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Background The microbiological diagnosis of pulmonary tuberculosis (Tb) in a pediatric population is hampered by both low pathogen burden and noncompliance with sputum sampling. Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been found useful for the evaluation of mediastinal pathologies in adults, for children, sparse data are available. Here, we have evaluated EBUS-TBNA as a diagnostic procedure in children and adolescents with suspected pulmonary Tb. Methods In this retrospective analysis, we reviewed the charts of unaccompanied refugee minors (URM) who were admitted between January 2016 and July 2018 and who, during their initial medical screening upon arrival in Germany, were found to have abnormal radiological pulmonary and mediastinal findings and/or immunological results indicative of Tb. For each patient, basic sociodemographic data, clinical features and data on diagnostic procedures performed were assessed. These included imaging, immunodiagnostic tests and microbiological data derived from sputum, bronchoalveolar lavage, EBUS-TBNA, bronchoscopy and pleural fluid sampling. All patients who underwent invasive sampling procedures were included in the study. Results Out of 42 URM with suspected Tb, 34 fulfilled the study’s inclusion criteria. Ages ranged from 14 to 17 years. All were of African origin, with 70.0% coming from Somalia, Eritrea and Ethiopia. Among the 21 patients for whom EBUS-TBNA was performed, the diagnostic yield was high: 66.7% positive results (MTb detected either by acid-fast stain, culture or PCR in 4.8, 42.9 and 61.9% of samples, respectively). Multidrug-resistant MTb was found in two patients from Somalia. No complications were associated with the procedure. Overall, pulmonary Tb was diagnosed in 29 patients (85.3%), miliary Tb in two patients (5.9%) and latent Tb in three patients (8.8%). Conclusions EBUS-TBNA is a sensitive and safe method with high diagnostic yield in the evaluation of pediatric patients with mediastinal pathology and suspected Tb. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06413-z.

There is a lack of data regarding the incidence and clinical significance of apnoea or bradycardia (AB) following immunisation with combination vaccines containing an acellular pertussis (Pa) component in respiratory stable preterm infants. Medical records of respiratory stable preterm infants who received a first dose of a combined diphtheria (D) and tetanus (T) toxoids, Pa, Haemophilus influenzae type b (Hib), inactivated poliovirus (IPV) vaccine with or without hepatitis B virus (HBV) in the neonatal intensive care unit (NICU) of the University Children’s Hospital Basel between January 2000 and June 2003 were analysed. For each infant, clinical data were recorded for a 72 h period before and after immunisation. Of 53 infants with a mean gestational age of 28 weeks, 7 (13%) showed a transient recurrence of or increase in episodes of AB following immunisation. Five of these seven infants required intervention ranging from tactile stimulation to bag and mask ventilation. Regarding risk factors, children with recurrent or increased AB were indistinguishable from those without such events. The rate of fever (>38°C) following immunisation was higher in affected infants compared to those without recurrence of or increase in AB (3/7 vs 2/46, P =0.01). Conclusion:Although most infants tolerated immunisation well, the incidence of recurrent or increased apnoea or bradycardia in respiratory stable preterm infants following the first immunisation with penta- or hexavalent vaccines was 13%. Most apnoea or bradycardia events required intervention but did not have serious consequences. Monitoring of all preterm infants following immunisation in the neonatal intensive care unit is recommended.

The aim of the present preliminary study was to evaluate the feasibility of measuring cerebral hemodynamic effects of a clinical dose of methylphenidate by near-infrared spectroscopy in 10 boys (median age, 10.7 years; range, 8.6-11.8 years) with developmental attention-deficit/hyperactivity disorder (ADHD). Using a Trail Making Test known to activate the left dorsolateral prefrontal cortex, cerebral hemodynamic changes show a lower increase of cerebral blood volume in the right prefrontal cortex ( P = .033) and a lower increase of the tissue oxygenation index in the left prefrontal cortex ( P = .015) in the condition after intake of methylphenidate compared with a drug-naive situation. A lower increase of the tissue oxygenation index indicates a changing regional oxygen metabolism and consumption induced by methylphenidate. Near-infrared spectroscopy is a sensitive tool for measuring pharmacological effects of methylphenidate on the cerebral hemodynamics.

