Randomized, multicenter trial of two different formulas for very early enteral feeding advancement in extremely-low-birth-weight infants.

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.

Unusual pattern of leukoencephalopathy after morphine sulphate intoxication.

We report a 14-year-old girl with an unusual pattern of leukoencephalopathy after intentional intoxication with morphine sulphate tablets. Toxicological analysis showed exceedingly high levels of morphine and its metabolites. MRI disclosed a leukoencephalopathy with high signal from the centrum semiovale, corpus callosum and cerebellar white matter on T2-weighted images. These findings could be only partially explained by a hypoxic-ischaemic event; neurotoxic effects must be considered in this atypical leukoencephalopathy.

Radical surgery in a neonate with craniopharyngioma. report of a case.

Ultrasonography revealed a suprasellar tumor in a fetus at 28 weeks of gestation. The male newborn, delivered 10 weeks later, was operated at the age of 17 days, and a craniopharyngioma was completely removed. Intraoperatively, inappropriate secretion of antidiuretic hormone occurred and was followed by diabetes insipidus causing imbalance of fluid and electrolytes. The tumor recurred and was totally removed 1 year later. Further development was uneventful and, at the age of 8 years, the boy is in generally good mental and physical condition except for a left-sided hemiparesis. In contrast to the poor outcome of neonatal craniopharyngioma reviewed in the literature, this case may encourage radical surgery even in the very young.

Perioperative fluid and electrolyte management in children undergoing surgery for craniopharyngioma. A 10-year experience in a single institution.

In a retrospective study, the intra- and early postoperative data of 39 children with 46 operations for craniopharyngioma were analyzed. Diabetes insipidus (DI) occurred in 30 out of 32 cases without preoperative evidence of DI. We observed that all children who did not have a pituitary stalk preserved and 5 out of 7 patients with preserved pituitary stalk developed DI within 18 h of surgery. Short-term inappropriate secretion of antidiuretic hormone (SIADH) occurred in 2 children, but was quickly followed by DI. The time of onset of DI and SIADH did not correlate with sex, age, body weight, location of tumor, or duration or extent of surgery. Parenteral desmopressin was an effective treatment for intra- and postoperative DI. The duration of the clinical effect of desmopressin administration varied in different patients between 4 and 23 h. An approach to the immediate intra- and postoperative management of children with craniopharyngioma is presented.

[Type IIB von Willebrand Jürgens syndrome as the cause of neonatal thrombocytopenia]. / von Willebrand Jürgens Syndrom Typ IIB als Ursache neonataler Thrombocytopenie.

Two newborn male infants with neonatal thrombocytopenia and von Willebrand disease (vWD) in their family history were admitted two our hospital during the last two years. The second patient was later on shown to suffer from vWD type IIB, in the first case there was a typical history but no analysis of the multimeric pattern. The vWD type IIB is a rare cause for neonatal thrombocytopenia. Therapy with platelet concentrates alone is not in all cases able to correct the platelet count for more than some hours. The finding of (recurrent) thrombocytopenia and a familial history of vWD in a newborn infant is of major diagnostic value to identify cases of this rare autosomal dominant disease.

Chemiluminescence activity of phagocytes from tracheal aspirates of premature infants after surfactant therapy.

The effect of surfactant on the respiratory burst of phagocytic cells was studied in the tracheobronchial tract of 40 mechanically ventilated neonates (gestational age 24-37 weeks) over the first week of life. We measured the luminol-dependent chemiluminescence (CL) activity of granulocytes and macrophages isolated from tracheal aspirates in 23 preterm infants 1-6 days after administration of bovine surfactant and in 17 untreated controls. Following stimulation by the chemotactic peptide N-formylmethionylleucylphenylalanine, CL activity was not or only slightly impaired in the surfactant group. In contrast, treatment with exogenous surfactant significantly reduced CL response to opsonized zymosan (OPZ), which involves phagocytosis, for up to 6 days (p < 0.05). The impairment of CL activity seemed to be dose dependent, as repeated surfactant applications (cumulative phospholipid dose of 200 mg/kg) reduced OPZ-elicited CL activity to a greater extent than application of a single dose of 100 mg/kg. In agreement with in vitro studies, our data suggest that high-dose application of exogenous surfactant may affect the antibacterial function of phagocytic cells in the lung.

Immunologic parameters in cord blood indicating early-onset sepsis.

Different immunologic parameters were measured in cord blood to test their usefulness in the early diagnosis of early onset sepsis. Cord blood levels of circulating intercellular adhesion molecule-1 (cICAM-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly elevated in septic compared to nonseptic neonates. No significant difference between either population was seen for cord blood C3a and elastase-alpha 1-proteinase inhibitor complex (E alpha 1 PI). Measured concentrations of cICAM-1, IL-6 and IL-8 in fetal and maternal blood did not correlate, indicating that the neonate's response to sepsis is clearly different from the mother. Our data suggest that cord blood measurements of cICAM-1, IL-6 and IL-8 might be useful in identifying neonates with early-onset sepsis.

