Early predictors of abnormal MRI patterns in asphyxiated infants: S100B protein urine levels.

OBJECTIVES: The early detection and stratification of asphyxiated infants at higher risk for impaired neurodevelopment is challenging. S100B protein is a well-established biomarker of brain damage, but lacks conclusive validation according to the "gold standard" methodology for hypoxic-ischemic encephalopathy (HIE) prognostication, i.e. brain MRI. The aim of the present study was to investigate the predictive role of urinary S100B concentrations, assessed in a cohort of HIE infants receiving therapeutic hypothermia (TH), compared to brain MRI. METHODS: Assessment of urine S100B concentrations was performed by immunoluminometric assay at first void and at 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120-h after birth. Neurologic evaluation, routine laboratory parameters, amplitude-integrated electroencephalography, and cerebral ultrasound were performed according to standard protocols. Brain MRI was performed at 7-10 days of life. RESULTS: Overall, 74 HIE neonates receiving TH were included in the study. S100B correlated, already at first void, with the MRI patterns with higher concentrations in infants with the most severe MRI lesions. CONCLUSIONS: High S100B urine levels soon after birth constitute trustable predictors of brain injury as confirmed by MRI. Results support the reliability of S100B in clinical daily practice and open the way to its inclusion in the panel of parameters used for the selection of cases suitable for TH treatment.

Intensive phototherapy and oxidant-antioxidant status in infants with jaundice.

OBJECTIVE: Conventional phototherapy converts unconjugated bilirubin to its oxidation products and consequently causes oxidative stress with lipid peroxidation products. New devices that deliver intensive phototherapy are efficacious in treating severe hyperbilirubinemia and minimizing the need for exchange transfusions. However, the oxidative stress status when using these devices has not been explored. Therefore, we aimed to study the impact of using intensive phototherapy on the oxidant-antioxidant status in severely jaundiced neonates. STUDY DESIGN: This prospective case-control study included term newborns admitted with severe hyperbilirubinemia managed with intensive phototherapy. Baseline oxidant-antioxidant concentrations were compared to healthy controls and re-measured after 8 h of intensive phototherapy exposure. RESULTS: The study included 40 cases with severe jaundice and 40 non-jaundiced apparently normal controls. Total serum bilirubin at enrollment was 23.4 ± 4.2 mg/dl that significantly decreased after 8 h of therapy to 15.4 ± 3.4 mg/dl (p < 0.001). The decline of total serum bilirubin was 1 mg/dl/h. Bilirubin: albumin ratio decreased from 3.45 ± 0.28 to 2.7 ± 0.21 (p < 0.001). Total antioxidant capacity (TAC), superoxide dismutase (SOD), malondialdehyde (MDA), and total oxidative stress (TOS) concentrations were lower in cases (p < 0.001, p < 0.001, p = 0.049, and p < 0.001 respectively) compared to controls. Following 8 h of intensive phototherapy, further decline of TAC (p = 0.016) with increased concentrations of TOS (p = 0.005) were noted. SOD and MDA did not change. CONCLUSIONS: Although efficacious, intensive phototherapy was associated with increased oxidative stress. The clinical correlates for harms related to such oxidative stress need further studying.

S100B protein, cerebral ultrasound and magnetic resonance imaging patterns in brain injured preterm infants.

OBJECTIVES: The early detection of preterm infants (PI) at risk for intraventricular hemorrhage (IVH) and neurological sequelae still constitutes an unsolved issue. We aimed at validating the role of S100B protein in the early diagnosis and prognosis of IVH in PI by means of cerebral ultrasound (CUS) and magnetic resonance imaging (MRI) today considered standard of care procedures. METHODS: We conducted an observational case-control study in 216 PI of whom 36 with IVH and 180 controls. Standard clinical, laboratory, radiological monitoring procedures and S100B urine measurement were performed at four time-points (first void, 24, 48, 96 h) after birth. Cerebral MRI was performed at 40-42 weeks of corrected gestational age. RESULTS: Elevated (p<0.001, for all) S100B levels were observed in the IVH group at all monitoring time-point particularly at first void when standard monitoring procedures were still silent or unavailable. S100B measured at first void correlated (p<0.001) with the grade of hemorrhage by means of CUS and with the site and extension of neurological lesion (p<0.001, for all) as assessed by MRI. CONCLUSIONS: The present results showing a correlation among S100B and CUS and MRI offer additional support to the inclusion of the protein in clinical daily management of cases at risk for IVH and adverse neurological outcome. The findings open the way to further investigations in PI aimed at validating new neurobiomarkers by means of S100B.

