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Background: Human milk-derived fortifier (HMDF) coupled with human milk feeding in extremely premature infants reduces the adverse outcome risks of early exposure to bovine milk ingredients but may not provide enough nutrients for adequate catch-up growth compared with bovine milk-derived fortifier (BMDF). Objective: This study aims to compare HMDF and BMDF effects on growth parameters and serum 25-hydroxy vitamin D (25OHD) levels in preterm very low birth weight (VLBW) infants during the first 8 weeks of life. Methods: We present a retrospective chart review of inpatient VLBW infants with birth weight <1,500â g and gestational age <32 completed weeks who received either their mother's milk or donor breast human milk fortified with HMDF or BMDF for the first 8 weeks. Weight, head circumference, length gain, and 25OHD level were calculated at 4 and 8 weeks of age. Results: A total of 139 VLBW infants (91 HMDF + 48 BMDF) received fortified human milk without any supplemental premature formula from birth to 4 weeks of age, of whom 44 (37 HMDF + 7 BMDF) continued until 8 weeks of age. There was no statistically significant difference in the growth parameters between the two groups at 4 and 8 weeks of age. Serum 25OHD level in the HMDF group was significantly higher compared with that in the BMDF group at 4 weeks of age despite receiving lower vitamin D supplementation. Conclusion: Similar gain in growth parameters in HMDF and BMDF groups at 4 and 8 weeks of age was observed, suggesting that HMDF provides adequate nutrients for growth in VLBW infants. A higher 25OHD level in HMDF may suggest better absorption.
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Pseudohypoaldosteronism (PHA) is a rare disease that can cause life-threatening hyperkalemia, which could lead to cardiac arrest and death if not recognized and treated quickly. We report a case of a neonate who was diagnosed with PHA type 1 and found to have a novel variant gene mutation on the NR3C2 gene. A 5-day-old newborn presented in cardiac arrest with severe hyperkalemia, hyponatremia, and metabolic acidosis. Hypothermia treatment was initiated due to suspected hypoxic-ischemic encephalopathy as well as electrolyte management with IV fluids and bicarbonate for the metabolic acidosis. Clinical suspicion and subsequent diagnostic testing led to a diagnosis of the renal form of PHA type 1. Genetic testing revealed a novel mutation on the NR3C2 gene of unknown significance (c.2891_2893dup plle964dup). The baby was discharged home on supplemental sodium and high-calorie formula for catch-up growth. Outpatient follow-up is ongoing, and the dose of sodium supplement was slowly decreased and discontinued at 2 years. There is evidence for developmental delays which is likely secondary to the cardiac arrest although the MRI during hospitalization was noted to be within normal limits. Having a high clinical suspicion for pseudohypoaldosteronism is paramount to initiating treatment and preventing potential cardiac arrest and death in these patients. Novel mutations such as this one need to be further explored to determine their significance with this disease.
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Continuous improvement in the clinical performance of neonatal intensive care units (NICU) depends on the use of locally relevant, reliable data. However, neonatal databases with these characteristics are typically unavailable in NICUs using paper-based records, while in those using electronic records, the inaccuracy of data and the inability to customize commercial data systems limit their usability for quality improvement or research purposes. We describe the characteristics and uses of a simple, neonatologist-centered data system that has been successfully maintained for 30 years, with minimal resources and serving multiple purposes, including quality improvement, administrative, research support and educational functions. Structurally, our system comprises customized paper and electronic components, while key functional aspects include the attending-based recording of diagnoses, integration into clinical workflows, multilevel data accuracy and validation checks, and periodic reporting on both data quality and NICU performance results. We provide examples of data validation methods and trends observed over three decades, and discuss essential elements for the successful implementation of this system. This database is reliable and easily maintained; it can be developed from simple paper-based forms or used to supplement the functionality and end-user customizability of existing electronic medical records. This system should be readily adaptable to NICUs in either high- or limited-resource environments.
