Transcutaneous Bilirubin Levels and Risk of Significant Hyperbilirubinemia in Early-Term and Term Newborns.

OBJECTIVE: To compare the course of the transcutaneous bilirubin (TcB) values of early-term newborns with those of term newborns in the first month of life and to investigate whether early-term newborns have an increased risk of significant hyperbilirubinemia requiring treatment. DESIGN: A prospective, controlled cohort analysis. SETTING: A tertiary level mother-child birth and health care center. PARTICIPANTS: Four hundred early-term (37 0/7 to 38 6/7 weeks) and 320 term (39 0/7 to 41 6/7 weeks) newborns born during a 27-month period. METHODS: A total of six TcB measurements in a longitudinal manner were made in early-term and term newborns: the first two at 6 and 48 hours after birth and the next four on routine examination days (Days 4, 7, 15, and 30). Demographic characteristics, values of daily TcB measurements, number of newborns with significant hyperbilirubinemia, and risk of jaundice requiring treatment were compared between the two groups. RESULTS: All six TcB values were significantly greater in the early-term group than in the term group (p < .001 for each). Early-term newborns had a statistically significant increased risk of jaundice requiring treatment compared to term newborns (risk ratio = 1.91; 95% confidence interval [1.23-2.96]; p = .0046). Results of the repeated-measures analysis of variance and post hoc adjusted multiple comparison analysis showed that TcB levels increased to and peaked at 96 hours after birth and then gradually decreased to baseline (first measurement) levels at 30 days after birth in each group. CONCLUSIONS: Early-term newborns should not be treated as full-term newborns because they have significantly higher TcB levels. These newborns should be closely monitored for pathologic jaundice because they have increased risk for significant hyperbilirubinemia requiring phototherapy.

Investigation of the relationship between cord clamping time and risk of hyperbilirubinemia.

BACKGROUND: Although the relationship between umbilical cord clamping time and various parameters such as hemoglobin (Hb) levels, iron deficiency, and risk of neonatal jaundice has previously been studied, to the best of our knowleadge there have been no studies investigating the relationship between cord clamping time and the risk of significant hyperbilirubinemia. We aimed to investigate the relationship between the time of umbilical cord clamping and transcutaneous bilirubin (TcB) measurements made on various postnatal hours, Hb and serum total bilirubin (STB) levels measured on postnatal 4th day, and the risk of development of significant hyperbilirubinemia requiring phototherapy treatment. METHODS: Eligible newborns were divided into two groups on the basis of the time of cord clamping: those clamped late (60 seconds or more; Group I) and those clamped early (less than 60 seconds; Group II). Groups were compared with respect to the parameters of cord Hb, postnatal TcB measurements at 6th, 48th, 96th and 168th hours, and 96th hour Hb, STB and direct bilirubin levels. RESULTS: TcB levels at the 96th and 168th hour were significantly higher in Group I when compared to Group II (p < 0.001 and p < 0.001, respectively). The 96th hour STB level was significantly higher in Group I when compared to Group II (p < 0.001). The need of phototherapy requirement was higher in Group I when compared to Group II (p=0.001). Increase in cord blood Hb for each 1 gr/dl caused a 3.94-fold increased risk in the requirement of phototherapy treatment. Cord clamping time showed statistically significant positive correlations with both cord blood and 96th hour venous Hb levels, with both 96th hour and 168th hour TcB levels, and with 96th hour STB levels. CONCLUSIONS: Newborns whose cords are clamped late should be followed up closely with respect to high postnatal bilirubin levels and other risks associated with significant hyperbilirubinemia requiring phototherapy treatment.

Association Between Early Idiopathic Neonatal Jaundice and Urinary Tract Infections.

BACKGROUND AND PURPOSE: Etiologic role, incidence, demographic, and response-to-treatment characteristics of urinary tract infection (UTI) among neonates, its relationship with significant neonatal hyperbilirubinemia, and abnormalities of the urinary system were studied in a prospective investigation in early (⩽10 days) idiopathic neonatal jaundice in which all other etiologic factors of neonatal hyperbilirubinemia were ruled out. PATIENTS AND METHODS: Urine samples for microscopic and bacteriologic examination were obtained with bladder catheterization from 155 newborns with early neonatal jaundice. Newborns with a negative urine culture and with a positive urine culture were defined as group I and group II, respectively, and the 2 groups were compared with each other. RESULTS: The incidence of UTI in whole of the study group was 16.7%. Serum total and direct bilirubin levels were statistically significantly higher in group II when compared with group I (P = .005 and P = .001, respectively). Decrease in serum total bilirubin level at the 24th hour of phototherapy was statistically significantly higher in group I compared with group II (P = .022). CONCLUSIONS: Urinary tract infection should be investigated in the etiologic evaluation of newborns with significant hyperbilirubinemia. The possibility of UTI should be considered in jaundiced newborns who do not respond to phototherapy well or have a prolonged duration of phototherapy treatment.

