Surfactant without intubation in preterm infants with respiratory distress: first multi-center data.

BACKGROUND: Recently in a report of a single center a method has been described to apply surfactant via a thin endotracheal catheter to very low birth weight infants spontaneously breathing with nasal continuous positive airway pressure. We now analyzed available multicenter data. PATIENTS AND METHODS: In a multicenter study investigating genetic risk factors, clinical and outcome data and data of antenatal and postnatal treatment of infants with a birth weight below 1,500 g were prospectively recorded. The measures of infants treated with the new method of surfactant application were compared to those of infants who received standard care. The analysis was restricted to infants with a gestational age below 31 weeks (n=1,541). RESULTS: 319 infants were treated with the new method and 1,222 with standard care. The need for mechanical ventilation during the first 72 h (29% vs. 53%, p<0.001), the rate of bronchopulmonary dysplasia defined as oxygen at 36 weeks of postmenstrual age (10.9 % vs. 17.5%, p=0.004) and the rate of death or bronchopulmonary dysplasia were significantly lower in the treatment group than in the standard care group. Surfactant, theophyllin, caffeine and doxapram were significantly more often and analgetics, catecholamines and dexamethasone were significantly less frequently used in the treatment group. CONCLUSIONS: A new method of surfactant application was associated with a lower prevalence of mechanical ventilation and better pulmonary outcome. A prospective controlled trial is required to determine whether this approach is superior to standard care.

Polymorphisms in the Renin-Angiotensin system and outcome of very-low-birthweight infants.

BACKGROUND: The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE-ins/del) and the angiotensin II type 1 receptor 1166A/C polymorphism (ATR1166A/C) were reported to be associated with several unfavorable outcome parameters in preterm infants like bronchopulmonary dysplasia, persistent ductus arteriosus and impaired insulin sensitivity. OBJECTIVE: To confirm the above-mentioned associations in a large cohort of very-low-birthweight (VLBW) infants. METHOD: Clinical data of VLBW infants were prospectively recorded. The ACE-ins/del polymorphism and the ATR1166A/C polymorphism were determined by polymerase chain reaction in 1,209 and 1,168 infants, respectively. RESULTS: There was no significant association between ACE-ins/del or ATR1166A/C genotype and outcome parameters (death, intraventricular hemorrhage, sepsis, bronchopulmonary dysplasia, ventilation, supplemental oxygen at discharge, postnatal treatment with insulin, surgery for intestinal perforation/necrotizing enterocolitis/retinopathy of prematurity/persistent ductus arteriosus. CONCLUSION: Both known functional polymorphisms of the renin-angiotensin system do not seem to be associated with the outcome of VLBW infants.

Oral mature teratoma containing epididymal tissue in a female neonate.

We describe a female neonate with an oral teratoma showing bone, teeth, and epidermis, but also epididymal (male) tissue. PCR amplification of Y-chromosomal DNA clearly showed male DNA from paraffin-embedded tumour tissue. The girl had a normal female karyotype without abnormalities of the genital organs. There are at least three hypotheses for the origin of teratomas: parthenogenesis, incomplete twinning, and totipotent somatic-cell origin. This case supports the hypothesis of an included dizygotic twin, and might contribute to the elucidation of the pathogenesis of extragonadal teratomas.

Improvement in respiratory compliance after surfactant therapy evaluated by a new method.

Descriptions of the effects of intratracheally applied surfactant on respiratory system compliance (C(rs)) have been somewhat controversial because the commonly used methods for assessing pulmonary function were designed for a linear pressure/volume (P/V) relation of the respiratory system. In infants with lung disease a linear P/V relation cannot be expected. Therefore, a new method (APVNL) was employed which enabled us to calculate respiratory system compliance (C(rs)) and resistance (R(rs)) based on changes in volume (V). This method is independent of the P/V relation, and was used to assess the effects of intratracheal instillation of surfactant. Fourteen infants (gestational age, 24 to 30 weeks) with respiratory distress syndrome were treated with bovine surfactant intratracheally while the fractional inspired oxygen concentration (FiO(2)) exceeded 50%. C(rs) was evaluated for the infants using the APVNL method and the method of linear regression (LR) based on the equation of motion designed for linear P/V relationships. Two hours after surfactant treatment, the median reduction of FiO(2) was 33% (95% CI: 20-50%; P < 0.01). There was no correlation between the change in FiO(2) and the change in C(rs), using either the APVNL method or the LR method. Two hours after surfactant treatment, the median improvement in C(rs) was 0.37 mL/cmH(2)O/kg (95% CI: 0.07-1. 16 mL/cmH(2)O) at a change in V of 1 mL/kg (P < 0.02) and 0.23 mL/cmH(2)O/kg (95% CI: 0-0.57 mL/cmH(2)O) at a change in V of 2 mL/kg (P < 0.05) when the APVNL method was used. The LR method could not show a significant change in C(rs) after surfactant treatment. Further, R(rs) did not show significant changes 2 hr after surfactant administration. We conclude that the APVNL method is more appropriate for evaluating changes of C(rs) elicited by surfactant treatment than the LR method. The APVNL method demonstrated significant initial improvements in compliance as lung volumes were increased; there were no significant further decreases in C(rs) as peak inspiratory pressures and the upper limits of tidal volume were approached.

