Neonatal Serum Bilirubin Research Articles

EFFECTIVENESS OF TRANSCUTANEOUS BILIRUBIN (TCBR) MEASUREMENT IN HIGH RISK NEONATES AND TO EVALUATE THE VALIDITY OF TRANSCUTANEOUS BILIRUBIN (TCBR) WITH TOTAL SERUM BILIRUBIN (TSBR) LEVELS IN BOTH LOW AND HIGH RISK NEONATES AT A TERTIARY CARE CENTER OF....

Objective: To evaluate the utility of a Transcutaneous Bilirubin nomogram in high risk neonates and to evaluate the validity of Transcutaneous Bilirubin and Total serum bilirubin in both low and high-risk neonates.
 Study Design: Cross-sectional study.
 Place and Duration of Study: Postnatal Ward, Aga Khan University Hospital, Karachi, from May to Oct 2019.
 Methodology: The participants will include all neonates born and admitted in the well baby nursery withjaundice. All neonates with gestational age of <35 weeks, requiring admission in Neonatal intensive care unit, and neonates with conjugated hyperbilirubinemia will be excluded. We will stratify our neonates into high and low risk population based on predefined criteria. Eighty five neonates in low risk group and 122 neonates in high risk group will be included.
 Results: We aim to assess the effectiveness of Transcutaneous Bilirubin nomogram in high risk neonates asan effective and non-invasive tool in the management of neonatal jaundice in high risk neonates. We will alsoassess the sensitivity and specificity of Transcutaneous Bilirubin and Total serum bilirubin measurementsand the analysis would be performed separately for high risk and low risk neonates to evaluate the validity ofTranscutaneous Bilirubin independently in both groups.
 Conclusion: We hope to establish a validated phototherapy guideline based on the Transcutaneous Bilirubinnomogram, as a cost effective and noninvasive tool in the management of neonatal jaundice in both high and low risk groups in Pakistan.

Serum 25-Hydroxyvitamin-D Level in Full-term Neonates with Indirect Hyperbilirubinemia at a Level Requiring Phototherapy

Background: Low antioxidant system may contribute to the severity of neonatal hyperbilirubinemia. Aim of the work: This study was performed to clarify the relationship between serum 25-hydroxyvitamin-D (25[OH] D) and the hyperbilirubinemia in full-term neonates. Methods: This is a cross sectional case control study performed with the aim of determining whether there is an association between serum indirect bilirubin and serum vitamin D levels in newborns with jaundice at a level necessitating phototherapy. The study was carried on 60 full term newborns admitted to the Neonatal Intensive Care Unit of Minia University Hospital, from April 2017 to December 2017. They were classified into 2 groups, Group I: (cases): Newborns with postnatal ages of 3-10 days and gestational ages of 37-40 weeks, with a bilirubin level above the pre-set threshold for phototherapy as recommended by the American Academy of Pediatrics (AAP). Group II :( controls) 30 matched apparently normal healthy newborns were enrolled in the study as a control group. The study included the mothers of case group. All laboratory investigations were done in clinical pathology department, Minia University hospital. Results: Serum Vitamin D levels were significantly lower in patients than controls (p < 0.01). There was a strong negative correlation between neonatal total serum bilirubin level and neonatal serum vitamin D in cases group. In addition, we observed that there was a highly statistically significant positive correlation between serum vitamin D level of neonates and their maternal serum level was present. Conclusions: Indirect hyperbilirubinemia in full-term neonates is associated with decreased serum levels of (25[OH] D)

Covered Skin Bilirubin Measurement during Phototherapy, in Comparison with Total Serum Bilirubin in Full Term Neonates

