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OBJECTIVE: The fecal microbiota and metabolome are hypothesized to be altered before late-onset neonatal meningitis (LOM), in analogy to late-onset sepsis (LOS). The present study aimed to identify fecal microbiota composition and volatile metabolomics preceding LOM. METHODS: Cases and gestational age-matched controls were selected from a prospective, longitudinal preterm cohort study (born <30 weeks' gestation) at nine neonatal intensive care units. The microbial composition (16S rRNA sequencing) and volatile metabolome (gas chromatography-ion mobility spectrometry (GC-IMS) and GC-time-of-flight-mass spectrometry (GC-TOF-MS)), were analyzed in fecal samples 1-10 days pre-LOM. RESULTS: Of 1397 included infants, 21 were diagnosed with LOM (1.5%), and 19 with concomitant LOS (90%). Random Forest classification and MaAsLin2 analysis found similar microbiota features contribute to the discrimination of fecal pre-LOM samples versus controls. A Random Forest model based on six microbiota features accurately predicts LOM 1-3 days before diagnosis with an area under the curve (AUC) of 0.88 (n=147). Pattern recognition analysis by GC-IMS revealed an AUC of 0.70-0.76 (P<0.05) in the three days pre-LOM (n=92). No single discriminative metabolites were identified by GC-TOF-MS (n=66). CONCLUSION: Infants with LOM could be accurately discriminated from controls based on preclinical microbiota composition, while alterations in the volatile metabolome were moderately associated with preclinical LOM.
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OBJECTIVES: To identify indications for exchange transfusions, assess the use and waste of exchange transfusion products (ie, reconstituted whole blood exchange transfusions), and determine nationwide distribution and prevalence of these transfuions in the Netherlands. STUDY DESIGN: All nine neonatal intensive care units (NICU) and 15 non-NICU hospitals participated in this retrospective, observational, cohort study. We retrieved data on indications for and use of all exchange transfusion products ordered by participating centers over an 11-year period. RESULTS: A total of 574 patients for whom 1,265 products were ordered were included for analyses. Severe ABO (32.6%) and non-ABO (25.2%) immune hemolysis and subsequent hyperbilirubinemia were the most frequent indications. Rare indications were severe leukocytosis in Bordetella pertussis (2.1%) and severe anemia (1.5%). Approximately half of all ordered products remained unused. In 278 of 574 neonates (48.4%), one or more products were not used, of which 229 (82.7%) were due to the resolving of severe hyperbilirubinemia with further intensification of phototherapy. The overall prevalence of neonates who received an exchange transfusion was 14.6:100,000 liveborn neonates. CONCLUSION: A considerable proportion of products remained unused, and annually a limited number of patients are treated with an exchange transfusion in the Netherlands, highlighting the rarity of the procedure in the Netherlands.
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IMPACT: Key message: Chest shielding during phototherapy does not reduce the incidence of symptomatic PDA in preterm infants and does not affect phototherapy's efficacy. This study adds to the existing literature by providing a double-blinded RCT confirming previous inconsistent findings on the impact of chest shielding on PDA incidence. However, phototherapy may exert cardiovascular changes, including vasodilatation. IMPACT: Chest shielding should not be recommended to be routinely performed in preterm infants during phototherapy.
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Measurement of total bilirubin (TBil) concentration in serum is the gold standard approach for diagnosing neonatal unconjugated hyperbilirubinemia. It is of utmost importance that the measured TBil concentration is sufficiently accurate to prevent under treatment, unnecessary escalation of care, or overtreatment. However, it is widely recognized that TBil measurements urgently require improvement in neonatal clinical chemistry. External quality assessment (EQA) programs for TBil assess for differences between laboratories and provide supporting evidence of significant differences between various methods, manufacturers and measurement platforms. At the same time, many countries have adopted or only slightly adapted the neonatal hyperbilirubinemia management guidelines from the USA or UK, often without addressing differences in the methodology of TBil measurements. In this report, we provide an overview of the components of bilirubin that are measured by laboratory platforms, the availability of current reference measurement procedures and reference materials, and the role of EQA surveys in this context. Furthermore, the current status of agreement in neonatal bilirubin against clinical decision thresholds is reviewed. We advocate for enhancements in accuracy and comparability of neonatal TBil measurements, propose a path forward to accomplish this, and reflect on the position of the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Working Group Neonatal Bilirubin (WG-NB) in this matter.
