Neuroserpin As an Adjuvant Therapy for Hypothermia on Brain Injury in Neonatal Hypoxic-Ischemic Rats.

OBJECTIVE: We aimed to assess the effects of neuroserpin and its combination with hypothermia on hypoxic-ischemic (HI) brain injury in neonatal rats. Neuroserpin is an axon-secreted serine protease inhibitor and is important for brain development, neuronal survival, and synaptic plasticity. STUDY DESIGN: Male Wistar-Albino rats on postnatal day 7 (P7) were randomly divided into five groups: sham group (n = 10), (HI; n = 10), hypoxic-ischemic hypothermia (HIH; n = 10), hypoxic-ischemic neuroserpin (HIN; n = 10), and hypoxic-ischemic neuroserpin-hypothermia (HINH; n = 10). The P7 rat brain's maturation is similar to a late preterm human brain at 34 to 36 weeks of gestation. HI was induced in rats on P7 as previously described. A single dose of 0.2 µM neuroserpin (HINH and HIN) or an equivalent volume of phosphate-buffered saline (sham, HIH, and HI) was administered intraventricularly by a Hamilton syringe immediately after hypoxia. In the follow-up, pups were subjected to systemic hypothermia or normothermia for 2 hours. Euthanasia was performed for histopathological evaluation on P10. Apoptosis was detected by caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and was counted in the hippocampus. RESULTS: In comparison to the HI group, the TUNEL-positive and caspase-3-positive neurons in the sham, HIN, HIH, and HINH groups were considerably lower (13.4 ± 1.0 vs. 1.9 ± 0.9, 6.0 ± 0.9, 5.3 ± 1.6, and 4.0 ± 1.1; p < 0.001) and (13.5 ± 1.7 vs. 1.2 ± 0.7, 9.1 ± 2.7, 4.8 ± 1.0, and 3.9 ± 1.6; p < 0.001). HIN, HIH, and HINH, compared to the sham group, showed more TUNEL-positive and caspase-3-positive neurons (6.0 ± 0.9, 5.3 ± 1.6, 4.0 ± 1.1 vs. 1.9 ± 0.9 and 9.1 ± 2.7, 4.8 ± 1.0, 3.9 ± 1.6 vs. 1.2 ± 0.7; p < 0.001). The HINH group (synergistic effect) had significantly fewer TUNEL-positive neurons and caspase-3-positive neurons than the HIN group (4.0 ± 1.1vs. 6.0 ± 0.9 and 3.9 ± 1.6 vs. 9.1 ± 2.7; p < 0.001). CONCLUSION: Our study showed that both neuroserpin alone and as an adjuvant treatment for hypothermia may have a neuroprotective effect on brain injury. KEY POINTS: · Neuroserpin decreased brain injury.. · Neuroserpin showed a synergistic effect when used as an adjuvant treatment for hypothermia.. · The neuroprotective effect of neuroserpine was related to its antiapoptotic properties..

Umbilical cord milking-benefits and risks.

The most common methods for providing additional placental blood to a newborn are delayed cord clamping (DCC) and umbilical cord milking (UCM). However, DCC carries the potential risk of hypothermia due to extended exposure to the cold environment in the operating room or delivery room, as well as a delay in performing resuscitation. As an alternative, umbilical cord milking (UCM) and delayed cord clamping with resuscitation (DCC-R) have been studied, as they allow for immediate resuscitation after birth. Given the relative ease of performing UCM compared to DCC-R, UCM is being strongly considered as a practical option in non-vigorous term and near-term neonates, as well as preterm neonates requiring immediate respiratory support. However, the safety profile of UCM, particularly in premature newborns, remains a concern. This review will highlight the currently known benefits and risks of umbilical cord milking and explore ongoing studies.

Effects of spontaneous first breath on placental transfusion in term neonates born by cesarean section: A randomized controlled trial.

