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OBJECTIVE: Measurement of incidence of neonatal seizures and evaluation of the therapeutic strategy used. SETTING: Neonatal intensive care unit, University Hospital, Groningen, the Netherlands. DESIGN: Retrospective, descriptive. METHODS: All patients admitted in a period of 5.5 years who had clinical seizures within 28 days from birth received pharmacological treatment in 4 steps. When a seizure remained clinically uncontrolled, the next step was taken. Step 1: methylphenobarbital 15-35 mg/kg i.v. Step 2: phenytoin 15-35 mg/kg i.v. After an initial loading dose of 15 mg/kg i.v., both the methylphenobarbital and the phenytoin loading dose were stepwise increased until reaching the maximum of 35 mg/kg. Step 3: clonazepam 1-2 x 0,15 mg/kg i.v. Step 4: thiopental 1-2 mg/kg/hour i.v. RESULTS: The incidence of neonatal seizures was 121/2068 (5.9%). For assessment of the efficacy of the therapeutic strategy used, data of 37 patients were not available: 16 patients because of missing data, 11 because of deviation from the strategy and 10 because they died during the strategy. Cases of 84 patients could be evaluated for treatment response. The cumulative response rates were 68% (57/84) controlled seizures for methylphenobarbital, 87% (73/84) for phenytoin, 94% (79/84) for clonazepam, and 96% (81/84) for thiopental. For both methylphenobarbital and phenytoin a marked increase in clinical response was seen at increasing loading doses. CONCLUSION: The stepwise therapeutic strategy used in this study proved to be successful in most cases of neonatal seizures. The anticonvulsive action of both methylphenobarbital and phenytoin appeared to be dose-related.

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Newborns are prone to severe infections and sepsis. Cytokines such as tumor necrosis factor-alpha and IL-1 beta play a major role in the initiation of the host response to infections. IL-1 receptor antagonist (IL-1ra) is a naturally occurring antagonist of IL-1 beta. We hypothesized that low IL-1ra plasma concentrations might contribute to the high morbidity and mortality of neonatal sepsis. We studied IL-1ra plasma concentrations during neonatal sepsis. Eleven newborns with severe infection or sepsis, 28 newborns suspected as having sepsis, and eight healthy newborns were enrolled in the study. IL-1ra plasma concentrations proved to be increased in the newborns with severe infections or sepsis (5635 +/- 411 ng/L) versus the concentrations in the suspected group (2597 +/- 433 ng/L) and the control group (273 +/- 88 ng/L) (p < 0.001). After the start of antibiotic therapy, the IL-1ra plasma concentrations remained high during the first 16 h. The IL-1 beta plasma concentrations were increased in the group with a proven infection (78 +/- 27 ng/L) versus the suspected group (37 +/- 7 ng/L) (p < 0.05). Interestingly, the mean Il-1RA plasma concentration is a factor 50-100 higher than the IL-1 beta plasma concentrations. We conclude that IL-1ra in newborns is produced in an amount equal to that in adults. An inadequate IL-1ra response does not seem to contribute to the increased morbidity and mortality of neonatal sepsis.

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The combination of a transcutaneous microdialysis probe and continuous flow analysis was tested for continuous glucose monitoring in eight newborn infants who were fed intravenously. The probe was placed on the skin, which was first stripped with cellophane tape to increase the skin permeability. The skin was stripped until the transepidermal water loss reached values greater than 80 gm/m2/hr. Dialysate concentrations were monitored for 165 minutes while the blood glucose concentrations were manipulated by changing the infusion rate of glucose. Blood glucose concentration was linearly related to the dialysate concentration. Because the dialysate/blood glucose ratio varied among the infants, the dialysate concentration was calibrated to estimated blood values with a single-point and a multiple-point calibration method. The latter method yielded more accurate estimates of the blood values. We conclude that transcutaneous microdialysis may be used for glucose monitoring in newborn infants.

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Infants of diabetic mothers are at risk of developing hypoglycemia postnatally. Strict control of blood glucose during pregnancy might result in adequate glucose homeostasis in the neonate. We followed 15 mother-infant pairs from the beginning of pregnancy until birth. Glucose kinetics in the infants were measured on the first day of life, using a stable isotope dilution technique. Furthermore, levels of alternative substrates, FFA, and ketone bodies were measured. All infants received i.v. glucose from birth onward at a rate of 3.4 +/- 0.7 mg/kg/min (mean +/- SD). There was no relationship between the parameters of control of the insulin-dependent diabetes mellitus in the mothers and glucose kinetics in their infants. Glucose turnover was 5.2 +/- 1.1 mg/kg/min, glucose production rate (GPR) was 1.8 +/- 1.1 mg/kg/min. GPR was significantly lower in the infants studied at the end of the first day of life (p < 0.01), irrespective of the glucose infusion rate. Furthermore, the lower GPR was associated with an increased concentration of ketone bodies, suggesting an increased production of ketone bodies in these infants. The relatively high GPR measured in the infants who were studied in the first hours postnatally may be the result of postnatal hormonal stimulation of glycogenolysis and/or gluconeogenesis. From this study, we conclude that glucose kinetics in infants of tightly controlled diabetic mothers appear to be normal. Interestingly, despite the near-optimal insulin therapy in the mothers, there is a relationship between the SD scores of birth weight and the mean 3rd-trimester blood glucose values.

