Despite advances in neonatal care, neonatal jaundice remains a common problem in maternity wards. The present retrospective epidemiological study collected data on a sample of 710 newborns and compared the incidence of neonatal jaundice in infants born to Rh (D) negative and 0 Rh (D) positive mothers. The primary aim was to determine whether the higher incidence of maternal alloimmunisation in newborns was causally related to a potentially higher incidence of neonatal jaundice in newborns of 0 Rh (D) positive mothers. To the end, we investigated a possible association between the incidence of neonatal jaundice in 0 Rh (D) positive mothers and the neonatal blood group. The incidence of neonatal jaundice was not found to differ between maternal blood groups. We discuss new preventive measures that may reduce the incidence of neonatal jaundice and thereby reduce the length of hospital stay.
- Klíčová slova
- AB0 and Rh (D) alloimmunisation, haemolytic disease of the foetus and newborn, neonatal jaundice,
- MeSH
- incidence MeSH
- krevní skupiny - systém Rh-Hr MeSH
- lidé MeSH
- novorozenec MeSH
- novorozenecká žloutenka * epidemiologie etiologie MeSH
- retrospektivní studie MeSH
- Rh izoimunizace epidemiologie MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- krevní skupiny - systém Rh-Hr MeSH
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.
- MeSH
- bilirubin krev MeSH
- biologické markery krev MeSH
- lidé MeSH
- novorozenec MeSH
- novorozenecká hyperbilirubinemie krev diagnóza terapie MeSH
- novorozenecká žloutenka krev diagnóza terapie MeSH
- novorozenecký screening * MeSH
- point of care testing * MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- reprodukovatelnost výsledků MeSH
- stupeň závažnosti nemoci MeSH
- upregulace MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- bilirubin MeSH
- biologické markery MeSH
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.
- MeSH
- bilirubin krev MeSH
- biologické markery krev MeSH
- časná diagnóza MeSH
- chytrý telefon MeSH
- lidé MeSH
- mobilní aplikace MeSH
- novorozenec MeSH
- novorozenecká hyperbilirubinemie krev diagnóza terapie MeSH
- novorozenecká žloutenka krev diagnóza terapie MeSH
- novorozenecký screening * přístrojové vybavení MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- reprodukovatelnost výsledků MeSH
- stupeň závažnosti nemoci MeSH
- upregulace MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- bilirubin MeSH
- biologické markery MeSH
Neonatal hyperbilirubinemia or jaundice is associated with kernicterus, resulting in permanent neurological damage or even death. Conventional phototherapy does not prevent hyperbilirubinemia or eliminate the need for exchange transfusion. Here we investigated the potential of therapeutic bile acids ursodeoxycholic acid (UDCA) and obeticholic acid (OCA, 6-α-ethyl-CDCA), a farnesoid-X-receptor (FXR) agonist, as preventive treatment options for neonatal hyperbilirubinemia using the hUGT1*1 humanized mice and Ugt1a-deficient Gunn rats. Treatment of hUGT1*1 mice with UDCA or OCA at postnatal days 10-14 effectively decreased bilirubin in plasma (by 82% and 62%) and brain (by 72% and 69%), respectively. Mechanistically, our findings indicate that these effects are mediated through induction of protein levels of hUGT1A1 in the intestine, but not in liver. We further demonstrate that in Ugt1a-deficient Gunn rats, UDCA but not OCA significantly decreases plasma bilirubin, indicating that at least some of the hypobilirubinemic effects of UDCA are independent of UGT1A1. Finally, using the synthetic, non-bile acid, FXR-agonist GW4064, we show that some of these effects are mediated through direct or indirect activation of FXR. Together, our study shows that therapeutic bile acids UDCA and OCA effectively reduce both plasma and brain bilirubin, highlighting their potential in the treatment of neonatal hyperbilirubinemia.
