in preterm populations; however, a subset of infants develops a hemodynamically significant PDA (hsPDA), which has been associated with adverse outcomes. The objective was to develop and internally validate a predictive model for hsPDA in preterm infants using a machine learning approach. METHODS: A prospective cohort study including infants born at <33 weeks of gestation. B-type natriuretic peptide (BNP) levels within the first 120 h, gestational age, birth weight, and surfactant use were used to train a random forest classifier. The outcome was hsPDA diagnosed by standardized echocardiography. Model performance was assessed using stratified 5-fold cross-validation. RESULTS: Sixty-seven infants were included; 46.3% had hsPDA. The random forest model achieved an area under the receiver operating characteristic curve (AUC) of 0.86, outperforming logistic regression using BNP alone (AUC 0.82). BNP was the strongest predictor (48% importance), followed by gestational age, birth weight, and surfactant use. CONCLUSION: A machine learning-based model combining BNP with clinical variables showed high accuracy in predicting hsPDA. The accompanying calculator may assist clinicians in early risk stratification, though external validation is required before clinical implementation.
INTRODUCTION: Postnatal weight loss in infants is physiological, but excessive loss predisposes for dehydration and other morbidities. Existing nomograms, primarily developed in temperate climates, may not apply to arid...INTRODUCTION: Postnatal weight loss in infants is physiological, but excessive loss predisposes for dehydration and other morbidities. Existing nomograms, primarily developed in temperate climates, may not apply to arid regions as environmental conditions influence weight loss patterns. This study aimed to develop hour-specific percentile nomograms for postnatal weight loss in exclusively breastfed, healthy infants (≥36 weeks) from an arid region, facilitating early identification of those at risk of excessive loss. METHODS: A prospective cohort study was conducted between November 2021 and February 2023 at a tertiary center in Western India. Exclusively breastfed infants ≥36 weeks without major morbidities were enrolled and weighed twice daily until 100 h after birth or discharge. Infants with abnormal clinical/biochemical findings or requiring any milk supplementation were censored. Quantile regression was used to generate percentile curves for weight loss. RESULTS: Out of 2,458 enrolled infants, 29.6% got censored, so 1,730 (1,134 vaginal, 596 cesarean) were included in the final analysis, contributing to 10,346 weight measurements. Median weight loss was 7.4% for vaginal and 8.7% for cesarean births; ≥10% loss occurred in 9.4% and 22.4% of infants, respectively. Distinct patterns and nadirs were observed based on mode of delivery. Compared to existing nomograms, our data showed greater early weight loss but quicker recovery after 48 h. CONCLUSIONS: These nomograms provide region-specific reference standards for monitoring postnatal weight loss among exclusively breastfed infants in a semiarid to arid region, offering a basis for further validation in other arid settings globally.
INTRODUCTION: Monitoring cerebral oxygenation during immediate foetal-to-neonatal transition may provide additional information in preterm neonates. Cerebral fractional tissue oxygen extraction (cFTOE), derived from cere...INTRODUCTION: Monitoring cerebral oxygenation during immediate foetal-to-neonatal transition may provide additional information in preterm neonates. Cerebral fractional tissue oxygen extraction (cFTOE), derived from cerebral oxygen saturation (crSO) and arterial oxygen saturation (SpO), reflects the relative extraction of oxygen from the arterial to the tissue compartment, providing information about the balance between oxygen delivery and oxygen consumption. We aimed to describe centiles of cFTOE during the first 15 min after birth in extremely and very preterm neonates. METHODS: This is a secondary outcome parameter analysis of the multicentre randomised-controlled COSGOD III trial. Neonates <32 weeks of gestational age included in the near-infrared spectroscopy-open group of the COSGOD III trial with favourable outcome, defined as survival without cerebral injury at term-equivalent age, were assigned for this analysis. CFTOE was calculated for every minute in each included neonate: cFTOE = (SpO-crSO)/SpO. CrSO2 was measured with the INVOS 5100 monitor with the neonatal sensor. Centiles of cFTOE (10th to 90th) from minute 2 to 15 after birth were described. RESULTS: A total of 199 preterm neonates with a median (interquartile range) gestational age of 29.7 (27.7-30.9) weeks and a weight of 1,200 (925-1,460) g were analysed. The 50th centile of cFTOE at minute 2, 5, 10, and 15 was 0.492, 0.296, 0.177, and 0.151, respectively. CONCLUSION: This study provides centile for cFTOE for extremely and very preterm neonates with favourable outcome independent of interventions during postnatal stabilisation period. These centile charts may assist in interpreting cerebral oxygenation patterns.
