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Objective:To explore the value of video-electroencephalography (VEEG) combined with amplitude-integrated electroencephalography (aEEG) in evaluating the condition and prognosis of neonatal hyperbilirubinemia brain injuries.Methods:A total of 120 children with hyperbilirubinemia treatedin the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from July 2019 to July 2020 were enrolled. According to MRI with or without T 1 weighted imging (T 1WI) hyperintensity changes in the globus pallidus, they were divided into the brain injury group (52 cases) and the normal group(68 cases). According to the severity of brain injury, the brain injury group was divided into bilirubin encephalopathy group (23 cases) and subclinical bilirubin brain injury group (29 cases). According to the scores of Gesell Development Scale, the brain injury group was divided into good prognosis group (37 cases)and poor prognosis group (15 cases). The diagnostic value in brain injury with hyperbilirubinemia, the evaluation of the severity of brain injury and the predictive value of VEEG and aEEG were analyzed. Results:The abnormal rates of VEEG and aEEG in the brain injury group were higher than those in the normal group: 76.92% (40/52) vs. 8.82% (6/68), 80.77% (42/52) vs. 11.76% (8/68), the differences were statistically significant ( χ2 = 57.81 and 57.73, P<0.01). The abnormal rates of VEEG and aEEG in bilirubin encephalopathy group were higher than those in subclinical bilirubin brain injury group: 91.30% (21/23) vs. 65.52% (19/29), 95.65% (22/23) vs. 68.97% (20/29), the differences were statistically significant ( χ2 = 4.80 and 5.88, P<0.05). There was no significant difference in abnormal rates of VEEG and aEEG between the good prognosis group and poor prognosis group ( P>0.05). The results of operating characteristic curve analysis showed that the areas under the curve of VEEG combined with aEEG in the diagnosis of brain injury with hyperbilirubinemia, evaluation of the severity of brain injury, predicting the prognosis of children were higher than those of each examination method used alone ( P<0.05). Conclusions:VEEG combined with aEEG has diagnostic value for neonatal brain injury with hyperbilirubinemia, and has evaluation value for severity and prognosis of the disease.
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Resumen | Hay pocos reportes de enfermedad hemolítica del feto y del recién nacido causada por aloanticuerpos contra el sistema de antígenos MNS, especialmente, porque los anticuerpos que se generan contra estos antígenos son del tipo IgM, los cuales tienen reactividad a temperaturas inferiores a los 37 °C, y, por lo tanto, no son de importancia clínica. A pesar de ello, se han reportado casos con presencia de anticuerpos anti-M de tipo IgG causantes de la enfermedad hemolítica del recién nacido e, incluso, casos de muerte intrauterina por incompatibilidad materno-fetal en el sistema MNS. El proceso hemolítico se asemeja al causado por los anticuerpos anti-Kell, con anemia progresiva por supresión hematopoyética que induce la destrucción de precursores hematopoyéticos en la médula ósea y ausencia de reticulocitos en la periferia. Se reporta el caso de una mujer con 38,5 semanas de gestación, que presentó discrepancia en la hemoclasificación directa y en la inversa. Como resultado, el recién nacido fue positivo en la prueba de Coombs directa sin que existiera incompatibilidad ABO con la madre. La correlación de estos resultados llevó a la detección de un anticuerpo anti-M en el suero materno. El diagnóstico definitivo fue posible gracias a la discrepancia en la hemoclasificación de la sangre materna. A pesar de que los anticuerpos anti-M usualmente no desempeñan un papel importante en la enfermedad hemolítica perinatal, este caso resalta la importancia de determinar la presencia de diferentes anticuerpos que pueden ser de vital interés a la hora de prevenir resultados graves asociados con dicha condición. Además, abre la puerta a nuevas recomendaciones relacionadas con la tamización y el tratamiento temprano de la hemólisis en los recién nacidos.
Abstract | There are few case reports of hemolytic disease in fetuses and newborns (HDFN) caused by alloantibodies against the MNS blood group system. The reason for this dearth is that antibodies toward these antigens are usually IgM, which not only cannot cross the placental circulation but also react at temperatures below 37°C. They are, therefore, of minimal clinical importance. Nevertheless, cases have been reported in which the presence of anti-M IgG antibodies caused severe HDFN and even intrauterine death in the presence of maternal-fetal MNS incompatibility indicating that they could have a high clinical impact. The hemolytic pattern observed in these cases is similar to that caused by anti-Kell antibodies. Progressive anemia is mediated and developed through hematopoietic suppression inducing the destruction of bone marrow precursor cells with the resulting absence of reticulocytes in peripheral blood. This occurred in the case of a woman at 38.5 weeks of gestation who showed a discrepancy between direct and reverse blood type determination. A direct Coombs test was performed on the newborn's blood, which was positive in the absence of maternal-fetal ABO incompatibility. Further tests were performed and anti-M antibodies were found in the maternal serum screening. Our final diagnosis was largely due to discrepancy issues in maternal blood. Although anti-M antibodies do not usually play a significant role in HDFN, this case stresses the importance of identifying the presence of antibodies that can be crucial in preventing HDFN and lead to new recommendations for the screening and prompt treatment of hemolysis in newborns.