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AIM: Sudden unexpected postnatal collapse is a life-threatening event and may occur in any newborn infant. Safe skin-to-skin contact, and awareness of sudden unexpected postnatal collapse are key to its prevention. The aim of this study was to survey the presence of skin-to-skin contact and/or sudden unexpected postnatal collapse protocols in the 70 perinatal centres in the Netherlands. METHODS: We performed a survey among Dutch paediatricians to examine the safe skin-to-skin contact and sudden unexpected postnatal collapse protocols. RESULTS: We received data from 59/70 (85%) perinatal centres. At least one case of sudden unexpected postnatal collapse was reported in 35/59 (59%) of these centres. Nearly half the centres had safe skin-to-skin contact and/or sudden unexpected postnatal collapse protocols. Ultimately, 16 protocols were available for analysis. They showed considerable differences in the type of perinatal care provided. Most protocols lacked recently published insights on safe skin-to-skin contact. Besides, protocols failed to incorporate awareness of and knowledge on how to prevent sudden unexpected postnatal collapse. CONCLUSION: This study underlines the importance of drawing up uniform, multidisciplinary guidelines containing recommendations for the prevention of sudden unexpected postnatal collapse in the Netherlands.
Subject(s)
Practice Guidelines as Topic , Sudden Infant Death , Humans , Infant, Newborn , Netherlands , Sudden Infant Death/prevention & control , Kangaroo-Mother Care Method , Guideline Adherence/statistics & numerical dataABSTRACT
Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.
Subject(s)
Pulmonary Surfactants , Respiratory Distress Syndrome, Newborn , Female , Humans , Infant , Infant, Newborn , Dyspnea , Follow-Up Studies , Infant, Premature , Lipoproteins , Pulmonary Surfactants/administration & dosage , Pulmonary Surfactants/therapeutic use , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome, Newborn/complications , Respiratory Distress Syndrome, Newborn/drug therapy , Respiratory Distress Syndrome, Newborn/therapy , Respiratory Sounds , Surface-Active Agents/administration & dosage , Surface-Active Agents/therapeutic use , Catheterization , Minimally Invasive Surgical Procedures , Continuous Positive Airway Pressure , Male , Child, PreschoolABSTRACT
BACKGROUND: Phototherapy (PT) is the standard treatment of neonatal unconjugated hyperbilirubinemia. The irradiance footprint, i.e., the illuminated area by the PT device with sufficient spectral irradiance, is essential for PT to be effective. Irradiance footprint measurements are not performed in current clinical practice. We describe a user-friendly method to systematically evaluate the high spectral irradiance (HSI) footprint (illuminated area with spectral irradiance of ≥30 µW cm-2 nm-1) of PT devices in clinical practice. MATERIALS AND METHODS: Six commercially available LED-based overhead PT devices were evaluated in overhead configuration with an incubator. Spectral irradiance (µW cm-2 nm-1) and HSI footprint were measured with a radiospectrometer (BiliBlanket Meter II). RESULTS: The average measured spectral irradiance ranged between 27 and 52 µW cm-2 nm-1 and HSI footprint ranged between 67 and 1465 cm2, respectively. Three, two, and one PT devices out of six covered the average BSA of an infant born at 22, 26-32, and 40 weeks of gestation, respectively. CONCLUSION: Spectral irradiance of LED-based overhead PT devices is often lower than manufacturer's specifications, and HSI footprints not always cover the average BSA of a newborn infant. The proposed measurement method will contribute to awareness of the importance of irradiance level as well as footprint measurements in the management of neonatal jaundice. IMPACT: While a sufficient spectral irradiance footprint is essential for PT to be effective, some PT devices have spectral irradiance footprints that are too small to cover the entire body surface area (BSA) of a newborn infant. This study introduces a user-friendly, accessible method to systematically evaluate the spectral irradiance level and footprint of PT devices. This study supports awareness on the role of the spectral irradiance footprint in the efficacy of PT devices. Irradiance footprint can be easily measured during phototherapy with the proposed method.