Homozygous deletion of arginine-173 in the CYP11B2 gene in a girl with congenital hypoaldosteronism. Corticosterone methyloxidase deficiency type II.

The first child of consanguineous parents presented with failure to thrive and feeding problems at age 6 weeks. Important laboratory findings were low plasma sodium and elevated potassium and renin. Salt wasting was caused by an enzymatic defect in the terminal aldosterone biosynthesis. The biochemical diagnosis of corticosterone methyloxidase (CMO) deficiency type II was established on the basis of plasma multisteroid analysis, showing a pathologic increase of 18-OH-corticosterone/aldosterone ratio. Sequence analysis of the CYP11B2 gene which encodes aldosterone synthase (P450c11Aldo), the enzyme required for the terminal steps in aldosterone biosynthesis, revealed a hitherto undescribed homozygous deletion of codon 173. CYP11B2 is polymorphic at this position, encoding arginine or lysine. Both parents were heterozygous carriers of the mutation. Amino acid residue 173 in P450c11Aldo is positioned in alpha-helix D. We presume that the secondary structure of the enzyme is changed by the single amino acid deletion. This report describes a novel mutation in the CYP11B2 gene, the third known mutation associated with CMO deficiency type II.

A new method to analyze lung compliance when pressure-volume relationship is nonlinear.

Changes in dynamic lung compliance during inspiration and expiration cannot be modeled accurately with conventional algorithms. We developed a simple method to analyze pressure-volume (P/V) relationships under condition of nonlinearity (APVNL) and tested it in a lung model with known resistance and nonlinear P/V relationship. In addition, pulmonary mechanics in 22 infants, 11 of them with nonlinear P/V relationships, were analyzed with the new method. The findings were compared with those obtained by a recently introduced algorithm, multiple linear regression analysis (MLR) of the equation of motion. The APVNL method described the changing compliance (C) of the lung model accurately, whereas the MLR method underestimated C especially in the first half of the breath. In infants the MLR method gave highly variable, often nonphysiological C values in the beginning of a breath. In contrast, the coefficient of variability of measurements obtained by the APVNL method was significantly smaller (p < 0.02), and the indices of model-fit showed better agreement between calculated and observed pressure than for the MLR method (p < 0.02). We conclude that the APVNL method accurately describes nonlinear P/V relationships present during spontaneous breathing or mechanical ventilation. The method may be helpful in identifying and preventing pulmonary overdistention.

The influence of mode of delivery on hematologic values in the umbilical vein.

A variable white blood cell count without clinical signs of sepsis or hematological disorders is often observed in newborns. The intention of this study was to investigate the effect of mode of delivery on hematologic measurements, especially white blood cell count in the umbilical vein. 121 term newborns were investigated prospectively. They were subdivided into three groups: spontaneous births (n = 83), vacuum extraction (n = 19) and cesarean sections (n = 19). The mode of delivery influenced the leukocyte count and the precursor cells. The mean leukocyte counts after spontaneous birth (14.6 +/- 4.0 leukocytes/nl) and after vacuum extraction (16.6 +/- 7.4 leukocytes/nl) were significantly higher than after cesarean section (12.1 +/- 4.4 leukocytes/nl; p < 0.05). The precursors of leukocytes were also significantly higher in infants with vacuum extraction (1.06 +/- 0.83 cells/nl) than in spontaneously delivered infants (0.54 +/- 0.47 cells/nl). An inverse relationship between the number of leukocytes and the arterial cord blood pH was observed (p < 0.05). No significant differences were observed in the effect of mode of delivery on erythrocyte and platelet counts.

