Angiotensin II receptor blocker induced fetopathy: 7 cases.

BACKGROUND: During a period of 12 months 7 newborns with a partially severe fetopathy caused most probably by maternal sartan-intake in pregnancy were treated in 5 German teaching hospitals. Sartans antagonize the effect of angiotensin II at the AT1-receptor and are used to treat arterial hypertension. METHOD: We presented 2 cases at the yearly GNPI meeting 2010 and we were informed about similar cases in other German teaching hospitals which we brought together in this publication. RESULTS: In the presented cases, maternal sartan intake was noticed at different times in pregnancy and was in part discontinued some weeks before delivery. In all pregnancies oligohydramnios was present and fetal kidneys displayed a hyperechogenic structure on ultrasound. The newborns' postnatal course varied: oligohydramnios sequence with lung hypoplasia, arterial hypotension and renal insufficiency were the predominant problems of the first days of life. The majority (4/7) of infants did not survive this period, in other cases there was a complete (1/7) recovery of renal function whereas others survived with renal impairment (2/7), in part requiring chronic dialysis. Further distinctive features seen frequently were disturbances of cranial ossification and flaccid paralysis of hands and feet with deviations as well as sensorineural hearing loss. CONCLUSION: These case reports again underline the hazardousness of maternal sartan intake with potential fatal outcome for the newborn. Though the use of sartans in pregnancy is contraindicated and several case reports of sartan induced fetopathies exist, the risk of sartan treatment generally seems to be underestimated.

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.

Influence of clinical and ventilatory parameters on morphology of bronchopulmonary dysplasia.

Our aim was to assess multiple factors which contribute to bronchopulmonary dysplasia (BPD) in prematurely born neonates. Specific morphologic features might relate to cumulative oxygen dose, barotrauma, prematurity, infection, and persistent ductus arteriosus (PDA). Seventy-two patients dying from BPD as defined by the histopathologic criteria of Stocker were analyzed retrospectively. Median (range) gestational age was 28 (25-35) weeks, and median survival was 16 (5-386) days. The infants were ventilated for 15 (15-149) days with a mean inspired oxygen fraction (FiO2) of 0.78. The cumulative oxygen dose and mean airway pressures were determined. The presence of neonatal infection, PDA, and interstitial lung emphysema (ILE) was assessed. Baseline lung disease was estimated as proposed by Palta. At autopsy, the degree of hyaline membranes, epithelial cell necrosis, emphysema, atelectasis, interstitial cell proliferation, and lung fibrosis was scored semiquantitatively (0 to 3+). The influence of neonatal infection, PDA, gestational age, survival, oxygen dose, or barotrauma on morphological findings was examined by multivariate analysis. We found "acute" BPD in 22, "reparative" in 34 and long-standing-"healed" in 16 cases. ILE within the first week was associated with interstitial cell proliferation and lung fibrosis in infants surviving more than 28 days. Initial barotrauma contributes to lung fibrosis in infants with BPD.

Acetylation of procainamide and isoniazid by a rat liver-N-acetyl-transferase.

The genetic variation of the enzyme isoniazid-N-acetyltransferase has been studied in man and other species. Homogenates of liver samples of adult LEW rats also acetylate procainamide. The kinetic properties of isoniazid and procainamide acetylation are similar and are consistent with a ping-pong Bi-Bi mechanism. The experimental data support the hypothesis that one acetyltransferase catalyses both procainamide and isoniazid. Furthermore, a simple spectrophotometric assay to determine procainamide acetylation is presented.

Very low birth weight infants have only few adverse events after timely immunization.

INTRODUCTION: Premature infants should be vaccinated at the appropriate vaccinating age, without correcting for their gestational week and regardless of their weight. Uncertainty with regard to possible severe adverse events exists among physicians. METHODS: In all, 473 patients with a birth weight under 1500 g were included in a prospective observational study for adverse events that included cardiorespiratory events, local reactions and fever. Three vaccination combinations were used at different time periods. RESULTS: The median birth weight was 910 (375 to 1495) g. Gestational week at birth was 27.6 (22.6 to 34.3). At the time of vaccination, the gestational week was 37.4 (31.5 to 48.3). The frequency of adverse events for local reactions/fever was 2.8% and for apnea/bradycardia it was 10.8%. Apnea appeared significantly more often in children who were younger at the time of immunization. This is in concordance with the fact that they were also younger at birth. If apnea appeared, the chance of the development of bradycardia had an odds ratio of 6.4 (3.2:13.0). Children with higher-grade hemorrhages and/or with periventricular leukomalacia did not experience more adverse events, except fever. CONCLUSION: Timely vaccination of premature infants with a birth weight under 1500 g is safe, but the occurrence of cardiorespiratory events is related to earlier gestational week.

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.