Acute bilirubin encephalopathy: Some lessons learned.

Acute bilirubin encephalopathy (ABE) is still an insufficiently addressed cause of mortality and long-term morbidity in low- and middle-income countries (LMICs). This article highlights that delayed or incorrect medical advice, inaccurate bilirubin measurements as well as ineffective phototherapy are some of the relevant causes predisposing jaundiced newborns to develop extreme hyperbilirubinemia [EHB, total serum/plasma bilirubin (TB) ≥ 25 mg/dL (428 µmol/L)] and subsequent ABE. Obstacles preventing state of the art management of such infants are also discussed. Prevention of ABE cannot occur without a system-based approach tailored to suit the needs and available resources of each community. Clear set protocols, rigorous training, monitoring, and accurate documentation together with simple innovative affordable technologies that can be locally produced, are essential to observe the change desired.

The spectrum of bilirubin neurotoxicity in term and near-term babies with hyperbilirubinemia: Does outcome improve with time?

BACKGROUND: While neonatal jaundice is generally a common benign condition; severe hyperbilirubinemia has a devastating potential for brain injury. AIM: To detect the impact of severe neonatal hyperbilirubinemia on motor and mental development and its progress over time in the first year of life using the Bayley scales of infant development (BSID) II. STUDY DESIGN AND PATIENTS: 177 term/near-term infants admitted for neonatal hyperbilirubinemia to the NICU of Cairo University Children's Hospital were enrolled. Clinical examination, BIND score and laboratory tests were performed at admission. Neurodevelopmental assessment using BSIDΙΙ was performed at 3 months for 147/177 neonates, and at 6 months and 12 months for 139/177 neonates. Auditory brainstem evoked potential was recorded at 3 months of age and repeated if abnormal. OUTCOME MEASURES: Psychomotor (PDI) and mental developmental indices (MDI) using BSIDII. Auditory impairment using Auditory Brainstem Response (ABR). RESULTS: TSB levels ranged from 10 to 63 mg/dL (179.6-1077 µmol/L) with a mean of 25.52 ±â€¯6.5 mg/dL (436 ±â€¯112.9 µmol/L) and BIND scores ranged from 0 to 7. By one year of age, 19/139 patients were affected; 8 had classic kernicterus, 3 had isolated auditory impairment, 1 had severe motor and mild mental delay and 7 had mild motor delay. TSB level and BIND score had positive correlation with auditory impairment and lower scores for PDI (which improved with time) and MDI (which remained stationary). Duration of exposure to hyperbilirubinemia negatively affected neurodevelopmental scores. CONCLUSION: The impact of severe hyperbilirubinemia is mainly on motor and auditory impairment. Mild mental delay was detected by BSIDII in few patients. Neurodevelopmental outcome improves over time.

Monitoring the effectiveness of hypothermia in perinatal asphyxia infants by urinary S100B levels.

Background Perinatal asphyxia is a major cause of mortality and morbidity in neonates: The aim of the present study was to investigate, by means of longitudinal assessment of urinary S100B, the effectiveness of hypothermia, in infants complicated by perinatal asphyxia and hypoxic-ischemic encephalopathy. Methods We performed a retrospective case-control study in 108 asphyxiated infants, admitted to nine tertiary departments for neonatal intensive care from January 2004 to July 2017, of whom 54 underwent hypothermia treatment and 54 did not. The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120 h after birth. The results were correlated with the achievement of S100B levels within normal ranges at 72 h from hypothermia treatment. Routine laboratory parameters, longitudinal cerebral function monitoring, cerebral ultrasound and neurologic patterns were assessed according to standard protocols. Results Higher S100B concentrations were found in hypothermia-treated infants in both moderate (up to 12 h) and severe (up to 24 h) hypoxic-ischemic encephalopathy. S100B levels returned to normal ranges starting from 20 h of hypothermia treatment in moderate and from 36 h in severe hypoxic-ischemic encephalopathy. Conclusions The present results offer additional support to the usefulness of longitudinal neuro-biomarkers monitoring in asphyxiated infants treated by hypothermia. The pattern of S100B concentrations during hypothermia supports the need for further investigations aimed at reconsidering the time-window for patient recruitment and treatment, and the optimal duration of the cooling and rewarming phases of the hypothermia procedure.

