[Universal newborn hearing screening. Methodical aspects]. / Universelles Neugeborenen-Hörscreening. Aspekte des methodischen Vorgehens.

BACKGROUND: In order to prepare for the introduction of a universal newborn hearing screening program on a larger scale, TEOAE and ABR were recorded on automated screening instruments from both ears of 501 newborns at the University Hospital Heidelberg over a period of 13 months. The parents of children in whom OAE and ABR could not be detected in both ears, were requested to allow a complete exploration of the auditory status of the children at the department of pediatric audiology. SUBJECTS AND METHODS: Internally available data networks were used for the acquisition and evaluation of data and for the organization of tracking and follow-up. Of the children 35% exhibited risk factors for congenital hearing impairment. RESULTS: The pass rate was 98.7% for the exclusion of binaural and 91.6% for monaural hearing disorders (TEOAE or ABR detectable). On the basis of the data it can be shown how pass rates can be optimized by selecting a suitable moment for the examination and by prescribing a minimum number of test repetitions (3 for TEOAE and 2 for AABR). CONCLUSION: Quality control of screening programs should include these parameters and, in particular the number of repetitions of test measurements in all screening steps.

Effects of a divided high loading dose of caffeine on circulatory variables in preterm infants.

BACKGROUND: A single high loading dose of 25 mg/kg caffeine has been shown to be effective for the prevention of apnoea, but may result in considerable reductions in blood flow velocity (BFV) in cerebral and intestinal arteries. OBJECTIVE: To assess the effects of two loading doses of 12.5 mg/kg caffeine given four hours apart on BFV in cerebral and intestinal arteries, left ventricular output (LVO), and plasma caffeine concentrations in preterm infants. DESIGN: Sixteen preterm neonates of <34 weeks gestation were investigated one hour after the first oral dose and one, two, and 20 hours after the second dose by Doppler sonography. RESULTS: The mean (SD) plasma caffeine concentrations were 31 (7) and 29 (7) mg/l at two and 20 hours respectively after the second dose. One hour after the first dose, none of the circulatory variables had changed significantly. One hour after the second caffeine dose, mean BFV in the internal carotid artery and anterior cerebral artery showed significant reductions of 17% and 19% (p = 0.01 and p = 0.003 respectively). BFV in the coeliac artery and superior mesenteric artery, LVO, PCO2, and respiratory rate had not changed significantly. Total vascular resistance, calculated as the ratio of mean blood pressure to LVO, had increased significantly one and two hours after the second dose (p = 0.049 and p = 0.023 respectively). CONCLUSION: A divided high loading dose of 25 mg/kg caffeine given four hours apart had decreased BFV in cerebral arteries after the second dose, whereas BFV in intestinal arteries and LVO were not affected.

Introducing DoT-U2--an XML-based knowledge supported checklist software for documentation of a newborn clinical screening examination.

In a project concerning the German newborn screening examination "U2" we developed a software system called DoT-U2 for concurrent documentation at the point of care. Physicians can enter findings in(to) a tree structured protocol with management of logical dependencies. Additionally, all findings except free text annotations can be entered by speech recognition. The software system program is written in Java and uses separate XML-based modules both for knowledge and language representation. It can, therefore, easily be adapted to other languages and further documentation scenarios. We showed the high flexibility of the software system by integrating it in a completely new setting in Salt Lake City without major problems. We found that modular software development with platform independent Java and XML leads to highly flexible software which can be adapted to very different scenarios without knowing their requirements ahead of time.

Hepatic failure with neonatal tissue siderosis of hemochromatotic type in an infant presenting with meconium ileus. Case report and differential diagnosis of the perinatal iron storage disorders.

We report on a female preterm infant with hepatic failure and neonatal tissue siderosis of hemochromatotic type diagnosed by using both histochemistry and atomic absorption spectroscopy. The infant presented with meconium ileus, signs of rapidly progressive hepatic failure, and hyperferritinemia (7132 ng/ml). Despite surgery and intensive care the infant died 32 days after birth. Postmortem examination showed a wrinkled liver with extensive collapse of the hepatic architecture and regenerating nodules as well as hepatic and extrahepatic iron accumulation of hemochromatotic type, sparing the reticuloendothelial system. Atomic absorption spectroscopy confirmed an increase in the iron content of various organs: liver, heart, pancreas, oral salivary gland, kidney, and adrenal gland. The increase in the iron content of various organs was determined by comparing the analysis of the propositus with those of 5 gestationally age-related preterm infants who had died in the intensive care unit: 2 died of meconium aspiration syndrome, the other 3 of hyaline membrane disease, bronchopulmonary dysplasia, and immaturity, respectively. We also compared the analysis of 15 fetuses having a a condition predisposing to iron accumulation (trisomy 21, trisomy 18, cytomegalovirus, amnion infection syndrome, Rhesus- and ABO-incompatibility, congenital hemolysis, anti-phospholipid syndrome, congenital heart disease). Delta F508, the most frequent mutation seen in cystic fibrosis patients, was excluded by gene sequencing. Different noxae causing iron accumulation in the neonatal period have led to the statement that neonatal hemochromatosis may collect different etiologies, such as metabolic disorders, infections, chromosomal aberrations, and immunological disorders. In this study, we report the singular evidence of neonatal iron accumulation of hemochromatotic type in an infant presenting with meconium ileus and propose a classification of the neonatal disorders associated with iron accumulation.