Background Jaundice is a prevalent problem among neonates. Patients undergoing phototherapy need a close follow-up of their serum bilirubin levels to determine the treatment response. To make a comparison between transcutaneous bilirubin measurements (TcB) from covered skin areas during phototherapy and total serum bilirubin (TSB) levels.Methods This prospective observational study was conducted on 30 full-term neonates with indirect hyperbilirubinemia requiring phototherapy. Some parts of the skin (forehead and sternum) were covered in each neonate using the BiliEclipsephoto opaque patch and this covered site was used to measure TcB during phototherapy and compare it with TSB. Both TSB and TcB estimation were performed on icteric newborns before, as well as 24 and 48 h of exposure to phototherapy.Results As demonstrated by the obtained results, TSB was not significantly different from TcB measured at forehead and sternum before phototherapy. Moreover, no significant difference was detected between TSB and TcB from the covered forehead and sternum in 24 and 48 h of phototherapy initiation. There was a highly significant positive correlation between TSB and covered forehead/sternum TcB during phototherapy. There was no significant difference in both covered forehead and sternum TcB according to different used TcB devices.Conclusion Measurement of TcB from the covered area of the skin during phototherapy using transcutaneous bilirubin meters is a reliable method to assess TSB in full-term neonates and could lead to a reduction in blood sampling and its complications.

Challenges of phototherapy for neonatal hyperbilirubinemia (Review).

Phototherapy is universally recognized as the first option for treating neonatal jaundice due to its unparalleled efficiency and safety in reducing the high serum free bilirubin levels and limiting its neurotoxic effects. However, several studies have suggested that phototherapy may elicit a series of short- and long-term adverse reactions associated with pediatric diseases, including hemolysis, allergic diseases, DNA damage or even cancer. The aim of the present review was to summarize the etiology, mechanism, associated risks and therapeutic strategies for reducing high neonatal serum bilirubin levels. In order to shed light on the negative effects of phototherapy and to encourage implementation of a reasonable and standardized phototherapy scheme in the clinic, the present review sought to highlight the current understanding of the adverse reactions of phototherapy, as it is necessary to further study the mechanism underlying the development of the adverse effects of phototherapy in infants in order to explore novel therapeutic alternatives.

Characteristics of Hyperbilirubinemic Neonates in Need of Exchange Transfusion and Their Mothers

Background: Severe hyperbilirubinemia is potentially neurotoxic and can lead to long-term complications inneonates. Exchange transfusion (ECT) is one of the most important treatments for hyperbilirubinemia. In thisregard, the present study aimed to determine the characteristics of hyperbilirubinemic neonates who need ECT andtheir mothers.Methods: This cross-sectional study was performed on 380 infants born after 35 weeks of gestation who were 2-14days old. The studied neonates had bilirubin levels higher than 17 mg/dl and underwent ECT in Ghaem Hospital inMashhad, Iran during 2010-20. Moreover, it should be noted that the participants were selected using the conveniencesampling method and the required data were collected using a checklist. This checklist was designed based on theneonatal examination, maternal (maternal age, parity), and neonatal status (age, gender, and weight) and seriallaboratory tests before and after ECT (total bilirubin, hematocrit, and platelet). Finally, these variables were comparedbased on the cause of hyperbilirubinemia.Results: The mean levels of serum bilirubin were 28.5 mg/dl and 26.5 mg/dl in male and female infants (P=0.096),respectively. Furthermore, the mean levels of serum bilirubin in neonates born by cesarean section and normal vaginaldelivery were 29.5 and 28.1 mg/dl, respectively (P=0.458). Based on the findings, 60% of the neonates suffered fromweight loss and 22% had more than 3% daily weight loss. In the present study, the most prevalent risk factors amongthe studied neonates were RH incompatibility, ABO incompatibility, and G6PD deficiency, in that order.Conclusion: Overall, these findings suggest that normal vaginal delivery, repeated breastfeeding, prevention ofsevere weight loss, early detection of RH and ABO incompatibility, and G6PD deficiency, as well as appropriatemanagement of hyperbilirubinemia, can reduce the need for ECT and alleviate complications of neonatalhyperbilirubinemia.

Neonatal Hyperbilirubinemia treatment by Locally Made Low-Cost Phototherapy Units.

