Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective (i) unconjugated bilirubin uptake and intrahepatic storage, (ii) conjugation of glucuronic acid to bilirubin (e.g., Gilbert syndrome, Crigler–Najjar syndrome, Lucey–Driscoll syndrome, breast milk jaundice), (iii) bilirubin excretion into bile (Dubin–Johnson syndrome), or (iv) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy.

Background: Human milk, which contains compounds beneficial to infants, is often expressed and stored before use. Changes in its antioxidant activity with storage have not been studied. Objectives: To measure antioxidant activity of fresh, refrigerated (4°C), and frozen human milk (−20°C), stored for two to seven days; to compare the antioxidant activity of milk from mothers delivering prematurely and at term; to compare the antioxidant activity of infant formulas and human milk. Methods: Sixteen breast milk samples (term and preterm) were collected from mothers within 24 hours of delivery and divided into aliquots. Fresh samples were immediately tested for antioxidant activity, and the rest of the aliquots were stored at −20°C or 4°C to be analysed at 48 hours and seven days respectively. The assay used measures the ability of milk samples to inhibit the oxidation of 2,2′-azino-di-3-(ethylbenzthiazolinesulphonate) to its radical cation compared with Trolox. Results: Antioxidant activity at both refrigeration and freezing temperatures was significantly decreased. Freezing resulted in a greater decrease than refrigeration, and storage for seven days resulted in lower antioxidant activity than storage for 48 hours. There was no difference in milk from mothers who delivered prematurely or at term. Significantly lower antioxidant activity was noted in formula milk than in fresh human milk. Conclusions: To preserve the antioxidant activity of human milk, storage time should be limited to 48 hours. Refrigeration is better than freezing and thawing.

Objective. Coagulase-negative staphylococci (CONS) are the most common causative agents in neonatal nosocomial septicemia. Because of widespread methicillin resistance among CONS, empiric therapy with vancomycin is recommended as the primary antibiotic regimen for these infections. In our unit, empiric treatment of nosocomially acquired septicemia consists of cephalothin and gentamicin, which are adjusted subsequently according to the determined bacterial susceptibility profile. Vancomycin is initiated only when the patient has been treated recently with cephalothin or when intravascular lines or endotracheal tube are colonized with oxacillin/cephalothin-resistant CONS strains. The aim of the present study was to evaluate the efficacy of our antibiotic regimen for CONS septicemia, in relation to methicillin-resistance and the carriage ofmec A gene, encoding methicillin resistance, among CONS blood isolates from our unit. Methods. Clinical symptoms of septicemia, clinical outcome, and laboratory parameters of septicemia (C-reactive protein) were studied retrospectively in 66 patients with CONS septicemia. The diagnosis of septicemia was made by the attending neonatologist and was defined by clinical symptoms of septicemia in the presence of a positive finding of a blood culture test, which was performed using a defined protocol. All CONS blood isolates were included to determinemec A gene carriage. Results. In the 66 patients, three treatment categories were distinguished: treatment with cephalothin (25 patients, 38%); with vancomycin (15 patients, 23%); and primary treatment with cephalothin, switched subsequently to vancomycin (26 patients, 39%). It was found that 92% of all CONS blood isolates (61/66) weremec A-positive. Concordance of mec A gene carriage with methicillin/oxacillin resistance was found in 56 of 66 isolates (85%); 10 of 61 (16%) isolates that were mec A-positive were determined as oxacillin-susceptible. Although 22 of the 25 blood isolates of the cephalothin-treated patients weremec A-positive, clinical recovery was uneventful. In the 26 patients in whom antibiotic therapy was switched from cephalothin to vancomycin, two strains were cephalothin-susceptible and 8 patients already had recovered clinically before the switch, which was based solely on susceptibility test results. Conclusions. Cephalothin was found to be clinically efficacious in the treatment of neonatal CONS septicemia, despite a steadily increasing mec A gene carriage of CONS blood isolates in our neonatal intensive care unit and a corresponding high methicillin/oxacillin resistance. Hence, cephalothin remained the antibiotic of first choice in the treatment of CONS septicemia in our unit, with vancomycin selected exclusively for cases not responding to initial cephalothin treatment, or for patients developing CONS septicemia during or after recent cephalothin treatment. By applying this approach in our unit, we were able to reduce vancomycin use from 62% in 1994 to 1995 to 21% in 1997. This shows that such a policy may result in an important reduction of vancomycin use, which may aid in postponing the threatening emergence of vancomycin resistance among Gram-positive cocci.

Research from JAMA Pediatrics — Effect of Chorioamnionitis on Neurodevelopmental Outcome in Preterm Infants

Incidence and time of onset of germinal matrix/intraventricular hemorrhage (GM/IVH) were prospectively ascertained in 1,105 infants weighing ≤2,000 g at birth, a cohort comprising about 85% of all births of that weight born from September 1984 to June 1987 in the central New Jersey counties of Ocean, Monmouth, and Middlesex. Cranial ultrasonography was performed as nearly as possible to age 4 hours, 24 hours, and 7 days. Each scan was reviewed by two Independent readers and, if necessary, a third; consensus was achieved on scan of first diagnosis of GM/IVH in 965 of the 1,079 infants with assessable scans. The cumulative incidence of GM/IVH in the first week of life was 24.6% (265/1,079). In the 965 infants with consensus diagnoses, the first scan, at 4.9 ± 2.2 hours, yielded the highest incidence-10.6% (95/899). Incidence by the second scan (25.1 ± 4.9 hours) was 6.0% (49/813), and by the third scan (7.2 ± 0.8 days), 9.0% (64/715). The iterative algorithm for interval-censored data developed by Tumbull (J R Stat Soc [B] 1976;8:290–5) was used to estimate the most likely time of onset based on time of first diagnosis. From 34% to 44% of hemorrhages were present at the first opportunity to scan, which in these data was at age 1 hour. At least a third of GM/IVH in infants ≤2,000 g appears to be of congenital or immediate postnatal onset.