Associations between erythrocyte membrane fatty acid compositions and insulin resistance in obese adolescents.

BACKGROUND/OBJECTIVE: Cytokines released from the adipose tissue and fatty acids (FAs) derived from lipolysis or uptake of fats go in to competition with glucose to be uptaken from the liver leads to insulin resistance (IR). We aimed to show the associations among serum lipid profile, FA compositions and IR. METHODS: Anthropometrical measurements, biochemical parameters and erythrocyte membrane (EM) FA levels of 95 obese adolescents (41 with IR) and 40 healthy controls were compared. RESULTS: LDL-C, fasting insulin levels, HOMA-IR were significantly higher and HDL-C levels were significantly lower in obese patients than in controls (p=0.013, p<0.001, p<0.001 and p<0.001, respectively). EM C 24:0, C 16:1 ω7 and C 22:1 ω9 FA levels were significantly higher, while C 20:5 ω3 (EPA) levels were significantly lower in obese subjects than in controls (p<0.001, p=0.018, p<0.001, p=0.043 and p<0.001, respectively). Moreover, when obese subjects divided into two groups according to the presence of IR; EM C 16:1 ω7 levels were still significantly higher and EPA levels were still significantly lower in both obese subjects with and without IR compared to controls (p<0.001 for both). CONCLUSION: Saturated FA intake should be decreased because of its role in the development of obesity and IR, and ω-3 group FA intake should be increased.

Effects of hyperbaric oxygen and dexamethasone on proinflammatory cytokines of rat cochlea in noise-induced hearing loss.

HYPOTHESIS: To investigate effects of dexamethasone and hyperbaric oxygen therapy (HBOT) on proinflammatory cytokines and hearing levels in the noise-exposed cochlea of rats. BACKGROUND: There is an arising concern about negative effects of early initiation of HBOT on hearing in noise-induced hearing loss. Furthermore, effects of HBOT and dexamethasone on cochlear cytokines are not fully elucidated. METHODS: Twenty-six rats were divided into 3 groups: control, noise, and treatment groups. Five rats served as control group. White noise at 115 dB sound pressure level was applied to the noise group of 4 rats for 10 days. This group was assigned to a positive control group as it was equivalent to treatment groups. The treatment group of 17 rats underwent the same noise exposure, and then, they were divided into 3 groups based on treatment protocol: 5 and 6 rats received HBOT at the third hour and 24th hour after the noise, respectively, and 6 rats received dexamethasone. Auditory brain stem response threshold was measured in all groups before being assigned to the groups, after the noise exposure and right before being killed. Cytokine levels at the cochlear soft tissues were measured using enzyme-linked immunoassay. RESULTS: Final thresholds (10 dB and 5 dB nHL-normal hearing level) of HBOT-24th hour and dexamethasone groups were significantly better than that of untreated noise group (22.5 dB nHL) (p < 0.05). There was no significant difference between HBOT-24th hour group (10 dB nHL) and dexamethasone group (5 dB nHL) (p > 0.05). IL-6 and IL-1ß of HBOT-third hour group (2.30 ng/mg and 185.43 pg/mg) were significantly higher than those of the noise group (0.91 ng/mg and 131.40 pg/mg), dexamethasone group (1.19 ng/mg and 112.29 pg/mg) and HBOT-24th hour group (1.34 ng/mg and 106.69 pg/mg) (p < 0.05). There was no significant difference in IL-6 and IL-1ß of HBOT-24th hour group, dexamethasone group, noise group, and control group (p > 0.05). There was no significant difference in TNF-α of the 3 treatment groups, noise group, and control group (p > 0.05). CONCLUSION: The results showed that the most effective method in the treatment of noise-induced hearing loss was early initiation of dexamethasone therapy. There could be negative effects of HBOT on hearing if it is commenced early after the noise (first 3 h). HBOT treatment, which was started at the 24th hour, was found to be an effective method.

Effect of mineral trioxide aggregate cements on transforming growth factor beta1 and bone morphogenetic protein production by human fibroblasts in vitro.