Hyperbilirubinemia is a very common finding in neonates and may occasionally cause severe morbidity and even mortality. Severe hyperbilirubinemia is typically treated, either with phototherapy or exchange transfusions. This study assessed the effectiveness of a locally manufactured phototherapy device for reducing serum bilirubin in neonates with severe hyperbilirubinemia. Retrospective chart review was carried out to assess the outcome of 32 infants who were treated for neonatal hyperbilirubinemia at Jimma Medical Center (JMC) from May, 2017 to April, 2018. RESULTS: Out of 75 charts reviewed, only 32 had subsequent bilirubin level determination, 18(56.3%) of them were males. The age at which jaundice was noticed and confirmed with plasma bilirubin level was 4 ± 2.7 days (mean±SD). Sepsis was thought to be the cause of hyperbilirubinemia in 13(40.5%) of the cases, while hemolysis from ABO incompatibility or RH incompatibility contributed in 5(15.6%) and 3(9.4) of the infants respectively. The mean (minimum, maximum) level of baseline TSB was 21.4(14, 55) mg/dL. Five infants (15.6%) had exchange transfusions because of extreme hyperbilirubinemia. The duration of phototherapy and decline in TSB were 5.34 ±2.8 days and 2.2±1.5mg/dl/day (mean±SD) respectively. The levels of TSB before and at the end of phototherapy were significantly different (p<0.001). Acceptable reduction of TSB was achieved by using locally manufactured PT devices. Benefits included better accessibility and lower price and maintenance costs. High mean baseline TSB was observed, and duration of phototherapy is prolonged which could indicate late diagnosis compared to similar studies.

Relationship between Transcutaneous and Serum Bilirubin in Preterm and Term Neonates before and during Phototherapy

Background Neonatal jaundice is a common condition. Total serum bilirubin (TSB) measuring is standard for bilirubin testing, while transcutaneous bilirubin (TcB) is an alternative method. We aimed to evaluate the correlation between TSB and TcB in term and preterm neonates. Materials and Methods This prospective cross-sectional study was conducted to on 93 term and preterm neonates in Fatemieh Hospital in 2018, Hamadan, Iran. The samples were categorized into two groups, including term and preterm icteric neonates. Neonates were evaluated to determine the necessity of bilirubin estimation with TSB measurement. After the confirmation of jaundice, the blood samples obtained were sent to the laboratory for bilirubin estimation, and at the same time, the TcB measurement was performed by the bilirubinometer. Selectra X-L was utilized by which the blood samples were analyzed through the dichloroanilin method. The Pearson correlation coefficient was used to evaluate the relationship and stringency of the correlation between the approaches. Results In general,61% and 38% of neonates were boys and girls, respectively. Before phototherapy, the TSB values were lower than TcB estimations in term and preterm neonates. The estimated Pearson correlation coefficients were obtained at r=0.729 (p <0.001), and r=0.802 (p <0.001) in term and preterm neonates, respectively. After phototherapy, contrary to the obtained results before phototherapy, the TSB concentration was higher than TcB concentrations. The difference between the measured values of the two approaches was more significant in term neonates. The Pearson correlation coefficient estimations were r=0.804 (p <0.001), and r=0.901 (p <0.001) in term and preterm neonates, respectively. Conclusion Based on the results, there was a significant correlation between the values of TSB and TcB in term and preterm neonates.

Cotoneaster manna oral drop for the management of neonatal hyperbilirubinemia; a randomized, double-blinded and placebo controlled clinical trial