Subject(s)
Blood Group Antigens , Erythroblastosis, Fetal , Blood Group Incompatibility , Coombs Test , Hyperbilirubinemia, Neonatal , Jaundice, NeonatalABSTRACT
Objective:To study the predictive value of hour-specific total serum bilirubin(TSB) nomogram combined with clinical risk factors in the risk of hyperbilirubinemia.Method:Perinatal clinical data of newborns born in Shanghai Pudong New Area Health Care Hospital for Women and Children, Shanghai Pudong New Area People's Hospital and Shanghai Pudong Hospital from August 2017 to July 2018 were collected in this prospective study. Transcutaneous bilirubin (TcB) was monitored before discharge from hospital. Enrolled neonates were followed up for 28 days. The patients were assigned to neonatal hyperbilirubinemia group (NHB) and non-hyperbilirubinemia group (Non-HB) according to the occurrence of hyperbilirubinemia. The predictive value of models for the risk of hyperbilirubinemia was evaluated by receiver operating characteristic (ROC) curves and Logistic regression analysis.Result:A total of 8 664 newborns were included in this study, with 1 196 cases of hyperbilirubinemia, with an incidence of 13.8%. Logistic regression analysis showed that maternal blood type O, premature rupture of membranes, male gender, gestational age 35~37 weeks, subcutaneous ecchymosis/cranial edema, and breastfeeding were independent risk factors for NHB ( P<0.05). The area under receiver operative characteristic curve (ROC) of predischarge bilirubin risk zone only was 0.874(95% CI 0.861~0.885, P<0.05)and for all independent risk factors was 0.664 (95% CI 0.647~0.680, P<0.05). The area under ROC curve was 0.891 (95% CI 0.880~0.902, P<0.05) by combining predischarge bilirubin risk zone with clinical risk factors. Conclusion:Predischarge bilirubin risk zone combined with clinical risk factors can reasonably predict neonatal hyperbilirubinemia well.
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Objective To study the effects of stored blood with low glucose 6-phosphate dehydrogenase (G6PD) activity for exchange transfusion (ET) in neonate hyperbilirubinemia.Method From January 2017 to December 2018,all neonates receiving ET for neonatal hyperbilirubinemia in neonatology department of our hospital were prospectively enrolled.G6PD activity in stored blood and in these neonates were examined.Their demographic information and other clinical data including post-ET total serum bilirubin (TSB) decrease,post-ET phototherapy duration and total hospital stay duration were collected.Result A total of 99 cases were enrolled,51 cases with normal G6PD and 48 G6PD deficiency.Among normal G6PDneonates,those receiving low G6PD activity blood had less decrease of post-ET TSB [(56.9 ± 8.4) ％ vs.(72.5 ± 14.4) ％],longer hospital stay and longer post-ET phototherapy duration [(6.4 ± 2.3) d vs.(4.9 ± 1.3) d,(70.8 ± 36.2) h vs.(52.3 ± 16.3) h] (P ＜ 0.05) than those receiving normal G6PD blood.Among G6PD deficiency neonates,those receiving low G6PD activity blood had less decrease of post-ET TSB [(58.8 ±6.2)％ vs.(67.3 ± 13.9)％],longer hospital stay and longer post-ET phototherapy duration [(5.5 ± 2.2) d vs.(4.4 ± 1.4) d,(60.6 ± 25.9) h vs.(47.9 ± 27.9) h] (P ＜ 0.05) than those receiving normal G6PD blood.The G6PD activity in stored blood had significant influences on duration of phototherapy (F =7.695,P =0.007),duration of hospital stay (F =12.528,P =0.001) and decrease of post-ET TSB (F =29.025,P ＜ 0.001).Conclusion ET with low G6PD activity stored blood has less favourable effects with less post-ET TSB decrease and prolonged duration of phototherapy and hospital stay.
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Objective To study the clinical significance of globus pallidus signal intensity and the intensity ratio of globus pallidus and putamen (G/P ratio) on magnetic resonance T1WI for the early recognition of neonatal bilirubin encephalopathy.Method From January to December 2017,full-term neonates with hyperbilirubinemia admitted to the neonatology department of our hospital were enrolled in the case group,and full-term neonates without hyperbilirubinemia in the control group.The clinical data,globus pallidus T1WI signal intensity,G/P ratio and the follow-up data were collected.According to the level of hyperbilirubinemia,the neonates in the case group were further assigned into mild hyperbilirubinemia group (serum bilirubin:222 to ＜256 μmol/L),moderate hyperbilirubinemia group (serum bilirubin:256 to ＜342 μmol/L),and severe hyperbilirubinemia group (serum bilirubin:≥ 342 μmol/L).According to the injury score of ABE,the neonates with ABE were assigned into mild ABE group,moderate ABE group and severe ABE group.The correlation of globus pallidus T1WI and T2WI signal values,G/P ratio and the serum bilirubin level and ABE degree were analyzed;receiver operating characteristic (ROC) curve was drawn to explore the predictive value of the T1WI signal value and G/P ratio for the diagnosis of ABE;the changes of globus pallidus T1WI and T2WI signal values during the first 6 months after birth and the results of follow-up to 1 year after discharge were also analyzed.Result A total of 175 neonates were included in the case group (65 in the mild hyperbilirubinemia group,71 in the moderate hyperbilirubinemia group and 39 in the severe hyperbilirubinemia group) and 43 neonates in the control group.39 neonates were diagnosed as ABE (21 mild ABE,12 moderate ABE,and 6 severe ABE).The first T1WI signal value and G/P ratio of neonates in the severe hyperbilirubinemia group was higher than the moderate hyperbilirubinemia group,the mild hyperbilirubinemia group and the control group;the T1WI signal value and G/P ratio in the moderate hyperbilirubinemia group was higher than the mild hyperbilirubinemia group and the control group (P ＜ 0.05).No significant difference existed between the mild group and the control group(P ＞ 0.05).T2WI values showed no differences among neonates with different bilirubin levels (P ＞ 0.05).The first T1WI signal value and G/P ratio in the severe ABE group were significantly higher than the moderate and mild ABE group,and the moderate ABE group higher than the mild ABE group (P ＜ 0.05).The ROC curve indicated the optimal cut-off value of T1WI signal and G/P ratio were 628 and 1.38,respectively.Among all the 175 neonates,9 had a decrease in T1WI signal value and an increase in T2WI signal value at 6 months after birth.After 1 year of follow-up visits,7 children were finally diagnosed as chronic bilirubin encephalopathy.All these children had increased signal intensity on T1WI in the acute phase,plus a decreased T1WI signal and an increased T2WI signal in 1 ～ 6 months after birth.Conclusion The globus pallidus T1WI signal and G/P ratio are closely related to the serum bilirubin level and ABE severity.If T1WI signal value ＞ 628 or G/P value ＞ 1.38,ABE should be considered.The T1WI signal value and G/P ratio play important roles as indicators for the early recognition of neonatal bilirubin encephalopathy.
