[Lavage with exogenous surfactant in neonatal meconium aspiration syndrome]. / Lavage mit exogenem Surfactant bei neonataler Mekoniumaspiration.

BACKGROUND: Meconium aspiration syndrome is a disease in near term infants which requires invasive techniques to decrease mortality. Lavage of the tracheobronchial tree with exogenous surfactant has been shown to be effective in animal studies. We studied the effectiveness of this technique in newborn infants and compared them with a historical control group. PATIENTS AND METHODS: From 1987 to 1998, we treated 18 neonates with meconium aspiration syndrome. In 11 babies a lavage with bovine derived diluted surfactant was carried out immediately after admission. In 7 infants of the control group only the meconium was suctioned or a lavage with saline performed. There were no differences between both groups concerning other therapeutic interventions like high frequency ventilation or inhalative NO. The control group contained significantly more outborn patients compared with the lavage group. Criteria of effectiveness were change in oxygenation index (OI), duration of mechanical ventilation and oxygen supplementation greater than 30 %. In addition, the two groups were compared for incidence of death, need for ECMO, and air leaks. RESULTS: One infant of the lavage group died, one had to be transferred to ECMO (no significant difference). There was a significant decrease in OI after surfactant lavage from 22 at admission to 5.1 one day later (p=0.007), whereas in the control group, OI did not change significantly over time (15.8 to 11.4). There were no differences in the duration of mechanical ventilation or oxygen supplementation. CONCLUSIONS: In our study, lavage with exogenous surfactant had only a short-term effect in decreasing OI in neonates with meconium aspiration. Larger numbers of patients need to be investigated to demonstrate an improvement in long-term outcome.

Congenital nemaline myopathy due to ACTA1-gene mutation and carnitine insufficiency: a case report.

A premature boy with a congenital form of nemaline myopathy due to mutation in the ACTA1-gene showed decreased carnitine levels in the eighth week of life. After sufficient oral carnitine substitution he improved gradually. In the first 15 months of life he made good progress; he reached full head control, learned to sit unsupported and was able to raise objects. At that time the carnitine levels were normal without substitution. Nemaline myopathy is clinically and genetically heterogenous. The pathogenesis of the muscle weakness is poorly understood. Disturbances of carnitine metabolism in this group of patients as one possibility are conceivable. Further investigations of carnitine metabolism in patients with nemaline myopathy may shed light on the pathogenesis of this entity.

[Postpartum risk factors in the development of children born to opiate-addicted mothers; comparison between mothers with and without methadone substitution]. / Postpartale Risikofaktoren in der Entwicklung von Kindern opiatabhängiger Mütter. Ein Vergleich zwischen Müttern mit und ohne Methadon-Substitution.

In a retrospective case control study at the University of Frankfurt, Germany, 101 babies born to opiate-addicted mothers were identified from birth charts from 1988 to 1995. After birth, they developed a withdrawal syndrome (neonatal abstinence syndrome). Fifty control infants and their mothers were selected from neonatal wards. The group of opiate-exposed babies was subdivided into a group born to mothers without methadone treatment (n = 48) and a group born to mothers who were enrolled in a methadone program (n = 51). The methadone infants had a significantly higher mean birth weight (2822 g) than children in the group without methadone (2471 g). The abstinence syndrome was much more intense in the methadone group (convulsions 47.1%) than in heroin-exposed babies without methadone treatment (convulsions 27.1%). Women in methadone maintenance programs lived in more stable socioeconomic conditions than opiate-addicted women without methadone substitution. Moreover, they cared significantly better for their babies: 81.3% of the methadone mothers visited their children on a regular basis and 90.9% cared adequately. The data emphasize the need in future research to look more closely at the role of methadone treatment programs in the development of opiate-exposed babies.

[Cerebral perfusion in newborn infants treated with high-frequency oscillation ventilation]. / Zerebrale Perfusion bei Neugeborenen unter Hochfrequenz-Oszillations-Beatmung.