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The etiologies of newborn deaths in neonatal intensive care units usually remain unknown, even after genetic testing. Whole-genome sequencing, combined with artificial intelligence-based methods for predicting the effects of non-coding variants, provide an avenue for resolving these deaths. Using one such method, SpliceAI, we identified a maternally inherited deep intronic PKHD1 splice variant (chr6:52030169T>C), in trans with a pathogenic missense variant (p.Thr36Met), in a newborn who died of autosomal recessive polycystic kidney disease at age 2 days. We validated the deep intronic variant's impact in maternal urine-derived cells expressing PKHD1. Reverse transcription polymerase chain reaction followed by Sanger sequencing showed that the variant causes inclusion of 147bp of the canonical intron between exons 29 and 30 of PKHD1 into the mRNA, including a premature stop codon. Allele-specific expression analysis at a heterozygous site in the mother showed that the mutant allele completely suppresses canonical splicing. In an unrelated healthy control, there was no evidence of transcripts including the novel splice junction. We returned a diagnostic report to the parents, who underwent in vitro embryo selection.
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Intrones , Riñón Poliquístico Autosómico Recesivo , Receptores de Superficie Celular , Humanos , Recién Nacido , Masculino , Intrones/genética , Mutación Missense , Riñón Poliquístico Autosómico Recesivo/genética , Riñón Poliquístico Autosómico Recesivo/diagnóstico , Receptores de Superficie Celular/genéticaRESUMEN
BACKGROUND: In neonates, blood flow to the brain as measured by peak systolic velocity (PSV) in the middle cerebral artery (MCA) is altered in pregnancies affected by chorioamnionitis. OBJECTIVE: We aim to determine whether PSV and other measures of flow in the MCA in the fetus are altered prior to the development of clinical chorioamnionitis following preterm prelabor rupture of membranes (PPROM). METHODS: This was a prospective observational study. Fifty patients from one institution were recruited after being diagnosed with PPROM between 23 weeks zero days and 33 weeks six days gestation. We performed measurements of the PSV in the fetal MCA on a weekly basis following PPROM and used the value taken closest to the time of delivery for our statistical analysis. The primary outcome assessed was clinical chorioamnionitis, and the exposure of interest was MCA PSV. Additional independent variables of interest were other Doppler measures of the MCA. Secondary outcomes included histological chorioamnionitis and other measures of neonatal health, including sepsis, days in the neonatal intensive care unit (NICU), and death. RESULTS: Of the 50 patients recruited to our study, eight (16%) developed clinical chorioamnionitis, similar to previously reported values in the general population. The PSV in the MCA was not significantly associated with the development of clinical chorioamnionitis. However, an elevated MCA pulsatility index (PI), a measure of resistance to flow, was associated with a higher probability of developing clinical chorioamnionitis. CONCLUSION: There does not appear to be a difference in the PSV of the MCA of fetuses in pregnancies following PPROM with impending chorioamnionitis. However, elevated PI in the MCA could be a marker of impending chorioamnionitis in PPROM. Larger studies are needed to confirm these findings.
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PURPOSE: To compare characteristics of laser treatment for high-risk type 1 retinopathy of prematurity (ROP) in eyes treated with primary laser versus laser after an initial treatment with intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS: The medical records of consecutive patients at a single academic institution treated for type 1 ROP before 36 weeks' postmenstrual age with primary laser versus laser after initial treatment with anti-VEGF were reviewed retrospectively. Outcome measures were laser spot number, mean laser power, total laser energy (Joules), and retinal vascularization to the nasal ora at time of laser treatment. RESULTS: Compared with the 46 eyes treated with primary laser, the 46 eyes treated with laser after anti-VEGF required fewer spots (mean, 775 vs 1418 [P < 0.01]), less power (182 vs 223 mW [P < 0.01]), and less total energy (27 vs 61 Joules [P < 0.01]), and showed greater vascularization to the nasal ora at the time of laser treatment (47.8% vs 6.5% [P < 0.01]). CONCLUSIONS: In our study cohort, laser after initial anti-VEGF treatment may have allowed for greater retinal vascularization and been less destructive than primary laser for high-risk type 1 ROP.