Neonatal RBC transfusions: Do benefits outweigh risks?

Preterm neonates represent one of the most transfused categories of patients. Their target hematocrits, however, are mainly based on expert opinion. The risk of transfusions are very high in the smallest preterm baby with a weak immune response, immature antioxidant ability, fragile germinal matrix and impaired cerebral autoregulation, yet red cell transfusions remain the only life saving measure in the baby with symptomatic anemia. Minimizing phlebotomy losses, following a restrictive transfusion policy and using screened, leukocyte depleted, irradiated, single donor blood remain the best means of avoiding the possible risks while maximizing the benefits of red cell transfusions in the preterm newborn.

Diagnostic Performance Analysis of the Point-of-Care Bilistick System in Identifying Severe Neonatal Hyperbilirubinemia by a Multi-Country Approach.

IMPORTANCE: The real prevalence and clinical burden of severe neonatal jaundice are undefined due to difficulties in measuring total serum bilirubin (TSB) outside secondary and tertiary clinical centers. OBJECTIVE: To assess the diagnostic performance of the point-of care Bilistick System (BS) in identifying neonatal jaundice patients requiring treatment. DESIGN: Between April 2015 and November 2016, 1911 neonates, were recruited to participate in the study. Blood samples were simultaneously collected for the TSB determination by BS and by hospital laboratory (Lab). Data were collected and sent to the Bilimetrix headquarter in Trieste where statistical analysis was performed. Newborns with neonatal jaundice were treated with phototherapy according to each center's guidelines. SETTING: 17 hospitals from Nigeria, Egypt, Indonesia, and Viet Nam. PARTICIPANTS: 1911 newborns were included, of which 1458 (76·3%) fulfilled the inclusion criteria. RESULTS: TSB level measured by BS agreed (p < .0001) with the lab result in all four countries. The diagnostic performance of BS showed a positive predictive value (PPV) of 92·5% and a negative predictive value (NPV) of 92·8%. CONCLUSIONS AND RELEVANCE: BS is a reliable system to detect neonatal jaundice over a wide range of bilirubin levels. Since Bilistick is a point-of-care test, its use may provide appropriate and timely identification of jaundiced newborns requiring treatment.

Prediction of 3- to 5-Month Outcomes from Signs of Acute Bilirubin Toxicity in Newborn Infants.

OBJECTIVE: To evaluate the ability of the bilirubin-induced neurologic dysfunction (BIND) score to predict residual neurologic and auditory disability and to document the relationship of BIND score to total serum bilirubin (TSB) concentration. STUDY DESIGN: The BIND score (assessing mental status, muscle tone, and cry patterns) was obtained serially at 6- to 8-hour intervals in 220 near-term and full-term infants with severe hyperbilirubinemia. Neurologic and/or auditory outcomes at 3-5 months of age were correlated with the highest calculated BIND score. The BIND score was also correlated with TSB. RESULTS: Follow-up neurologic and auditory examinations were performed for 145/202 (72%) surviving infants. All infants with severe acute bilirubin encephalopathy (BIND scores 7-9) either died or suffered residual neurologic and auditory impairment. Of 24 cases with moderate encephalopathy (BIND 4-6), 15 (62.5%) resolved following aggressive intervention and were normal at follow-up. Three of 73 infants with mild encephalopathy (BIND scores 1-3) but severe jaundice (TSB ranging 33.5-38 mg/dL; 573-650 µmol/L) had residual neurologic and/or auditory impairment. A BIND score ≥4 had a specificity of 87.3% and a sensitivity of 97.4% for predicting poor neurologic outcomes (receiver operating characteristic analysis). BIND scores trended higher with severe hyperbilirubinemia (r2 = 0.54, P < .005), but 5/39 (13%) infants with TSB ≥36.5 mg/dL (624 µmol/L) had BIND scores ≤3, and normal outcomes at 3-5 months. CONCLUSIONS: The BIND score can be used to evaluate the severity of acute bilirubin encephalopathy and predict residual neurologic and hearing dysfunction.