[Newborn metabolic screening]. / Analyse der Zeitabläufe des Neugeborenenscreenings.

BACKGROUND: Guidelines for neonatal screening for inborn errors of metabolism published by the Federal Joint Committee of physicians and health insurances in Germany include preanalytical specifications, e. g. blood collection at 36 to 72 hours of life and rapid sample transportation which is necessary with respect to those target diseases of the German program that might lead to very early metabolic decompensation. METHODS AND RESULTS: Analysis of 149 854 data sets containing all necessary informations out of a total of 173 221 screening samples sent to our laboratory from April 2006 to the end of March 2007 showed significant discrepancies between the requested and the actual times recorded for blood collection. 11.5 % of samples were drawn later than required. Looking at outpatients only, 43 % of the samples were taken after 72 hours. Sample shipping was delayed in several hospitals and private practises, especially on weekends. This was the reason why 31.2 % of all samples could not be reported on within 72 hours after blood collection as required. In addition the quality of 914 samples (0.52 %) was insufficient so that a repeat sample had to be analysed. CONCLUSION: In the future, as a rule, every baby should have his/her blood taken around the 48th hour, in any case between the 36th and 72nd hour of life. Moreover, sample shipping needs to be optimised in order to guarantee early diagnosis of inborn errors of metabolism. Also, more attention has to be paid to the quality of blood samples.

Prevalence of two tumor necrosis factor gene polymorphisms in premature infants with early onset sepsis.

BACKGROUND: Tumor necrosis factor (TNF) is a central mediator of sepsis. The NcoI polymorphism within the TNF locus has been described as a prognostic marker for mortality in adult patients with sepsis. OBJECTIVES: The aim of our study was to investigate the genotype and allele distribution of 2 TNF gene polymorphisms in preterm infants <32 weeks of gestational age, who developed early-onset sepsis. METHODS: A double-blinded retrospective cohort study was carried out on stored Guthrie blood spot cards with group A including 67 premature infants <32 weeks of gestational age with proven early-onset sepsis and group B including 102 healthy newborn infants (>32 + 0 weeks of gestation). The genotype andallele distribution of the study population were also compared to reference groups of healthy adult volunteers (n = 252 for TNF-beta NcoI and n = 233 for -308 TNF-alpha promoter). Polymorphisms of the TNF-alpha promoter -308 region and the NcoI site of the TNF-beta gene were assessed using PCR followed by melting curve analysis or NcoI digestion. The groups were compared by estimation of Hardy-Weinberg equilibrium. RESULTS: The overall allele frequency and genotype distribution of the -308 TNF-alpha and NcoI polymorphism of the TNF-beta gene were comparable to the values found in the controls. CONCLUSION: The study results suggest that none of the analyzed TNF gene polymorphisms may serve as a prognostic marker for preterm infants at high risk of sepsis.

Interleukin-6-174-genotype, sepsis and cerebral injury in very low birth weight infants.

We investigated the association between the interleukin 6 (IL-6)-174-genotype and unfavorable outcomes in preterm infants since it has been reported that the IL-6-174GG-genotype is associated with increased susceptibility to sepsis, and the IL-6-174CC-genotype is more common in preterm infants with severe intraventricular hemorrhage (IVH). We studied 1206 preterm infants with a birth weight below 1500 g. In contrast to previously published data, the frequency of IVH grade IV, periventricular leukomalacia, ventricular-peritoneal-shunting or death was not different between infants with different IL-6-genotypes: IL-6-174GG (n = 430) 8%, IL-6-174GC (n = 605) 9% and IL-6-174CC (n = 167) 12% (P = 0.2 for IL-6-174CC vs GG + GC). Furthermore, we were not able to confirm previously reported association between sepsis and the IL-6-174GG-genotype. Blood-culture-proven sepsis occurred in 19% of IL-6-174GG-carriers (n = 157), 26% of IL-6-174GC-carriers (n = 193) and 27% of infants carrying the IL-6-174CC-genotype (n = 67). We were not able to confirm previously reported associations between sepsis, cerebral injury and the IL-6-174-genotype in VLBW-infants.

Altered ribosomal protein synthesis in congenital non-progressive myopathy.

Ribosomes isolated from fibroblasts, muscle tissues, and blood cells of a patient with congenital non-progressive myopathy were used for in vitro measurement of protein synthesis in a heterologous poly(U)-directed polyphenylalanine synthesis system. The activity of ribosomes obtained from the patient was 35% lower than that in normal controls.

[Transient unilateral oculomotor paralysis]. / Passagere einseitige Okulomotoiusparese.