Objective To evaluate bronchopulmonary dysplasia (BPD), serious brain injury, and severe retinopathy of prematurity (ROP) as predictors of poor long-term outcome in very low birth weight infants. Study design We examined the associations between counts of the 3 morbidities and long-term outcomes in 1514 of 1791 (85%) infants with birth weights of 500-1250 g who were enrolled in the Caffeine for Apnea of Prematurity trial from October 1999, to October 2004, had complete morbidity data, and were alive at 36 weeks postmenstrual age (PMA). BPD was defined as use of supplemental oxygen at 36 weeks PMA. Serious brain injury on cranial ultrasound included grade 3 and 4 hemorrhage, cystic periventricular leucomalacia, porencephalic cysts, or ventriculomegaly of any cause. Poor long-term outcome was death after 36 weeks PMA or survival to 5 years with 1 or more of the following disabilities: motor impairment, cognitive impairment, behavior problems, poor general health, deafness, and blindness. Results BPD, serious brain injury, and severe ROP occurred in 43%, 13%, and 6% of the infants, respectively. Each of the 3 morbidities was similarly and independently correlated with poor 5-year outcome. Rates of death or disability (95% CI) in children with none, any 1, any 2, and all 3 morbidities were 11.2% (9.0%-13.7%), 22.9% (19.6%-26.5%), 43.9% (35.5%-52.6%), and 61.5% (40.6%-79.8%), respectively. Conclusions In very low birth weight infants who survive to 36 weeks PMA, a count of BPD, serious brain injury, and severe ROP predicts the risk of a late death or survival with disability at 5 years.

The aim of the present study was to evaluate the hemodynamic changes in both prefrontal regions induced by a cognitive task in children with a developmental attention-deficit disorder in comparison to normal controls using near-infrared spectroscopy (NIRS). A total of 11 boys with a mean age of 10.4 (+/-1.2) years that met the DSM-IV criteria for attention-deficit hyperactivity disorder (ADHD) participated in the study and were compared with 9 healthy age- and sex-matched controls. Using a trail-making test designed for the task of connecting numbers from 1-90 in four sets, changes in oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin, tissue oxygenation index (TOI), and cerebral blood volume (CBV) were measured by near-infrared spectroscopy. During the first test set, designed as a short-attention task, the children with ADHD showed significant increases in O2Hb and CBV, whereas the controls showed no significant changes. During the 4 task cycles in which extended attention was demanded, both groups showed increases in O2Hb and CBV, but only the controls showed an additional increase in HHb in the left prefrontal region. In the ADHD group only, TOI showed an increase mainly on the left side. NIRS is a sensitive tool for measuring differences in hemodynamic changes between boys with ADHD and normal controls. Overall, the normal controls showed lateralized oxygen consumption in the left prefrontal cortex during an extended-attention task, whereas the boys with ADHD showed an imbalance between oxygenated and deoxygenated hemoglobin during the short- and extended-attention tasks.

The objective of this study is to determine whether the fetus compensates for fetal alloimmune thrombocytopenia (FAITP) by increasing serum concentrations of thrombopoietin (TPO) and interleukin-11 (IL-11). TPO and IL-11 concentrations were measured in cord blood sera of 12 neonates with FAITP, and 35 preterm and 25 term controls. TPO concentrations in the 12 patients (median 129 pg/mL, range 73 to 325 pg/mL) were similar to those of 35 healthy preterm neonates (median 183 pg/mL, range 71 to 290 pg/mL) and the 25 term controls (median 180 pg/mL, range 93 to 302 pg/mL), although the platelet counts were significantly lower in FAITP. TPO concentrations did not correlate with the platelet counts, platelet nadir after birth, or time to recovery of normal platelet count. IL-11 reached detectable concentrations only in four patients with FAITP (median 54 pg/mL). After birth, these patients had a more rapid recovery of the platelet count. Cord blood serum concentrations of TPO are not significantly elevated in FAITP and do not predict the severity of the thrombocytopenia. Elevated IL-11 may signal a more rapid platelet recovery in FAITP.

To assess the occurrence of muscle rigidity after fentanyl administration in premature and term neonates.Prospective case series, observational study.A university hospital neonatal intensive care unit.8/89 preterm and term infants (25-40 wks gestational age) who received fentanyl for perioperative analgesia and sedation or intensive care procedures.Mechanical or bag mask ventilation and antagonization with naloxone.We observed chest wall rigidity in 8 patients after low dosage of fentanyl (3-5 microg/kg body weight). All patients presented with respiratory distress, hypercapnia, and hypoxemia leading to bradycardia. In two patients, laryngospasm was noted and associated with muscle rigidity, thus making intubation impossible. Naloxone (20-40 microg/kg body weight) reversed the laryngospasm and muscle rigidity immediately, allowing restitution within 1 min. In our patient population, we found fentanyl-induced chest wall rigidity in 4% of neonates after fentanyl administration.Even low doses of fentanyl can lead to thoracic rigidity in neonates. Additionally, we observed laryngospasm in two patients and speculate that it might be a variant of muscle rigidity.