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Objective To study the effects of exchange transfusion(ET) and intensive phototherapy (IPT) on neurodevelopment in neonates with severe hyperbilirubinemia reaching ET criteria.Method From January 2015 to March 2016,neonates with severe hyperbilirubinemia reaching ET criteria with gestational age ≥35 weeks,and hospitalized in the Department of Neonatology of our hospital were enrolled in the study.The parents were informed of the risks of acute bilirubin encephalopathy (ABE) and both the advantages and disadvantages of IPT and ET.Based on the different choices of their parents,the neonates were assigned into the ET group and the IPT group.General conditions,treatment effects,the incidences of ABE and the prognosis were recorded and analyzed.Result A total of 335 patients were included in this study,147 in the ET group and 188 in the IPT group.Before intervention,the peak of total serum bilirubin (TSB) in ET group (475.8± 100.6 μmol/L) was higher than IPT group (398.3±39.8 μmol/L) (the difference of TSB between two groups was 77.4 μmol/L,P＜0.001),and the incidences of high risk factors such as blood incompatibilities,sepsis,cranial hematoma and intracranial hemorrhage in ET group were higher than IPT group (P＜0.05).Compared with at admission,the incidence of ABE in the ET group increased from 32.0％ to 34.0％ at discharge,mainly due to moderate and severe ABE (the ratio of moderate ABE increased from 2.7％ to 10.2％,and severe ABE increase from 2.7％ to 4.8％).Statistically significant differences existed in the proportion of ABE with different severity at admission and discharge in ET group (P＜0.05),while that in IPT group wasn't statistically significant.241 patients were followed up (follow-up rate 71.9％),with the age ranging from 20 to 36 months.6 cases (5.7％,6/106) in the ET group showed hearing disorder while none (0％,0/135) in the IPT group (P＜0.05).The incidences of neuromotor dyskinesia,language development disorder and spasm in ET group were higher than IPT group(7.5％ vs.3.7％,3.8％ vs.1.5％,4.7％ vs.4.4％,respectively),but the differences weren't statistically significant(P＞ 0.05).No deaths were observed in both groups.Conclusion In neonates with severe hyperbilirubinemia whose TSB exceeding the upper limit of current ET criteria (and within upper limit+5 mg/dl),if the neonates have no risk factors nor clinical symptoms of moderate or severe ABE,only IPT and without ET does not increase the incidence of unfavourable prognosis of central nervous system.
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Objective Magnetic resonance diffusion tensor imaging ( DTI) technique was used to investigate the changes of DTI parameters in nerve fiber bundles of children with hyperbilirubinemia. Meth-ods A retrospective analysis of DTI imaging data of 43 children with hyperbilirubinemia and 24 normal controls in our hospital using the German Siemens 3. 0t Trio superconducting magnetic resonance imaging in-strument from December 2016 to March 2018. Children with hyperbilirubinemia were divided into two groups, total serum bilirubin mildly elevated group (34 cases) and total serum bilirubin moderate to severe elevation group (9 cases). The right and left cerebellar dentate nuclei were selected as the regions of inter-est. Relevant parameters were measured, and the parameters of each group were analyzed and compared. Results Compared with the normal control group,the fractional anisotropy ( FA) of the total serum biliru-bin mildly elevated group was decreased ( P=0. 022 ) and the volume ratio ( VR ) of that was increased (P=0. 036). Compared with the normal control group, the FA of the total serum bilirubin moderate to se-vere elevation group was decreased (P=0. 002) and the VR of that was increased (P=0. 047). Compared with the total serum bilirubin mildly elevated group,the FA of the total serum bilirubin moderate to severe elevation group was decreased (P=0. 035). In addition, in the cerebellar dentate nucleus, there was a lin-ear negative correlation (r= -0. 201, P=0. 029) between the FA values and the total bilirubin level, while linear positive correlation (r=0. 245, P=0. 045) between the VR value and the total bilirubin level. Conclusions There are changes in FA and VR values of the cerebellar dentate nucleus in children with hy-perbilirubinemia,which of them are linearly related to bilirubin levels. It can early indicate the destruction or dysplasia of nerve fiber bundles in children.