A three-year-old girl was admitted to the hospital one day after the acute onset of drooping of the left eyelid, associated with oculomotor external ophthalmoplegia. General neurological and physical examination was unremarkable. Results of serological tests as well as the clinical course of the disease (spontaneous recovery) show that the unilateral oculomotor neuropathy was most likely due to a self-limited enteroviral infection. The virus could not be cultured in the CSF. Echovirus type 11 as well as Coxsackie B4 virus might have caused the disease. During treatment with prednisone for 3 weeks in decreasing doses the girl recovered, by the seventh day she was able to raise her eyelid. 3 1/2 months later she had no evidence of residual ptosis and full range of ocular movements.

Myoglobinuria in hereditary progressive muscular dystrophies.

Myoglobin (Mb) levels in pooled urine samples were investigated and compared in patients with different types of hereditary progressive muscular dystrophies (MD). The samples were taken before and after physical exercise. The Mb levels in the patients were significantly higher than in controls under both resting and exercise conditions. The formation of separate clusters of Mb values enabled us to distinguish patients with different types of MD according to the clinical diagnosis. Urine protein detection with SDS-acrylamide electrophoresis showed an abnormal pattern in patients compared to healthy controls.

Biochemical changes in hereditary progressive muscular dystrophies. Defect of protein synthesis in fibroblasts, muscle tissues and blood cells.

80S ribosomes and ribosomal subunits were isolated from fibroblasts, muscle tissues and blood cells of patients with different muscular dystrophies (MD) as well as of controls and were used for in vitro measurement of ribosomal protein synthesis (RPS) in a poly(U)-directed polyphenylalanine synthesis system. The activity of ribosomes from the patients showed a disease-dependent decrease compared to normal controls. Examination of hybrid 80S ribosomes consisting of 40S and 60S subunits of patients and the corresponding control cells revealed that the loss of RPS activity was related to one or both of the ribosomal subunits depending on the type of MD.

[Heart failure caused by myocardial hypertrophy in diabetic fetopathy]. / Herzinsuffizienz infolge Myokardhypertrophie bei diabetischer Fetopathie.

Diabetic fetopathy is still a common clinical problem correlated with a high morbidity of the neonate. These children are often macrosome, suffer from respiratory distress syndrome due to delayed lung maturity, acidosis, hypoglycaemia, electrolyte-imbalances and polycythaemia. We describe a male neonate with diabetic fetopathy as a result of gestational diabetes of the mother. In addition to the symptoms described above, our patient clinically presented with severe hypertrophy of the right ventricle associated with intrauterine heart failure. The boy was born with serious prenatal asphyxia which made initial neonatal intensive care treatment necessary. The hypertrophic cardiomyopathy normalized within 6 weeks after birth without further treatment. Different causes of a hypertrophic cardiomyopathy (infections, metabolic disorders, neurologic affections, syndromes) could be ruled out, so that the diabetic fetopathy was the most probable cause for the condition. If we are looking at the heart only, this case-report suggests a good prognosis of septumhypertrophy as well as right ventricular hypertrophy in patients with diabetic fetopathy. The case also elucidates that not only the diabetes type I can entail serious fetal damage but also gestational diabetes can. Therefore, in suspect mothers screening for gestational diabetes should be expanded to oral glucose tolerance testing.

Hydrops fetalis: manifestation in lysosomal storage diseases including Farber disease.

UNLABELLED: The authors describe a case of disseminated lipogranulomatosis (Farber disease) presenting as nonimmune hydrops fetalis. This is the tenth lysosomal storage disease which can show this clinical manifestation. The literature is reviewed for all hydrops cases associated with lysosomal storage diseases. CONCLUSION: Although rare, the lysosomal storage diseases collectively are significant causes of nonimmune hydrops and appropriate investigations are required in all cases of unexplained hydrops fetalis.

Accelerated lung maturation following maternal steroid treatment in infants born before 30 weeks gestation.

A meta-analysis was performed of 9 controlled trials of maternal beta-/dexamethasone treatment in which the incidence of RDS in infants born before 30 weeks gestation was reported. A significant decrease could be shown in 250 immature infants. The number of cases was to small for analysis of lower gestational ages or for the demonstration of a reduction in mortality. In a separate study of 135 infants born before 30 weeks gestation tracheal aspirate phospholipid analysis was performed using thin layer chromatography. 64 of them had been exposed prenatally to steroids. Significantly more of these infants had a mature L/S ratio > or = 2.7 (p < 0.02) and prenatal glucocorticoid treatment was associated with a markedly increased survival rate (odds ratio 2.4, p < 0.02). We conclude from the meta-analysis of the literature and from the findings of our study, that accelerated lung maturation follows prenatal steroid treatment with a reduction in RDS-incidence even in very immature fetuses. Consequently it would be appropriate to administer glucocorticoids combined with tocolysis since this has been shown to be beneficial for those women threatening to deliver prematurely at less than 30 weeks gestation.