Background: The role of umbilical cord management in placental transfusion in cesarean section (CS) requires clarification. The spontaneous first breath may be more important than the timing of cord clamping for placental transfusion in neonates born by CS. Objective: This study aimed to evaluate the impact of cord clamping after the first spontaneous breath on placental transfusion in neonates born by CS. Methods: We recruited women with a live singleton pregnancy at ≥37.0 weeks of gestation admitted for CS. The interventions performed, such as physiologic-based cord clamping (PBCC), intact-umbilical cord milking (I-UCM), 30-s delay in cord clamping (30-s DCC), and 60-s delay in cord clamping (60-s DCC), were noted and placed in a sealed envelope. The sealed envelope was opened immediately before delivery to perform randomization. Results: A total of 123 infants were eligible for evaluation. Of these, 31, 30, 32, and 30 were assigned to the PBCC, I-UCM, 30-s DCC, and 60-s DCC groups, respectively. The mean hemoglobin (Hb) and mean hematocrit (Hct) were significantly higher in the 60-s DCC group than in the PBCC group (p = 0.028 and 0.019, respectively), but no difference was noted among the I-UCM, 30-s DCC, and PBCC groups at 36 h of age. Further, no significant differences were observed in the mean Hb and mean Hct among the I-UCM, 60-s DCC, and 30-s DCC groups. Peak total serum bilirubin (TSB) levels were higher in the 60-s DCC group than in the I-UCM and PBCC groups (p = 0.017), but there was no difference between the 60-s DCC and 30-s DCC groups during the first week of life. The phototherapy requirement was higher in 60-s DCC than in IUCM and 30-sDCC (p = 0.001). Conclusions: Our findings demonstrated that PBCC, 30-s DCC, and I-UCM in neonates born by CS had no significant differences from each other on placental transfusion. The Hb and Hct in the neonates were higher after 60-s DCC than after PBCC.

Umbilical Cord Management in Late Preterm and Term Infants: A Randomized Controlled Trial.

OBJECTIVE: The study aimed to compare the effects of three different methods of umbilical cord management on hematological parameters in term and late-preterm infants. STUDY DESIGN: A randomized controlled trial comparing intact-umbilical cord milking (I-UCM) with cut-umbilical cord milking (C-UCM) and immediate cord clamping (ICC) in neonates born >35 weeks' gestation. RESULTS: A total of 587 infants were evaluated. Of these, 197 were assigned to I-UCM, 190 to C-UCM, and 200 to ICC. Mean hemoglobin and hematocrit levels at 48 hours of age were higher in I-UCM group compared with the ICC group (p = 0.002 and p = 0.010, respectively). CONCLUSION: These findings suggest that I-UCM is more beneficial choice. Further trials are needed to assess the various long- and short-term effects of different cord milking methods. KEY POINTS: · This is the first study comparing these three methods (I-UCM, C-UCM, and ICC) concurrently.. · I-UCM is more beneficial choice.. · Although the terms I-UCM and C-UCM are often used interchangeably, these are different procedures..

Impact of antenatal corticosteroid exposure on thymus size in premature infants.

BACKGROUND: This study examined the effect of corticosteroids on the thymic index (TI) and the thymus/weight index (TWI) in infants exposed to antenatal corticosteroids (ACS). METHODS: This prospective study was conducted between August 2014 and October 2018. A thymus ultrasound was performed to assess thymus size on the second day of life. Thymus size was assessed as TI and TWI. RESULTS: In total, 167 neonates (≤34 weeks gestation)  constituted the study population, including 94 ACS-exposed infants and 73 untreated infants. The treatment group exhibited significantly lower birth weight and significantly shorter birth length than the ACS (-) group. Therefore, TI was smaller in the treatment group than in the untreated group (6.96 ± 4.05 cm3 vs. 5.64 ± 3.39 cm3). The TWI was 3.69 ± 1.8 cm3/kg in the ACS (-) group versus 3.32 ± 1.56 cm3/kg in the ACS (+) group. The median anteroposterior diameter of the right lobe was 1.33 cm (range, 0.45-2.40) in the ACS (-) group compared to 1.15 cm (range, 0.47-2.40) in the ACS (+) group. The median anteroposterior diameter of the left lobe was 1.40 cm (range, 0.43-2.20) in the ACS (-) group and 1.19 cm (range, 0.32-2.36) in the ACS (+) group. The median largest sagittal area was 2.64 cm2 (range, 0.5-5.46) in the ACS (-) group versus 2.20 cm2 (range, 0.55-5.90) in the ACS (+) group. CONCLUSION: We found that TWI was not significantly changed by ACS exposure in premature infants.