Subject(s)
Hyperbilirubinemia, Neonatal , Jaundice, Neonatal , Humans , Hyperbilirubinemia, Neonatal/therapy , Infant, Newborn , Jaundice, Neonatal/therapy , PhototherapyABSTRACT
BACKGROUND: The role of intestinal microbiota in the pathogenesis of late-onset sepsis (LOS) in preterm infants is largely unexplored but could provide opportunities for microbiota-targeted preventive and therapeutic strategies. We hypothesized that microbiota composition changes before the onset of sepsis, with causative bacteria that are isolated later in blood culture. METHODS: This multicenter case-control study included preterm infants born under 30 weeks of gestation. Fecal samples collected from the 5 days preceding LOS diagnosis were analyzed using a molecular microbiota detection technique. LOS cases were subdivided into 3 groups: gram-negative, gram-positive, and coagulase-negative Staphylococci (CoNS). RESULTS: Forty LOS cases and 40 matched controls were included. In gram-negative LOS, the causative pathogen could be identified in at least 1 of the fecal samples collected 3 days prior to LOS onset in all cases, whereas in all matched controls, this pathogen was absent (P = .015). The abundance of these pathogens increased from 3 days before clinical onset. In gram-negative and gram-positive LOS (except CoNS) combined, the causative pathogen could be identified in at least 1 fecal sample collected 3 days prior to LOS onset in 92% of the fecal samples, whereas these pathogens were present in 33% of the control samples (P = .004). Overall, LOS (expect CoNS) could be predicted 1 day prior to clinical onset with an area under the curve of 0.78. CONCLUSIONS: Profound preclinical microbial alterations underline that gut microbiota is involved in the pathogenesis of LOS and has the potential as an early noninvasive biomarker.
Subject(s)
Gastrointestinal Microbiome , Infant, Premature, Diseases , Sepsis , Case-Control Studies , Humans , Infant , Infant, Newborn , Infant, PrematureABSTRACT
The Platelets for Neonatal Thrombocytopenia (PlaNeT-2) trial reported an unexpected overall benefit of a prophylactic platelet transfusion threshold of 25 × 109/L compared with 50 × 109/L for major bleeding and/or mortality in preterm neonates (7% absolute-risk reduction). However, some neonates in the trial may have experienced little benefit or even harm from the 25 × 109/L threshold. We wanted to assess this heterogeneity of treatment effect in the PlaNet-2 trial, to investigate whether all preterm neonates benefit from the low threshold. We developed a multivariate logistic regression model in the PlaNet-2 data to predict baseline risk of major bleeding and/or mortality for all 653 neonates. We then ranked the neonates based on their predicted baseline risk and categorized them into 4 risk quartiles. Within these quartiles, we assessed absolute-risk difference between the 50 × 109/L- and 25 × 109/L-threshold groups. A total of 146 neonates died or developed major bleeding. The internally validated C-statistic of the model was 0.63 (95% confidence interval, 0.58-0.68). The 25 × 109/L threshold was associated with absolute-risk reduction in all risk groups, varying from 4.9% in the lowest risk group to 12.3% in the highest risk group. These results suggest that a 25 × 109/L prophylactic platelet count threshold can be adopted in all preterm neonates, irrespective of predicted baseline outcome risk. Future studies are needed to improve the predictive accuracy of the baseline risk model. This trial was registered at www.isrctn.com as #ISRCTN87736839.
Subject(s)
Hemorrhage/prevention & control , Infant, Premature , Platelet Transfusion/mortality , Thrombocytopenia, Neonatal Alloimmune/therapy , Female , Hemorrhage/mortality , Humans , Infant , Infant, Newborn , Male , Platelet Count , Prognosis , Risk Factors , Survival Rate , Thrombocytopenia, Neonatal Alloimmune/blood , Thrombocytopenia, Neonatal Alloimmune/mortalityABSTRACT
Invasive bilirubin measurements remain the gold standard for the diagnosis and treatment of infants with severe neonatal hyperbilirubinemia. The present paper describes different methods currently available to assess hyperbilirubinemia in newborn infants. Novel point-of-care bilirubin measurement methods, such as the BiliSpec and the Bilistick, would benefit many newborn infants, especially in low-income and middle-income countries where the access to costly multi-analyzer in vitro diagnostic instruments is limited. Total serum bilirubin test results should be accurate within permissible limits of measurement uncertainty to be fit for clinical purposes. This implies correct implementation of internationally endorsed reference measurement systems as well as participation in external quality assessment programs. Novel analytic methods may, apart from bilirubin, include the determination of bilirubin photoisomers and bilirubin oxidation products in blood and even in other biological matrices. IMPACT: Key message: Bilirubin measurements in blood remain the gold standard for diagnosis and treatment of severe neonatal hyperbilirubinemia (SNH). External quality assessment (EQA) plays an important role in revealing inaccuracies in diagnostic bilirubin measurements. What does this article add to the existing literature? We provide analytic performance data on total serum bilirubin (TSB) as measured during recent EQA surveys. We review novel diagnostic point-of-care (POC) bilirubin measurement methods and analytic methods for determining bilirubin levels in biological matrices other than blood. Impact: Manufacturers should make TSB test results traceable to the internationally endorsed total bilirubin reference measurement system and should ensure permissible limits of measurement uncertainty.
