M. Knüpfer

Transcutaneous bilirubinometry in preterm infants

The aim of this study was to evaluate the accuracy and safety of transcutaneous bilirubinometry in preterm infants using the new bilirubin analyser BiliCheck±. The study included 145 preterm children (23–36 wk gestation). Capillary blood sampling for determination of serum bilirubin (BS) was combined with transcutaneous bilirubin measurement (BTc) every morning until the sixth postnatal day and related to several clinical data (phototherapy (PT), infection signs, breathing disturbances, skin bleeding, etc.). Overall bilirubin concentration ranged from 17 to 371 μmol/l, and from 21 to 325 μmol/l for BS and BTc, respectively. Mean values obtained by BTc were significantly higher than BS values. The correlation coefficient between BS and BTc was r= 0.64 for the whole group, and r= 0.73 in infants without PT. As demonstrated by multiple regression analysis, BS‐BTc correlations were related only to gestational age (beta ‐0.32) and breathing disturbances (beta 0.29), indicating that the lower the gestational age and the more seriously ill the baby, the higher the incoherence between BS and BTc.

Cardiac adaptation in small for gestational age neonates after prenatal hemodynamic disturbances

BACKGROUND Small for gestational age neonates with prenatal hemodynamic disturbances are at increased risk for neonatal morbidity. Investigations of fetal cardiac function have proved some functional impairments. The aim of the study was to investigate postnatal cardiac adaptation in these neonates in comparison with neonates without prenatal hemodynamic impairments. METHODS AND RESULTS Forty-one neonates with prenatal hemodynamic disturbances and 40 neonates with undisturbed prenatal hemodynamics were observed during the first 5 days of life. Doppler sonographic measurements of left ventricular time intervals, stroke volume, cardiac output and the incidence of patent ductus arteriosus were obtained in all neonates of both groups. Heart rate and blood pressure were recorded simultaneously. RESULTS A higher incidence of patent ductus arteriosus and a diminished stroke volume, but increased cardiac output, based on a significantly increased heart rate, were determined in SGA neonates with prenatal hemodynamic disturbances. In contrast, systolic left ventricular time intervals were not changed in these neonates, as expected. CONCLUSIONS The described findings could be signs of persistent hemodynamic impairments in growth-retarded neonates with prenatal disturbed hemodynamics. The neonates revealed a reduced ability to compensate the prenatal hemodynamic disturbances. This aspect should be included in the discussion of perinatal management in cases of severe growth retardation.

Cisplatin (CDDP)-induced radiation resistance is not associated with CDDP resistance in 86HG39 and A172 malignant glioma cells

Malignant gliomas are often treated with cisplatin (cis-diamminedichloroplatinum(II), CDDP) and radiation but results remain unsatisfactory. The development of resistance might explain the poor prognosis. The aim of this study was to investigate whether two human malignant glioma cell lines, 86HG39 and A172, develop resistance to CDDP and/or radiation after CDDP pretreatment. The cells are incubated three times with 10(-6) M CDDP for 24 h, allowed to recover from the treatment and then tested for sensitivity to CDDP and radiation (9 Gy, 60Co) using a colorimetric assay (MTT). A172 pretreated and wild-type cells showed no difference in sensitivity to CDDP, whilst 86HG39 cells became more sensitive following pretreatment. This indicates that no resistant phenotype towards CDDP developed in any of the cell lines. In contrast, the CDDP-pretreated cells, after radiation, had significantly higher growth rates compared with the wild-type cells in both cell lines (A172: 4.4 +/- 0.5 versus 2.5 +/- 0.3, respectively, 192 h after radiation; 86HG39: 6.2 +/- 0.7 versus 2.3 +/- 0.3, respectively, 216 h after radiation; P < 0.05) indicating resistance against radiation. The level of glutathione (GSH), which is known to mediate resistance against radiation, was 157.2 +/- 61.3 ng/mg protein in A172 cells and 93.2 +/- 16.9 ng/mg protein in 86HG39 cells, and there was no significant difference between levels in wild-type and pretreated cells (A172: 130.1 +/- 34; 86HG39: 81.6 +/- 10.4). These data show that CDDP pretreatment can induce resistance against radiation in vitro independently of CDDP cross-resistance mediated by a mechanism different from GSH.

Cesarean section increases the risk of respiratory adaptive disorders in healthy late preterm and two groups of mature newborns.

The rates of delivery by Cesarean section (CS) have been trending upwards in recent decades, perhaps leading to higher rates of dysfunction in respiratory adaptation in newborns. We present epidemiological data for pulmonary adaptation by mode of delivery for healthy late preterm and term infants born at a regional tertiary care center. The overall CS rate was 22% with the largest proportion of these in late preterms (39%). This drops to 30% in infants born after 37 weeks gestation and to 11% for those born after 40 weeks. Infants needing respiratory support decreased significantly as gestational age increased: 88% at 34 weeks, 67% at 35 weeks, 28% at 36 weeks, 17% at 37 weeks and 8% at 40 weeks. The risk of respiratory morbidity following CS as compared to vaginal delivery (VD) was substantially higher. 50% of infants born by CS needed respiratory support compared to only 12% following VD. 82% of all late preterm infants born by CS developed respiratory morbidity compared to 36% following VD. Comparable data for infants born after 37 and 40 weeks gestation were 33% compared to 9% and 26% compared to 6% respectively. Late preterm infants born after 36 weeks gestation showed the most marked difference by mode of birth with 66% needing respiratory support following CS as compared to only 9% following VD. Our data could be useful in counselling parents about risk associated with delivery by Cesarean section. A critical view should be taken of increasing CS rates worldwide because of a clear correlation in increased morbidity in infants, especially late preterm infants.