Objective. To determine the incidence and risk factors for hearing disorders in a selected group of neonates and the feasibility of selective hearing screening. Settings. Multicenter prospective trial at five centers in Germany. Methods. Enrollment criteria: in addition to previously defined risk factors by the Joint Committee on Infant Hearing (family history of hearing loss, in utero infections, craniofacial anomalies, birth weight 5 days, stigmata, or syndromes associated with hearing loss), the impact of maternal drug abuse, birth weight Results. Seven hundred seventy recordings from 777 infants enrolled consecutively constitute the basis of this analysis. Mean gestational age was 33.8 ± 4.3 weeks, birth weight 2141 ± 968 g; 431 infants being male and 339 female; 41 (5.3%) infants exhibited pathologic A-ABR results (16 bilateral and 25 unilateral). Meningitis or sepsis, craniofacial malformations, and familial hearing loss were independent significant risk factors. Median total test time was 25 minutes. Follow-up examinations in 31 infants revealed persistent hearing loss in 18 infants (13 infants sensorineural, 5 from mixed disorders), 7 requiring amplification. Conclusion. Hearing screening in high-risk neonates revealed a total of 5% of infants with pathologic A-ABR (bilateral 2%). Significant risk factors were familial hearing loss, bacterial infections, and craniofacial abnormalities. Other perinatal complications did not significantly influence screening results indicating improved perinatal handling in a neonatal population at risk for hearing disorders.

Based on animal experiments, a switch of the erythropoietin (EPO) production site from the liver in the fetus to the kidneys in the adult has been postulated. To study the switch in humans, we have quantitated EPO mRNA expression in liver, kidney, spleen, and bone marrow of human fetuses and neonates by means of a competitive polymerase chain reaction (PCR). Tissue samples from 66 routine postmortem examinations were obtained. EPO mRNA was expressed in 97% of the tissue specimen derived from the liver (n = 66) and in 93% of those from the kidneys (17 weeks of gestation until 18 months after birth; n = 59). For the first time the EPO gene was found expressed in vivo in human spleen (96% of 64 samples) and in fetal and neonatal bone marrow (81% of 21 samples). EPO mRNA expression in the kidneys increased significantly beyond 30 weeks of gestation (P < .05). Although there was a slight decrease in EPO mRNA content per g liver tissue towards birth, the liver accounted for about 80% of the total body EPO mRNA. The contribution of the spleen and bone marrow were minor compared with liver and kidneys. Our results indicate that in humans the liver is the primary site of EPO gene expression not only in fetal, but also in neonatal life. A significant increase of renal EPO mRNA expression after 30 weeks of gestation might indicate the beginning switch. © 1998 by The American Society of Hematology.

Two patients with X-chromosomal hydrocephalus internus (aqueduct stenosis, clasped thumbs, mental retardation and spasticity) habe been described. In both cases the family history revealed further affected relatives. The intra- and interfamilial variability of this rare X-chromosomal recessive disease will be demonstrated. In this context differentialdiagnoses like X-linked MASA syndrome and X-linked spastic paraplegia have been discussed on the basis of a variable expressivity of different mutations in the same gene.

The ability of parameters like umbilical arterial pH and Apgar-score to predict and/or to reflect fetal distress is limited. It is known that erythropoietin (EPO) increases due to hypoxic stimulation. Therefore we studied the levels of EPO in the cord blood of stressed neonates (n = 75). In addition, reference values for EPO were established in a group of healthy term infants (n = 54) (mean +/- SD: 20.02 +/- 6.4; median 17.8; range 8.7-40.3 (mU/ml]) and in premature infants (n = 77) according to gestational age (median/range: < 30 weeks 11.0, 5.5-17.5; 30-32 weeks 18.1, 5.5-136; 33-34 weeks 17.7, 8.3-422.9; 35-37 weeks 17.3, 5.5-272 [mU/ml]). EPO concentrations significantly increased in the stressed group: in acute stress (n = 27): mean 153.4, range 6.5-641.7 [mU/ml], p < 0.003; and in chronic stress (n = 48): mean 102.6, range 12.4-544 [mU/ml], p < 0.002. However, parameters like hemoglobin, hematocrit, umbilical arterial pH and Apgar-score did not correlate with EPO values. A sensitivity of 59% and a specificity of 92% was calculated. We conclude that serum EPO concentrations are capable of detecting acute and chronic stress. In part EPO also allows to grade stress in pregnancies, which are complicated by diseases like preeclampsia.

Objective. To evaluate whether the mean gastric residual volume (GRV) and green gastric residuals (GR) themselves are significant predictors of feeding intolerance in the early enteral feeding advancement in extremely low birth weight (ELBW; Design. Ninety-nine ELBW infants were fed following a standardized protocol (day 3–14). At 48 hours of age, milk feeding was started (12 mL/kg/d increments, 12 meals per day). GR were checked before each feeding, and a GRV up to 2 mL/3 mL in infants ≤750 g/>750 g was tolerated. In cases of increased GRV, feedings were reduced or withheld. The color of GR was assessed as clear, milky, green-clear, green-cloudy, blood-stained, or hemorrhagic. Multiple regression analysis was used to study the effect of the mean GRV and the color of GR on the feeding volume on day 14 (V14). Results. The median V14 was 103 mL/kg/d (0–166). V14 increased with an increasing percentage of milky GR, whereas the mean GRV and the color green did not have a significant effect. Conclusions. 1) Early enteral feeding could be established in ELBW infants. The critical GRV seems to be above 2 mL/3 mL because there was no significant negative correlation between the mean GRV and V14. 2) Green GR were not negatively correlated with V14 and should not slow down the advancement of feeding volumes in absence of other clinical signs and symptoms.