Subject(s)
Bilirubin/blood , Hyperbilirubinemia, Neonatal/diagnosis , Jaundice, Neonatal/diagnosis , Neonatal Screening , Point-of-Care Testing , Biomarkers/blood , Humans , Hyperbilirubinemia, Neonatal/blood , Hyperbilirubinemia, Neonatal/therapy , Infant, Newborn , Jaundice, Neonatal/blood , Jaundice, Neonatal/therapy , Predictive Value of Tests , Prognosis , Reproducibility of Results , Severity of Illness Index , Up-RegulationABSTRACT
Severe neonatal hyperbilirubinemia (SNH) is a serious condition that occurs worldwide. Timely recognition with bilirubin determination is key in the management of SNH. Visual assessment of jaundice is unreliable. Fortunately, transcutaneous bilirubin measurement for screening newborn infants is routinely available in many hospitals and outpatient settings. Despite a few limitations, the use of transcutaneous devices facilitates early recognition and appropriate management of neonatal jaundice. Unfortunately, however, advanced and often costly screening modalities are not accessible to everyone, while there is an urgent need for inexpensive yet accurate instruments to assess total serum bilirubin (TSB). In the near future, novel icterometers, and in particular optical bilirubin estimates obtained with a smartphone camera and processed with a smartphone application (app), seem promising methods for screening for SNH. If proven reliable, these methods may empower outpatient health workers as well as parents at home to detect jaundice using a simple portable device. Successful implementation of ubiquitous bilirubin screening may contribute substantially to the reduction of the worldwide burden of SNH. The benefits of non-invasive bilirubin screening notwithstanding, any bilirubin determination obtained through non-invasive screening must be confirmed by a diagnostic method before treatment. IMPACT: Key message: Screening methods for neonatal hyperbilirubinemia facilitate early recognition and timely treatment of severe neonatal hyperbilirubinemia (SNH). Any bilirubin screening result obtained must be confirmed by a diagnostic method. What does this article add to the existing literature? Data on optical bilirubin estimation are summarized. Niche research strategies for prevention of SNH are presented. Impact: Transcutaneous screening for neonatal hyperbilirubinemia contributes to the prevention of SNH. A smartphone application with optical bilirubin estimation seems a promising low-cost screening method, especially in low-resource settings or at home.
Subject(s)
Bilirubin/blood , Hyperbilirubinemia, Neonatal/diagnosis , Jaundice, Neonatal/diagnosis , Neonatal Screening , Biomarkers/blood , Early Diagnosis , Humans , Hyperbilirubinemia, Neonatal/blood , Hyperbilirubinemia, Neonatal/therapy , Infant, Newborn , Jaundice, Neonatal/blood , Jaundice, Neonatal/therapy , Mobile Applications , Neonatal Screening/instrumentation , Predictive Value of Tests , Prognosis , Reproducibility of Results , Severity of Illness Index , Smartphone , Up-RegulationABSTRACT
Neonatal organ and tissue donation is not common practice in the Netherlands. At the same time, there is a transplant waiting list for small size-matched organs and tissues. Multiple factors may contribute to low neonatal donation rates, including a lack of awareness of this option. This study provides insight into potential neonatal organ and tissue donors and reports on how many donors were actually reported to the procurement organization. We performed a retrospective analysis of the mortality database and medical records of two largest neonatal intensive care units (NICUs) in the Netherlands. This study reviewed records of neonates with a gestational age >37 weeks and weight >3000g who died in the period from January 1, 2005 through December 31, 2016. During the study period, 259 term-born neonates died in the two NICUs. In total, 132 neonates with general contra-indications for donation were excluded. The medical records of 127 neonates were examined for donation suitability. We identified five neonates with documented brain death who were not recognized as potential organ and/or tissue donors. Of the remaining neonates, 27 were found suitable for tissue donation. One potential tissue donor had been reported to the procurement organization. In three cases, the possibility of donation was brought up by parents.Conclusion: A low proportion (2%) of neonates who died in the NICUs were found suitable for organ donation, and a higher proportion (12%) were found suitable for tissue donation. We suggest that increased awareness concerning the possibility of neonatal donation would likely increase the identification of potential neonatal donors. What is Known: ⢠There is an urgent need for very small organs and tissues from neonatal donors What is New: ⢠A number of neonates who died in the NICU were suitable organ or/and tissue donors but were not recognized as donors. ⢠Knowledge on neonatal donation possibilities is also important for proper counseling of parents who sometimes inquire for the possibility of organ and tissue donation.