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Objective To study the predictive values of the general movements (GMs) assessment in writhing stage for motor development outcomes in infants with severe neonatal jaundice.Method From December of 2012 to December of 2017,infants with severe neonatal jaundice (serum bilirubin reaching the corresponding level of exchange transfusion according to the reference nomogram) in our hospital were enrolled in the study.Inclusion criteria included corrected gestational age of 37 to 48 weeks,serum bilirubin level below phototherapy intervention value after treatment and general and detailed assessment were carried out in writhing stage when the infant was stable.The patients were regularly followed-up until one-year-old to evaluate the predictive values.Result A total of 241 patients with severe neonatal jaundice were enrolled in the study,including 153 males (63.5％) and 88 females (36.5％),with gestational age between 35 and 42 weeks.The mean gestational age was (37.9± 1.8) weeks,the average birth weight was (3 057±480) g,and the mean serum bilirubin value was (458.9± 119.1) μmol/L.The general evaluation of the GMs was normal in 15 cases (6.2％),and abnormal in 226 cases (93.8％) with 217 cases (90.0％) were poor repertoire (PR) and 9 cases (3.7％) were cramped-synchronized (CS).The predictive values of abnormal GMs for abnormal motor development outcomes were as following:sensitivity 100％,specificity 7.6％,negative predictive value(NPV) 100％.The predictive values of CS for cerebral palsy were as following:sensitivity 22.2％,specificity 97.8％,NPV 94.0％.Detailed evaluation of 241 subjects showed that 13 items had statistically significant differences in the prediction of cerebral palsy (P＜0.05),and 18 items in the prediction of abnormal motor development (P＜0.05).Conclusion The CS pattern and detailed assessment of GMs in the writhing stage may be correlated with the outcomes of motor development in infants with severe neonatal jaundice until one-year-old.
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Objective To study the risk factors of severe complications possibly associated with exchange transfusion (ET) for patients with extreme hyperbilirubinemia.Method From May 2001 to May 2018,neonates with severe complications of ET were assigned into adverse event group.The propensity score principle was used to match adverse event group/the control group with the ratio of 1 ∶ 3.The neonates in the control group received ET without any severe complications.The demographic characteristics of patients,and other clinical data were reviewed.The Logistic regression analysis was used to determine the risk factors of severe complications of ET.Result Among the 1 535 neonates who received ET during the past 17 years,71 neonates (4.6％) were identified with severe adverse events,including apnea (30.6％),necrotizing enterocolitis (18.8％),heart failure (14.1％),respiratory failure (12.9％),and shock (8.2％).The Logistic regression analysis showed that acute bilirubin encephalopathy (ABE) score ≥ 3 (OR=6.383,95％CI 2.550～15.979),ETs ≥ 2 times (OR=11.825,95％CI 2.464～56.755),cardiac murmur ≥ grade Ⅲ (OR=20.417,95％CI 4.705～40.590),and dramatic blood pressure fluctuation during ET ≥ 30 mmHg (OR=13.612,95％CI 1.795～43.342) were risk factors of ET related severe complications (all P＜0.05).Conclusion The indications should be carefully assessed before ET.The patients with ABE score ≥ 3,ETs ≥ 2 times,cardiac murmur ≥ grade Ⅲ,or dramatic blood pressure fluctuation during ET ≥ 30 mmHg should be monitored carefully and ET should be stopped in time if necessary.
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Objective To study the relationship between uridine diphosphate glucuronic acid (UGT1A1) gene polymorphism and unexplained neonatal unconjugated hyperbilirubinemia in Jinhua.Method Full-term infants with unidentified non-binding hyperbilirubinemia were selected as hyperbilirubinemia group from January 2016 to December 2017 in the obstetrics or neonatal intensive care unit of Jinhua Central Hospital,healthy full-term neonates and those with physiological jaundice admitted during the same period were selected as control group.Whole blood DNA was extracted and UGT1A1 was sequenced and then annotated with human gene mutation database.The distribution and frequency of UGT1A1 genotype were analyzed.The correlation between different genotypes and unexplained unconjugated hyperbilirubinemia in neonates was also studied.Result Two hundred and forty cases were enrolled in the hyperbilirubinemia group,and 216 cases were enrolled in the control group.Four single nucleotide variation (SNV) sites associated with the disease were found on UGT1A1,which were c.211G＞A (Gly71Arg),c.686C＞A (Pro229Gln),c.1091C＞T (Pro364Leu) and c.1456T＞G (Tyr486Asp),accounting for 83.9％(141/168),1.8％(3/168),8.9％(15/168) and 5.4％(9/168) in the experimental group respectively.The genotype frequency and allele frequency analysis showed that the distribution of the two SNV sites of c.211G＞A and c.1456T＞G were statistically different between the experimental group and the control group (P＜0.05),whereas there was no statistical difference of the other two SNV sites of c.686C＞A and c.1091C＞T between the two groups.Binary Logistic regression analysis showed that c.211G＞A and c.1456T＞G were related to the occurrence of unexplained hyperbilirubinemia,The OR values (95％CI) were 5.412 (3.567～ 8.212) and 8.377 (1.052～66.670) respectively,but no correlation was found of the other two polymorphic loci.At the different genotypes of c.211G＞A locus,the levels of total bilirubin and non-binding bilirubin in infants with homozygous mutant (AA) were higher than those in infants with heterozygous mutant (GA) and wild type (GG),which was statistically significant (P＜0.05).Conclusion The most common mutation site of the UGT1A1 gene in Jinhua is c.211G＞A.The mutations of c.211G＞A and c.1456T＞G are risk factors forunconjugated hyperbilirubinemia in neonates.Of the different genotypes of c.211G＞A locus,the serum bilirubin level of homozygous mutant group was significantly higher than heterozygous mutant group and wild type group.