Oxy-, deoxyhemoglobin and total blood volume were studied by near-infrared spectroscopy (NIRS) during surfactant replacement therapy. These parameters were compared with parameters watched during conventional noninvasive monitoring (pulseoximetry, transcutaneous pO2 and pCO2, heart rate). Seven premature infants (28 +/- 3 weeks of gestation, 940 g birth weight) were given surfactant intratracheally. Immediately after surfactant administration, oxyhemoglobin decreased, deoxyhemoglobin and total blood volume increased. The prior status was re-established after 60-220 s and then oxyhemoglobin increased to a very stable maximum. NIRS allows continuous bedside noninvasive monitoring of all parameters.

We report on an 7 weeks old male infant with hydrocephalus internus, dysplastic low-set ears, micrognathia, vitium cordis, hypogenitalism, and polyhydramnios in pregnancy. The variability of the Hydrolethalus syndrome will be demonstrated. Our patient shows, that this syndrome is not a lethal in all cases. We report on an 7 weeks old male infant with hydrocephalus internus, dysplastic low-set ears, micrognathia, vitium cordis, hypogenitalism, and polyhydramnios in pregnancy.

OBJECTIVE: To determine the extent that social variables influence cognitive development of very low birth weight (VLBW) infants across the preschool years. STUDY DESIGN: Participants were VLBW (500-1250 g) children enrolled in the Caffeine for Apnea of Prematurity randomized trial between 1999 and 2004. We investigated the relationships between 4 potential social advantages: higher maternal education, higher paternal education, caregiver employment, and 2 biologic parents in the same home--and gain in cognitive scores. Cognitive assessments were performed at the corrected ages of 18 months (Mental Development Index score on the Bayley Scales of Infant Development II) and 5 years (Full Scale IQ on the Wechsler Preschool and Primary Scale of Intelligence III). Cognitive gain was computed by subtracting each individual 18-month Mental Development Index score from the corresponding Full Scale IQ at 5 years. RESULTS: Data were available for 1347 children. Mean (SD) cognitive scores were 90.8 (15.7) at 18 months and 98.9 (14.5) at 5 years. Multivariable regression showed that higher maternal education, higher paternal education, and caregiver employment had independent and additive effects of similar size on cognitive gain (P < .001); the mean cognitive gain between 18 months and 5 years increased by 3.6 points in the presence of each of these advantages. When all 3 were present, cognitive scores improved on average by 10.9 points compared with children without any of these advantages. CONCLUSION: In VLBW children, a count of 3 social advantages strongly predicts gains in cognitive scores across the preschool years.

Aims: Magnetic resonance imaging (MRI) is accepted as the gold standard for the diagnosis of arterial cerebral infarction (ACI), but few studies have reported the incidence of neonatal ACI based on MRI findings. We provide new population-based epidemiologic and diagnostic data on all infants diagnosed between 1997 and 2002 in our center with an MRI-confirmed diagnosis of unilateral neonatal ACI. Results: Nine patients were identified, giving an incidence of 1:2300 unilateral ACIs in our inborn population. In all patients the middle cerebral artery was affected. Seven patients showed epileptic seizures, usually starting within the first 3 days of life. EEG was pathologic in all patients. Only three infarctions were diagnosed by ultrasound. Initial MRI established diagnosis of ACI in eight out of nine patients and subsequent MRI described the exact location of infarctions in all patients. Six out of nine patients developed hemiparesis and five had deficits in language development. There is a substantial need for special care facilities and long-term therapeutic interventions. Conclusions: The incidence of neonatal ACI is higher than previously reported. The sensitivity of early cerebral ultrasound for diagnosis of ACI is low. Seizures in the first 3 days of life combined with pathologic EEG findings should lead to MRI, regardless of normal cerebral ultrasound.