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Neovascularización Retiniana , Retinopatía de la Prematuridad , Humanos , Recién Nacido , Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Factores de Crecimiento Endotelial/uso terapéutico , Edad Gestacional , Inyecciones Intravítreas , Coagulación con Láser , Rayos Láser , Neovascularización Retiniana/tratamiento farmacológico , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/cirugía , Estudios Retrospectivos , Factor A de Crecimiento Endotelial VascularRESUMEN
OBJECTIVE: Elevation of serum troponin I has been reported in newborns with hypoxic ischemic encephalopathy (HIE), but it is diagnostic and prognostic utility for newborn under 6 hours is not clear. Study the predictive value of early serum troponin I levels in newborns with HIE undergoing therapeutic hypothermia (TH) for persistent residual encephalopathy (RE) at discharge. STUDY DESIGN: Retrospective chart review of newborns admitted with diagnosis of HIE to neonatal intensive care unit (NICU) for TH over a period of 3 years. Troponin levels were drawn with the initial set of admission laboratories while initiating TH. Newborns were followed up during hospital course and stratified into three groups based on predischarge examination and their electrical encephalography and cranial MRI findings: Group 1: no RE, Group 2: mild-to-moderate RE, and Group 3: severe RE or needing assisted medical technology or death. Demographic and clinical characteristics including troponin I levels were compared in each group. RESULTS: Out of 104 newborns who underwent TH, 65 infants were in Group 1, 26 infants in Group 2, and 13 newborns in Group 3. All groups were comparable in demographic characteristics. There was a significant elevation of serum troponin in group 2 (mild-to-moderate RE) and group 3 (severe RE) as compared with group 1 (no RE). Receiver operator curve analysis for any RE (groups 2 and 3) compared with group 1 (no RE as control) had 0.88 (0.81-0.95) area under curve, p < 0.001. A cut-off level of troponin I ≥0.12 µg/L had a sensitivity of 77% and specificity of 78% for diagnosis of any RE, positive predictive value of 68%, and a negative predictive value of 84%. CONCLUSION: In newborns undergoing TH for HIE, the elevation of troponin within 6 hours of age predicts high risk of having RE at discharge. KEY POINTS: · Troponin I elevation is a biomarker of myocardial ischemia in adults and children.. · Myocardial ischemia may be part of multi-organ injury in neonatal HIE.. · Early elevation of troponin I level may correlate with the severity of neonatal HIE and predict residual encephalopathy in newborn at discharge from initial hospitalization..
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Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Isquemia Miocárdica , Troponina I , Progresión de la Enfermedad , Humanos , Hipoxia-Isquemia Encefálica/diagnóstico , Hipoxia-Isquemia Encefálica/terapia , Recién Nacido , Isquemia Miocárdica/terapia , Alta del Paciente , Estudios Retrospectivos , Troponina I/sangreRESUMEN
The phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B (KAT6B, a.k.a. MORF, MYST4) results in several interrelated syndromes including Say-Barber-Biesecker-Young-Simpson Syndrome and Genitopatellar Syndrome. Here we present 20 new cases representing 10 novel KAT6B variants. These patients exhibit a range of clinical phenotypes including intellectual disability, mobility and language difficulties, craniofacial dysmorphology, and skeletal anomalies. Given the range of features previously described for KAT6B-related syndromes, we have identified additional phenotypes including concern for keratoconus, sensitivity to light or noise, recurring infections, and fractures in greater numbers than previously reported. We surveyed clinicians to qualitatively assess the ways families engage with genetic counselors upon diagnosis. We found that 56% (10/18) of individuals receive diagnoses before the age of 2 years (median age = 1.96 years), making it challenging to address future complications with limited accessible information and vast phenotypic severity. We used CRISPR to introduce truncating variants into the KAT6B gene in model cell lines and performed chromatin accessibility and transcriptome sequencing to identify key dysregulated pathways. This study expands the clinical spectrum and addresses the challenges to management and genetic counseling for patients with KAT6B-related disorders.