Impacts of ß-estradiol on intestinal injury in newborn rats.

OBJECTIVE: Necrotizing enterocolitis has been investigated and debated extensively in recent years; however, there is still no effective treatment. The aim of this study was thus to examine the effects of ß-estradiol on intestinal injury in rats. METHODS: Twenty-four newborn female rat pups were divided into three groups. In group 1 (sham), hypoxia-re-oxygenation was not performed. In group 2 (saline), the rats were injected with saline after hypoxia-re-oxygenation, and the process was repeated for 5 d. In group 3 (ß-estradiol treatment), the rats were subjected to hypoxia-re-oxygenation and then given ß-estradiol intraperitoneally once a day for 5 d. After these procedures, the terminal ileum was removed for analysis. RESULTS: Statistically significant differences in histological grades were found between groups 1 and 2 (p = 0.000), groups 1 and 3 (p = 0.028), and groups 2 and 3 (p = 0.021). There were also differences in TNF-α and IL-6 levels between groups 2 and 3 (p = 0.000 and p = 0.038, respectively) and between groups 1 and 2 (p = 0.000 and p = 0.000); there was no difference between groups 1 and 3 (p = 0.574 and p = 0.195, respectively). Electron microscopy examination revealed a decrease in lipid droplets at the apical cytoplasm of the columnar cells in group 2; in group 3, the absorption of the lipids as lipid droplets was similar to that of group 1. CONCLUSION: In this study, ß-estradiol was found to decrease the intensity of intestinal injury significantly by inhibiting TNF-α and IL-6.

Is umbilical cord milking always an advantage?

OBJECTIVE: The role of cord milking as an alternative to delayed cord clamping is an area that requires more research. Purpose of this clinical trial was to investigate the impact of umbilical cord milking on the absolute neutrophil counts (ANCs) and the neutropenia frequency of preterm infants. METHODS: Fifty-eight pregnant women were randomly assigned to one of the umbilical cord milking and control groups. A total of 54 preterm infants (gestational age ≤ 32 weeks) were enrolled into the study. The umbilical cords of 25 infants were clamped immediately after birth, and in 29 infants, umbilical cord milking was performed first. RESULTS: The ANCs were statistically significantly lower in the cord milking group compared with the control group on days 1, 3 and 7. The frequency of neutropenia was higher in the cord milking group compared with the control group. CONCLUSION: In our study, ANCs were lower in the cord milking group and the frequency of neutropenia was higher. Umbilical cord milking plays a role on the ANCs of preterm infants.

Idiopathic central diabetes insipidus presenting in a very low birth weight infant successfully managed with lyophilized sublingual desmopressin.

Neonatal central diabetes insipidus (DI) is an extremely rare disorder that can cause severe morbidity and mortality. We have reported a very low birth weight infant with idiopathic central DI presenting in the first month of life who was successfully treated with sublingual desmopressin therapy. In this report, we emphasize that central DI should be kept in mind in an infant with unexplained hypernatremia and polyuria. Timely diagnosis and treatment with lyophilized desmopressin may prevent severe morbidity and mortality.

Effects of caffeine on neuronal apoptosis in neonatal hypoxic-ischemic brain injury.