We report on a term girl born by urgent caesarean section due to variable foetal decelerations during labour. Weight 3830 g, Apgar scores 4/6/8 (1’/5’/10’) and arterial umbilical cord pH 6.89. Suffering a mild respiratory distress syndrome for the first day of life with a maximum FiO2 of 0.3, she was transferred to the neonatal intensive care unit. Transient arterial hypotension down to 29 mm Hg mean arterial pressure was rapidly corrected by two intravenous bolus administrations of 0.9% saline solution. Initially the capillary blood gases showed metabolic acidosis (pH 7.14, pCO2 30 mm Hg, BE –18 mmol/l), but recovered completely and spontaneously within 12 hours of life. No body surface cooling was applied. The neurological findings after 24 hours of life were normal and breastfeeding was started on day 2 without problems. Cranial ultrasound including doppler studies on day 2 revealed no signs of cerebral oedema or bleeding. The child was discharged to maternity in good health on day 5, but was readmitted on day 6 with obviously painful, firm, large erythematous nodules and plaques on her back, dorsal neck and upper arms (fig. 1). She was placed in the prone position and received paracetamol. Histological examination of a biopsy specimen from a nodule on her back revealed patchy fat necrosis with fat crystallisation. In addition, macrophages and foreign-body giant cells, neutrophils, lymphocytes and eosinophils were present in the inflammatory infiltrate (fig. 2). These findings were consistent with the diagnosis of subcutaneous fat necrosis of the newborn (SCFN). Additional diagnostic workup showed normal serum calcium levels of 2.2–2.6 mmol/l (1.3–1.6 mmol/l ionised calcium), no thrombocytopenia and no hyperlipidaemia. Starting on day 16, the cutaneous lesions gradually decreased in size and intensity, were less erythematous and no longer painful. The newborn was finally discharged home. At 12 weeks of age the cutaneous symptoms had resolved. She did not develop hypercalcaemia in the first year of life and neurological follow-up was excellent.

Unilateral hydrocephalus caused by occlusion of the foramen of Monro is rare. We report two cases in neonates caused by prenatal hemorrhage, their radiographic findings, and surgical treatment. With posthemorrhagic progressive unilateral hydrocephalus, early intervention with fenestration of septum pellucidum should be considered.

In eight right-handed healthy males aged 9.6-12.9 years, changes in the frontal cerebral concentrations of oxygenated, deoxygenated, and total hemoglobin, as well as in tissue oxygenation index and cytochrome oxidase aa 3 were measured by near-infrared spectroscopy. The males were evaluated using a trail-making test with four test cycles interrupted by relax breaks. During the first cycle of this task, a significant increase in deoxygenated hemoglobin was documented in the left frontal region. In the extended course of the test, a significant increase in oxygenated and total hemoglobin was observed on both sides, indicating an increase in cerebral blood volume. However, only on the left side was an increase in deoxygenated hemoglobin documented. In children, changes in cerebral oxygenation induced by a cognitive task could be measured by near-infrared spectroscopy. In a short and extended attention task, a lateralized increase in oxygen consumption was documented by an increase in deoxygenated hemoglobin. In an extended attention task, an increase in oxygenated and total hemoglobin was recorded additionally in both frontal brain regions, indicating a compensatory increase in cerebral perfusion. Further studies are required to examine the significance of this technique in testing differences in children with neurobehavioral disabilities.

Please cite this article in press as:Willi B, Paediatric Neurology (2011), doi:10.1016/j 1090-3798/$ e see front matter a 2011 Europ doi:10.1016/j.ejpn.2011.01.004 Dear Editor, Neurological dysfunctions are important complications of influenza wild virus infections. The most common complications following H1N1 infection are related to the respiratory tract. However, especially among children below 5 years of age, neurological complications such as seizures, neuropsychological alterations, and signs of encephalitis have been reported in 5%e10% of children who were admitted to hospital for H1N1 influenza. Encephalopathy following a vaccination against influenza is a rare, but well-known complication. The exact cause and pathogenesis of vaccination-induced encephalopathy has to be determined. Until now several cases of encephalopathies were reported after vaccination against seasonal influenza. We report about a 4-year, 8-month-old boy suffered from a central congenital hypoventilation syndrome associatedwith a virtually total intestinal aganglionosis, known asHaddad Syndrome. The boywas treated via tracheostoma by home ventilation for several hours a day and the whole night. Parenteral nutrition was routinely given via central venous catheter.Before theH1N1pandemystartedinourregion, theboy was vaccinated against H1N1 with the first dose of a pandemic influenza vaccine (Pandemrix ; H1N1, split virion, inactivated, adjuvanted) A/California/7/2009 (H1N1)v like strain (X-179A). One day after the vaccination he developed fever up to 38 C without any other clinical symptoms. During the

Background: In extremely-low-birth-weight (ELBW) infants, formula feeding is required if human milk is not available. The tolerance of a new 'high' lactose (55 g/L), low protein, low phosphate, hydrolyzed protein formula (HLF) for early enteral feeding advancement of ELBW infants was compared with that of a low lactose (1 g/L) hydrolyzed protein formula (LLF). Methods: In a randomized multicenter trial, 99 ELBW infants were fed according to a standardized protocol beginning at 48 hours of age with 12 ml/kg daily increments. Primary outcome was the cumulative milk feeding volume (CFV) from days 3 to 14. The authors hypothesized that feeding HLF as a supplement to human milk would increase the CFV at least by 20% in at least 60% of matched pairs compared with LLF. A secondary issue was to investigate whether human milk would increase the CFV compared with formula. Results: The CFV was 720 mL/kg (range, 0-962 mL/kg) with HLF and 613 mL/kg (range, 3-1,283 mL/kg) with LLF feeding. There was no 20% difference. On day 14, the median feeding volume was 103 mL/kg. The CFV was 533 mL/kg (range, 0-962 mL/kg) in infants who received less than 10% of human milk and 832 mL/kg (range, 74-1,283 mL/kg) in infants who received more than 10%. Necrotizing enterocolitis (Bell stage > or =2) occurred only with LLF feeding (n = 5; P < 0.05). Conclusions: The study failed to find the hypothesized 20% advantage of the new HLF. The observed advantage of human milk supports the hypothesis that it should be the first diet in ELBW infants; however, this hypothesis still must be confirmed in a controlled, randomized trial.