Introduction: Neonatal hyperbilirubinemia is a common physiologic condition, which is occurred in early days after birth with an estimated incidence of about 50% in term neonates. Objectives: The aim of this study was to evaluate the effect of Cotoneaster nummularioides manna on reducing neonatal total serum bilirubin (TSB) levels, and shortening hospitalization period. Patients and Methods: One hundred breast-fed term neonates with hyperbilirubinemia were randomly assigned to the intervention group or control group. The Newborns of the intervention group were received Cotoneaster manna drop in the dosage of 1 g/d divided into three doses every 8 hours for at least 3 days and the control group received placebo drops. Total serum bilirubin levels were measured at baseline, at 12, 24 hours and then daily through hospitalization days (day 9). Secondary outcome (discharge from hospital, TSB &lt;10 mg/dL) was also documented with risk ratio calculation. Results: TSB levels were declined in both groups; however, this was more prominent in the manna group than the placebo group. The greatest difference of mean TSB levels between the intervention and control groups was seen on days two (10.01 versus 13.04 mg/dL; mean difference [95% CI]: - 3.03 [-3.60 to -2.46]; P&lt;0.001). On day four, significantly more newborns in the intervention group versus the control group were discharged (70% versus 6.1%; risk ratio = 11.43, 95% CI= 3.76, 34.74). No major side effects were recorded in both groups. Conclusion:Cotoneaster nummularioides manna drop combined with phototherapy was superior to the control group in reducing TSB levels and reaching this observation more rapidly and shortening hospitalization period with no major side effects. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical trials (identifier: IRCT20160531028188N4; https://en.irct.ir/trial/27765, ethical code #IR.MAZUMS.REC.1394.1316).

The accuracy of transcutaneous bilirubin to identify hyperbilirubinemia in jaundiced neonates

Objective To compare transcutaneous bilirubin (TcB) to total serum bilirubin (TSB) in jaundiced neonates by using a JM-103 bilirubinometer. Methods We conducted a retrospective study in jaundiced infants ≥35 weeks’ gestation. Infants’ and maternal information, TcB measurements, and TSB levels were collected. The correlation and consistency between TcB and TSB were analyzed by Pearson’s correlation analysis and the Bland–Altman plot. Multivariate regression analysis was used to identify characteristics associated with the difference between TcB and TSB, underestimation by TcB and overestimation by TcB. Results A total of 787 paired samples were collected. There was a strong correlation between TcB and TSB with a Pearson correlation coefficient of 0.708 (p < .001). In preterm infants, outpatients and infants with high TSB levels, the TcB measurements were less precise. The TcB–TSB difference was significantly associated with gender, maternal hypertension disease, ABO hemolytic disease, and outpatient setting (p < .05). Only the outpatient setting had statistical significance in the underestimation of TSB ≥2 mg/dL. Conclusions Generally, TcB by a JM-103 bilirubinometer had a good correlation and consistency with the TSB values. However, small for gestational age, postnatal age of hour, ABO hemolytic disease, and outpatient setting may lead to inconsistencies between the TcB and TSB.

The impact of COVID-19 on routine patient care from a laboratory perspective.

Globally, few studies have examined the effect of the COVID-19 pandemic on routine patient care and follow-up. To evaluate the effect of the COVID-19 response on biochemical test requests received from outpatient departments (OPDs) and peripheral clinics serviced by the National Health Laboratory Service Chemical Pathology Laboratory at Tygerberg Hospital, Cape Town, South Africa (SA). Request volumes were used as a measure of the routine care of patients, as clinical information was not readily available. A retrospective audit was conducted. The numbers of requests received from OPDs and peripheral clinics for creatinine, glycated haemoglobin (HbA1c), lipid profiles, thyroid-stimulating hormone (TSH), free thyroxine, free tri-iodothyronine (fT3), serum and urine protein electrophoresis, serum free light chains and neonatal total serum bilirubin were obtained from 1 March to 30 June for 2017, 2018, 2019 and 2020. The biggest impact was seen on lipids, creatinine, HbA1c, TSH and fT3. The percentage reduction between 1 March and 30 June 2019 and between 1 March and 30 June 2020 was 59% for lipids, 64% for creatinine and HbA1c, 80% for TSH and 81% for fT3. There was a noteworthy decrease in overall analyte testing from March to April 2020, coinciding with initiation of level 5 lockdown. Although an increase in testing was observed during June 2020, the number of requests was still lower than in June 2019. This study, focusing on the short-term consequences of the SA response to the COVID-19 pandemic, found that routine follow-up of patients with communicable and non-communicable diseases was affected. Future studies are necessary to evaluate the long-term consequences of the pandemic for these patient groups.

Predictive Models for Neonatal Follow-Up Serum Bilirubin: Model Development and Validation.