The aim of this study was to evaluate and compare the effects of two commercial mineral trioxide aggregate (MTA) cements (ProRoot MTA and MTA Angelus) on transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP)-2 levels produced by cultured human gingival fibroblasts (HGFs). Human gingival tissues were obtained from individuals with healthy periodontium. HGFs were grown at 37 degrees C in humidified atmosphere of 5% CO(2) in Dulbecco's modified Eagle's medium, supplemented with 10% fetal calf serum, penicillin, and streptomycin. After 24 and 72 hours of exposure to the MTA products, HGF viability was determined by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay. TGF-beta1 and BMP-2 levels in cell-free culture media were determined by enzyme-linked immunosorbent assay. Cell viability of the test groups was significantly lower than that of control at 24 and 72 hours (p < 0.05) but showed an increase at 72 hours (p < 0.05). Both test groups showed increased TGF beta-1 levels at 72 hours (p < 0.05), whereas the MTA Angelus group displayed higher TGF beta-1 levels than control and ProRoot MTA groups at 24 and 72 hours (p < 0.05). At 24 hours, BMP-2 levels of the ProRoot group were significantly higher than that of MTA Angelus (p < 0.05). Both test materials increased the BMP-2 levels within time (p < 0.05) and displayed similar levels at 72 hours (p > 0.05). These results suggest that both MTA products are capable of stimulating HGF to produce BMP-2, whereas the stimulatory effect for TGF beta-1 is material dependent.

Exogenously administered and endogenously produced melatonin reduce hyperbaric oxygen-induced oxidative stress in rat lung.

Hyperbaric oxygen (HBO) is a widely used treatment modality in many diseases. A known side effect of HBO is the production of reactive oxygen species. Many antioxidants such as vitamins C and E, riboflavin and selenium have been used successfully to scavenge the reactive oxygen species caused by HBO administration. In this study, we aimed to see if melatonin, a newly discovered antioxidant, has a protective effect against the overproduction of reactive oxygen species produced by HBO in rat lung tissue. Sixty male Sprague-Dawley rats were divided into 5 groups as follows: control, daytime HBO (3 ATA, 120 min), daytime HBO plus melatonin (10 mg/kg), nighttime HBO and nighttime HBO (under light exposure). The MDA, SOD and CAT levels of daytime and nighttime HBO (under light exposure) increased significantly. This significance was not found in the daytime HBO plus melatonin and nighttime HBO groups when compared with the control. In this study, HBO caused oxidant stress, and melatonin decreased the levels of MDA, SOD and CAT. Moreover, endogenous melatonin was found to be a more effective antioxidant than exogenous 10 mg/kg melatonin.

Incidence, course, and prediction of hyperbilirubinemia in near-term and term newborns.

OBJECTIVE: In this study, we investigated prospectively the incidence of significant hyperbilirubinemia and demographic and laboratory characteristics and pattern of serum bilirubin levels of near-term newborns (35-37 weeks' [245-265 days'] gestation) by comparing them with those of term newborns (38-42 weeks' [266-294 days'] gestation) longitudinally in the first 7 days of life; we also aimed to determine the value of an early (6th-hour) serum bilirubin measurement in predicting the development of significant hyperbilirubinemia later during the first week of life in near-term newborns. METHODS: Serum total bilirubin measurements were initially made at the 6th hour of life and repeated daily for the next 4 days, and a last measurement was performed on the 7th day (150th hour) in 219 term newborns (term group) and 146 near-term newborns (near-term group). Newborns with serum total bilirubin levels of > or =8 and > or =12 mg/dL on day 2, > or =12 and > or 15 mg/dL on day 3, and > or =14 and > or =17 mg/dL on days 4, 5, and 7 for birth weights 2000 to 2500 g and >2500 g, respectively, were defined to have significant hyperbilirubinemia, and phototherapy treatment was started. The predictive ability of the 6th-hour serum total bilirubin value in determining the development of significant hyperbilirubinemia in the near-term group was assessed on the basis of the placement of any of the first week's serum bilirubin measurements in the > or =95th percentile of the study population. A Gaussian distribution curve, the 5th, 30th, 60th, and 95th percentiles, and 4 percentile tracks were obtained from mean serum total bilirubin values. On the basis of the percentile tracks with various sensitivity, specificity, and negative and positive predictive values, a nomogram demonstrating the 4 percentile tracks as risk-zone demarcators with divided risk zones was produced. RESULTS: Twenty-three newborns (10.5%) in the term group and 37 newborns (25.3%) in the near-term group had significant hyperbilirubinemia and required phototherapy. When the daily mean serum bilirubin levels of the 2 groups were compared, the first 4 days' values did not significantly differ between the 2 groups, whereas the 5th and 7th days' values were significantly higher in the near-term group. There were significant differences between the 2 groups with respect to the incidence of significant hyperbilirubinemia, hematocrit, Apgar score, and mode of delivery. On the age-specific nomogram, the zone >95th percentile was labeled as high risk, and that <5th percentile was labeled as low risk. Serum total bilirubin values between the 5th and 30th, 30th and 60th, and 60th and 95th percentiles were designated as being in the low-intermediate, intermediate, and high-intermediate risk zones, respectively. The 5th and 95th percentiles on the nomogram had the highest sensitivity (100%) and specificity (98.2%), respectively, in predicting the subsequent development of significant hyperbilirubinemia. CONCLUSIONS: Near-term newborns should not be treated as term newborns in the approach to management of hyperbilirubinemia, because infants of 35 to 37 weeks' gestation had significantly lower birth weights, significantly higher serum total bilirubin levels on days 5 and 7, and were 2.4 times more likely to develop significant hyperbilirubinemia than those of 38 to 42 weeks' gestation in the present study. In near-term newborns of 35 to 37 weeks' (245 to 265 days') gestation, the decision to diagnose and treat significant hyperbilirubinemia should be made on the basis of risk status (percentile distribution of the serum bilirubin values on postnatal age) rather than using birth-weight-based thresholds. A nomogram constructed from daily serum bilirubin values of each population, as we present herein, can be used in assessing the age (hour)-specific jaundice risk (high, intermediate, or low) of each near-term newborn.