Subject(s)
Tissue and Organ Procurement , Brain Death , Death , Humans , Infant , Infant, Newborn , Retrospective Studies , Tissue DonorsABSTRACT
Necrotizing enterocolitis (NEC) is one of the most common and lethal gastrointestinal diseases in preterm infants. Early recognition of infants in need for surgical intervention might enable early intervention. In this multicenter case-control study, performed in nine neonatal intensive care units, preterm born infants (< 30 weeks of gestation) diagnosed with NEC (stage ≥ IIA) between October 2014 and August 2017 were divided into two groups: (1) medical (conservative treatment) and (2) surgical NEC (sNEC). Perinatal, clinical, and laboratory parameters were collected daily up to clinical onset of NEC. Univariate and multivariate logistic regression analyses were applied to identify potential predictors for sNEC. In total, 73 preterm infants with NEC (41 surgical and 32 medical NEC) were included. A low gestational age (p value, adjusted odds ratio [95%CI]; 0.001, 0.91 [0.86-0.96]), no maternal corticosteroid administration (0.025, 0.19 [0.04-0.82]), early onset of NEC (0.003, 0.85 [0.77-0.95]), low serum bicarbonate (0.009, 0.85 [0.76-0.96]), and a hemodynamically significant patent ductus arteriosus for which ibuprofen was administered (0.003, 7.60 [2.03-28.47]) were identified as independent risk factors for sNEC.Conclusions: Our findings may support the clinician to identify infants with increased risk for sNEC, which may facilitate early decisive management and consequently could result in improved prognosis. What is Known: ⢠In 27-52% of the infants with NEC, a surgical intervention is indicated during its disease course. ⢠Absolute indication for surgical intervention is bowel perforation, whereas fixed bowel loop or clinical deterioration highly suggestive of bowel perforation or necrosi, is a relative indication. What is New: ⢠Lower gestational age, early clinical onset, and no maternal corticosteroids administration are predictors for surgical NEC. ⢠Low serum bicarbonate in the 3 days prior clinical onset and patent ductus arteriosus for which ibuprofen was administered predict surgical NEC.
Subject(s)
Ductus Arteriosus, Patent , Enterocolitis, Necrotizing , Case-Control Studies , Ductus Arteriosus, Patent/surgery , Enterocolitis, Necrotizing/diagnosis , Enterocolitis, Necrotizing/surgery , Female , Humans , Ibuprofen/therapeutic use , Infant , Infant, Newborn , Infant, Premature , Pregnancy , Risk FactorsABSTRACT
Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.