BackgroundHyperbilirubinemia affects many newborn infants and, if not treated appropriately, can lead to irreversible brain injury.ObjectiveThis study aims to develop predictive models of follow-up total serum bilirubin measurement and to compare their accuracy with that of clinician predictions.MethodsSubjects were patients born between June 2015 and June 2019 at 4 hospitals in Massachusetts. The prediction target was a follow-up total serum bilirubin measurement obtained <72 hours after a previous measurement. Birth before versus after February 2019 was used to generate a training set (27,428 target measurements) and a held-out test set (3320 measurements), respectively. Multiple supervised learning models were trained. To further assess model performance, predictions on the held-out test set were also compared with corresponding predictions from clinicians.ResultsThe best predictive accuracy on the held-out test set was obtained with the multilayer perceptron (ie, neural network, mean absolute error [MAE] 1.05 mg/dL) and Xgboost (MAE 1.04 mg/dL) models. A limited number of predictors were sufficient for constructing models with the best performance and avoiding overfitting: current bilirubin measurement, last rate of rise, proportion of time under phototherapy, time to next measurement, gestational age at birth, current age, and fractional weight change from birth. Clinicians made a total of 210 prospective predictions. The neural network model accuracy on this subset of predictions had an MAE of 1.06 mg/dL compared with clinician predictions with an MAE of 1.38 mg/dL (P<.0001). In babies born at 35 weeks of gestation or later, this approach was also applied to predict the binary outcome of subsequently exceeding consensus guidelines for phototherapy initiation and achieved an area under the receiver operator characteristic curve of 0.94 (95% CI 0.91 to 0.97).ConclusionsThis study developed predictive models for neonatal follow-up total serum bilirubin measurements that outperform clinicians. This may be the first report of models that predict specific bilirubin values, are not limited to near-term patients without risk factors, and take into account the effect of phototherapy.

Vitamin D Levels in Full-Term Neonates with Indirect Hyperbilirubinemia

Background: Jaundice is a common clinical sign in neonatal medicine. Considering the different roles of vitamin D, its lower level may be correlated with neonatal jaundice. Objectives: This study aimed to demonstrate the relationship between serum vitamin D level and neonatal hyperbilirubinemia and to measure its level in their mothers. Subjects and methods: This case-control study was conducted on 90 neonates and their mothers, 60 neonates with hyperbilirubinemia in patients group and 30 healthy neonates age and sex matched in control group . Blood samples from neonates and their mothers were obtained and sent for laboratory estimation of 25-hydroxy vitamin D, calcium, magnesium, phosphorus, alkaline phosphatase and parathyroid hormone. Results: There is highly significant decrease of vitamin D levels among patients than controls, significant negative correlation between vitamin D levels and serum bilirubin in neonates and no significant difference regarding different laboratory parameters among their mothers. Conclusion: Decreased levels of vitamin D were significantly correlated with neonatal indirect hyperbilirubinemia so, low vitamin D can be included among risk factors for neonatal jaundice.

The Effect of Intensive Phototherapy Treatment on CD4 and CD8 T-Lymphocyte subsets in Neonatal Jaundice

Introduction: Jaundice is the most common condition that requires medical attention and hospital readmission in neonates. Serum bilirubin levels may rise excessively, which can be cause lifelong neurologic sequelae (kernicterus). Objectives: To investigate the effect of intensive phototherapy on the expression of CD4 and CD8 lymphocyte subsets in neonates with indirect hyperbilirubinemia. Patients and Methods: This is a prospective study included 30 full term neonates admitted to neonatal intensive care unit, Minia university hospital and 20 full term healthy neonates during the period from October 2016 to October 2017. Results: There were no significant differences regarding CD4%, CD8% and CD4/CD8 ratios in neonates with indirect hyperbilirubinemia either before or after phototherapy. After phototherapy there were no significant differences between cases and controls as regarding CD4% and CD4/CD8 ratio while there was a significant decrease in CD% in cases compared to controls (p value 0.03). A significant positive correlation between CD4% and age (r- value 0.39, p-value 0.02) was present in cases. Conclusions: The results demonstrated that in addition to the well-known positive effect of phototherapy on neonatal serum bilirubin level, this treatment have no effect on the function of the immune system in neonates as regards CD4 and CD8 subsets as well as CD4/CD8 ratio .