Inappropriate secretion of umbilical plasma catecholamines in preterm compared to term neonates.

To investigate the gestation and stimulus related catecholamine secretion and degradation at birth free and sulfoconjugated adrenaline, noradrenaline and dopamine were analysed in the umbilical artery and vein of 35 preterm and 75 term neonates. A highly sensitive radioenzymatic assay was used for the determination of free catecholamine levels, sulfoconjugated catecholamines were analysed after addition of 25 mU arylsulfatase type VI. Levels of free catecholamines were significantly lower in preterm as compared to term newborns. Hereby, adrenaline levels significantly correlated with the gestational age, birth weight, and birth length. Sulfoconjugated catecholamine levels were similarly lower, but only sulfoconjugated noradrenaline reached differences of statistical significance. The placental extraction rate of adrenaline and noradrenaline was significantly lower in preterm as compared to term neonates. Only in term but not in preterm neonates, arterial pH- and pCO2-levels significantly correlated with arterial plasma catecholamine levels. Therefore, lower catecholamine levels in preterm compared to term neonates result from lower secretion of catecholamines rather than increased degradation and may contribute to their frequent surfactant deficiency. In addition, the inadequate and diminished catecholamine secretion of preterm neonates may play a significant part in their postnatal adaptation problems like hypoglycaemia, hypothermia and occurrence of wet lungs.

Plasma catecholamines after endotracheal administration of adrenaline during postnatal resuscitation.

To analyse the degradation of adrenaline after cardiopulmonary resuscitation of preterm neonates, free and sulphoconjugated adrenaline, noradrenaline, and dopamine were determined in 31 preterm neonates by a radioenzymatic method. Nine of the neonates received a high dose (250 micrograms/kg) of endotracheally administered adrenaline (1:1000); three of them had more than one dose of adrenaline. With the exception of sulphoconjugated dopamine, the free and sulphoconjugated catecholamine concentrations in preterm infants treated with adrenaline initially exceeded those in the untreated group. The concentrations decreased to the same range about two hours after birth. Free and sulphoconjugated adrenaline concentrations remained significantly increased in the adrenaline treated group, however, indicating a plateau effect. The correlation between free adrenaline and noradrenaline concentrations with their respective sulphoconjugated concentrations was highly significant. It is concluded that free catecholamines are rapidly degraded by sulphoconjugation in preterm neonates.

[Antepartum prevention and postnatal therapy of respiratory distress syndrome]. / Präpartale Prophylaxe und postnatale Therapie des Atemnotsyndroms.

The introduction of surfactant in the therapy of respiratory distress syndrome (RDS) reduced mortality and long term complications in very premature infants. Nevertheless, the obstetric management influences critically the outcome. In a prospective study of 116 premature infants with RDS treated with natural surfactant preparations after birth, mortality was significantly reduced by antepartum corticosteroid therapy suggesting a synergistic effect of corticosteroids and surfactant on the immature lung. It is assumed that a preventive administration of surfactant immediately after birth would benefit neonates at risk for RDS more than a delayed surfactant replacement after the development of RDS. But without a reliable assessment of fetal lung maturity before birth more than 50% of our premature infants with birth weights less than 1500 g would be exposed to surfactant unnecessarily. It is important that fetal asphyxia is avoided. Acquired respiratory distress syndrome occur even in premature infants after shock or meconium aspiration and may respond poorly to surfactant replacement. This is also the case in lung hypoplasia or perinatal infection, where the combined efforts of obstetricians and neonatologists are needed to attain better results.

[Effect of body position and positioning changes on lung function of ventilated premature and newborn infants]. / Einfluss von Körperposition und Lageveränderungen auf die Lungenfunktion beatmeter Früh- und Neugeborener.

We studied 21 intubated premature infants (wts 800-2800 g) with respiratory distress syndrome between day 2 and 10 to evaluate the effect of body position on lung mechanics and gas exchange. The dynamic compliance of the total respiratory system was similar in the prone and supine position. When the infant was turned from the supine or the prone position to the other one, a significant improvement of oxygenation was seen temporarily. Positioning did not significantly affect the dynamic compliance, the minute volume or pCO2. In circulatory stable premature infants a change of the body position probably alters the regional ventilation to perfusion ratio and leads to a reduction of intrapulmonary venous admixture.

Polymerase chain reaction-amplification of urease genes: rapid screening for ureaplasma urealyticum infection in endotracheal aspirates of ventilated newborns.

Ureaplasma urealyticum infection has been considered to play an important role in the development of bronchopulmonary dysplasia (BPD) in premature infants. Since standard culture methods of U. urealyticum are difficult to perform, new rapid and sensitive methods are needed to detect lung infection of ventilated newborns. Here we describe the polymerase chain reaction as a rapid method to screen endotracheal aspirates for ureaplasma infection. Urease-specific sequences could only be detected in 1 out of 36 ventilated newborns. The procedure described in this paper may facilitate further studies to determine the role of U. urealyticum in development of BPD.