UNLABELLED: The effects of high-frequency oscillatory ventilation (HFOV) on hemodynamic parameters have been shown in animal as well as in clinical studies. In a further study we could demonstrate, that after change of a conventional positive pressure ventilation (CMV) to HFOV flow velocities in cerebral arteries decreased. In the following we added to the dopplerflow method the continuous examination of cerebral oxygenation with near infrared spectroscopy (NIRS). PATIENTS: 19 measurements were prospectively conducted in 18 neonates. The infants were mechanically ventilated with HFOV and were in a stable condition. METHODS: Before change from HFOV to CMV doppler signals of the anterior cerebral artery were measured. We repeated this at the end of the study in each patient. NIRS-optodes were placed on the front and the os parietale of each infant. After stabilization of the system we changed from HFOV to CMV without disconnection of the patient from the machine. PCO2 was registered continuously via a transcutaneous probe, as well as oxygen saturation via pulse oxymetry. Statistical analysis was performed with Wilcoxon test. RESULTS: There were no significant changes of doppler-signals during the study (median vs. 25 cm/s (+/- 6) during HFOV, 28 cm/s (+/-/) during CMV). The parameter of NIRS, oxygenated hemoglobin HbO [-1.5 U (+/- 22.78)] at 15 minutes after change), reduced hemoglobin HbR [-1.17 U (+/- 5.26)] and total hemoglobin HbT [-2.68 U (+/- 18.7)] remained stable during the change from HFOV to CMV, too. In five infants there was a decrease and in two an increase of HbO 15 minutes after change, which correlated with decrease or increase of pCO2. CONCLUSION: In a combined measurement of dopplerflow and NIRS we found no special effect of HFOV on cerebral hemodynamics comparing with CMV. Changes of cerebral oxygenation in NIRS correlated with pCO2.

Invasive pulmonary aspergillosis in a critically ill neonate: case report and review of invasive aspergillosis during the first 3 months of life.

We report a fatal case of invasive pulmonary aspergillosis in a severely ill neonate and review 43 additional cases of invasive aspergillosis reported from 1955 through 1996 that occurred during the first 3 months of life. Eleven of the 44 patients had primary cutaneous aspergillosis, 10 had invasive pulmonary aspergillosis, and 14 had disseminated disease. Most infections were nosocomial in origin. Prematurity (43%); proven chronic granulomatous disease (14%); and a complex of diarrhea, dehydration, malnutrition, and invasive bacterial infections (23%) accounted for the majority of underlying conditions. At least 41% of the patients had received corticosteroid therapy before diagnosis, but only one patient had been neutropenic. Among patients who received medical and/or surgical treatment, outcome was relatively favorable, with an overall survival rate of 73%. Invasive aspergillosis may occur in neonates and young infants and warrants consideration under certain circumstances. Current therapeutic approaches consist of high-dose amphotericin B and appropriate surgical interventions.

A prospective, randomized, multicenter trial of high-frequency oscillatory ventilation compared with conventional ventilation in preterm infants with respiratory distress syndrome receiving surfactant.

OBJECTIVES: To compare high-frequency oscillatory ventilation (HFOV) and intermittent positive pressure ventilation (IPPV) as a primary ventilation mode in preterm infants with respiratory distress syndrome. Primary end points were survival and maintenance of the randomized ventilation mode. STUDY DESIGN: Prospective, multicenter, randomized clinical trial. SETTING: Level III neonatal intensive care units at three university children's hospitals. PATIENTS: Ninety-six premature infants (gestational age < 32 weeks) randomly assigned to HFOV or IPPV within the first 2 hours of life. All patients received a natural surfactant. No differences were found between the study groups with respect to the demographic data or the severity of respiratory distress syndrome. Infants were stratified at randomization, by birth weight, into two groups: 750 to 1000 gm (n = 32) and 1001 to 1500 gm (n = 64). The centers involved complied with a study protocol that planned a reduction in respiratory pressures when the infant's oxygen requirement had reached a fractional concentration of inspired oxygen of 0.6. RESULTS: Five patients in the HFOV group died, and eight patients did not respond to the randomized ventilation mode; whereas four patients in the IPPV group died, and nine were switched to HFOV. No differences were found in gas exchange or ventilator support over the first 72 hours. Premature infants with a birth weight < 1000 gm had a significantly shorter course to reach fractional concentration of inspired oxygen of 0.21 while receiving IPPV than those receiving HFOV (9.3+/-4.5 days vs 27.5+/-10.2 days, p = 0.01). No differences were found between the groups in extraalveolar air (HFOV seven; IPPV, seven) and intracranial bleeding (HFOV, nine; IPPV, eight). CONCLUSION: After surfactant treatment, HFOV, as a primary ventilation mode in premature infants with respiratory distress syndrome, is as safe and efficacious as conventional ventilation.