Subject(s)
Biological Products/administration & dosage , Bronchopulmonary Dysplasia/prevention & control , Continuous Positive Airway Pressure , Infant, Premature , Phospholipids/administration & dosage , Pulmonary Surfactants/administration & dosage , Respiratory Distress Syndrome, Newborn/drug therapy , Female , Humans , Infant, Newborn , Infant, Premature, Diseases/mortality , Male , Respiratory Distress Syndrome, Newborn/mortality , Respiratory Distress Syndrome, Newborn/therapy , Single-Blind MethodABSTRACT
The etiology of nonimmune hydrops fetalis is extensive and includes genetic disorders. We describe a term-born female neonate with late onset extensive nonimmune hydrops, that is, polyhydramnios, edema, and congenital bilateral chylothorax. This newborn was successfully treated with repetitive thoracocentesis, total parenteral feeding, octreotide intravenously and finally surgical pleurodesis and corticosteroids. A genetic cause seemed plausible as the maternal history revealed a fatal nonimmune hydrops fetalis. A homozygous truncating variant in GDF2 (c.451C>T, p.(Arg151*)) was detected with exome sequencing. Genetic analysis of tissue obtained from the deceased fetal sibling revealed the same homozygous variant. The parents and two healthy siblings were heterozygous for the GDF2 variant. Skin and lung biopsies in the index patient, as well as the revised lung biopsy of the deceased fetal sibling, showed lymphatic dysplasia and lymphangiectasia. To the best of our knowledge, this is the first report of an association between a homozygous variant in GDF2 with lymphatic dysplasia, hydrothorax and nonimmune hydrops fetalis.
Subject(s)
Craniofacial Abnormalities/genetics , Growth Differentiation Factor 2/genetics , Hydrops Fetalis/genetics , Lymphangiectasis, Intestinal/genetics , Lymphedema/genetics , Polyhydramnios/genetics , Craniofacial Abnormalities/diagnosis , Craniofacial Abnormalities/pathology , Female , Homozygote , Humans , Hydrops Fetalis/diagnosis , Hydrops Fetalis/pathology , Infant, Newborn , Lymphangiectasis, Intestinal/diagnosis , Lymphangiectasis, Intestinal/pathology , Lymphedema/diagnosis , Lymphedema/pathology , Polyhydramnios/diagnosis , Polyhydramnios/pathology , Pregnancy , Thoracentesis , Ultrasonography, Prenatal , Exome SequencingABSTRACT
Over 75% of severely thrombocytopenic neonates receive platelet transfusions, though little evidence supports this practice, and only 10% develop major bleeding. In a recent randomized trial, giving platelet transfusions at a threshold platelet count of 50x109/L compared to a threshold of 25x109/L was associated with an increased risk of major bleeding or mortality. This finding highlights the need for improved and individualized guidelines on neonatal platelet transfusion, which require accurate prediction of bleeding risk. Therefore, the objective of this study was to develop a dynamic prediction model for major bleeding in thrombocytopenic preterm neonates. This model allows for calculation of bleeding risk at any time-point during the first week after the onset of severe thrombocytopenia. In this multicenter cohort study, we included neonates with a gestational age <34 weeks, admitted to a neonatal intensive care unit, who developed severe thrombocytopenia (platelet count <50x109/L). The study endpoint was major bleeding. We obtained predictions of bleeding risk using a proportional baselines landmark supermodel. Of 640 included neonates, 71 (11%) had a major bleed. We included the variables gestational age, postnatal age, intrauterine growth retardation, necrotizing enterocolitis, sepsis, platelet count and mechanical ventilation in the model. The median cross-validated c-index was 0.74 (interquartile range, 0.69-0.82). This is a promising dynamic prediction model for bleeding in this population that should be explored further in clinical studies as a potential instrument for supporting clinical decisions. The study was registered at www.clinicaltrials.gov (NCT03110887).
Subject(s)
Hemorrhage/diagnosis , Hemorrhage/etiology , Infant, Premature , Thrombocytopenia/complications , Thrombocytopenia/diagnosis , Biomarkers , Disease Management , Humans , Infant, Newborn , Infant, Premature/blood , Models, Statistical , Platelet Count , Prognosis , Reproducibility of ResultsABSTRACT
BACKGROUND: Phototherapy (PT) is the standard treatment of neonatal unconjugated hyperbilirubinemia. Fluorescent tube (FT)-emitted PT light is known to induce oxidative DNA damage in neonates. Nowadays, however, FTs have largely been replaced by light-emitting diodes (LEDs) for delivering PT. Until now, it is unknown whether LED-PT causes oxidative DNA damage. We aim to determine whether LED-PT induces oxidative DNA damage in hyperbilirubinemic rats. METHODS: Adult Gunn rats, with genetically unconjugated hyperbilirubinemia, received LED-PT in the clinically relevant doses of 10 or 30 µW/cm2/nm. Urine was collected at 0, 24, and 48 h of PT. A group of young Gunn rats received intensive LED-PT of 100 µW/cm2/nm for 24 h. Urine was collected every 8 h and analyzed for the levels of oxidative DNA damage marker 8-hydroxy-2'deoxyguanosine (8-OHdG) and creatinine. DNA damage was evaluated by immunohistochemistry (γH2AX) of skin and spleen samples. RESULTS: LED-PT of 10 and 30 µW/cm2/nm did not affect urinary concentrations of 8-OHdG and creatinine or the 8-OHdG/creatinine ratio. Likewise, intensive LED-PT did not affect the 8-OHdG/creatinine ratio or the number of γH2AX-positive cells in the skin or spleen. CONCLUSIONS: Our results show that LED-PT does not induce oxidative DNA damage in hyperbilirubinemic Gunn rats either at clinically relevant or intensive dosages.
