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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.

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.

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.

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.

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.

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.

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.

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.