[Hemodynamic effects of high-frequency oscillating ventilation in preterm and term infants]. / Hämodynamische Auswirkungen der hochfrequenten Oscillationsbeatmung bei Früh- und reifen Neugeborenen.

To study the effects of high frequency oscillating ventilation (HFOV) on cerebral and abdominal circulation we measured blood flow velocities in three cerebral arteries and in the A. mesenterica superior by pulsed doppler ultrasound in 13 preterm (mean gestational age 28 weeks [25-31]) and 3 term infants during conventional ventilation (intermitted positive pressure ventilation, IPPV) and HFOV. In the preterm infants systolic blood flow velocities decreased under HFOV in all cerebral arteries. Statistically significant differences were found in the A. cerebri anterior (45.8 cm/s [sd +/- 20.6] versus 34.3 [sd +/- 10.8]; p < 0.02) and in the A. basilaris (52.8 cm/s [sd +/- 26.4] versus 44.1 [sd +/- 18.7]; p < 0.05). There was also a distinct decrease of systolic blood flow velocity in the A. mesenterica (111 cm/s [ +/- 31.3] versus 61.8 cm/s [sd +/- 18.6]; p < 0.002). The enddiastolic blood flow velocity and the Resistance Index of Pourcelot did not change significantly. The systemic blood pressure did not change during conventional ventilation or HFOV. Mean airway pressure and pCO2 were lower during HFOV, but there was not strong correlation with the reduction of flow velocities in the studied arteries (r = 0.48). In the three term infants presenting with a persistent pulmonary hypertension of the newborn, there was an increase in systolic and enddiastolic flow velocities in all studied arteries under HFOV.

[High-frequency oscillating ventilation in premature infants under 1500 gram birth weight]. / Hochfrequente Oszillationsbeatmung bei Frühgeborenen unter 1500 g Geburtsgewicht.

In 58 premature infants with a birthweight < 1500 g High-Frequency-Oscillating-Ventilation (HFOV) was initiated within the first 48 hours of life. Indications for HFOV were: no response to surfactant application (N = 41), respiratory distress syndrome without surfactant application (N = 9), pulmonary interstitial emphysema (N = 8). Mean gestational age of the enrolled patients was 27.6 weeks (24-32) and mean birthweight was 964 g (490-1450). 23 infants died, 5 from non-pulmonary causes. Of the remainder 2 had B-Strept.-septicemia, 1 lunghypoplasia, and 1 patient died on the 70th day of life from chronic lung disease. There were no statistical differences between survivors and nonsurvivors in gestational age, birthweight, umbilical pH, 1 min APGAR score or time on conventional ventilation prior to HFOV. Alveolar-arterial-O2-difference dropped in the group of surviving patients from x487 mm Hg (sd +/- 60) to 252 mm Hg (sd +/- 89) after 6 hours (p < 0.0001) and in the nonsurvivors from x517 mm Hg (sd +/- 74) to x373 mm Hg (sd +/- 106) (p = 0.002). Oxygenationindex fell from x25 (sd +/- 10) to x5 (sd +/- 1.5) in the survivors and from 25 (sd +/- 11) to x9 (sd +/- 5.5) in the nonsurvivors within 6 hours (p < 0.0001). Mean airway pressure could be lowered in survivors from x7.6 cm H2O (sd +/- 0.6) to 5.3 cm H2O (sd +/- 0.8) and in nonsurvivors from x8.6 cm H2O (sd +/- 0.6) to 5.7 cm H2O (sd +/- 0.9) (p = 0.0002). The promising results of HFOV as a rescue therapy require a controlled study for its use as a primary mode of ventilation in premature infants.