Neonatal Jaundice in Low- and Middle-Income Countries: Lessons and Future Directions from the 2015 Don Ostrow Trieste Yellow Retreat.

Severe neonatal hyperbilirubinemia, defined as total serum bilirubin (TSB) ≥20 mg/dl, is associated with a higher risk of permanent neurological sequelae and death. Jaundice can and should be promptly diagnosed and treated. Reliable methods for TSB assay are not always readily available, particularly in low- and middle-income countries, making the true incidence of severe neonatal jaundice (NNJ) difficult to estimate. To gather a more comprehensive picture, a symposium addressing NNJ worldwide was organized during the 2015 Don Ostrow Trieste Yellow Retreat. Data collected by several researchers in different regions of the world were presented and differences/similarities discussed. This report points out the need for: (1) a coordinated worldwide effort to define the burden and the causes of severe NNJ and its consequences; (2) aggressive educational programs for families and health personnel to facilitate timely care-seeking, and (3) accurate diagnostics and effective phototherapy.

Revisiting the Criteria for Exchange Transfusion for Severe Neonatal Hyperbilirubinemia in Resource-Limited Settings.

BACKGROUND: Exchange transfusion (ET) for severe neonatal hyperbilirubinemia (SNH) is frequently undertaken in low- and middle-income countries (LMIC), in sharp contrast to the prevailing practice in high-income countries. However, the criteria for initiating this procedure in settings with limited resources for treating infants with SNH have not been systematically explored. OBJECTIVE: To identify key considerations for initiating ET in resource-poor countries to curtail its unnecessary use for the prevention of kernicterus. METHODS: A review of the existing guidelines and literature on the management of neonatal hyperbilirubinemia worldwide was conducted to identify criteria and underlying factors for initiating ET. RESULTS: There is a dearth of evidence from randomized clinical trials to support clear criteria for indicated ET worldwide. Because risk assessment for kernicterus based solely on the levels of total serum bilirubin (TSB) has often proved inadequate, a combination of plasma/serum bilirubin estimation and clinical evaluation for acute bilirubin encephalopathy (ABE) has been recommended for predicting the risk of kernicterus. However, there is a lack of consistency regarding the TSB levels for which ET should be initiated in relation to the clinical signs/symptoms of ABE and hemolytic disorders. CONCLUSIONS: A decision-making framework that combines TSB thresholds and evidence of neurotoxicity is needed for evaluating the risk of kernicterus and prioritising infants for ET in LMICs to curtail unnecessary interventions.

Management of late-preterm and term infants with hyperbilirubinaemia in resource-constrained settings.

Hyperbilirubinaemia is a ubiquitous transitional morbidity in the vast majority of newborns and a leading cause of hospitalisation in the first week of life worldwide. While timely and effective phototherapy and exchange transfusion are well proven treatments for severe neonatal hyperbilirubinaemia, inappropriate or ineffective treatment of hyperbilirubinaemia, at secondary and tertiary hospitals, still prevails in many poorly-resourced countries accounting for a disproportionately high burden of bilirubin-induced mortality and long-term morbidity. As part of the efforts to curtail the widely reported risks of frequent but avoidable bilirubin-induced neurologic dysfunction (acute bilirubin encephalopathy (ABE) and kernicterus) in low and middle-income countries (LMICs) with significant resource constraints, this article presents a practical framework for the management of late-preterm and term infants (≥ 35 weeks of gestation) with clinically significant hyperbilirubinaemia in these countries particularly where local practice guidelines are lacking. Standard and validated protocols were followed in adapting available evidence-based national guidelines on the management of hyperbilirubinaemia through a collaboration among clinicians and experts on newborn jaundice from different world regions. Tasks and resources required for the comprehensive management of infants with or at risk of severe hyperbilirubinaemia at all levels of healthcare delivery are proposed, covering primary prevention, early detection, diagnosis, monitoring, treatment, and follow-up. Additionally, actionable treatment or referral levels for phototherapy and exchange transfusion are proposed within the context of several confounding factors such as widespread exclusive breastfeeding, infections, blood group incompatibilities and G6PD deficiency, which place infants at high risk of severe hyperbilirubinaemia and bilirubin-induced neurologic dysfunction in LMICs, as well as the limited facilities for clinical investigations and inconsistent functionality of available phototherapy devices. The need to adjust these levels as appropriate depending on the available facilities in each clinical setting and the risk profile of the infant is emphasised with a view to avoiding over-treatment or under-treatment. These recommendations should serve as a valuable reference material for health workers, guide the development of contextually-relevant national guidelines in each LMIC, as well as facilitate effective advocacy and mobilisation of requisite resources for the optimal care of infants with hyperbilirubinaemia at all levels.