OBJECTIVE: Hypoxia-ischemia (HI) in rat pups leads to strong activation of apoptosis, and apoptosis contributes significantly to cerebral damage in the perinatal period. Caffeine displays a broad array of actions on the brain. The aim of this study was to investigate the effects of caffeine on neuronal apoptosis in a hypoxic-ischemic neonatal model. METHODS: Twenty-four seven-day-old Wistar rat pups were subjected to right common carotid artery ligation and hypoxia for 2 h. Sham group (n = 8) had a median neck incision, but the rats were not subjected to ligation or hypoxia. The pups were treated with 20 mg/kg/day caffeine citrate (n = 8) or saline (n = 8) immediately before HI and at 0, 24, 48 and 72 h post-hypoxia. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and caspase-3 in the hippocampus and parietal cortex of both hemispheres. RESULTS: The numbers of apoptotic cells in the hippocampus and parietal cortex were significantly higher in the saline group than they were in the sham group (p < 0.0001). The number of apoptotic cells in the hippocampus (p < 0.0001) and parietal cortex (p < 0.0001, TUNEL and p = 0.001, caspase-3) were higher in the caffeine-treated group than they were in the sham group, but the number of apoptotic cells decreased significantly in the caffeine-treated group compared with the saline group in the hippocampus (p < 0.0001, TUNEL and p = 0.001, caspase-3) and parietal cortex (p = 0.001, TUNEL and p = 0.002, caspase-3). CONCLUSIONS: We show that caffeine administration in hypoxic-ischemic brain injury reduces neuronal apoptosis in the developing brain. We suggest that caffeine may be effective in reducing brain injury.

Is it accurate to separate glucose-6-phosphate dehydrogenase activity in neonatal hyperbilirubinemia as deficient and normal?

BACKGROUND: The aim of this study was to investigate glucose 6-phosphate dehydrogenase (G6PD) activity in term and late preterm babies with severe neonatal hyperbilirubinemia and its relationship to the severity and treatment of this disorder, regardless of level of G6PD activity (deficient/normal). METHODS: A total of 529 term and late preterm (≥35 weeks) infants (228 female, 301 male) who were diagnosed with severe hyperbilirubinemia were included in this study. In each case, serum was collected to evaluate blood group, direct Coombs' test, complete blood cell count, total and direct bilirubin, thyroid-stimulating hormone, and G6PD activity. A partial correlation analysis was carried out to assess the relationship between G6PD activity and total bilirubin levels. RESULTS: A significant correlation was found between the severity of hyperbilirubinemia and G6PD activity in both males and females. Male neonates who had G6PD levels <12 U/g Hb required more phototherapy time than neonates who had G6PD levels ≥12 U/g Hb; and female neonates who had G6PD levels <16 U/g Hb required more phototherapy time than neonates who had G6PD levels ≥16 U/g Hb (p < 0.0001). When we analyzed only breastfed infants, a significant difference also emerged in both sexes. Decreased G6PD activity was associated with increased phototherapy time and the need for exchange transfusion. CONCLUSION: Routine checks of G6PD level in hyperbilirubinemic neonates are very important in providing proper medical management to prevent bilirubin-induced neurological dysfunction. Appropriate identification of G6PD (<12 U/g Hb for male infants and <16 U/g Hb for female infants) raises awareness of the severity of the condition and the necessity for immediate care of severe hyperbilirubinemic infants.

Peripherally inserted central venous catheters in critically ill premature neonates.