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Resumen El síndrome del bebe bronceado es una rara discromía que se presenta como una complicación de la fototerapia en recién nacidos con ictericia neonatal. Aunque el fenotipo común se ha descrito en pacientes con hiperbilirrubinemia directa secundaria a colestasis, también se conocen casos con hiperbilirrubinemia indirecta en quienes se invierte el patrón de hiperbilirrubinemia e, incluso, otros con hiperbilirrubinemia indirecta aislada. La fisiopatología de la enfermedad sigue siendo motivo de controversia, por lo que no se ha establecido claramente cuál es la mejor aproximación diagnóstica y terapéutica. En general, el síndrome se considera leve y se resuelve con la suspensión de la fototerapia; no suele prolongarse más allá del periodo neonatal y no tiene secuelas a largo plazo. Sin embargo, su aparición constituye una contraindicación absoluta para continuar la fototerapia. En caso de persistir, se recomienda disminuir los niveles de bilirrubina y recurrir a la exanguinotransfusión, pero dado que esta implica riesgos para el neonato, una conducta adecuada sería suspender la fototerapia y reiniciarla si la bilirrubina directa disminuye y se ha descartado el compromiso colestásico, aunque siempre evaluando en forma seriada posibles manifestaciones de encefalopatía aguda por bilirrubina. El objetivo de este estudio fue presentar el caso de un recién nacido con incompatibilidad de grupo sanguíneo ABO que presentó el síndrome del bebé bronceado. El bebé respondió satisfactoriamente a la suspensión de la fototerapia y a su posterior reanudación, sin necesidad de recurrir a la exanguinotransfusión.
Abstract The bronze baby syndrome is an infrequent dyschromia resulting from phototherapy in newborn babies with neonatal jaundice. Even though the common phenotype has been described in patients with direct neonatal hyperbilirubinemia secondary to cholestasis, several cases of patients with indirect neonatal hyperbilirubinemia who have managed to reverse it have been reported, as well as patients with isolated hyperbilirubinemia. Currently, the physiopathology of this condition is still a subject of controversy and, therefore, there is a lack of clear conducts for its correct diagnosis and treatment. Generally, this syndrome has been considered as a mild condition that is resolved with the suspension of phototherapy. Its duration is usually not greater than the neonatal period, and it has no long-term sequelae. However, its occurrence is considered an absolute contraindication for the continuation of phototherapy. In case of persistence, the recommendation is to decrease bilirrubin levels and proceed with exchange transfusion; this procedure, however, represents risks for the newborn, so our recommendation is to suspend phototherapy and reinitiate it if the direct bilirrubin value decreases, and cholestasis compromise has been discarded. Serial evaluations of acute encephalopathy caused by bilirrubin are absolutely recommended. The objective of this paper was to describe the case of a newborn with ABO incompatibility who developed the bronze baby syndrome. This patient responded satisfactorily to the suspension and resumption of phototherapy without exchange transfusion.
Subject(s)
Humans , Infant, Newborn , Male , Phototherapy/adverse effects , Hyperpigmentation/etiology , Syndrome , Jaundice, Neonatal/therapyABSTRACT
The role of genetic factors in the modulation of serum bilirubin levels and the pathophysiology of neonatal hyperbilirubinemia is being increasingly recognized.Heme oxygenase-1 (HO-1) is the rate-limiting enzyme by which heme is catabolized to biliverdin and thence to bilirubin,with the simultaneous release of equimolar quantities of ferrous iron (Fe3 +) and carbon monoxide.Polymorphisms of the HO-1 gene promoter may modulate transcriptional activity,thereby augmenting or attenuating HO-1 expression with resultant modulation of the production of bilirubin.At present,some articles have elucidated the role of these polymorphisms in neonatal bilirubin production,but in different races,the results are different.
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Objective To study the risk factors of acute bilirubin encephalopathy (ABE) in neonates with severe hyperbilirubinemia (total serum bilirubin ≥ 427.5 μmol/L).Method Clinical information of neonates with severe hyperbilirubinemia admitted to the Neonatal Department of Baoan Maternal and Child Health Hospital in Shenzhen from December 2013 to October 2017 were collected.The enrolled cases were grouped as ABE and the control group (without ABE).The risk factors for ABE were compared between the two groups and the Logistic regression analysis was used to evaluate the independent risk factor.Result A total of 104 neonates were recruited.There were 32 cases in the ABE group and 72 cases in the control group.The level of total serum bilirubin and indirect bilirubin,the ratio of total bilirubin/albumin,the incidence of glucose-6-phosphate dehydrogenase deficiency and metabolic acidosis and sepsis,the rate of using traditional Chinese medicine and the failure of treatment in other hospitals and non-resident population were all significantly higher in the ABE group than the control (P ＜ 0.05).Logistic regression analysis showed that total serum bilirubin (OR =1.013,95％ CI 1.007 ～ 1.020) and sepsis (OR =6.343,95％ CI 1.801 ～22.338) were the independent risk factors for ABE.Conclusion The severe hyperbilirubinemia infants,particularly with sepsis,are at higher risk of developing acute bilirubin encephalopathy.