An early (sixth-hour) serum bilirubin measurement is useful in predicting the development of significant hyperbilirubinemia and severe ABO hemolytic disease in a selective high-risk population of newborns with ABO incompatibility.

OBJECTIVE: In the era of early discharge of newborns from the hospital, newborns with ABO incompatibility are at especially greater risk for developing a subsequent significant hyperbilirubinemia because some of these infants also may present with some degree of ABO isoimmune disease. In this study, we aimed to determine prospectively the critical serum total bilirubin level to predict significant hyperbilirubinemia and severe hemolytic disease in healthy term newborns with ABO incompatibility based on a serum bilirubin measurement made at a postnatal age at which all newborns are at the hospital before discharge and at which any therapeutic intervention, if necessary, could be started as early as possible. METHODS: A total of 136 healthy term newborns with ABO (O-A or O-B) blood group incompatibility were followed prospectively with daily serum total bilirubin measurements for the first 5 days of life. Newborns with serum total bilirubin levels of > or =5 mg/dL and an increase in serum total bilirubin concentration of >0.5 mg/dL/h in the first 24 hours, > or =12 mg/dL on day 2, > or =15 mg/dL on day 3, and > or =17 mg/dL on days 4 and 5 were defined to have significant hyperbilirubinemia and were started on phototherapy treatment. Additional treatment modalities, including intense phototherapy, intravenous immunoglobulin treatment, and exchange transfusion, were used when serum bilirubin concentrations exceeded 20 mg/dL or increased by >1 mg/dL/h despite a phototherapy treatment of at least 4 hours. The additional assessment of the predictive ability of the sixth-hour serum total bilirubin value in determining the development of significant hyperbilirubinemia was made on the basis of the placement of any of the first 5 days' serum bilirubin measurements in the > or =90th percentile of the study population. On the basis of the percentile tracks constructed from the 10th, 35th, 50th, 60th, and 90th percentiles of serum total bilirubin values, a nomogram demonstrating the 3 percentile tracks as risk zone demarcators with divided risk zones was produced. RESULTS: Twenty-nine newborns (21.3%) had significant hyperbilirubinemia. There were significant differences between the newborns who did and the newborns who did not develop significant hyperbilirubinemia with respect to the reticulocyte count (4.39 +/- 3.46% vs 2.95 +/- 1.63) and the presence of a direct antiglobulin test positivity (6 of 23 vs 0 of 107) and a sibling with neonatal jaundice (6 of 23 vs 5 of 102). A mean serum bilirubin level of > or =4 mg/dL at the sixth hour of life was determined to have the highest sensitivity (86.2%) and negative predictive value (94.5%) and a positive predictive value of 39.7% to predict the newborns who would develop significant hyperbilirubinemia. At the mean serum bilirubin level of 6 mg/dL, the sensitivity, specificity, and negative and positive predictive values were 100%, 91.5%, 100%, and 35.3%, respectively, in diagnosing 6 cases of severe ABO hemolytic disease. On the hour (age)-specific percentile-based nomogram, the zone above the 90th percentile was determined as high risk and that below the 35th percentile as low risk. CONCLUSIONS: The reticulocyte count, a positive direct antiglobulin test, and the presence of a sibling with neonatal jaundice were determined to be the good predictors for the development of significant hyperbilirubinemia and severe hemolytic disease of the newborn. A serum bilirubin measurement and the use of the critical bilirubin levels of 4 mg/dL and 6 mg/dL at the sixth hour of life will predict nearly all newborns who will have significant hyperbilirubinemia and those who will develop severe hemolytic disease of the newborn, respectively. An hour (age)-specific percentile-based nomogram can be used to predict which newborn is at high risk (> or =90th percentile), intermediate risk (35th-90th percentiles), and low risk (<35th percentile) for developing significant hyperbilirubinemia. The 35th and 90th percentile tracks, approximating the serum bilirubin levels of 3.3 mg/dL and 6.5 mg/dL at the sixth hour of life, respectively, can be used as safe risk demarcators in deciding about the time of discharge of ABO-incompatible newborns from the hospital.