Patient-triggered ventilation: a comparison of tidal volume and chestwall and abdominal motion as trigger signals.

Patient-triggered synchronized ventilation requires reliable and early detection of the infant's inspiratory effort. Several trigger methods have been developed that frequently lack the sensitivity to detect inspiration in small preterm infants (trigger failure), or show a high rate of breaths triggered by artifacts in the respiratory signal (autotrigger). The purpose of this study was to determine the effectiveness of the following trigger signals: abdominal movement sensed by a newly developed induction technique, chestwall motion detected by changes in transthoracic impedance, and tidal volume measured by anemometry at the endotracheal tube connector. Ten preterm infants (birth weight, 580-1,424 g; median weight, 943 g; study weight, 535-1,415 g; median weight, 838 g; gestation age, 26-32 weeks, median gestational age, 28 weeks, study age, 1-50 days, median study age, 11 days) were included in the study. A Sechrist SAVI ventilator was triggered by one of three signals: chestwall or abdominal movement, or tidal volume generated by the infants. Response time between beginning of inspiratory flow, the occurrence of the trigger signal (signal delay), and the onset of the triggered breath (trigger delay) were determined for each of the three signals. The signal response time was -13.5 msec (95% CI, -33 to -2 msec) for the abdominal movement signal, indicating that it started before inspiratory flow; 0.0 msec for the volume signal; and 44.0 msec (95% CI, 29-73 msec) for the chestwall signal (P < 0.002); this long delay was secondary to chestwall distortion and a subsequent delay in outward ribcage movement in many infants. The trigger delay for the abdominal signal was 90.0 msec (95% CI, 55-104 msec), 135.5 msec (95% CI: 82-186 msec) for the volume signal, and 176.5 msec (95% CI: 165-232 msec) for the chestwall signal, indicating that there was a difference in the rise time of signal voltage between the three methods (P < 0.01). The rate of autotriggered breaths was 3.2% (95% CI, 0.3-9.3%) when using the abdominal signal, 0.55% (95% CI, 0.0-2.1%) for the tidal volume signal, and 11.25% (95% CI, 0.5-27.8%) for the chestwall signal (P < 0.05). The incidence of trigger failure was low with all three signals and was not significantly different between the techniques. In summary, the chestwall signal had a long trigger delay and was highly susceptible to false triggering. It is, therefore, not a reliable trigger signal for synchronized mechanical ventilation in preterm infants. In contrast, tidal volume and abdominal movement signals had an acceptable trigger delay and a low rate of autotriggering, making them useful clinical trigger signals.

Comparison of umbilical arterial versus umbilical venous blood pH correlated with arterio-venous glucose difference and cardiotocographic score.

The value of clinical parameters and umbilical arterial blood pH as indicator of prenatal hypoxia is disputed. In a prospective study of 86 vaginally delivered full-term infants, cardiotocographic (CTG) findings obtained 0-30 min and 30-60 min before birth were compared to pH values, O2 and CO2 partial pressures and glucose difference in umbilical arterial and venous blood. CTG findings were expressed as a score, higher values indicating fetal hypoxia. The venous but not the arterial blood pH was significantly related to the later (0-30 min) CTG score. The arterio-venous glucose difference was significantly related to both CTG scores. There was a significant statistical relationship between glucose difference and venous but not arterial blood pH. The later CTG score (0-30 min) also correlated significantly with O2 and CO2 partial pressures and base excess in the umbilical vein of all vaginally born infants. If CTG is accepted as an objective indicator of fetal hypoxia before birth, the arterio-venous glucose difference, and in the investigated range of pH-values, umbilical venous blood pH are more suitable than the arterial blood pH to ascertain the peripartal situation of the newborn.

Cloning properties of T lymphocyte subpopulations after treatment with 8-methoxypsoralen and UVA irradiation.

The cloning rate of PHA-stimulated T lymphocytes after treatment with 8-methoxypsoralen plus UVA irradiation described by Wunder and Reischmann (1983) gives a linear dose-effect relationship at low dosages. However, with increasing doses a flattening of the negative gradient occurs. This relationship deviates from the classical exponential curve which can be observed when fibroblasts are treated with mutagens and which is explainable by a 'recovery plateau' at lower dosages. In this study we show that some subpopulations of T lymphocytes, in particular the T-helper and T-suppressor cells, influence the overall dose-effect relationship. These isolated subpopulations exhibit varying sensitivities in comparison with their depleted cell populations. It may be assumed that heterogeneous cell populations exist within each isolated subpopulation which may be separated into further subclasses according to their specific sensitivity.