INTRODUCTION: The use of reliable, validated, and multidimensional tools for pain evaluation has been recommended to manage neonatal pain. However, these tools have limited use in Japan due to their complexity, which inv...INTRODUCTION: The use of reliable, validated, and multidimensional tools for pain evaluation has been recommended to manage neonatal pain. However, these tools have limited use in Japan due to their complexity, which involves numerous evaluation and observation items, making thorough observation challenging. METHODS: We developed a new method based on the Premature Infant Pain Profile-Revised (PIPP-R), a multidimensional evaluation tool that includes physiological and behavioral indicators, to simplify the evaluation of facial expressions. Instead of assessing three facial expressions individually, we evaluate them in four categories. We also created a system that automatically records changes in vital signs and calculates scores. In this study, we determined if the facial expression score aligns with the conventional PIPP-R-based facial expression score. The scoring methods were categorized into three types: (1) a real-time new method, where facial expressions were evaluated concurrently with the puncture procedure using a new method; (2) an individual assessment method using recorded videos from the puncture sessions with facial expressions scored later using the PIPP-R; and (3) a new video-based method, in which facial expressions were evaluated using the new method while watching recorded videos. RESULTS: The study included 63 healthy neonates (born at ≥37 weeks' gestation) delivered at our hospital. The degree of agreement among the methods and the inter-rater agreement showed high levels of consistency. CONCLUSION: The new facial expression assessment method based on the PIPP-R demonstrated equivalence to conventional scoring in full-term neonates. Further validation, particularly in preterm infants and diverse clinical settings, is needed.
UNLABELLED: <p>Introduction: The primary aim of this study was to evaluate the total seizure burden (TSB) and maximum hourly seizure burden (MSB) before and after the administration of lidocaine (LDC) as add-on therapy i...UNLABELLED: <p>Introduction: The primary aim of this study was to evaluate the total seizure burden (TSB) and maximum hourly seizure burden (MSB) before and after the administration of lidocaine (LDC) as add-on therapy in neonates with amplitude-integrated electroencephalography (aEEG)-confirmed seizures. Secondary aims were documenting the need for additional ASM at 4, 12, and 24 h after LDC and the rate of seizure freedom for at least 24, 48, and 72 h after LDC. METHODS: This single-center, retrospective cohort study included neonates with persistent seizures after phenobarbital who received add-on LDC therapy. Neonates were monitored with a continuous 2-channel aEEG. The TSB and MSB were calculated using raw EEG data collected 4 h before and after the administration of LDC. RESULTS: Sixty-one neonates were included. Seizure etiology consisted of hypoxic-ischemic encephalopathy (n = 24), hemorrhagic or ischemic stroke (n = 16), central nervous system infection (n = 7), genetic (n = 8), metabolic disorders (n = 4), and unknown etiology (n = 2). After LDC administration, median TSB decreased significantly from 31 (interquartile range [IQR] 16-68) to 0 min (IQR 0-0, p < 0.01) and MSB from 10 (IQR 6-41) to 0 min/h (IQR 0-0, p < 0.01). The need for additional ASM was 3% (2/61) within 4 h and 41% (25/61) within 24 h. Seizure freedom after LDC was achieved in 71% (42/59) for at least 24 h and 52% (29/56) for 72 h. DISCUSSION: LDC significantly reduced TSB and MSB in neonates with (a)EEG-confirmed seizures, achieving 100% seizure reduction in the majority, with half of the neonates remaining seizure-free for at least 72 h. </p>.