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Objective To study the clinical efficacy of LED blue light tube phototherapy in severe hyperbilirubinemia with acute bilirubin encephalopathy (ABE).Method Clinical data of newborns admitted to neonatal department of our hospital between Dec.2013 and Dec.2016 were retrospectively reviewed.Infants with gestational age ≥ 35 weeks who were diagnosed with severe hyperbilirubinemia and ABE were collected and analyzed.From Dec.2013 to Nov.2014,infants treated with common blue light tube were assigned into traditional blue light group (traditional group).From Dec.2014 to Dec.2016,infants treated with LED blue light tube were assigned to LED blue light group (LED group).Total serum bilirubin (TSB) levels and bilirubin induced neurological dysfunction (BIND) scores were analyzed between the two groups.Neuron specific enolase (NSE) levels before and after phototherapy were also compared.Follow-up data for three months after discharge were analyzed.Result Fifty-one infants with severe hyperbilirubinemia and ABE were included,with 24 cases in traditional group and 27 cases in LED group.There were no significant differences in TSB levels and BIND scores between the two groups before phototherapy (P ＞ 0.05).TSB levels at 4 h,24 h and 48 h after phototherapy in LED group were significantly lower than traditional group respectively [(331.3 ±21.8) μmol/L vs.(372.1 ±25.2) μmol/L,(233.6 ± 20.4) μmol/L vs.(269.4 ± 19.8) μmol/L,(184.5 ± 15.2) μmol/L vs.(226.3 ± 22.7) μmol/L,P ＜ 0.05].However,there was no significant difference in TSB levels at 12 h after phototherapy between the two groups (P ＞ 0.05).BIND scores at 4 h after phototherapy in LED group were significantly lower than traditional group [(4.0 ± 0.6) vs.(4.7 ± 0.8),P ＜ 0.05].There were no significant differences in BIND scores at other time points after phototherapy between the two groups (P ＞ 0.05).In both groups,serum NSE levels after phototherapy were lower than before phototherapy.Serum NSE level after phototherapy in the LED group was significantly lower than the traditional group (P ＜ 0.05).Total phototherapy duration of the LED group was significantly shorter than the traditional group (P ＜ 0.05).The incidence of exchange transfusion in LED group was significantly lower than traditional group.The incidence of abnormal brainstem auditory evoked potential in LED group were significantly lower than traditional group at 1 month and 3 months after birth (P ＜ 0.05).The proportion of abnormal cranial MRI between the two groups showed no statistical differences (P ＞ 0.05).Conclusion TSB levels and brain injury indicators should be closely monitored and evaluated in infants with severe hyperbilirubinemia and ABE.Active LED blue light phototherapy can rapidly reduce TSB levels,effectively control the progress of ABE,and reduce the ratio of exchange transfusion.Adverse reactions of LED blue light phototherapy are not observed in this study.
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Objective To investigate the association between cerebral hemodynamic changes and neonatal hyperbilirubinemia.Methods A total of 67 neonates with hyperbilirubinemia who were admitted to our hospital from January 2014 to November 2015 were enrolled as study group,and another 36 normal healthy neonates were enrolled as control group.The two groups were compared in terms of end-diastolic velocity (Vd),systolic peak velocity (Vs),mean blood flow velocity (Vm),resistancc index (RI),and pulsatility index (PI),and the serum level of bilirubin and systemic symptoms were observed after treatment.The t-test was used for comparison of continuous data between groups,and a Pearson correlation analysis was also performed.Results At the time of enrohnent and on day 3 of treatment,the control group had significantly lower Vd,Vs,and Vm than the study group (before treatment:t =75.873,81.589,64.600,19.834,30.453;day 3 of treatment:t =39.476,55.729,35.274,6.069,9.382,all P ＜0.001).The study group had improvements in Vd,Vs,Vm,1RI,and PI on day 3 of treatment.On day 5 of treatment,there were no significant differences in hemodynamic parameters between the two groups (all P ＞ 0.05).Serum level of bilirubin was positively correlated with Vd (r =0.387,P ＜ 0.001),Vs (r =0.483,P ＜ 0.001),and Vm (r =0.412,P＜0.001) and negatively correlated with RI (r=-0.492,P＜0.001) andPI (r=-0.497,P＜0.001).Conclusion Serum level of bilirubin interacts with cerebral hemodynamics,and cerebral hemodynamic parameters can provide objective evidence for evaluating disease progession and prognosis of neonatal hyperbilirubinemia.
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Objective To compare the clinical efficacy between single and double volume exchange transfusion for neonatal hyperbilirubinemia,and to verify whether single volume exchange transfusion had advantages in maintaining homeostasis and reducing blood transfusion related complications.Methods Clinical materials of 86 neonates with neonatal hyperbilirubinemia who received blood exchange transfusion,from December 2013 to December 2014,in the diagnosis and treatment center of our hospital were retrospectively analyzed.Cases were divided into the single volume group (35 cases,with a blood volume 80-110 mL/kg) and double volume group (51 cases,with a blood volume 150-180 mL/kg) based on blood volume per kilogram of body weight.Comparisons of the homeostasis changes between pre-transfusion and post-transfusion were performed for each group,and the incidence rate of major adverse events were compared between the two groups.Results (1)In the single volume group and double volume group,the average blood exchange transfusion volumes were (98.16 ± 10.75) mL/kg and (157.78 ± 7.37) mL/kg,the exchange rate of bilirubin were (41.68± 8.52) ％ and (50.22 ± 13.14) ％,and the average time for blood transfusion were (85.60 ±18.66) min and(1 1B.22± 24.81)min respectively,and there were statistically significant differences in the exchange rate of bilirubin and average time for blood transfusion between the two groups (P＜0.05).(2)Compared with pre-transfusion,WBC and platelet (PLT)count,levels of serum total bilirubin (TBIL),albumin,serum potassium,serum sodium,serum chlorine,serum calcium and HCO3-,and pH value were significantly decreased after blood exchange transfusion,while RBC count,PT,APTT and blood glucose were significantly increased in the two groups (P＜0.01).Moreover,the changes of blood glucose,PLT and TBIL in the double volume group were more significantly than those in the single volume group,there were statistically significant differences (P＜0.05).No statistically significant difference was found in the rate of major adverse events between the two groups (P＞0.05).Conclusion Compared with double blood exchange transfusion therapy,single volume exchange transfusion can significantly decrease plasmic bilirubin level with less change of homeostasis,less blood volume for transfusion and less human resources consumption,its value in clinical application is recognized.