Clinical Management of Small-for-Gestational-Age Babies

As is well known, the long-term outcome of small-for-gestational-age (SGA) children is impaired, when compared to appropriate-for-gestational-age (AGA) children. Opposite to the long-term outcome, this article deals with the immediate postnatal clinical situation of preterm SGA children and shows that these children need some special considerations. The article tries to give rules for the termination of gestation and the preferable way of delivery. Immediately after delivery many data show that SGA preterm infants have more complications compared to AGA children. When analyzing development in the first postnatal days, it has to be stated that SGA children generally have more difficulties compared to their AGA counterparts. First, this article analyses the literature to get an analysis of the particularities of SGA children. We then describe our own experiences with the management of this patient group. Some clinical recommendations for diagnostic and therapeutic strategies are given at the end of each section.

Gastric perforation in a newborn.

THE LANCET • Vol 363 • February 28, 2004 • www.thelancet.com 703 35 Anastasiou R, Papadelli M, Georgalaki MD, Kalantzopoulos G, Tsakalidou E. Cloning and sequencing of the gene encoding X-prolyldipeptidyl aminopeptidase (PepX) from Streptococcus thermophilus strain ACA-DC 4. J Appl Microbiol 2002; 93: 52–59. 36 Goldstein JM, Banbula A, Kordula T, Mayo JA, Travis J. Novel extracellular x-prolyl dipeptidyl-peptidase (DPP) from Streptococcus gordonii FSS2: an emerging subfamily of viridans Streptococcal x-prolyl DPPs. Infect Immun 2001; 69: 5494–501. 37 Jones CH, Bolken TC, Jones KF, Zeller GO, Hruby DE. Conserved DegP protease in gram-positive bacteria is essential for thermal and oxidative tolerance and full virulence in Streptococcus pyogenes. Infect Immun 2001; 69: 5538–45. 38 Harris TO, Shelver DW, Bohnsack JF, Rubens CE. A novel streptococcal surface protease promotes virulence, resistance to opsonophagocytosis, and cleavage of human fibrinogen. J Clin Invest 2003; 111: 61–70.

Treatment of myocardial dysfunction and pulmonary oedema in an infant chimpanzee.

Abstract:  The care of any critically ill infant requires special technical equipment for monitoring of cardiac and pulmonary functions including mechanical ventilators and blood gas analysers. The present paper describes the treatment of myocardial dysfunction and pulmonary distress, complicated by severe brain oedema in an infant chimpanzee admitted to an intensive care unit in the Department of Neonatology of the Childrens Hospital of the University of Leipzig. The condition of the chimpanzee was diagnosed and monitored by standard clinical tooös including radiography, echocardiography, cerebral Doppler sonography and laboratory parameters. The chimpanzee was treated in close cooperation between veterinarians and paediatricians.

Predictive value of umbilical cord blood bilirubin for postnatal hyperbilirubinaemia: Umbilical cord blood bilirubin and hyperbilirubinaemia

Aim: The study investigated the predictive value of umbilical cord serum (UCS) bilirubin for the postnatal course of bilirubinaemia in healthy term and near‐term newborns. Methods: Term appropriate‐for‐gestational‐age (AGA; n=1100), small‐for‐gestational‐age (SGA; n=163) and near‐term infants (GA 34–36 wk; n=78) were included and separated according to their UCS bilirubin levels, starting from <20 (group 1), 20–<30 (2), 30–40 (3) and >40 (4) μmol/l. The newborns were followed for at least 5 postnatal days, and UCS bilirubin values were correlated with the development of hyperbilirubinaemia and phototherapy (PT) treatment. Results: A clear relation between UCS bilirubin and the development of hyperbilirubinaemia was found in all three patient populations. None of the 75 AGA patients of group 1 developed postnatal bilirubin values above 300 μmol/l, whereas 0.3, 3.4 and 8.6% of the patients in groups 2–4, respectively, did so. The frequency of PT increased from 0% in group 1 up to 9.6% in group 4. For the prediction of further need of PT using a UCS bilirubin cut‐off level of 30 μmol/l, we found a sensitivity of 90% and a negative predictive value of 99.1%, indicating that all patients with UCS bilirubin values below 30 μmol/l (443/1100 or 40.2%) were at a very low risk of developing dangerous hyperbilirubinaemia. Similar results were obtained in SGA children with a sensitivity of 94.1% and a negative predictive value of 98.6%. In comparison to term newborns, we generally found higher bilirubin values in preterms. A total of 6.4% of preterm children developed bilirubin values over 300 μmol/l, compared with 3% of term children, and 47.4% of preterms had to be treated with PT. Predicting the need of PT by using a UCS bilirubin cut‐off level of 30 μmol/l revealed a sensitivity of 70.3% and a negative predictive value of 65.6%.

Frühgeborenes mit auffälligem Phänotyp

Ein weibliches Frühgeborenes der 31. Schwangerschaftswoche zeigt auffällige Veränderungen wie einen glockenförmigen Thorax, ein ausladendes Abdomen und weitere Dysmorphiezeichen. Die humangenetische Untersuchung ergab eine paternale uniparentale Disomie 14.

Life-Threatening QT Prolongation in a Preterm Infant

Introduction Temporary QT-interval prolongation following intracranial hemorrhage and hydrocephalus has been repeatedly reported in adults. Case We report a case of excessive QT prolongation with sudden bradycardia resulting in 2:1 atrioventricular conduction in a preterm infant most likely associated with a congenital hydrocephalus. Pathomechanisms are discussed. Conclusion Congenital hydrocephalus predisposes to excessive QT prolongation in preterm infants.