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Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Histona Acetiltransferasas/genética , Mutación , Fenotipo , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Alelos , Blefarofimosis/diagnóstico , Blefarofimosis/genética , Estudios de Cohortes , Hipotiroidismo Congénito/diagnóstico , Hipotiroidismo Congénito/genética , Anomalías Craneofaciales/diagnóstico , Anomalías Craneofaciales/genética , Facies , Asesoramiento Genético , Sitios Genéticos , Genotipo , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/genética , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/genética , Riñón/anomalías , Masculino , Rótula/anomalías , Trastornos Psicomotores/diagnóstico , Trastornos Psicomotores/genética , Escroto/anomalías , Anomalías Urogenitales/diagnóstico , Anomalías Urogenitales/genéticaRESUMEN
OBJECTIVE: In preterm infants, the standard pharmacologic treatment for a hemodynamically significant patent ductus arteriosus (hsPDA) is either ibuprofen or indomethacin. However, these medications may be less effective after 2 weeks of age. We investigated the use of acetaminophen in hsPDA closure beyond 2 weeks of age. METHODS: An observational study of 11 infants, <30 weeks' gestation at birth and postnatal age > 2 weeks, who received acetaminophen treatment for their hsPDA. Echocardiograms (ECHOs), B-type natriuretic peptide (BNP) levels, and the fraction of inspired oxygen (FiO2) were obtained before and after treatment to analyze ductal characteristics. Renal and liver functions were monitored pretreatment and posttreatment to look for potential medication side effects. RESULTS: Of the 10 infants with ECHO data for before and after acetaminophen treatments, 4/10 (40%) had a decrease in PDA size, with no infants having complete closure immediately posttreatment. Eight of 11 (73%) infants had a decreased FiO2 requirement after treatment. Of the 5 infants with pretreatment and posttreatment BNP data, 2/5 (40%) infants had a decrease in BNP level. One infant received an additional course of acetaminophen. Four infants underwent a surgical ligation. Two infants died. No medication side effects occurred with regard to hepatic and renal function. CONCLUSION: Acetaminophen is a safe and effective pharmacologic treatment to reduce the significance of the hsPDA in some infants beyond 2 weeks of age, as shown by ECHO and BNP data.
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PURPOSE: To compare respiratory outcomes after treatment of retinopathy of prematurity (ROP) between infants treated with laser therapy under general anesthesia and infants treated with intravitreal bevacizumab under bedside sedation. DESIGN: Retrospective cohort study. PARTICIPANTS: One hundred thirty-eight consecutive infants treated for ROP from September 2010 through September 2018 at 1 institution. METHODS: Retrospective medical, procedural, and ophthalmologic data were collected, including preprocedure (baseline) and postprocedure (24 hours, 48 hours, 7 days, and 28 days) respiratory status, birth weight, gestational age, gender, ROP treatment method, postmenstrual age at treatment, and coincident nonocular procedures during anesthesia. Respiratory outcomes at 48 hours were compared between infants treated with laser therapy under general anesthesia and infants treated with intravitreal bevacizumab under local sedation using multivariate logistic regression analysis to control for potentially confounding factors. MAIN OUTCOME MEASURES: Proportion of infants who had returned to their respiratory baseline by 48 hours after ROP treatment. RESULTS: Return to respiratory baseline was significantly less common among 119 infants initially treated with laser therapy compared with 19 infants initially treated with bevacizumab at 24 hours (40% vs. 74%; P = 0.0115), 48 hours (53% vs. 79%; P = 0.0453), and 7 days (79% vs. 100%; P = 0.0242). In a multivariate logistic regression analysis, infants treated with laser therapy were less likely to return to respiratory baseline at 48 hours (odds ratio, 0.14; 95% confidence interval, 0.04-0.54). At 28 days, no difference was found between groups (laser, 97%; bevacizumab, 100%; P > 0.99). CONCLUSIONS: Infants treated with intravitreal bevacizumab using bedside sedation returned to their preprocedure respiratory baseline faster than infants treated with laser under general anesthesia, with the differences persisting at least to 7 days or more after the procedure.