Neurodevelopmental outcome at 6 months of age in full-term healthy newborns with neonatal hyperbilirubinemia

Background: Neonatal hyperbilirubinemia (NNH) is an important cause of preventable brain damage among infants. Neurodevelopmental assessment and Brainstem-Evoked Response Audiometry (BERA) may help in the early identification and management of neurodevelopmental sequelae. Objectives: The objectives of this study were to find the association between neonatal peak serum bilirubin levels and the neurodevelopmental outcomes at 6 months in term infants with NNH and to assess the changes in BERA of these neonates. Methodology: A prospective cohort study was conducted in the Department of Pediatrics, Gandhi Medical College, Bhopal. All healthy, full-term, appropriate-for-date neonates, admitted from December 2014 to June 2015 with hyperbilirubinemia and serum bilirubin >12 mg/dL, were included in the study and were followed up till 6 months of age. The neurodevelopmental assessment was done using the Denver Developmental Screening Test II and BERA was done at an average age of 69 ± 6 days. Results: A total of 77 newborns were enrolled, and 73 completed the study. Of these 77 neonates, 40 (51.65%) had abnormal BERA results, whereas 3 (3.9%) had neurodevelopmental abnormalities. BERA and neurodevelopmental abnormalities were associated with a mean serum bilirubin of 22.58 mg/dL and 31.33 mg/dL, respectively. The cutoff value of serum bilirubin was 16.3 mg/dL and 23.8 mg/dL, respectively, to detect BERA and neurodevelopmental abnormalities, respectively. All patients (11) who received exchange transfusion had BERA abnormalities, and 3/11 (27.3%) had neurodevelopmental abnormalities. The association of ABO incompatibility was significant (P

The Role of Oral Phenobarbital Therapy in the Management of Neonates with Prolonged Unconjugated Hyperbilirubinemia

Background: Prolonged jaundice is a type of neonatal jaundice, which occurs in infants with high bilirubin levels (&gt;10 mg/dl) persisting beyond day 14 of life in term neonates, and beyond day 21 in preterm neonates. Prolonged jaundice may be caused by predominantly conjugated or unconjugated hyperbilirubinemia. Distinguishing between these types of jaundice helps to determine the risk for pathological causes of prolonged jaundice.&#x0D; Phenobarbital has been used to treat neonatal jaundice since the 1960s. Numerous clinical trials have shown that both administration of phenobarbital to pregnant mothers before delivery and phenobarbital administration to neonates after delivery limit the severity of unconjugated hyperbilirubinemia, reduce the peak serum total bilirubin concentrations caused by physiologic jaundice by 50%, and the need for exchange transfusion.&#x0D; Objective: The aim of this study was to evaluate the role of phenobarbital in reducing the total serum bilirubin(TSB) in neonates with prolonged unconjugated hyperbilirubinemia. &#x0D; Methods: This is a prospective clinical trial study that was performed in Karbala teaching hospital for children from 18th of December 2017 to the end of December 2018. A total of 101 neonate with prolonged unconjugated hyperbilirubinemia were included in this study. All neonates who included in this study received phenobarbital tablet (5 mg /kg/day) twice a day for 10 days and some of them need phototherapy according to American Academy Of Pediatrics Guidelines for phototherapy,&#x0D; Results: There was a highly statistically significant decrease in TSB for the patients who were treated with phenobarbital compared to the baseline level, mean baseline TSB 14.57± 2.31 mg/dl versus TSB after phenobarbital 6.79±1.62 mg/dl (P value &lt;0.001). There was a highly statistically significant decrease in TSB for the patients who were treated with phototherapy in addition to phenobarbital compared to the baseline level, mean baseline TSB 19.94±1.36 mg/dl versus TSB after phototherapy and phenobarbital 6.33±1.37 mg/dl (P value &lt;0.001).&#x0D; Conclusions: &#x0D; &#x0D; Oral phenobarbital supplementation in the neonates with prolonged unconjugated hyperbilirubinemia can significantly accelerate reduction in serum bilirubin levels.&#x0D; Phenobarbital was safe, tolerable and no obvious adverse effects had been reported.&#x0D; No need for cessation of breast feeding in cases of presumed breast milk jaundice.&#x0D;