Subject(s)
DNA Damage , Oxidative Stress , Phototherapy/methods , Animals , Hyperbilirubinemia, Neonatal , Rats , Rats, GunnABSTRACT
BACKGROUND: In Indonesia, the burden of severe hyperbilirubinemia is higher compared to other countries. Whether this is related to ineffective phototherapy (PT) is unknown. The aim of this study is to investigate the performance of phototherapy devices in hospitals on Java, Indonesia. METHODS: In 17 hospitals we measured 77 combinations of 20 different phototherapy devices, with and without curtains drawn around the incubator/crib. With a model to mimic the silhouette of an infant, we measured the irradiance levels with an Ohmeda BiliBlanket Meter II, recorded the distance between device and model, and compared these to manufacturers' specifications. RESULTS: In nine hospitals the irradiance levels were less than required for standard PT: < 10 µW/cm2/nm and in eight hospitals irradiance failed to reach the levels for intensive phototherapy: 30 µW/cm2/nm. Three hospitals provided very high irradiance levels: > 50 µW/cm2/nm. Half of the distances between device and model were greater than recommended. Distance was inversely correlated with irradiance levels (R2 = 0.1838; P < 0.05). The effect of curtains on irradiance levels was highly variable, ranging from - 6.15 to + 15.4 µW/cm2/nm, with a mean difference (SD) of 1.82 (3.81) µW/cm2/nm (P = 0.486). CONCLUSIONS: In half of the hospitals that we studied on Java the levels of irradiance are too low and, in some cases, too high. Given the risks of insufficient phototherapy or adverse effects, we recommend that manufacturers provide radiometers so hospitals can optimize the performance of their phototherapy devices.
Subject(s)
Hyperbilirubinemia, Neonatal/therapy , Luminescence , Phototherapy/instrumentation , Bilirubin/blood , Equipment Failure Analysis/methods , Fluorescence , Humans , Hyperbilirubinemia, Neonatal/blood , Indonesia , Infant, Newborn , Interior Design and FurnishingsABSTRACT
OBJECTIVES: Biliary atresia (BA) occurs in 0.54 of 10.000 of overall live births in the Netherlands. BA has an unfavorable prognosis: <40% of patients are cleared of jaundice after Kasai portoenterostomy (KPE), 4-year transplant-free survival rate is 46% and the 4-year survival rate is â¼75%. Little is known on difficulties in diagnosis and the outcome of BA in preterm infants. We aimed to analyze the incidence and outcome of BA in preterm infants in the Netherlands. METHODS: Retrospective study including Dutch preterm infants treated for BA. Parameters included gestational age, congenital anomalies, age at KPE, days between first symptoms, and KPE and referral interval (first hospital to KPE). Outcome parameters were clearance of jaundice (COJ) and (transplant-free) survival. Data are presented as medians (ranges). RESULTS: Included 28 preterm infants (13 boys/15 girls) between March 1988 and December 2015. The incidence of BA was 1.06 of 10.000 preterm live births. Gestational age was 34.8 (27.3-36.9) weeks. Congenital anomalies were present in 11 of 28 (39%) infants. Time between first symptoms and KPE was 57 (9-138) days. Referral interval was 28 (8-86) days. Age at KPE was 70 (35-145) days. COJ was achieved in 23% of cases. Four-year transplant-free survival rate was 21%. Four-year overall survival was 61%. CONCLUSIONS: BA has a higher incidence in the preterm population compared to the overall BA population. The outcome of BA in preterm infants is poor, regarding COJ and (transplant-free) survival. We speculate that timely recognition of BA-related signs and symptoms in preterm infants will improve prognosis.