PURPOSE: To evaluate the safety of peripherally inserted central venous catheters (PICCs) and their complications in critically ill premature neonates. METHODS: A retrospective collection of data of infants with very low birth weight (VLBW) who underwent PICC placement over a 2-year period. Gestational age, birth weight (BW), sex, site of catheter placement, reason for catheter removal, duration of the catheter use, proven sepsis, type of the reported organism and the rate of complications were collected. The infants were classified into two groups according to BWs: Group 1-VLBW infants (BW between 1,000 and 1,500 g) and Group 2-BW <1,000 g (extremely low birth weight, ELBW group). RESULTS: During the study period, 90 VLBW infants were admitted to the neonatal intensive care unit. PICCs were attempted in 71 patients. A PICC was successfully inserted into 62 patients (87.3%). Totally, 68 PICCs were inserted into 62 infants. PICCs placed in either the upper or the lower extremity have no differences in complication rates. The median time of catheter insertion was 10 (1-22) days for Group 1 and 16 (1-47) days for Group 2 (p=0.001). The median duration of PICCs was 9 (2-18) and 12.0 (3-30) days, respectively (p=0.012). There were no significant differences between groups for the reasons for removal (p=0.859). CONCLUSIONS: PICCs are convenient for the administration of long course antibiotics and parenteral nutrition for both VLBW and ELBW infants. The risk of catheter complications did not increase in ELBW infants. Although the technique of insertion is easy and using PICCs has many benefits, serious and fatal complications may occur in premature neonates in critical states.

Lactate and lactate dehydrogenase in predicting the severity of transient tachypnea of the newborn.

OBJECTIVE: Low Apgar score is strongly associated with the incidence of transient tachypnea of the newborn (TTN) and other respiratory diseases of the newborn. We aimed to investigate the relationship between hypoxia determinants and the prolonged oxygen and respiratory support requirement even if the Apgar scores were normal. METHODS: Retrospective case-controlled study. Infants born after 35 weeks of gestational age with clinical signs, chest X-ray findings and clinical course consistent with TTN were included. Receiver operating characteristic curves were used to assess the predictive values of determinants in predicting the risk for prolonged oxygen requirement and mechanical ventilatory support. RESULTS: We showed a positive correlation between the duration of oxygen with lactate and lactate dehydrogenase (LDH) levels. LDH offered the best predictive value for prolonged oxygen requirement with a positive predictive value (PPV) of 88.9%. The predictive value of lactate exceeds the predictive value of LDH, aspartate aminotransferase, and percentage of normoblasts to predict the requirement of respiratory support with a PPV of 88.5%. CONCLUSIONS: Lactate and LDH might be useful for clinicians at first level hospitals for decision making to refer the TTN patient to the secondary or tertiary level neonatal intensive care unit before the clinical situation is worsened.

The effect of levetiracetam on neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury.

BACKGROUND: Hypoxic-ischemic brain injury (HIBI) is a common cause of neonatal mortality and morbidity. The use of levetiracetam (LEV), as a potential neuroprotective in brain ischemia, receives an increasingly high attention, and it could have a crucial role in the regulation of epileptogenesis and neuroprotection. Potential effects of LEV on neuronal apoptosis in HIBI have not previously been reported in literature. OBJECTIVES: The aim of this study is to evaluate the possible effects of LEV on neuronal apoptosis in neonatal rat model of HIBI. METHODS: Seven-day-old Wistar rat pups were subjected to right common carotid artery ligation and hypoxia (92% nitrogen and 8% oxygen) for 2h. The pups were treated with LEV or saline after hypoxia. In sham group rats, neither ligation, nor hypoxia was performed. Neuronal apoptosis was evaluated by the terminal deoxynucleotidyl-transferase- mediated dUTP nick-end labeling (TUNEL) methods. RESULTS: The counts of apoptotic cells in both hippocampus and cerebral cortex were significantly higher in the saline treatment group than in the sham group. The counts of apoptotic cells in both hippocampus and cerebral cortex were similar to those in the sham group and in the LEV treatment group. The number of apoptotic cells decreased significantly in the LEV-treated group compared with the saline group. CONCLUSIONS: These results show that LEV administration after hypoxia reduces neuronal apoptosis. Thus, we propose that LEV, as an effective antiepileptic and antiapoptotic drug, may be a viable choice for the control of seizure activity in neonates with HIBI.

Resistin--a novel feature in the diagnosis of sepsis in premature neonates.