Associations between Neonatal Serum Bilirubin and Childhood Obesity in Term Infants

Inverse correlations between serum bilirubin level and obesity had been reported in adults. We aimed to investigate the associations between neonatal hyperbilirubinemia and childhood obesity. Data was obtained from the U.S. Collaborative Perinatal Project (CPP), a multicenter study from 1959 to 1976. Data of serum bilirubin in term newborns were used to observe the association with obesity at age of 7 years. Logistic regression models were performed to calculate adjusted odds ratios (aORs) for obesity. For children from the same mother sharing similar factors, Generalized Estimating Equation (GEE) model was used to correct for intracluster correlation. Relative to newborns with total serum bilirubin (TSB) < 3 mg/dl, there are lower risks for obesity in those with 3 mg/dl ≤ TSB < 6 mg/dl (aOR 0.91; 95%CI 0.81, 1.02), 6 mg/dl ≤ TSB < 9 mg/dl (aOR 0.88; 95%CI 0.78, 0.99), 9 mg/dl ≤ TSB<13 mg/dl (aOR 0.83; 95%CI 0.71, 0.98). By stratifying for subtypes of bilirubin, the inverse correlations only existed in exposure to unconjugated bilirubin. By using the GEE model correcting for intracluster correlations, the results are consistent. In summary, exposure to bilirubin up to 13 mg/dl is inversely associated with obesity at the age of 7 years in term infants.

A Neglected and Promising Predictor of Severe Hyperbilirubinemia Due to Hemolysis: Carboxyhemoglobin

Aims: We investigated the relationship between total serum bilirubin (TSB) and carboxyhemoglobin (COHb) in term neonates with detected and treated hemolysis within a particular time frame with the aim of augmenting the case for early diagnosis and prevention of morbidity in hemolysis. Materials and Methods: The study group comprised term newborns who were above the 95th percentile for TSB, underwent intravenous immunoglobulin (IVIG) or applied total exchange transfusion due to hemolysis. Newborns without hemolysis who were above the 95th TSB percentile and required phototherapy comprised the control group. Results: At a cutoff COHb value of 2.2%, 80.8% sensitivity, 95.5% specificity, 18.1 likelihood ratio, positive predictive value of 94.7%, and negative predictive value of 83.2% were identified. Conclusion: We found that COHb is a sensitive and specific method for detecting hemolysis, and it can be used in the early diagnosis of hemolytic diseases causing early and severe hyperbilirubinemia.

Associations between neonatal serum bilirubin and childhood hypertension.

Mild hyperbilirubinemia is inversely associated with cardiometabolic diseases in adults. The aim of this study was to evaluate the association between neonatal serum bilirubin levels and childhood hypertension. Data were obtained from the U.S. Collaborative Perinatal Project conducted at 12 U.S. medical centers from 1959 to 1965. This multicenter study recruited participants before phototherapy was routinely used, thereby excluding the influence of phototherapy. In 37,544 newborns (31,819 term and 5,725 preterm births), a generalized linear model and a logistic regression model were used to calculate the linear coefficients and adjusted odds ratios (ORs) of blood pressure and hypertension at 7 years of age based on neonatal serum bilirubin levels. No significant correlation was observed between serum bilirubin at 48 hours after birth and blood pressure at the age of 7 years in the whole study population and in the subgroup of term infants. In preterm infants, a lower total serum bilirubin and unconjugated bilirubin of 3 mg/dl were associated with a higher systolic blood pressure of 62 mmHg (0.38–0.86, p <0.001) and 0.70 mmHg (0.10–1.30, p <0.05) respectively. Relative to a total serum bilirubin level <3 mg/dl among preterm infants, total serum bilirubin levels of 3–6 mg/dl (adjusted OR 1.36; 95% CI: 0.98–1.89), 6–9 mg/dl (adjusted OR 1.35; 95% CI: 0.98–1.85), 9–12 mg/dl (adjusted OR 1.55; 95% CI: 1.10–2.19), and ≥12 mg/dl (adjusted OR 1.42; 95% CI: 1.01–2.00) were associated with higher risks of hypertension. After stratifying for the subtypes of bilirubin, the associations only existed for unconjugated bilirubin. In addition, consistent findings existed when using maximum neonatal serum bilirubin as an exposure factor. Neonatal serum bilirubin levels are positively associated with childhood blood pressure/hypertension in preterm infants. Our findings may shed some light on the role of bilirubin in the prevention of hypertension.