Serum bilirubin and bilirubin/albumin ratio as predictors of bilirubin encephalopathy.

BACKGROUND AND OBJECTIVE: Bilirubin/albumin ratio (B/A) may provide a better estimate of free bilirubin than total serum bilirubin (TSB), thus improving identification of newborns at risk for bilirubin encephalopathy. The objective of the study was to identify thresholds and compare specificities of TSB and B/A in detecting patients with acute and posttreatment auditory and neurologic impairment. METHODS: A total of 193 term/near-term infants, admitted for severe jaundice to Cairo University Children's Hospital, were evaluated for neurologic status and auditory impairment (automated auditory brainstem response), both at admission and posttreatment by investigators blinded to laboratory results. The relationships of TSB and B/A to advancing stages of neurotoxicity were compared by using receiver operating characteristic curves. RESULTS: TSB and B/A ranged from 17 to 61 mg/dL and 5.4 to 21.0 mg/g, respectively; 58 (30%) of 193 subjects developed acute bilirubin encephalopathy, leading to kernicterus in 35 infants (13 lethal). Auditory impairment was identified in 86 (49%) of 173 infants at admission and in 22 of 128 at follow-up. In the absence of clinical risk factors, no residual neurologic or hearing impairment occurred unless TSB exceeded 31 mg/dl. However, transient auditory impairment occurred at lower TSB and B/A (22.9 mg/dL and 5.7 mg/g, respectively). Intervention values of TSB and B/A set at high sensitivity to detect different stages of neurotoxicity had nearly the same specificity. CONCLUSIONS: Both TSB and B/A are strong predictors of neurotoxicity, but B/A does not improve prediction over TSB alone. Threshold values detecting all affected patients (100% sensitivity) increase with advancing severity of neurotoxicity.

Urine S100 BB and A1B dimers are valuable predictors of adverse outcome in full-term asphyxiated infants.

AIM: To investigate whether S100A1B and BB dimers are predictors of early perinatal death in newborns with perinatal asphyxia (PA). METHODS: The study compared 38 full-term newborns with PA [neonatal death n = 11; hypoxic ischaemic encephalopathy (HIE): n = 27] with a control group of 38 healthy infants. Clinical and laboratory parameters were recorded at eight time points and urine collected for S100B assessment. Multivariate analysis was performed in order to analyse the influence of various clinical parameters on the occurrence of neonatal death. RESULTS: A1B and BB in PA nonsurvivor infants were significantly higher (p < 0.001) than in controls at all monitoring time points. BB at first void (cut-off>42 ng/L) was the best predictor of early neonatal death (p < 0.05) of all the clinical and laboratory parameters studied. CONCLUSION: These results suggest that S100s are valuable predictors of adverse outcome in PA infants. It is also suggested that these biomarkers be used in daily clinical practice, due to their low cost and stress, reproducibility and the possibility of longitudinal monitoring.

Perinatal asphyxia: kidney failure does not affect S100B urine concentrations.