OBJECTIVE: To evaluate the diagnostic potential of resistin in sepsis and to compare results with C-reactive protein (CRP) in infants < 32 weeks of gestation. STUDY DESIGN: A total of 64 infants were prospectively included in the study. Blood samples were collected for basal CRP and resistin within the first hour of life. When sepsis was suspected, samples were collected for CRP and resistin before the treatment was started (pretreatment CRP and resistin). On the third day of sepsis, CRP and resistin levels were measured for evaluating the treatment response (follow-up CRP and follow-up resistin). Culture-proven septic patients were divided into groups according to early or late-onset sepsis (EOS and LOS) and gram-negative or gram-positive sepsis (GNS and GPS). RESULTS: Pretreatment and follow-up resistin levels were significantly higher than basal resistin levels in both EOS and LOS groups (p < 0.01), with a positive correlation with CRP levels. To predict the GNS and GPS area under curve, values of pretreatment CRP and resistin were 0.714 and 0.984, respectively (p = 0.039). CONCLUSION: Resistin had a superior potential to that of CRP in the diagnosis of sepsis in preterm infants. Resistin may be used as an early marker for sepsis in premature infants.

Serum prohepcidin levels and iron parameters in term small-for-gestational-age newborns.

AIM: To understand the effect of prenatal chronic hypoxia on prohepcidin levels in term newborns. METHOD: We determined prohepcidin (Pro-Hep) levels in both term appropriate-for-gestational age (AGA) and term small-for-gestational-age (SGA) infants. Uteroplacental insufficiency had exposed all SGA infants to chronic hypoxia. Serum samples were collected from nine full-term SGA infants. Samples were analyzed for complete blood count, serum iron and ferritin concentrations, iron-binding capacity, and prohepcidin levels. RESULTS: The mean serum Pro-Hep level was 156.4 ? 46.7 ng/ml for SGA infants and 482 ? 371.9 ng/ml for 16 healthy term AGA infants (historical controls); this difference was statistically significant. Statistical analyses revealed significant between-group differences for hemoglobin, hematocrit, mean corpuscular volume, red blood cell distribution width, and serum ferritin and Pro-Hep levels. CONCLUSION: This study showed that compared with AGA infants, Pro-Hep levels were lower in term SGA infants, suggesting that prenatal chronic hypoxia decreases Pro-Hep synthesis.

Effect of feeding type on the efficacy of phototherapy.

OBJECTIVE: The objective of this study was to assess the efficacy of phototherapy for nonhemolytic hyperbilirubinemia and rebound bilirubin levels in breast-fed newborns as compared with mixed-fed (breast milk and formula) newborns. STUDY DESIGN/SETTING: Prospective study of effects of feeding type on response to phototherapy in newborns. METHODS: The subjects were 53 full-term healthy newborns with nonhemolytic hyperbilirubinemia [defined as total serum bilirubin 12 mg/dL (205.2 micromol/L) in the first 48 hours of life or 15 mg/dl (256.5 micromol/L), on subsequent days]. Groups were formed according to type of feeding. Group 1 consisted of 28 breast-fed newborns and group 2 consisted of 25 mixed-fed newborns. Phototherapy was terminated when total serum bilirubin concentration fell to 14 mg/dL (< 239.4 micromol/L). Rebound bilirubin measurements were obtained 24 hours after phototherapy ended. RESULTS: The groups were comparable with respect to age at the start of phototherapy. The amount of weight loss (relative to birth weight) recorded at the start of phototherapy was significantly greater in group 1 than in group 2 (8.1+/- 3.9% vs. 5.4+/- 2.6% p = 0.004). The duration of phototherapy was significantly longer in group 1 than in group 2 (38.6+/- 12.6 h vs. 26.8+/- 9.4 h; P < 0.001). The 24-hour rate of decrease in bilirubin concentration in group 2 was significantly higher than that in group 1 [5.4+/- 2.2 mg/dL/d (92.3+/-37.6 micromol/L/d) vs. 4+/- 1.3 mg/dL/d (68.4+/- 22.2 micromol/L/d); p = 0.01]. The overall rate of decrease in bilirubin concentration in group 1 was significantly lower than that in group 2 [0.16+/- 0.05 mg/dL/h (2.73+/- 0.85 micromol/L/h) vs. 0.22+/- 0.09 mg/dL/h (3.76+/- 1.53 micromol/L/h); p = 0.01]. There was no significant difference between the two groups with respect to rebound bilirubin concentration (P = 0.184). CONCLUSION: Phototherapy effectively reduced bilirubin levels in breastfed newborns with hyperbilirubinemia, but these patients show significantly slower response to this treatment than mixed-fed newborns.