- MeSH
- bilirubin krev MeSH
- ileum účinky léků metabolismus MeSH
- isoxazoly farmakologie MeSH
- játra účinky léků metabolismus MeSH
- krysa rodu Rattus MeSH
- kyselina chenodeoxycholová analogy a deriváty terapeutické užití MeSH
- kyselina ursodeoxycholová terapeutické užití MeSH
- myši MeSH
- novorozenecká hyperbilirubinemie krev farmakoterapie MeSH
- potkani Gunn MeSH
- receptory cytoplazmatické a nukleární agonisté metabolismus MeSH
- výsledek terapie MeSH
- žlučové kyseliny a soli terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- bilirubin MeSH
- farnesoid X-activated receptor MeSH Prohlížeč
- GW 4064 MeSH Prohlížeč
- isoxazoly MeSH
- kyselina chenodeoxycholová MeSH
- kyselina ursodeoxycholová MeSH
- obeticholic acid MeSH Prohlížeč
- receptory cytoplazmatické a nukleární MeSH
- žlučové kyseliny a soli MeSH
Phototherapy is a standard treatment for severe neonatal jaundice to remove toxic bilirubin from the blood. Here, the wavelength-dependent photochemistry of vinylneoxanthobilirubic acid methyl ester, a simplified model of a bilirubin dipyrrinone subunit responsible for a lumirubin-like structural rearrangement, was thoroughly investigated by liquid chromatography and mass and absorption spectroscopies, with the application of a multivariate curve resolution analysis method supplemented with quantum chemical calculations. Irradiation of the model chromophore leads to reversible Z → E photoisomerization followed by reversible photocyclization to a seven-membered ring system (formed as a mixture of diastereomers). Both the isomerization processes are efficient (ΦZE ∼ ΦEZ ∼ 0.16) when irradiated in the wavelength range of 360-410 nm, whereas the E-isomer cyclization (Φc = 0.006-0.008) and cycloreversion (Φ-c = 0.002-0.004) reactions are significantly less efficient. The quantum yields of all processes were found to depend strongly on the wavelength of irradiation, especially when lower energy photons were used. Upon irradiation in the tail of the absorption bands (490 nm), both the isomers exhibit more efficient photoisomerization (ΦZE ∼ ΦEZ ∼ 0.30) and cyclization (Φc = ∼0.07). In addition, the isomeric bilirubin dipyrrinone subunits were found to possess important antioxidant activities while being substantially less toxic than bilirubin.
- MeSH
- bilirubin MeSH
- fotochemie MeSH
- fototerapie MeSH
- isomerie MeSH
- lidé MeSH
- novorozenec MeSH
- novorozenecká žloutenka * MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- bilirubin MeSH
BACKGROUND: Neonatal hyperbilirubinemia is a common condition that frequently requires treatment with phototherapy and less commonly by exchange transfusion, especially in preterm infants. It is important to identify and monitor infants at risk of severe unconjugated hyperbilirubinemia early in the postnatal period to instigate appropriate management plans. AIMS: To evaluate transcutaneous bilirubinometry (TCB) as a screening tool at 24 and 48 h of age to predict the need for phototherapy during hospital stay in preterm infants. STUDY DESIGN: A single centre prospective cohort study in a level III perinatal centre. SUBJECTS: Preterm infants (23+0 to 36+6 weeks of gestation) were eligible for enrolment. OUTCOME MEASURES: Primary outcome was to assess the predictive value of TCB at 24 and 48 h of age for the need of phototherapy during hospital stay. RESULTS: A total of 338 preterm infants were enrolled. The majority of infants (98.1%) born below 32 weeks of gestation required phototherapy. For infants born at >31 + 6 weeks of gestation, TCB at 24 h of age ≥81 μmol/l had sensitivity 83%, specificity 56%, positive predictive value (PPV) 54.7% and negative predictive value (NPV) 84%. TCB at 48 h of age ≥145 μmol/l had sensitivity 65%, specificity 62%, PPV 24% and NPV 90%. CONCLUSION: TCB performed poorly at 24 and 48 h of age as a predictor of phototherapy during hospital stay in preterm infants. The negative predictive value of the test at 48 h of age might be helpful for infants born after 31 + 6 weeks of gestation.
- Klíčová slova
- Hyperbilirubinemia, Jaundice, Phototherapy, Preterm infants, Transcutaneous bilirubinometry,
- MeSH
- bilirubin krev MeSH
- biochemická analýza krve přístrojové vybavení metody MeSH
- délka pobytu MeSH
- dospělí MeSH
- fototerapie MeSH
- lidé MeSH
- novorozenci extrémně nezralí MeSH
- novorozenec nedonošený MeSH
- novorozenec MeSH
- novorozenecká hyperbilirubinemie diagnóza terapie MeSH
- novorozenecký screening metody MeSH
- prospektivní studie MeSH
- senzitivita a specificita MeSH
- věk matky MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- bilirubin MeSH
Although phototherapy (PT) is a standard treatment for neonatal jaundice, no validated clinical methods for determination of bilirubin phototherapy products are available. Thus, the aim of our study was to establish a such method for clinical use. To achieve this aim, a LC-MS/MS assay for simultaneous determination of Z-lumirubin (LR) and unconjugated bilirubin (UCB) was conducted. LR was purified after irradiation of UCB at 460 nm. The assay was tested on human sera from PT-treated neonates. Samples were separated on a HPLC system with a triple quadrupole mass spectrometer detector. The instrument response was linear up to 5.8 and 23.4 mg/dL for LR and UCB, respectively, with submicromolar limits of detection and validity parameters relevant for use in clinical medicine. Exposure of newborns to PT raised serum LR concentrations three-fold (p < 0.01), but the absolute concentrations were low (0.37 ± 0.16 mg/dL), despite a dramatic decrease of serum UCB concentrations (13.6 ± 2.2 vs. 10.3 ± 3.3 mg/dL, p < 0.01). A LC-MS/MS method for the simultaneous determination of LR and UCB in human serum was established and validated for clinical use. This method should help to monitor neonates on PT, as well as to improve our understanding of both the kinetics and biology of bilirubin phototherapy products.