The purpose of this study was to determine the neurodevelopmental risks in patients with twin-to-twin transfusion syndrome, a rare but serious complication of monochorionic twin gestations. From a total sample of 94 twins with twin-to-twin transfusion syndrome, admitted during 1989 and 1993, 49 patients survived and 40 patients were followed to a mean age of 24 months. Neurological status and psychomotor development (Denver and Griffiths Developmental Tests) were determined. Parameters of the neonatal period were evaluated for their potential prediction. Of the 40 tested patients 18 showed a normal psychomotor development. Thirteen patients exibited a specific delay in language development and/or showed minor neurological dysfunctions. Nine twins had severe psychomotor retardation in combination with cerebral palsy. Major neurological sequelae were found, more common in recipients than in donors (6/19 vs 3/21). Correspondingly, neonatal ultrasound showed more pathological results (especially periventricular leucomalacia) in recipients. Neither anaemia nor polycythaemia at birth can predict developmental outcome. Apart from a high prenatal mortality rate, both twins, donators as well as recipients, are highly at risk for brain damage of different aetiology, associated with abnormal neonatal cerebral ultrasound.

Thrombopoietin (TPO) regulates megakaryopoiesis and platelet production. In the adult, TPO is mainly produced by the liver and the kidneys. This study focuses on fetal and neonatal TPO mRNA expression. In 26 human fetuses and preterm neonates, samples from liver, kidney, spleen, lung, and bone marrow were extracted for total RNA. We measured platelet counts, TPO serum concentrations by enzyme-linked immunosorbent assay, and TPO mRNA contents by reverse transcription/competitive polymerase chain reaction. TPO mRNA concentrations per microgram total RNA were similar in liver, spleen, and bone marrow, slightly lower in kidney, and significantly lower in lung. When related to gram tissue, TPO mRNA levels were highest in the liver. Considering the total amount of TPO mRNA produced in liver, kidney, and spleen, the liver accounted for 95.3%. No correlations between TPO mRNA expression and serum TPO concentration, blood platelet count, or gestational age were observed. In conclusion, the liver is the primary site of TPO gene expression in human fetuses and neonates. The spleen may contribute to TPO production during fetal life. Like in the adult, TPO mRNA is expressed in fetal bone marrow.

To the Editor .— Ohls et al1 recently reported in Pediatrics that recombinant erythropoietin (rEpo), given in a randomized, controlled clinical trial to reduce transfusions in extremely low birth weight (ELBW) infants, did not significantly influence the neurodevelopmental outcome at 18 to 22 months’ corrected age. The question of the neurodevelopmental outcome of rEpo-treated ELBW infants became of highest interest since animal studies using a variety of models for hypoxic-ischemic brain injury (see refs 2 and 3 for review) as well as the first clinical trial in humans with stroke provided substantial evidence for significant neuroprotective effects of rEpo.4 It is indeed neither unexpected nor disappointing that ELBW infants who received rEpo (400 U/kg body weight 3 times weekly, given intravenously[ iv] or subcutaneously [sc]) from 96 hours of age and until the 35th postmenstrual week did not show a benefit in the neurodevelopmental outcome. This needs additional explanation, because specific aspects of the biology of Epo and its receptor (Epo-R) in the central nervous system (CNS) need to be considered for future strategies in using rEpo as a neuroprotective agent in neonates. Such aspects concern (1) Epo-R expression, (2) endogenous Epo production, and (3) time and dosage of rEpo treatment, particularly regarding its transport across …

Since the introduction of postpartal and prepartal Anti-D-prophylaxis (Bowman et al., 1978; Thornton et al., 1989), the rate of sensibilisation to the rhesus system has decreased in Germany from 1:20.000 before prophylaxis to 1:1.000 today (Maas et al., 1991). There is, however, little chance that the future could hold an even lower incidence of infants with isoimmunisation caused by Rhesus incompatibility, since prophylaxis has a constant failure rate. In addition, there are other types of isoimmunisations caused by other blood groups, especially anti-c, Kell and Duffy, where no prophylaxis is yet possible. Therefore exchange transfusion (ET) will continue to be a part of the postnatal management in neonates suffering from Morbus haemolyticus.