PHACES syndrome with small, late-onset hemangiomas.

Although hemangiomas are the hallmark of the PHACES syndrome, they may be nonexistent at birth and may not develop until later in early infancy. We report an infant who presented initially with cardiac defect, sternal nonunion, supraumbilical raphé, and congenital hypothyroidism without any hemangioma, and who subsequently developed facial hemangiomas at 2 months of age. We noted that there is a possibility that hemangiomas may subsequently develop later in early infancy and congenital hypothyroidism may be associated with the PHACES syndrome.

Early onset conjugated hyperbilirubinemia in newborn infants.

OBJECTIVES: To determine the causes and related outcomes of early onset conjugated hyperbilirubinemia in a group of newborn infants and to determine the incidence of sepsis in these neonates. METHODS: The charts of 42 babies with conjugated hyperbilirubinemia were retrospectively reviewed. RESULTS: The mean gestational age was 37 weeks and the mean postnatal age at presentation was 10 days. Culture-proven sepsis was identified in 15 babies (35.7% of total). Gram-negative bacteria were isolated in 10 cases and E. coli was the most common of these agents (7 cases). Perinatal hypoxia-ischemia was the second most frequent etiology (7 patients; 16.7% of total). The other diagnoses were blood group incompatibility (n=5), Down syndrome (n=3), cholestasis associated with parenteral nutrition (n=3), neonatal hepatitis (n=2), metabolic liver disease (n=1), biliary atresia (n=1), portal venous thrombosis (n=1) and unknown (n=4). Thirteen babies with sepsis recovered completely with treatment, whereas the prognosis for those with perinatal hypoxia-ischemia was grave (six of seven died). CONCLUSIONS: The findings suggest that early onset cholestatic jaundice in newborn infants is more commonly from non-hepatic causes, so it is reasonable to monitor these infants carefully for a period of time before undertaking time-consuming or invasive investigations towards a primary liver disease.

Extreme hyperbilirubinemia in newborn infants.

This study was undertaken to determine the frequency and investigate the etiology of extreme hyperbilirubinemia (total serum bilirubin [TSB]>or=25 mg/dL [428 micromol/L]) in newborns admitted to a neonatal intensive care unit in southern Turkey. The charts of 93 term and near-term infants admitted with TSB levels of 25 mg/dL (428 micromol/L) or greater in the first 30 days after birth were retrospectively reviewed. During the 4.5-year study period, 774 infants were admitted to our unit with neonatal jaundice. Ninety-three (12%) of these infants had TSB levels of 25 mg/dL (428 micromol/L) or greater. The mean TSB level in the 93 cases was 30.1+/-5.7 mg/dL (514.7+/-97.5 micromol/L), and the peak levels ranged from 25.0 to 57.4 mg/dL (428-981.5 micromol/L). Thirty-three (35.5%) of the 93 babies had TSB levels of 30 mg/dL (513 micromol/L) or greater. Eighty-nine of 93 infants were being exclusively breast-fed. Nineteen babies were isoimmunized, 7 were bacteremic, 2 of the 39 babies tested for glucose-6-phosphate dehydrogenase had this enzyme deficiency, and 1 of the 71 infants tested for thyroid function had hypothyroidism. No cause for extreme hyperbilirubinemia was found in 61 (65.6%) cases.