INTRODUCTION: Neonatal gastrointestinal perforation is a life-threatening condition that requires timely and accurate diagnosis. However, interpreting abdominal radiographs in this population is often challenging. In thi...INTRODUCTION: Neonatal gastrointestinal perforation is a life-threatening condition that requires timely and accurate diagnosis. However, interpreting abdominal radiographs in this population is often challenging. In this study, we aimed to develop a deep convolutional neural network (DCNN) model to segment pneumoperitoneum on neonatal abdominal radiographs and to evaluate its potential to assist in detecting neonatal gastrointestinal perforation. METHODS: This multicenter retrospective study included 1,187 abdominal radiographs (181 perforation and 1,006 control images) from neonates with gastrointestinal perforation and controls. Pneumoperitoneum regions were annotated by experienced clinicians. The dataset was randomly divided into training (n = 830), validation (n = 118), and test (n = 239) sets. A DeepLabV3+ model with ResNet50 backbone was fine-tuned for pixel-level segmentation. A single pixel-based threshold, derived from ROC analysis, was used to classify gastrointestinal perforation, with diagnostic performance subsequently compared to that of clinicians. RESULTS: The DCNN model achieved a median Dice similarity coefficient of 0.81 on the test dataset, indicating strong overlap between predicted and actual pneumoperitoneum regions. Furthermore, segmentation performance was positively correlated with pneumoperitoneum volume (Spearman ρ = 0.83, p < 0.001). Classification using the pixel-based cut-off demonstrated excellent diagnostic accuracy (AUC, 0.999; sensitivity, 100%; specificity, 98.5%), comparable to experienced clinicians. CONCLUSION: The DCNN model demonstrated robust segmentation and classification performance, highlighting its potential as a clinical decision support tool for early detection of gastrointestinal perforation in neonates. Future studies should validate the model's generalizability and assess its integration into clinical practice.
INTRODUCTION: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. However, current screening guidelines may be overly broad, necessitating better models to detect high-risk infants. METHODS: From...INTRODUCTION: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. However, current screening guidelines may be overly broad, necessitating better models to detect high-risk infants. METHODS: From a multicenter cohort of 103,701 infants (3,301 [3.2%] treated for ROP) discharged from 298 neonatal intensive care units from 2006 to 2017 with birth weight ≤1,500 grams or gestational age ≤30 weeks, we used clinically relevant variables to develop machine learning (ML) models at 2-week intervals from postnatal day 14 to 98 to stratify infants by ROP treatment timing. We assessed model performance by concordance index, area under the receiver operating characteristic curve (AUROC), and average precision (AP), validated performance in a cohort of 25,105 infants across 231 sites from 2018 to 2020, and compared model performance to a logistic regression (LR) model. RESULTS: In the validation cohort, the day 28 ML model outperformed the LR model by AUROC (0.916 [0.905-0.926] vs. 0.903 [0.892-0.914]; p < 0.001) and AP (0.190 [0.167-0.217] vs. 0.160 [0.140-0.183]; p < 0.001). Using the ML model at a 100% sensitivity threshold would have negative predictive value of >99.9% and could reduce the number of infants needing screening by 14% compared to current guidelines. CONCLUSION: ML models can effectively predict the need for ROP treatment and stratify infants by risk, potentially reducing unneeded screening. Future work is needed to translate model-based ROP predictions to the clinical setting.
INTRODUCTION: Pulse oximeters may systematically overestimate arterial oxygen saturation in neonates with darker skin pigmentation. We performed a survey in practicing neonatologists to explore knowledge of this bias and...INTRODUCTION: Pulse oximeters may systematically overestimate arterial oxygen saturation in neonates with darker skin pigmentation. We performed a survey in practicing neonatologists to explore knowledge of this bias and the implications for clinical care. METHODS: An email survey was distributed assessing knowledge of melanin-related pulse oximeter bias, perceived clinical significance, and communication practices. Responses were compared to data from emergency medicine (EM) clinicians. RESULTS: Survey results from 120 neonatologists showed that 45.0% agreed that bias exists in pulse oximetry based on skin pigmentation. Among respondents aware of the bias, less than half correctly identified its direction. Most clinicians reported no change in clinical management for dark-skinned neonates. Compared to EM clinicians, neonatologists changed clinical practice less often and rated discussions with families as less important. CONCLUSION: Awareness of pulse oximetry bias related to skin pigmentation remains limited among neonatologists, with low rates of modification to daily clinical practice.