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Pregnancy in transplant recipients is not uncommon. Cyclosporin A may be used as an immunosuppressive drug in these patients. Almost no data exist on the effects of cyclosporin A on the immune system of infants who have been exposed to this drug in utero. The infant of a liver transplant recipient was followed during the first 2 years of life. Shortly after birth all lymphocyte subsets were low, especially for B-cells. The distribution of lymphocytes returned to low normal ranges within the first 2 years of life, except for CD8 values that stayed below normal. There were no signs of persistent adverse effects of cyclosporin A on the functional integrity of the immune system.

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A case is reported in which qualitatively, grossly abnormal fetal breathing movements turned out to be indicative of complete tracheal atresia. Fetal breathing movements were vigorous and jerky and of large amplitude; similarly abnormal movements were observed after birth. At postmortem tracheal atresia was diagnosed, in combination with other congenital abnormalities, which pointed to a VATER-association. The combination of a VATER-association with tracheal atresia has only been reported once before. An absence of the normal Hering-Breuer reflex in this case of complete tracheal atresia, probably explains the abnormal fetal breathing pattern. This case is in line with a growing number of reports in literature in which qualitatively abnormal fetal movements were indicative of congenital malformations.

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Methods for the continuous in vivo monitoring of glucose and lactate were applied in man for studies of peripheral metabolism and, in rats, for cerebral examinations. Lactate ('lactography') and glucose were continuously measured by the enzyme formation of NADH or NADPH using appropriate dehydrogenases. Glucose was monitored with a transcutaneous probe in neonates or with probes placed directly in the brain of conscious rats. In neonates a high correlation was seen between the dialysate and blood levels. A correlation between the age of the neonates and glucose levels in the dialysate was found, suggesting that the thickness of the skin determined to a large extent the diffusion of glucose into the probe. In the rat brain transient changes in the extracellular glucose levels were seen during electroconvulsive shock and immobilization stress. Lactography was applied to striatum or hippocampus during stress, electroconvulsive shock or systemic and intracerebral drug applications. Extracellular lactate decreased during intracerebral deoxyglucose infusion and was increased by excitatory neuronal activity and the presence of glucose in the perfusion medium. The present studies show that microdialysis in combination with continuous flow analysis can be used to study metabolic trafficking in vivo and in clinical studies. In the brain both neurons and glia may contribute to extracellular lactate levels.

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D2O and H2(18)O are often used as tracers for the determination of total body water (TBW). For newborn infants, the commonly used noninvasive method has not been validated. In this study TBW was calculated from D2O concentrations in blood and compared with TBW calculated from D2O concentrations in urine. TBW calculated from all urine portions voided at least 6 h after D2O administration on average was 1.0% lower. TBW calculated from only three urine portions voided 6, 12, and 24 h after D2O administration was 0.6% (mean) lower compared to TBW calculated from D2O concentrations in blood. This study indicates that the noninvasive method to measure TBW can be considered a reliable method when used in newborn infants.

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The sonographic findings in five newborn infants with agenesis of the corpus callosum are reported. Besides abnormal shape and position of the lateral and third ventricles of the brain, it was noted that echoreflections from the pericallosal artery were missing in all infants. Normally the pericallosal artery, which follows the surface of the corpus callosum, can be easily detected in the midline sagittal scanplane on sonography through the anterior fontanelle. It is suggested that a missing pericallosal artery is an easily detectable sign of agenesis of the corpus callosum in newborn infants.

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Sonographic pictures of the brain of 19 newborn infants who died at a mean age of 4.2 days after birth (range 1-23 days) were examined independently by five experienced sonographers. In all infants information on postmortem brain pathology was available. Diagnoses made by the sonographers based on the sonographic pictures were compared with the gross postmortem findings. The results of the study show that except for one infant with a subarachnoid hemorrhage all cerebral hemorrhages were diagnosed accurately by all sonographers. Non-hemorrhagic periventricular leucomalacia (PVL), however, was missed on sonography in 2 of the 3 cases. Surprisingly, PVL was diagnosed on sonography in 1 (8%) to 6 (50%) of 12 infants in which postmortem examination of the brain revealed no PVL. It is concluded that non-hemorrhagic PVL cannot be diagnosed accurately using sonography in the first days of life, if a 5 MHz transducer is used.

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25 singleton pregnancies were terminated by cesarean section between 28 and 33 weeks of gestation because of suspected growth retardation and abnormal unstressed cardiotocograms. Only infants with birth weights below the tenth centile were considered. 17 survived and were neurologically examined at 2.5-7 years of age. 2 were neurologically abnormal (1 had an adrenogenital syndrome) and 1 showed minor neurological dysfunction. Cesarean section appears acceptable in the management of intrauterine growth retardation with fetal distress in the early third trimester.

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2,3-Dihydroxybutane, a compound not observed in normal urines, was identified in the urine of two patients by combined gas chromatography-mass spectrometry. It is suggested, that this 2,3-dihydroxybutane is derived from pyruvate by bacterial metabolism.

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Different materials were compared as implants in performing a myringoplasty on rats immediately after making a total perforation, (autologous fascia, homologous tympanic membrane, homologous collagen, heterologous collagen, heterologous amnion and proplast). As a reference one group of rats had no myringoplasty done after perforating their drums. The animals were examined regularly, then killed after 40 and 64 weeks. Macroscopically and microscopically proplast and homologous collagen were very inferior to homograft tympanic membrane and autologous fascia. The best results were obtained both macroscopically and histologically with heterologous collagen and heterologous amnion.

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