[Congenital candida infections]. / Kongenitale Candidainfektionen.

Congenital candida infection is a rare disease, although the incidence of candida vaginitis during pregnancy is high. We report on five cases each showing patterns considered typical for candida infection. The infective agent can cause chorioamnionitis even in the presence of intact fetal membranes. An intrauterine device (IUD) has been proved to be a risk factor for a congenital candida infection. The pathogenetic significance of contamination with candida for the fetus appears to depend largely on gestational age. A premature infant with a birth-weight less than 1500 g presented with bilateral candida endophthalmitis which was cured by intravenous Fluconazole therapy. Another premature infant weighing 800 g at birth developed a systemic candida infection. The other three more mature infants had milder symptoms, two of them presented with cutaneous candidiasis.

[Persistent pulmonary hypertension in the newborn infant caused by aneurysm of the vein of Galen]. / Persistierende pulmonale Hypertension des Neugeborenen bei Aneurysma der Vena Galeni.

A male full-term neonate is described in whom cardiac insufficiency developed within 24 hours post partum. Ultrasound revealed an arterio-venous fistula of the vein of Galen. The patient's condition did not allow surgical correction and he died on the 22nd day of life. Persistent pulmonary hypertension was an important accompanying feature. The literature is reviewed with respect to the prognosis and the up to now seldom reported complication of persistent pulmonary hypertension of the newborn (PPHN).

One-sided high-frequency oscillating ventilation in the treatment of neonatal unilateral pulmonary emphysema.

We describe a preterm infant (31 weeks' gestation) with unilateral pulmonary emphysema. Bronchoscopy showed no bronchial obstruction. After 20 days of right-sided high-frequency oscillating ventilation, the emphysema in the left lung had completely resolved and the patient could be extubated.

Urinary malondialdehyde concentration in preterm neonates: is there a relationship to disease entities of neonatal intensive care?

In a retrospective study, urinary malondialdehyde concentration in 45 preterm neonates (25-35 weeks' gestation) during their first month of life was measured by HPLC. Urine was collected on different days of life as a 3-h sample. The frequency of urine collection and measurement varied between one (n = 22) and seven times (n = 8) per child. The study group was divided into three categories according to birth weight: low-birth-weight infants (LBW) (n = 16), very low-birth-weight infants (VLBW) (n = 17) and extremely low-birth-weight infants (ELBW) (n = 12). Urinary malondialdehyde concentration was highest in the ELBW group: 1.15 (0.66, 2.12) mumol/l (median and quartiles) versus 0.58 (0.34, 1.18) mumol/l in the VLBW and 0.60 (0.40, 1.06) mumol/l in the LBW groups (ELBW versus VLBW, p < 0.005; ELBW versus LBW, p < 0.02). In oxygen-treated neonates, significantly higher malondialdehyde values were found compared to those without supplementary oxygen (0.89 (0.48, 1.74) versus 0.58 (0.32, 0.89) mumol/l; p < 0.005). Likewise, a higher malondialdehyde concentration was found in infants requiring mechanical ventilation (intermittent mandatory IMV or high frequency ventilation) compared to those breathing spontaneously (intermittent mandatory ventilation: 0.80 (0.42, 1.66); p > 0.05 and high frequency ventilation: 1.20 (0.83, 2.13); p < 0.001 versus 0.57 (0.33, 0.88) mumol/l). Malondialdehyde concentrations correlated significantly with FiO2 values of the individual patients (r = 0.22; p < 0.02). Comparing urinary malondialdehyde concentrations in infants with and without bronchopulmonary dysplasia, a significantly higher malondialdehyde concentration was found in the former group (0.96 (0.51, 2.07) versus 0.60 (0.32, 0.98) mumol/l; p < 0.005)).(ABSTRACT TRUNCATED AT 250 WORDS)

Development of thyroid gland volume during the first 3 months of life in breast-fed versus iodine-supplemented and iodine-free formula-fed infants.