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Bevacizumab/administración & dosificación , Coagulación con Láser/métodos , Retinopatía de la Prematuridad/terapia , Inhibidores de la Angiogénesis/administración & dosificación , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Inyecciones Intravítreas , Masculino , Retinopatía de la Prematuridad/diagnóstico , Estudios Retrospectivos , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
PURPOSE: To perform a stratified comparison of the short-term risk of retinal detachment after treatment of type 1 retinopathy of prematurity treated with panretinal photocoagulation laser versus intravitreal bevacizumab. METHODS: The medical records of consecutive infants treated for type 1 ROP between 2010 and 2018 were retrospectively reviewed. An a priori decision was made to divide infants into two groups, those treated before postmenstrual age (PMA) of 36 0/7 weeks and those treated at or after PMA of 36 0/7 weeks. The primary outcome was presence of any retinal detachment (stage 4A, 4B, or 5) during the 8 weeks following treatment. RESULTS: A total of 222 eyes of 115 infants were included. In eyes treated before 36 0/7 weeks' PMA, retinal detachment occurred in 0 of 34 eyes treated initially with bevacizumab compared with 9 of 56 (16%) treated with laser (P = 0.0112); in eyes treated at or after 36 0/7 weeks, in 0 of 2 eyes treated with bevacizumab and 1 of 130 eyes (0.8%) treated with laser. CONCLUSIONS: The short-term risk of retinal detachment among infants requiring treatment for type 1 ROP prior to 36 0/7 weeks' PMA was lower in eyes treated with intravitreal bevacizumab than in eyes treated with laser, presumably due to the faster effect of bevacizumab in eyes that have more aggressive ROP.
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Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Coagulación con Láser , Desprendimiento de Retina/etiología , Retinopatía de la Prematuridad/terapia , Peso al Nacer , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Inyecciones Intravítreas , Masculino , Desprendimiento de Retina/fisiopatología , Retinopatía de la Prematuridad/tratamiento farmacológico , Retinopatía de la Prematuridad/fisiopatología , Retinopatía de la Prematuridad/cirugía , Estudios Retrospectivos , Medición de Riesgo , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
AIM: Few published reports have established B-type natriuretic peptide (BNP) levels in preterm infants without a patent ductus arteriosus (PDA). This study addressed that gap in our knowledge by establishing a reference range for BNP levels during the first two weeks of life in preterm infants without a PDA. METHODS: We enrolled 36 preterm infants between 24 and 32 weeks of gestation in this prospective, noninterventional study. Infants with a PDA, congenital heart disease, possible or confirmed sepsis and, or, meningitis, or perinatal depression requiring chest compressions were excluded. BNP levels were measured on postnatal days one, five, 10 and 15, with an echocardiogram on day five. Statistical analyses were performed using the ANOVA and Mann-Whitney U-tests. RESULTS: BNP levels were significantly higher on day one than on days five, 10 and 15, and there was no statistical difference between days five, 10 and 15. The levels were not statistically different between infants of less than and greater than 29 weeks of gestation. CONCLUSION: BNP levels were significantly elevated on postnatal day one in preterm infants without a PDA, but then decreased by day five and continued to stay low after that. Gestational age did not have an effect on BNP levels.
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Recien Nacido Prematuro/sangre , Péptido Natriurético Encefálico/sangre , Femenino , Humanos , Recién Nacido , Masculino , Estudios Prospectivos , Valores de ReferenciaRESUMEN
We investigated whether a standardized feeding bundle reduces central line utilization in very low birth weight neonates. A chart review of infants ≤1500 g requiring a central line was prepared for 2009 to 2012. Infants were stratified into 3 weight groups: ≤750 g, 751 to 1000 g, and 1001 to 1500 g. The number of central line-associated bloodstream infections (CLABSIs) was recorded. Central line utilization decreased in all of the groups: 0.45 to 0.28 in ≤750 g infants, 0.4 to 0.27 in 751 to 1000 g infants, and 0.39 to 0.3 in 1001 to 1500 g infants (all of the Pâ<â0.001). The CLABSIs rate was unchanged. Implementation of a feeding bundle decreased central line utilization. A feeding bundle had no effect on the rate of CLABSIs.