Les parametres biochimiques, par exemple le pH de l'artere du cordon ombilical et l'Apgar sont peu adaptes pour detecter ou prevoir les etats de detresse foetale. On sait que les concentrations d'erythropietine dans le serum augmentent en reaction a un apport d'oxygene insuffisant des tissus et, au niveau biologique, peuvent donc etre en correlation avec la detresse foetale. En consequence, nous avons etudie les taux d'erythropoietine du sang du cordon chez les nouveau-nes en etat de detresse (n = 75). Nous avons etabli les valeurs temoins d'erythropoietine sur un groupe d'enfants nes matures et ne presentant aucun signe de detresse (n = 54) (± SD moyen 20,02 ± 6,4 [mU/ml] et un groupe de prematures (n = 77). Nous avons releve une elevation sensible des concentrations d'erythropoietine dans le groupe des enfants en situation de detresse: 153,4 ± 418,8 [mU/ml], p < 0,003, n = 27) en etat de detresse aigue et en etat de detresse chronique (102,6 ± 127,1 [mU/ml], p < 0,002, n = 48). Les autres parametres, par exemple l'hemoglobine, les hematocrites, le pH de l'artere du cordon et l'Apgar ne presentent aucune correlation avec l'erythropoietine. Les taux ont ete de 59% pour la sensibilite et de 92% pour la specificite. Nous en concluons que les concentrations d'erythropoietine du serum sont l'indice de la detresse foetale aigue et chronique et peuvent etre utilises comme methode de controle. Les taux d'erythropoietine permettent dans une certaine mesure de mesurer le degre de detresse dans les grossesses au profil complique par les troubles tels que la preeclampsie.

Aiming at a better understanding of the pathophysiologic basis of perinatal encephalopathy, we evaluated patterns of tissue oxygenation during hypoxia and hyperoxia. We utilized both laserspectroscopy and invasive tissue-Po2 microneed measurements synchronously in five newborn lambs (141-143 days of gestation). The model of artificial placentation provided defined changes of the blood gases, using a extracorporeal circuit with interposition of membrane lung. During hyperoxia, the Po2 at the blood outlet port of the lung was raised to300 mmHg for five minutes. During hypoxia, Po2 was diminished as oxygen at the gas phasis was replaced by nitrogen. After the induction of hyperoxia, a rise of tissue-Po2 was observed. The synchronously recorded data of the laserspectroscopy showed adequately rising HbO2 values in concordance (r = 0.97, p0.001). As a constant finding we did not observe Cyt-aa3 changes during induced hyperoxia with tissue-Po2 values of40 mmHg. Furthermore, no changes in blood volume occurred in this case. A different pattern of the laserspectroscopic parameters was found when the tissue-Po2 rose above a value of40 mmHg and Cyt-aa3 rose after a lag-time occurred. During induced hypoxia an immediate fall of tissue-Po2 corresponding with a fall of HbO2 in the spectroscopic tracing occurred (r = 0.87, p0.001). A fall of the Cyt-aa3 level was seen with a lag-time when the tissue-Po2 had reached values of below 10 mmHg. In addition, a rise of blood volume was recorded in all cases of induced hypoxia. In conclusion, the results indicated that cellular redoxe state remains stable over a large range of oxygen partial pressure changes.

The alternative use of flame photometry and ion selective electrodes for electrolyte determinations in neonatology led to the question how the two methods agree. 104 routine blood samples were taken as matched pairs for a comparison of sodium and potassium determinations. Pre-analytical error was avoided by the mode of blood collection. The influence of the protein and lipid content of blood on the differences between the methods was determined by calculating its water content and making a post-correction of the flame values. Thus the differences for sodium could be reduced, whereas the differences for potassium slightly increased. As long as the imprecision of sodium determination is a meaningful methodological problem, the influence of the protein and lipid content of neonatal blood is not the main factor for differences between ISE and flame photometry.

By introducing surfactant replacement therapy in clinical routine, the spectrum of treating respiratory distress syndrome in infants (IRDS) could be dramatically improved (Segerer and Obladen,1990). However, there are still a lot of open questions regarding its action on oxygen supply to the brain, cerebral hemodynamics and intracellular redox state.

Mittels eines Nah-Infrarot-Laserspektrometers der Firma Radiometer (Kopenhagen) wurde -kontinuierlich und nicht invasiv — an 20 reifen und spontangeborenen Kindern, unmittelbar post partum, die intrakraniellen Veranderung von Cytochrom aa3 oxygeniertem und reduziertem Hamoglobin sowie des Blutvolumens gemessen.