Identification of a subtle t(16;19)(p13.3;p13.3) in an infant with multiple congenital abnormalities using a 12-colour multiplex FISH telomere assay, M-TEL.

There is increasing evidence that cytogenetically invisible chromosome rearrangements are an important cause of genetic disease. Clues to the chromosomal location of these rearrangements may be provided by a specific clinical diagnosis, which can then be investigated by targeted FISH or molecular studies. However, the phenotypic features of some microdeletion syndromes are difficult to recognise, particularly in infants. In addition, the presence of other chromosome aneuploidy may mask the typical clinical features. In the present study, the presence of tubers on cranial magnetic resonance imaging (MRI) of a 5-week-old infant prompted an investigation, by FISH, with probes from the tuberous sclerosis gene, TSC2. This and further FISH deletion mapping studies revealed a submicroscopic deletion encompassing the entire TSC2 gene and the adjacent PKD1 gene on one chromosome 16, confirming a del(16)(p13.3). Because of the large number of abnormal phenotypic features in this infant, we performed a 12-colour FISH assay (M-TEL) to screen for subtelomeric rearrangements involving the del(16p). The M-TEL assay revealed a cryptic der(16)t(16;19)(p13.3;p13.3). Further FISH with 19p and 19q subtelomeric probes demonstrated that this was derived from a balanced maternal t(16;19)(p13.3;p13.3). Importantly, 24-colour painting by multiplex FISH (M-FISH) failed to detect the translocation in either the infant or his mother. Based on our FISH mapping studies, we estimate the size of the trisomic region from 19p13.3 to be approximately 2 Mb, and the region of monosomy for 16p13.3 as 2.25 Mb. This case adds to the growing literature which indicates that many apparent chromosomal deletions are unbalanced translocations. The M-TEL assay provides a sensitive alternative to M-FISH for the detection of these subtle telomeric rearrangements.

Refractory congenital ascites as a manifestation of neonatal sialidosis: clinical, biochemical and morphological studies in a newborn Syrian male infant.

A Syrian newborn with coarse facies, hepato-splenomegaly, and refractory ascites is reported. Examination of the ascitic fluid showed vacuolated lymphocytes and thin-layer chromatography of urinary oligosaccharides revealed an abnormal pattern indicative of sialidosis. Despite intensive care, the baby died of respiratory insufficiency 28 days after birth. In cultured skin fibroblasts an increase of the incorporation of [14C]methylamine pointed to excessive lysosomal storage and the demonstration of an isolated deficiency of alpha-N-acetylneuraminidase (sialidase) led to the diagnosis of a sialidosis. At postmortem examination, foam cells were found mostly in bone marrow, liver, and brain. To date very few cases of neonatal sialidosis have been reported, and, to the best of our knowledge, this is the first child with neonatal sialidosis from Syria and the first case of neonatal sialidosis studied by the [14C]methylamine incorporation assay.

Huge fetal sacrococcygeal teratoma with a completely formed eye and intratumoral DNA ploidy heterogeneity.

Preterm infants and newborns with sacrococcygeal teratomas are at high risk for prenatal and perinatal complications. The prognosis depends on size and histology of the tumor, degree of prematurity, associated malformations, route of delivery, and prompt and complete surgical removal. Virtually any tissue can be present in a sacrococcygeal teratoma, but to date, ocular lens has been documented only as lentinoids (lens-like cells), whereas flow-cytometric data have been variably interpreted. We describe a case of a sacrococcygeal teratoma in an infant of 29 weeks gestational age that is remarkable for the weight (4500 g), the presence of a completely formed eye, and intratumoral DNA ploidy heterogeneity.

Fatal course of veno-occlusive disease of the liver (endophlebitis hepatica obliterans) in a preterm infant.

