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.

Neonatal diabetes can be either permanent or transient. We have recently shown that permanent neonatal diabetes can result from complete deficiency of glucokinase activity. Here we report three new cases of glucokinase-related permanent neonatal diabetes. The probands had intrauterine growth retardation (birth weight <1,900 g) and insulin-treated diabetes from birth (diagnosis within the first week of life). One of the subjects was homozygous for the missense mutation Ala378Val (A378V), which is an inactivating mutation with an activity index of only 0.2% of wild-type glucokinase activity. The second subject was homozygous for a mutation in the splice donor site of exon 8 (intervening sequence 8 [IVS8] ؉ 2T3 G), which is predicted to lead to the synthesis of an inactive protein. The third subject (second cousin of subject 2) was a compound heterozygote with one allele having the splice-site mutation IVS8 ؉ 2T3 G and the other the missense mutation Gly264Ser (G264S), a mutation with an activity index of 86% of normal activity. The five subjects with permanent neonatal diabetes due to glucokinase deficiency identified to date are characterized by intrauterine growth retardation, permanent insulin-requiring diabetes from the first day of life, and hyperglycemia in both parents. Autosomal recessive inheritance and enzyme deficiency are features typical for an inborn error of metabolism, which occurred in the glucose-insulin signaling pathway in these subjects. Diabetes 52: 2854 -2860, 2003 N eonatal diabetes, insulin-requiring hyperglycemia occurring within the first month of life is often associated with intrauterine growth retardation (IUGR) and can be either transient or permanent (1). Transient neonatal diabetes is associated with abnormalities of chromosome 6, including paternal uniparental disomy and paternal duplications of 6q24, with loss of imprinting (1,2) and increased risk of diabetes later in life. Mutations in the insulin promoter factor-1, a transcription factor implicated in pancreatic development and the regulation of insulin gene expression, result in permanent neonatal diabetes (PNDM) caused by pancreatic agenesis (3). We have recently shown that complete deficiency of the glycolytic enzyme glucokinase is another cause of PNDM (4). Two patients presented with IUGR, permanent insulin requirement from shortly after birth and homozygosity for mutations in the glucokinase gene (GCK). Here we present the results of screening eight cases of PNDM for mutations in glucokinase. Three of these had glucokinase-related PNDM, including a subject who inherited different inactivating mutations from each parent. RESEARCH DESIGN AND METHODSSubjects. The screening included eight cases of PNDM, defined as a diagnosis of permanent diabetes before age 1 month. The probands of families 1-3 were identified by one of the authors (P.R.N.) by a PubMed literature search, after which the corresponding authors (N.S. and S.U.S.) were contacted. The other PNDM patients were from the Department of Pediatrics, University of Be...

ABSTRACT. 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 >5 mg/dL and an increase in serum total bilirubin concentration of >0.5 mg/dL/h in the first 24 hours, >12 mg/dL on day 2, >15 mg/dL on day 3, and >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 >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 >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 perc...

A serum bilirubin measurement and the use of the critical bilirubin level of 6 mg/dL in the first 24 hours of life will predict nearly all of the term newborns who will have significant hyperbilirubinemia and will determine all those who will require a phototherapy treatment later during the first days of life.

A controlled study was conducted to assess the role of high-dose i.v. immunoglobulin (HDIVIG) therapy in neonatal immune haemolytic jaundice. Patients with ABO and/or Rh incompatibilities proved by significant hyperbilirubinaemia (>204 mmol l(-1)), positive direct antiglobulin test and high reticulocyte count (> or =10%) were randomly assigned to receive either conventional phototherapy alone or phototherapy with high-dose i.v. immunoglobulin (1 g kg(-1), over 4 h) as soon as the diagnosis was established. Exchange transfusions were performed if serum bilirubin concentrations exceeded 290 mmol l(-1) and increased by more than 17 mmol l(-1) per h despite both treatment manoeuvres. Eight of 58 patients in the HDIVIG group required exchange transfusions, whereas it became necessary in 22 of 58 patients in the control group (p<0.001). The durations of phototherapy and hospitalization in terms of hours were significantly shorter in the HDIVIG group (p<0.05). No side effects of HDIVIG therapy were observed. In conclusion, HDIVIG therapy in newborns with ABO or Rh haemolytic diseases reduces haemolysis, serum bilirubin levels and the need for blood exchange transfusion, a procedure which has potential complications and carries a risk of mortality.