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Objective To develop a high-resolution melting ( HRM ) assay for rapidly screening Gilbert syndrome ( GS) and Crigler-Najjar syndrome ( CNS) associated with UGT1A1 defects.Method Methodology was developed .Then, we applied the established method to analyze 61 clinical samples from neonatal patients with severe unexplained unconjugated hyperbilirubinemia .Neonates with known risk factors for developing hyperbilirubinemia , such as ABO hemolysis, G6PD deficiency, sepsis, hypoxic ischemic encephalopathy were excluded .Five pairs of PCR primers were designed to detect the five common mutations (G211A, C686A, C1091T, C1352T and T1456G) in Asia population.PCR and HRM Assay conditions were optimized.UGT1A1 genotyping in clinical samples was performed by using the established HRM analysis , and all results were subsequently confirmed by direct DNA sequencing .Results The mutants were readily differentiated by using HRM analysis .In this study, 42 neonates were identified with UGT1A1 mutation, and 4 different known variants were detected .Conclusion HRM analysis in this study was economical, convenient, rapid, effective for screening UGT1A1 gene mutations, which can serve as an reliable method for the clinical diagnosis of GS and CNS and the large-scale molecular epidemiological research of UGT1A1 gene-related diseases.
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Objective To predict the risk of neonatal hyperbilirubinemia by transcutaneous bilirubin (TcB) nomograms and clinical risk factors.Methods Healthy term and late-preterm newborns (≥ 35 gestational weeks,and birth weight ≥ 2 000 g) born in Guizhou Maternal and Child Care Hospital between January 1,2013 and December 31,2013,were included.TcB levels were continuously recorded within 168 hours after birth.The value of hour-specific TcB nomogram combined with receiver operating characteristic (ROC)curves and Logistic regression model for predicting risk of hyperbilirubinemia was evaluated.Pearson's Chisquare test was also used for statistical analysis.Results A total of 5 250 cases were enrolled.TcB increased rapidly in the first 40 hours after birth,slowly increased between 40 to 96 hours,and reached a high level after 96 hours.Among them,the 95th percentile TcB stablized at 96 hours after birth.The 40th,75th and 95th percentile TcB peak levels were 173,217 and 248 μmol/L.Among the 5 250 neonates,there were 277 cases (5.3％) in the high-risk zone within 72 hours.The positive predictive value (PPV) was 22.02％;1 087 cases (20.7％) and 1 854 cases (35.3％) were in the medium-high risk and medium-low risk zones along with the PPV of 10.58％and 3.72％,respectively.There were 2 032 cases (38.7％) in the low-risk zone with the PPV of 1.38％.Multivariate analysis showed that the TcB high-risk zone after 72 hours was associated with gestational age,delivery mode,feeding mode and TcB level of risk zones within 72 hours.Compared to those born at ≥ 40 gestational weeks,those born at ≥ 37-＜40 gestational weeks were more likely in the TcB high-risk zone after 72 hours (OR=1.80,95％CI:1.29-2.51).The likelihood was reduced by 42％ among neonates born with cesarean section compared to those delivered vaginally in term of the TcB high-risk zone after 72 hours.Infants who received mixed feeding were less likely to be in the TcB high-risk zone after 72 hours when compared to breastfed infants (OR=0.51,95％CI:0.29-0.88).With the reduction of the high-risk zone level within 72 hours,the likelihood in the TcB high-risk zone after 72 hours was also decreased.ROC curve showed that the area under the curve (AUC) for predicting hyperbilirubinemia was 0.75 and its 95％CI was 0.72-0.78,with a sensitivity of 90.00％ and specificity of 40.00％.The AUC of a combination of predictive results obtained by the Logistic regression model with significant variables in univariate analysis and high-risk zone after 72 hours was 0.66,and its 95％CI was 0.62-0.69.AUC estimated by Logistic regression model according to the TcB levels of risk zones within 72 hours combining with clinical risk factors was 0.79,and its 95％CI was 0.76-0.82 (P＜0.01).Conclusions Hour-specific TcB nomograms of newborns in our hospital have been obtained,which facilitates the prediction and early intervention of neonatal hyperbilirubinemia.