INTRODUCTION: The PREMOD2 trial, comparing cord milking (CM) and deferred cord clamping (DCC) in preterm infants, was stopped for increased severe intraventricular hemorrhage (sIVH) with CM. Six of 9 centers had approval...INTRODUCTION: The PREMOD2 trial, comparing cord milking (CM) and deferred cord clamping (DCC) in preterm infants, was stopped for increased severe intraventricular hemorrhage (sIVH) with CM. Six of 9 centers had approval for waiver of antenatal consent. METHODS: We examined the relationship of enrollment procedures with characteristics and outcomes of trial-enrolled patients. RESULTS: A total of 474 infants were enrolled. Participants enrolled at sites with waiver of consent (N = 375, 79% of participants) were less likely exposed to antenatal steroids and magnesium. The overall effect of CM on sIVH was independently observed in sites with a waiver but not observed in sites without a waiver. However, the effects of CM observed between sites based on availability of waiver were not different. Chorioamnionitis exposure also modified the risk of sIVH from CM vs. DCC. CONCLUSIONS: Trial-enrolled infants differed between hospitals with and without access to initial waiver, including in exposure to chorioamnionitis. These observations may be helpful to designing future studies.
INTRODUCTION: High-dose ambroxol is an effective pharmacological chaperone therapy for the systemic and neurological symptoms of Gaucher disease (GD). However, no clinical evidence of perinatal-onset GD has been document...INTRODUCTION: High-dose ambroxol is an effective pharmacological chaperone therapy for the systemic and neurological symptoms of Gaucher disease (GD). However, no clinical evidence of perinatal-onset GD has been documented. CASE PRESENTATION: The patient had perinatal-onset neuronopathic GD (PnGD) and received high-dose ambroxol, beginning at 10 days of life after a newborn screening report. There was a transient hematological response after combined ambroxol and enzyme replacement therapy; however, laryngospasm, epileptic seizures, liver dysfunction, and heart failure progressed. The patient died 95 days after birth. Genetic testing revealed a homozygous L483R variant in GBA1. A literature review of 56 patients with nGD confirmed poor survival outcomes for patients with PnGD. CONCLUSION: Ambroxol therapy may be insufficient to improve the prognosis of patients with PnGD, underscoring the limitations of early intervention in newborn-screened patients with GD. Therefore, pre-emptive therapeutic strategies are required to rescue and cure neonates with PnGD.
UNLABELLED: <p>Introduction: Metalloporphyrins, competitive heme oxygenase (HO) inhibitors, may potentially be used as drugs for preventing neonatal hyperbilirubinemia. Metalloporphyrins that specifically target the indu...UNLABELLED: <p>Introduction: Metalloporphyrins, competitive heme oxygenase (HO) inhibitors, may potentially be used as drugs for preventing neonatal hyperbilirubinemia. Metalloporphyrins that specifically target the inducible HO-1 without inhibiting the constitutive HO-2 are the most ideal. Zinc protoporphyrin (ZnPP) has the most promise. We have derived a plant-based ZnPP (ZnPP-Plant) and evaluated its inhibitory potency and selectivity for the HO-1 isozyme. METHODS: Eleven-µM ZnPP-Plant or technical grade ZnPP (ZnPP-TG) were added to reaction vials containing heme, NADPH, and adult mouse spleen, brain, and liver sonicates. Gas chromatography was used to measure total in vitro HO activity in sonicates. Percent inhibition of control HO activity was then compared. RESULTS: At a 11-µM concentration, ZnPP-Plant and ZnPP-TG inhibited HO activity in the liver (69.7 ± 9.3% and 74.2 ± 10.3%, respectively); spleen (65.8 ± 17.9% and 46.8 ± 8.7%, respectively); and brain (54.1 ± 13.3%, and 38.1 ± 13.9%, respectively). CONCLUSION: ZnPP-Plant has equal inhibitory potency as ZnPP-TG, and thus has potential use for treating neonatal hyperbilirubinemia. </p>.