- MeSH
- bilirubin analogy a deriváty krev chemie MeSH
- chromatografie kapalinová MeSH
- fototerapie metody MeSH
- lidé MeSH
- molekulární struktura MeSH
- novorozenec MeSH
- novorozenecká žloutenka krev terapie MeSH
- sérum chemie MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- bilirubin MeSH
- lumirubin MeSH Prohlížeč
BACKGROUND: Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder with varying symptomatology depending on the age of onset. The diagnosis of NP-C is challenging due to heterogeneous nonspecific clinical presentation of the disease. NP-C Suspicion Index (SI) was developed to aid screening and identification of patients with suspicion of NP-C for further clinical evaluation. Here we assess the performance of five NP-C SI models to identify patients with NP-C compared with clinical practice to determine the best SI model for identification of each clinical form of NP-C by age. METHODS: This was a post hoc analysis of a retrospective chart review of patient data collected from five expert NP-C centers. The study assessed the proportion of patients with NP-C who could have been identified using the Original SI, Refined SI, 2/7 SI, 2/3 SI, and Early-Onset SI and evaluated the performance of each SI against clinical practice. A score above a threshold of 70 points for the Original SI, 40 points for the Refined SI, 6 points for the Early-Onset SI, and 2 points for the 2/7 and 2/3 SIs represented identification of NP-C. RESULTS: The study included 63 patients, and of these, 23.8% had a family history of NP-C. Of the available SI tools, the Refined SI performed well in identifying patients with NP-C across all age groups (77.8% infantile, 100% juvenile and 100% adult groups), and earlier identification than clinical diagnosis would have been possible in 50.0% of infantile, 72.7% of juvenile and 87.0% of adult patients. Patients who were not detected by the Refined SI prior to clinical diagnosis mainly presented with delayed developmental milestones, visceral manifestations, neurologic hypotonia, clumsiness, ataxia, vertical supranuclear gaze palsy, parent or siblings with NP-C, dysarthria/dysphagia and psychotic symptoms. CONCLUSION: This study demonstrated the applicability of various SI models for screening and identification of patients with NP-C for further clinical evaluation. Although NP-C is rare and the patient population is limited, this study was conducted in a real-world setting and confirms SI models as useful screening tools that facilitate identification of patients with NP-C earlier in their disease course.
- Klíčová slova
- Clinical diagnosis, Hepatosplenomegaly, NP-C, NP-C Suspicion Index, NP-C disability scales, Neonatal jaundice, Neurologic findings, Niemann-Pick disease Type C, Patient detection, Screening,
- MeSH
- hodnocení rizik MeSH
- lidé MeSH
- Niemannova-Pickova nemoc typu C diagnóza MeSH
- novorozenecká žloutenka diagnóza MeSH
- psychotické poruchy diagnóza MeSH
- retrospektivní studie MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The action spectrum for bilirubin photodegradation has been intensively studied. However, questions still remain regarding which light wavelength most efficiently photodegrades bilirubin. In this study, we determined the in vitro effects of different irradiation wavelength ranges on bilirubin photodegradation. METHODS: In our in vitro method, normalized absolute irradiance levels of 4.2 × 1015 photons/cm2/s from light-emitting diodes (ranging from 390-530 nm) and 10-nm band-pass filters were used to irradiate bilirubin solutions (25 mg/dL in 4% human serum albumin). Bilirubin and its major photoisomer concentrations were determined; the half-life time of bilirubin (t1/2) was calculated for each wavelength range, and the spectral characteristics for bilirubin photodegradation products were obtained for key wavelengths. RESULTS: The in vitro photodegradation of bilirubin at 37 °C decreased linearly as the wavelength was increased from 390 to 500 nm with t1/2 decreasing from 63 to 17 min, respectively. At 460 ± 10 nm, a significantly lower rate of photodegradation and thus higher t1/2 (31 min) than that at 500 nm (17 min) was demonstrated. CONCLUSION: In our system, the optimum bilirubin photodegradation and lumirubin production rates occurred between 490 and 500 nm. Spectra shapes were remarkably similar, suggesting that lumirubin production was the major process of bilirubin photodegradation.
- MeSH
- bilirubin analogy a deriváty krev chemie účinky záření MeSH
- fotolýza účinky záření MeSH
- fototerapie metody MeSH
- isomerie MeSH
- lidé MeSH
- lidský sérový albumin chemie účinky záření MeSH
- novorozenec MeSH
- novorozenecká hyperbilirubinemie krev terapie MeSH
- spektrofotometrie MeSH
- světlo * MeSH
- techniky in vitro MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- bilirubin MeSH
- lidský sérový albumin MeSH
- lumirubin MeSH Prohlížeč