Evaluation of Rh-Hemolytic Disease in Neonates and Management with Early Intensive Phototherapy in the Neonatal Intensive Care Unit.

In neonates with Rh-hemolytic disease, light emitting diode (LED) phototherapy allows delivery of high spectral irradiance (SI). A linear correlation exists between SI and efficacy of phototherapy with no saturation point. There is scant data on evaluation and early phototherapy using LED units in Rh-hemolytic disease. This study aimed to describe the hemoglobin (Hb), hematocrit (Hct), total serum bilirubin (TSB), phototherapy parameters and short-term outcomes in neonates with Rh-hemolytic disease. Maternal parameters for Rh-isoimmunization were recorded and monitoring of fetal anemia by Doppler ultrasound was done. Early intensive phototherapy within 1 h of birth was initiated for cord blood Hb below 13.6 g/dl and/or TSB greater than 2.8 mg/dl. Fifty Rh positive neonates were enrolled of which 11/50 (22%) received intrauterine transfusions. The maximum TSB remained below 18 mg/dl in 42/50 (84%) of neonates. The mean SI on the trunk was 56.260 ± 8.768 µW/cm2/nm and duration of phototherapy was 7 ± 3.29 days (mean ± SD). There was a positive correlation between strength of indirect antiglobulin test and cord blood Hb: correlation coefficient (r) = 0.295; direct antiglobulin test and duration of phototherapy: r = 0.331. Early packed red blood cell (PRBC) transfusion was required in 8/50 (16%) neonates while 20/50 (40%) required late transfusions. With a mean SI of 56.260 ± 8.768 µW/cm2/nm on the trunk, TSB remained below 18 mg/dl in majority thereby avoiding exchange transfusion. Early or late PRBC transfusion requirement was 1 (1-2) (median ± interquartile range).

Association between neonatal serum bilirubin and childhood obesity in preterm infants.

Serum bilirubin levels are inversely associated with obesity in adults. We are interested in whether neonatal jaundice is associated with childhood obesity in preterm infants. Data were obtained from the US Collaborative Perinatal Project. Neonatal bilirubin levels were used as exposure factors for obesity at age 7 years. Logistic regression models were used to control for potential confounders and calculate odds ratios (ORs). A generalized estimating equation (GEE) model was used to correct for intracluster correlation coefficient. SAS was used for all statistical analyses. In the study subjects, 865 of 5019 preterm infants were obese at age 7 years. While neonatal total serum bilirubin (TSB) rose 1 mg/dl, body mass index (BMI) increased 0.03 kg/m2 (95% confidence interval (CI) 0.02, 0.04). Compared with infants with TSB <3 mg/dl, the ORs (95% CIs) for obesity in infants with 3 mg/dl≤ TSB <6 mg/dl, 6 mg/dl≤ TSB <9 mg/dl, 9 mg/dl≤ TSB <12 mg/dl and TSB ≥12 mg/dl were, respectively, 1.18 (0.87, 1.59), 1.25 (0.93, 1.67), 1.52 (1.11, 2.09), and 1.67 (1.22, 2.07). By using subtypes of bilirubin as exposure factors and the GEE model to correct for intracluster correlation coefficient, similar trends of associations were observed. Neonatal bilirubin levels have positive trends of associations with childhood obesity in preterm infants.