[Brain abnormality within the scope of a VACTERL association]. / Hirnfehlbildung im Rahmen einer VACTERL-Assoziation.

We report the unusual finding of brain malformations in a male newborn with anomalies of VACTERL association. Magnetic resonance imaging revealed hypoplasia of cerebellum, pons and corpus callosum as well as kinking of diencephalon and mesencephalon. These malformations of ectodermal tissue are suggestive of a defect of morphogenesis that occurred earlier than usually postulated for VACTERL cases. They resulted in severe neurologic complications and an early death. The fact that a cousin of this patient has VACTERL anomalies without cerebral involvement indicates that variable expressivity in genetically predisposed individuals may be possible for this subgroup of VACTERL cases.

[Clinical course of premature and newborn infants of mothers with HELLP syndrome]. / Klinische Verläufe bei Früh- und Neugeborenen von Müttern mit HELLP-Syndrom.

The HELLP-syndrome is complicated by a maternal mortality of 3.5% and a perinatal mortality between 9.5 and 60%. It is a variant of severe preeclampsia which includes hemolysis, elevated liver enzymes and low platelets. It is described in the literature that neonates of mothers with HELLP-syndrome show characteristic symptoms especially thrombocytopenia, leukocytopenia and prenatal somatic dystrophy. In this retrospective investigation of 36 preterm and term infants of mothers with HELLP-syndrome we found the following results: 1. Thrombocytopenia was seen in 11% and leucocytopenia in 12% of the analysed cases. Anemia was seen in 10% of the analysed neonates. They needed transfusion of blood. The rate of prenatal somatic dystrophy was increased (58%). 2. Elevated blood pressure was observed in 29% of the neonates within the analysed interval. The time of artificial ventilation of preterm infants with maternal HELLP-syndrome was in 37% extended in comparison with infants without HELLP-syndrome in pregnancy. 3. The perinatal mortality was 8%. All observed infants during delivery and of the neonatal period in our collective survived.

[Effect of a heat and humidity exchanger (Humid-Vent-Mini) on the carbon dioxide washout effect of a neonatal ventilation model]. / Einfluss des Wärme- und Feuchtigkeitsaustauschers (Humid-Vent-Mini) auf den Kohlendioxydauswascheffekt am Neugeborenenbeatmungsmodell.

The influence of the heat-und humidity-exchanger Humid-Vent-Mini on CO2-washout was examined in an neonate lung model varying leakage, pressure and flow. We compared the performance of Humid-Vent-Mini to an exchanger modified and simplified by us in which the filter has been attached directly to the connector of the tracheal tube and to a system without any exchanger. In order to examine the influence of dryness and humidity we examined the exchanger in both states. Under all conditions the heat- and humidity exchanger Humid-Vent-Mini exhibited a significant CO2-retention (p less than 0.01). The modified type also showed a CO2-retention which was markedly lower compared to Humid-Vent-Mini (p less than 0.01). The CO2-washout effect (when measured under conditions of small leakage, reduced pressure and flow) was slightly better in a moist state of the filter compared to complete dryness (p less than 0.01). These results show, that the use of heat- and humidity-exchanger is not advisable.

Perinatal glucose metabolism as an indicator for stress and hypoxia during different forms of delivery.

In 82 term newborns divided into three groups (spontaneous delivery, caesarean section and vacuum extraction) we investigated umbilical artery pH, artery and vein glucose levels and calculated the veno-arterial difference of glucose. The three groups showed significant differences of artery and vein glucose levels. The highest umbilical artery (UA) and umbilical vein (UV) glucose levels were found after vacuum extractions (n = 13, UA: 98 mg/dl, UV: 104 mg/dl), the lowest levels were present in the group of caesarean section (n = 16, UA: 52 mg/dl, UV: 65 mg/dl). After spontaneous deliveries the intermediate levels were observed (n = 55, UA: 70 mg/dl, UV: 84 mg/dl). The mean of UA-UV-glucose difference was low after vacuum extractions and statistically different from the values after caesarean section and spontaneous deliveries. The mean of UA-pH did not show statistically significant differences in the three groups. The regression analysis between UA-pH and UA-UV-glucose difference revealed a highly significant dependency in the group of caesarean section (p less than 0.01) but no dependency after vacuum extraction. Significant dependency was also found in the group of spontaneous delivery (p less than 0.05).