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Objective To explore the influence of regular measurement of transcutaneous bilirubin (TcB) on clinical outcome of neonatal hyperbilirubinemia.Methods Healthy term and late-preterm newborns (gestational age ≥ 35 weeks) born between January 1 and December 31,2013 at Peking University Third Hospital were reviewed retrospectively.All neonates were divided into monitoring group (n=1 071)or control group (n=2 437) according to whether regular monitoring of TcB was performed.General clinical information and TcB levels on admission were recorded.The incidence of hyperbilirubinemia and readmission for hyperbilirubinemia,level of bilirubin and length of hospital stay were compared between the two groups.Chi-square test or independent sample t test were used for statistical analysis.Results (1) The incidence of hyperbilirubinemia and readmission rate for hyperbilirubinemia were lower in monitoring group when compared with control group [4.7％ (50/1 071) vs 7.1％ (172/2 437) and 1.3％ (14/1 071) vs 3.3％ (81/2 437) respectively,P＜0.05].There was no significant difference of bilirubin level and hospital stay between the two groups (P＞0.05).(2) Of all the 222 hyperbilirubinemia patients,the number of neonates with gestational age ＜37 weeks,37-38 weeks and ＞38 weeks was 26 (11.7％),33(14.9％) and 163(73.4％),respectively.There was no significant difference of gestational age,birth weight and gender proportion between the two groups.(3) The follow-up rate in January was 41.5％ (49/118),and the mean follow-up rate in February,April,July and October (with revised follow-up methods) was 83.1％ (345/415),higher than that in January (x2=82.505,P＜0.01).(4) The first three causes of hyperbilirubinemia in all 222 patients were early-onset breast milk jaundice (72 cases,32.4％),perinatal causes (60 cases,27.0％) and unknown reasons (50 cases,22.5％).The first three causes of hyperbilirubinemia in monitoring group (50 cases) were unknown reasons (24 cases,48.0％),early-onset breast milk jaundice (14 cases,28.0％) and hemolysis (9 cases,18.0％).Those in the control group (172 cases) were early-onset breast milk jaundice (58 cases,33.7％),perinatal causes (57 cases,33.1％) and unknown reasons (26 cases,15.1％).Conclusions Regular monitoring of TcB can reduce the incidence ofhyperbilirubinemia and the readmission for hyperbilirubinemia.
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Posterior al nacimiento el recién nacido cursa por un periodo de transición para ajustarse a los cambios fisiológicos que implican el estar fuera del vientre materno. Durante este periodo es común la aparición de complicaciones como la ictericia neonatal, padecimiento común a nivel mundial, que se define como la coloración amarilla de la piel resultado de los altos niveles circulantes de bilirrubina. Representa una de las principales causas de morbilidad, tanto en recién nacidos de término como en pretérmino. Su etiología se encuentra relacionada con distintos factores de riesgo maternos y/o neonatales y, aunque sus índices de mortalidad son bajos, el retraso en su diagnóstico y tratamiento conlleva severas complicaciones, como el kernicterus . Dentro de los factores de riesgo maternos la hiperbilirrubinemia por incompatibilidad sanguínea entre la madre y el recién nacido, como en el presente caso, requiere de la inmediata y oportuna atención del profesional de enfermería que labora dentro de los servicios de cuidados neonatales, con el objetivo de limitar el daño, favorecer la pronta recuperación, la reunión del binomio y la posterior integración del recién nacido a la dinámica familiar. El presente estudio de caso fue elaborado bajo el marco conceptual del modelo de adaptación de Roy, y a través del proceso enfermero, como herramienta metodológica para priorizar el cuidado. Aunque no fue posible documentar una disminución considerable en los niveles de bilirrubina, los resultados obtenidos se consideraron satisfactorios, ya que se logró mejorar el nivel de adaptación del recién nacido en el modo adaptativo fisiológico.
After being born, the baby goes through a period of transition of physiological changes and adjustments. During this period, the newly born can experience neonatal jaundice, an imbalance characterized by the yellow pigmentation of the skin as the result of the high levels of circulating bilirubin. This problem is one of the main causes of both on-term and pre-term neonatal mortality. There are different maternal and neonatal risk factors involved in the issue and, although its mortality rates are low, a delay in diagnosing and treating neonatal jaundice leads to severe complications such as kernicterus. A hyperbilirubinemia due to blood incompatibility between the mother and the baby, like in this particular case, requires immediate attention from the neonatal-care nursing professional in order to limit the damage, and to favor a prompt recovery, the reunion of the mother and her baby, and the integration of the baby into other family dynamics. This study was conducted within the conceptual frame of the Roy's Adaptation Model and through the nursing process. Although, a considerable decrease in the bilirubin level was not achieved, the obtained results were considered satisfactory since the level of physiological adaptation of the newborn improved significantly.
Posterior ao nascimento, o recém-nascido mantém um período de transição para se ajustar aos câmbios fisiológicos que implicam estar fora do ventre materno. Durante este período, é comum a aparição de complicações como a icterícia neonatal, padecimento comum a nível mundial, que se define como a coloração amarela da pele, resultado dos altos níveis circulantes de bilirrubina. Representa uma das principais causas de morbidade tanto em recém-nascidos de término e pré-término. A sua etiologia encontra-se relacionada a distintos fatores de risco maternos e/ou neonatais e, ainda que seus índices de morbidade seja baixos, o retraso no seu diagnóstico e tratamento envolve severas complicações, como o kernicterus. Dentro dos fatores de risco maternos, a hiperbilirrubina por incompatibilidade sanguínea entre a mãe e o recém-nascido, como no presente caso, requer da imediata e oportuna atenção do profissional de enfermagem que trabalha dentro dos serviços de cuidados neonatais, com o objetivo de limitar o dano, favorecendo a rápida recuperação, a reunião do binômio e a posterior integração do recém-nascido à dinâmica familiar. O presente estudo de caso foi elaborado sob o marco conceitual do Modelo de Adaptação de Roy e através do Processo Enfermeiro, como ferramenta metodológica para priorizar o cuidado. Ainda que não foi possível documentar uma diminuição considerável nos níveis de bilirrubina, os resultados obtidos consideraram-se satisfatórios, já que conseguiu melhorar o nível de adaptação do recém-nascido no modo adaptativo fisiológico.