We describe the fatal course of a preterm infant of 34 weeks' gestation with veno-occlusive disease of the liver and refractory ascites. Despite aggressive medical management, the baby died twenty-two hours post partum because of cerebral haemorrhage before potentially life-saving organ transplantation could take place. At autopsy, paucity of lymphoid tissue in lymph nodes, thymus, spleen, and gastrointestinal tract were also seen. To our knowledge, this is the youngest infant with veno-occlusive disease of the liver reported in the literature.

Wolf-Hirschhorn syndrome: case report and review of the chromosomal aberrations associated with diaphragmatic defects.

A female fetus showing severe growth retardation was delivered at 31 weeks of gestation because of fetal distress. At birth, the infant showed bradycardia and no spontaneous breathing. Although high frequency oscillatory ventilation was started, severe asphyxia persisted and the infant died of respiratory insufficiency. At the autopsy, the propositus showed microcephaly, prominent glabella, broad bridge of the nose, ocular hypertelorism, poorly differentiated and low-set ears, bilateral palatoschisis, and micrognathia. Midline closure defects of the cervical spine bodies, lower jaw, and skull base were seen at postmortem radiography. An extreme hypoplasia of both lungs, a large defect of the left diaphragm with upward displacement of viscera, and multiple cortical cysts in both kidneys were seen at postmortem examination. Karyotyping revealed a chromosomal imbalance with 46, XX, del(4) (pter-->13), characterizing the Wolf-Hirschhorn syndrome. Because diaphragmatic defects can occur in association with specific recognizable patterns of human malformation careful pathologic and genetic workup of all affected infants in crucial for accurate genetic counseling.

Meconium aspiration syndrome complicated by massive intravascular thrombosis.

Fetal aspiration of meconium in amniotic fluid during fetal distress by newborn infants can induce the meconium aspiration syndrome (MAS), a form of neonatal respiratory distress. Should this event occur, admission to a Neonatal Intensive Care Unit and vigorous airway management and monitoring are required. We present a term gestation resulting in MAS complicated by a massive intravascular thrombosis. Despite airway management considered appropriate, the infant developed respiratory distress a few hours after birth and died 5 days later. Postmortem examination showed a diffuse alveolar damage of the lungs with alveoli filled with meconium and amniotic epithelial cells as well as disseminated thrombi in the pulmonary vascular tree, portal system, suprahepatic veins, and peripheral arterial vascular tree.

[Bronchopulmonary dysplasia. Retrospective analysis of various forms of treatment and development of a staged therapeutic plan]. / Bronchopulmonale Dysplasie. Retrospektive Analyse verschiedener Behandlungsformen und Entwurf eines therapeutischen Stufenplans.

50 premature infants with bronchopulmonary dysplasia (BPD) were treated in the Perinatal Center of the University of Heidelberg from January 1990 to December 1992. Gestational age was 24-31 weeks and birthweight was 500 to 1430 grams. 27 infants received dexamethasone only and 14 were initially given dexamethasone followed by beclomethasone inhalation. Nine infants without assisted ventilation were only treated with inhaled beclomethasone. Infants with fluid intake > 150 ml/kg/d and < or = 150 ml/kg/d were analysed separately. Extubation in ventilated infants was possible 1 to 29 days after the beginning of dexamethasone treatment. Most infants who were not ventilated any more could be weaned from oxygen during the period of dexamethasone treatment. Inhaled beclomethasone allowed reduction in supplemental oxygen in all infants. Effects of treatment with dexamethasone and beclomethasone were similar in infants with fluid intake of < 150 ml/kg/d and > 150 ml/kg/d. Our data show that dexamethasone and inhaled beclomethasone improved the clinical course of BPD in premature infants. Fluid intake had no influence on clinical outcome. Based on our results, we suggest guidelines for the treatment of BPD.

"Partial trisomy 22 and 11" due to a paternal 11;22 translocation associated with Hirschsprung disease.

The 11;22 translocation seems to be the most frequent, non-Robertsonian, translocation in man. Approximately 50 cases with an unbalanced karyotype 47,XX (or XY),+der(22), t(11q;22q), due to a 3:1 meiotic disjunction in the parental translocation carrier, have been reported in the literature. We present an additional patient with that chromosome aberration, whose father was shown to be the translocation carrier. He presented with many of the more or less typical signs of the syndrome, but had an extraordinary additional finding, namely Hirschsprung disease. Although anal stenosis is a rather frequent finding in the syndrome, Hirschsprung disease has never been described in the literature. Furthermore the most important genetic and cytogenetic data on that chromosome aberration are given, including implications for genetic counselling.