The spontaneous development of thyroid gland volume (TGV) during the first 3 months of life was studied in entirely breast-fed infants (n = 21) and compared to those fed an iodine-supplemented formula (n = 19), an iodine-free formula (n = 5), or partially breast-fed in addition to an iodine-free (n = 4) or an iodine-supplemented formula (n = 16). The TGV of the infants and their mothers was determined sonographically in addition to their urinary iodine concentrations 5-7 days postpartum and 3 months later. In ten additional lactating mothers the breast milk concentrations of thyroid hormones and iodine were determined. It was shown that at 3 months of age an infant consuming about 1000 ml breast milk per day receives about 2 micrograms thyroid hormones and 55 micrograms iodine per day. At the end of their first week of life the infants showed a TGV between 0.28 and 1.5 ml (median 0.61 ml) and a urinary iodine concentration between 0.03 and 16.3 micrograms/dl (median 3.0 micrograms/dl). At 3 months of age the TGV of the breast-fed infants had decreased by a median of 0.24 ml (= -34%; median of percentage changes) whereas those fed a formula without iodine had increased by a median of 0.26 ml (= +50%; median of percentage changes). Those receiving an iodine-supplemented formula showed a TGV reduction of 0.14 ml (= +2%; median of percentage changes). The TGV development of the partially breast-fed infants lay between those being exclusively breast or formula fed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Treatment of disseminated intravascular coagulation with antithrombin III concentrate in children with verified infection]. / Behandlung der Verbrauchskoagulopathie mit Antithrombin III-Konzentrat bei Kindern mit nachgewiesener Sepsis.

Consumption coagulopathy in childhood is still a serious problem. Besides treatment of the underlying diseases therapy of consumption coagulopathy was performed with heparin and nowadays with substitution of coagulation factors, especially antithrombin III concentrate, alone or in combination with heparin. We performed administration of AT III concentrates only, without additional heparin treatment in children with proven septicaemia (preterm infants n = 21, children beyond the newborn period n = 18). Antithrombin III, platelet count, fibrinogen, PT, aPTT and TT were assayed. These coagulation parameters turned to be normal 48 hours after normalisation of the antithrombin III plasma level-AT III increased to normal values within 24 hours after the initial substitution in all children. Lethal outcome was not observed after sole administration of AT III as well as no other side effects have been seen. In summary, these data indicate that consumption coagulopathy in childhood can be managed successfully with early substitution of AT III concentrate.

[Pulmonary sequelae of long-term ventilation of very low birth weight premature infants. Results of a follow-up study of 6-to-9-year-old children]. / Die pulmonalen Folgen der Langzeitbeatmung von very low birth weight Frühgeborenen. Ergebnisse einer Nachuntersuchung der Kinder im Alter von 6-9 Jahren.

Fifty six children with a birth weight of less than 1500 g and gestational age less than 34 weeks were studied at a mean age of 7.7 years. All had required mechanical ventilation, 36 suffered from hyaline membrane disease, 17 from atelectasis and three from pneumonia. Of these patients 37 developed broncho-pulmonary dysplasia (BPD). The study included skin prick test, measurement of ciliary beat frequency, chest X-ray, whole-body plethysmography and histamine challenge. Eight patients suffered from recurrent pulmonary infections up to the age of 4 years. Eleven children had a positive skin prick test. Three suffered from allergic asthma and six from hay-fever. The family history of atopy in these premature infants was no different from that of the general population. Ciliary beat frequency was normal in all cases (frequency: 11.8 +/- 1.8 Hz). In 34 patients X-rays showed minimal changes (peribronchial thickening n = 6, mild emphysema n = 28). Pulmonary function was normal except for an increase of thoracic gas volume which was correlated to grade of BPD according to Northway. There was a significant correlation between oxygen-score and radiological stage of BPD (r = 0.7). Histamine challenge showed hyperresponsiveness in 53% of the children. Eight patients showed a threshold similar of mild asthma (less than 1000 micrograms histamine per ml). The degree of airway hyperreactivity was correlated to the grade of BPD (r = 0.7; p less than 0.01) and the oxygen-score (r = -0.63; p less than 0.05). The oxygen-score may be considered a predictor of hyperresponsiveness and pulmonary outcome in later childhood.