Erythropoietin (EPO) ist ein Glucoprotein, das entscheidend auf die Proliferation und Differenzierung der erythrozytaren Vorlauferzellen wirkt. Die hepatische und renale EPO-Synthese wird hauptsachlich durch den Sauerstoffpartialdruck und die Sauerstoffsattigung im Gewebe reguliert. Ein hypoxischer Reiz stimuliert die EPO-Synthese uber verschiedene Botenstoffe; es kommt uber eine gesteigerte Erythrocytenbildung zur verbesserten Sauerstoffversorgung. EPO ist nicht plazentagangig. Wahrend der Fetalperiode sind bis zur vollstandigen Ausreifung der Nieren, also etwa bis zur 32.Schwangerschaftswoche (SSW), die Zellen der Hep 3 B- und der Hep 2 G-Linie der Leber die hauptsachlichen EPO -Produktionsstatten (ca. 85%). Im dritten Trimester ubernehmen die peritubularen Zellen der Niere die EPO-Bildung, und mit steigendem Gestationsalter kommt es zu stetig zunehmenden EPO-Gesamtkonzentrationen. Veranderte EPO-Spiegel sind bei Einlingen nach chronischem intrauterinen oder akutem peripartalem Stres sowie bei verschiedenen Erkrankungen beschrieben.

Congenital hyperinsulinism is considered to be the most frequent cause of persistent recurrent hypoglycaemia in infants. The clinical presentation and response to pharmacological treatment may vary significantly depending on the underlying pathology. We report a case of a female infant with mild but early onset of recurrent hypoglycaemia. Metabolic workup revealed hyperinsulinism combined with mild hyperammonaemia as well as elevation of α-ketoglutarate in urine. Genetic testing demonstrated a de novo mutation in exon 7 of the glutamate dehydrogenase gene on chromosome 10. Episodes of hypoglycaemia responded to treatment with diazoxide. The differential diagnosis, pathophysiology and treatment of congenital hyperinsulinism is discussed.

Laserspectroscopy with near-infrared light is newly available for clinical application. The equipment consists of a near-infrared data collection unit (NIRDCU) and a personal computer. Emission of laser light at wavelengths of 775, 805, 845 and 904 nm is provided by the four laser diodes of the NIRDCU. By analyzing changes of optical density during laser radiation, information is obtained regarding the intracellular redox state and relative changes of blood volume. During measurement with the system on the fetal scalp during delivery we were able to get a first impression of the method's potential. While the application of the laser sensors is still cumbersome, signals providing information of the relative changes of hemoglobin concentration, relative changes of blood volume and cytochrome aa3 seems achievable. Laserspectrophotometric monitors may become safe, low cost and portable instruments for the non-invasive assessment of the biochemical and biophysical status in the fetus.

Die Effektivitat des Gasaustausches uber einen kunstlichen Umbilikalkreislauf wurde tierexperimentell uberpruft und das Verfahren mit herkommlichen ECMO-Techniken verglichen [1, 2, 3]. Fur die Untersuchung haben wir 20 pramature Lammer mit einem Gestationsalter von 128 Tagen per Sectio entbunden. Sofort post partum wurden die Tiere intubiert, nach einem festen Schema beatmet und an das Perfusionssystem angeschlossen. In unseren Versuchen wurden zwei verschiedene Kanulierungssysteme verwandt: 1. arteriovenos mittels Arteria und Vena Uterina und 2. venoarteriell mittels Arteria carotis und Vena subclavia. Die Uberwachung erfolgte durch kontinuierliche Erfassung des PO2 und PCO2 im zufuhrenden Schenkel des extrakorporalen Perfusionssystems sowie durch die laserspektroskopische Messung des HbO2, HbR und des Cytochrom aa3 im Bereich des Schadels. Daruberhinaus wurden in definierten Intervallen diese Werte durch Blutgasanalysen kontrolliert.

OBJECTIVE: Recommended indications for exchange transfusions (ET) according to cord blood bilirubin concentrations vary between 4.5 and 7.0 [mg/dl]. There is no proof that cord blood bilirubin is able to predict the postnatal course of bilirubin concentrations. Only a few data are available on fetal bilirubin metabolism and postnatal bilirubin dynamics in the hemolytic disease of the newborn.

A decrease in cerebral blood flow and in cerebral blood flow velocity caused by indometbacin administration is well known (Child Neurol 1987;29: 776-82; Eur J Pediatr 1988;147:315-61. For a deeper view on the cellular base we studied seven premature infants (1080g, 30 + 2 weeks), who received indomethacin for closure of PDA (0.2 mg/kg weight, i. v.) with the near infrared technique. Cerebral blood volume (CBV) decreased in every child exept one just after starting the indomethacin administration and remained on a lower level during the monitoring time (30 min). The balance of the redox state of cytochrome a/a3 shifted to a decrease of the oxidised part of the enzyme. Table 1 shows the relative concentration change of the CBV and the CYT.

The recurrent non-immunological hydrops fetalis is classified as a separate entity. It is usual to differentiate between the chylous and the idiopathic form. The case presented indicates that the recurrent non-immunological hydrops fetalis should not be seen as an idiopathic but as a chylous form. Only in enterally fed children the initially amber coloured pleural effusion becomes opaque and the triglycerides are then elevated. This points to a fault in the development of lymph vessels.