Complement fragment C3a in plasma of asphyxiated neonates.

Recent clinical studies with adult polytrauma patients indicate that elevated plasma levels of anaphylatoxin C3a correlate with the subsequent development of the adult respiratory distress syndrome (ARDS). However, there are no parameters which allow a reliable diagnosis of ARDS in neonates. As the most predisposing condition for ARDS seems to be shock, plasma C3a was determined in 30 ventilated premature infants and neonates with respiratory distress syndrome (birth weights 660-3350 g) within the first 24 h post partum or 6-24 h after acute asphyxia or shock during the neonatal period. The range of C3a, measured by ELISA, was between 57 and 1000 ng/ml. In the asphyxia group (n = 15) peak levels of C3a in plasma (mean 388 ng/ml) were significantly higher (P less than 0.001) than in the control group (mean 153 ng/ml). In some neonates with suspected ARDS, additional samples were taken. A rise in C3a between days 2 and 8 was associated with a fatal outcome of the disease. As in adults, C3a might be a useful indicator for ARDS in neonates.

[Dexamethasone in the treatment of bronchopulmonary dysplasia]. / Dexamethason in der Behandlung der bronchopulmonalen Dysplasie.

Dexamethasone has been reported to benefit premature infants with bronchopulmonary dysplasia. 13 ventilator-dependent premature infants (birth weight 780-1270 g) with chronic lung disease received dexamethasone 0.5 mg/kg/day with tapering doses over 3 weeks. Dexamethasone therapy was associated with a temporary increase in urine output and blood pressure. All infants showed a significant fall in oxygen requirement and an increase of total pulmonary compliance during the first week. The endotracheal tube was successfully removed in all infants with Northway stage I/II BPD within the first week of treatment and no infant relapsed. But in Northway stage III/IV, only 2/9 infants could be weaned from the ventilator during the first course of treatment and in the majority treatment led only to a temporary improvement of pulmonary status. In parallel to the improvement of lung function we found in 7 infants a decrease of the total cell counts, the ratio PMN/macrophages and albumin in relation to urea in the bronchial lavages with a secondary rise in cases of a clinical relapse. Free elastase and fibronectin/albumin ratio in the bronchial lavage did not correlate to the clinical course. Dexamethasone seems to have not only an effect on fluid balance but also on the alveolar capillary leakage and the PMN influx into the lung. This might explain the superior effect of dexamethasone in patients with Northway stage I/II BPD in comparison to infants with Northway stage III/IV.

[Causes of and change in bacterial infections in newborn infants]. / Ursachen und Wandel bakterieller Infektionen bei Neugeborenen.

Despite all the progress made in modern neonatology the morbidity rate caused by bacterial infections has rather gone up than down. The reasons why premature and newborn infants have a greater disposition to bacterial infections have been largely explored; at the same time one must accept these infants to be increasingly vulnerable to infections, the vulnerability being the larger the greater the degree of immaturity is. Every 5th to 10th death of newborn infants is caused by infection. One will have to be constantly on the watch and acquire profound knowledge of channels of infection and the bacterial spectrum to be expected. Since the early beginnings of neonatology, some 60 years ago, a continuous change in bacterial spectra has been going on showing incredible regularity in crossing even borders and continents. With gram-positive cocci (A streptococci) prevailing at the beginning, there was a considerable increase in gram-negative enterobacteriaceae in the 60ies and 70ies, when neonatal intensive medicine was started. There were mainly nosocomial infections resulting from too generously administered antibiotics. Today, plasmacoagulase-negative staphylococci, for a long period thought not to be pathogenous, are the essential bacteria in nosocomial infections. On the whole, one usually has to do with infections vertically transmitted by the mother, especially to preterm infants. The greatest threat still comes from B streptococci since they will lead to pulmonary changes such as pneumonia and RDS. The development reported on is based on data from the literature and my own experience as well as on comprehensive results of the Neonatalerhebung of Lower Saxony and Bavaria.

[Diagnosis of monozygosity in multiple births by DNA fingerprinting]. / Diagnose der Monozygotie bei Mehrlingen durch DNA-Fingerprinting.

The incidence of monozygotic twins is one in 250 pregnancies. Triplets are estimated to occur in 1 of 86(2) pregnancies. Determination of zygosity may be done by comparison of physical characteristics, blood group or tissue typing, chromosome studies, or examination of various other polymorphic protein markers. Here we describe the differentiation between monozygotic and dizygotic twins and triplets by DNA-fingerprinting. This is a fast, non-invasive and reliable (error probability 0.003%) method to determine monozygosity of twins or triplets. It is also a reliable paternity test.