BACKGROUND: S100B protein is a well-established marker of brain damage. Its importance in urine assessment is the convenience of a collection and sampling procedure that can be repeated without risk for the newborn. Since S100B is mainly eliminated by the kidneys and perinatal asphyxia (PA) is often associated with kidney failure we investigated whether S100B release might be kidney-mediated, thereby modifying the protein's reliability as a brain-damage marker. METHODS: We examined a cohort of healthy (n=432) and asphyxiated newborns (n=32) in whom kidney function parameters (blood urea and creatinine concentrations and urine gravity) and urine S100B concentrations were assessed in the first hours after birth. Data were analyzed by multiple logistic regression analysis with S100B as independent variable among a variety of clinical and laboratory monitoring parameters. RESULTS: S100B urine concentrations were significantly higher (P<0.01) in PA newborns than controls. No significant correlations (P>0.05, for all) between total urine S100B levels and kidney function parameters such as creatinine (r=0.03), urea (r=0.04) and urine gravity (r=0.06) were found. Multiple logistic regression analysis of a series of clinical and laboratory monitoring parameters (odds ratio at sampling: 9.47) with S100B as independent variable showed a positive significant correlation only between S100B levels (P<0.001) and the occurrence of PA. CONCLUSION: The present study shows that altered kidney function is not an adverse and/or confounding factor in urine S100B assessment and marks a new step towards the introduction of longitudinal monitoring of brain constituents in clinical practice.

Risk factors for neurotoxicity in newborns with severe neonatal hyperbilirubinemia.

OBJECTIVE: To evaluate the importance of total serum bilirubin (TSB) and neurotoxicity risk factors in predicting acute bilirubin encephalopathy (ABE) at admission or posttreatment bilirubin encephalopathy (BE) in infants with severe hyperbilirubinemia. METHODS: We analyzed the interaction of TSB and risk factors as determinants of ABE and BE in 249 newborns admitted with a TSB level of ≥ 25 mg/dL (427 µmol/L) to Cairo University Children's Hospital during a 12-month period. RESULTS: Admission TSB values ranged from 25 to 76.4 mg/dL. Forty-four newborns had moderate or severe ABE at admission; 35 of 249 infants (14%) had evidence of BE at the time of discharge or death. Rh incompatibility (odds ratio [OR]: 48.6) and sepsis (OR: 20.6) greatly increased the risk for ABE/BE, but TSB levels correlated poorly with the presence or absence of ABE or BE in these patients. The OR for ABO incompatibility with anemia (1.8) was not statistically significant. Low admission weight (OR: 0.83 per 100 g) increased the risk for BE, especially when other risk factors were present. The threshold TSB level that identified 90% of infants with ABE/BE was 25.4 mg/dL when neurotoxicity risk factors were present. In contrast, neurotoxicity was first observed at a TSB level of >31.5 mg/dL in 111 infants without risk factors. CONCLUSIONS: Newborns without risk factors for neurotoxicity have a higher tolerance for hyperbilirubinemia than recognized in management guidelines. The risk for BE in hemolytic disease varies with etiology. The great variation in response to TSB indicates that biological factors other than TSB values are important in the pathogenesis of BE.

MEFV mutations in Egyptian patients suffering from familial Mediterranean fever: analysis of 12 gene mutations.

The objective of the study is to screen 12 MEFV gene mutations in Egyptian patients with familial Mediterranean fever (FMF) and to study the initial hypothesis that the phenotypic expression of the disease may be attributable to the existence of a particular mutation. We enrolled 136 Egyptian patients (74 males, and 62 females) with a clinical diagnosis of FMF. DNA was amplified by PCR and subjected to reverse hybridization for the detection of 12 MEFV gene mutations. The phenotypic expression of the disease was compared in two subgroups according to the presence of homozygote E148Q and M694V gene mutations. The most frequent gene mutations in the studied group were V726A, M694V, M680I, E148Q and M694I in 41.2, 32.4, 29.4, 25 and 20.6%, respectively. At least one of these main five founder mutations was present in 132 patients (97.1%). Thirty-two patients (23.5%) were homozygote for one of the main five founder mutations. The most common homozygote gene mutations were E148Q and M694V, each in 12 patients (8.8%). Significant increase in abdominal pain and arthritis was found in patients with homozygote M694V mutation compared to those with E148Q mutation. All patients with amyloidosis had M694V gene mutation. The increased frequency of V726A gene mutation and the rarity of amyloidosis in this study suggest that Egyptian patients may have a milder form of FMF compared to other populations. The five main founder mutations account for the vast majority of cases of FMF. M694V gene mutation may be associated with increased frequency of abdominal pain, arthritis and the presence of amyloidosis.

Urinary S100A1B and S100BB to predict hypoxic ischemic encephalopathy at term.

Urinary S100A1B and S100BB were measured to detect cases at risk of hypoxic-ischemic encephalopathy (HIE) in asphyxiated newborns. We recruited 42 asphyxiated infants and 63 healthy term neonates. S100A1B and S100BB were measured at first urination (time 0) and at 4 (time 1), 8 (time 2), 12 (time 3), 16 (time 4), 20 (time 5), 24 (time 6), 72 (time 7) hours after birth. 20 infants had no/mild HIE with good prognosis (Group A) and 22 had moderate/severe HIE with a greater risk of neurological handicap (Group B). Urine S100A1B and S100BB levels were significantly (P less than 0.0.01, for all) higher at all monitoring time-points in Group B than Group A and controls, but not between Group A and controls. Both S100A1B and S100BB have great sensitivity and specificity for HIE since their first measurement. In conclusion, S100A1B and S100BB are increased in urine collected from asphyxiated newborns who will develop HIE since first urination, and their measurement may be useful to early predict HIE when monitoring procedures are still of no avail.

Diagnostic accuracy of S100B urinary testing at birth in full-term asphyxiated newborns to predict neonatal death.

BACKGROUND: Neonatal death in full-term infants who suffer from perinatal asphyxia (PA) is a major subject of investigation, since few tools exist to predict patients at risk of ominous outcome. We studied the possibility that urine S100B measurement may identify which PA-affected infants are at risk of early postnatal death. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study between January 1, 2001 and December 1, 2006 we measured S100B protein in urine collected from term infants (n = 132), 60 of whom suffered PA. According to their outcome at 7 days, infants with PA were subsequently classified either as asphyxiated infants complicated by hypoxic ischemic encephalopathy with no ominous outcome (HIE Group; n = 48), or as newborns who died within the first post-natal week (Ominous Outcome Group; n = 12). Routine laboratory variables, cerebral ultrasound, neurological patterns and urine concentrations of S100B protein were determined at first urination and after 24, 48 and 96 hours. The severity of illness in the first 24 hours after birth was measured using the Score for Neonatal Acute Physiology-Perinatal Extension (SNAP-PE). Urine S100B levels were higher from the first urination in the ominous outcome group than in healthy or HIE Groups (p<0.001 for all), and progressively increased. Multiple logistic regression analysis showed a significant correlation between S100B concentrations and the occurrence of neonatal death. At a cut-off >1.0 microg/L S100B had a sensitivity/specificity of 100% for predicting neonatal death. CONCLUSIONS/SIGNIFICANCE: Increased S100B protein urine levels in term newborns suffering PA seem to suggest a higher risk of neonatal death for these infants.

Topically applied sunflower seed oil prevents invasive bacterial infections in preterm infants in Egypt: a randomized, controlled clinical trial.

BACKGROUND: Because the therapeutic options for managing infections in neonates in developing countries are often limited, innovative approaches to preventing infections are needed. Topical therapy with skin barrier-enhancing products may be an effective strategy for improving neonatal outcomes, particularly among preterm, low birth weight infants whose skin barrier is temporarily but critically compromised as a result of immaturity. METHODS: We tested the impact of topical application of sunflower seed oil 3 times daily to preterm infants <34 weeks gestational age at the Kasr El-Aini neonatal intensive care unit at Cairo University on skin condition, rates of nosocomial infections and mortality. RESULTS: Treatment with sunflower seed oil (n = 51) resulted in a significant improvement in skin condition (P = 0.037) and a highly significant reduction in the incidence of nosocomial infections (adjusted incidence ratio, 0.46; 95% confidence interval, 0.26-0.81; P = 0.007) compared with infants not receiving topical prophylaxis (n = 52). There were no reported adverse events as a result of topical therapy. CONCLUSIONS: Given the low cost (approximately .20 dollars for a course of therapy) and technologic simplicity of the intervention and the effect size observed in this study, a clinical trial with increased numbers of subjects is indicated to evaluate the potential of topical therapy to reduce infections and save newborn lives in developing countries.