Peter Bartmann

Fentanyl-induced chest wall rigidity and laryngospasm in preterm and term infants.

Objective: To assess the occurrence of muscle rigidity after fentanyl administration in premature and term neonates. Design: Prospective case series, observational study. Setting: A university hospital neonatal intensive care unit. Patients: 8/89 preterm and term infants (25‐40 wks gestational age) who received fentanyl for perioperative analgesia and sedation or intensive care procedures. Interventions: Mechanical or bag mask ventilation and antagonization with naloxone. Measurements and Main Results: We observed chest wall rigidity in 8 patients after low dosage of fentanyl (3‐5 μg/kg body weight). All patients presented with respiratory distress, hypercapnia, and hypoxemia leading to bradycardia. In two patients, laryngospasm was noted and associated with muscle rigidity, thus making intubation impossible. Naloxone (20‐40 μg/kg body weight) reversed the laryngospasm and muscle rigidity immediately, allowing restitution within 1 min. In our patient population, we found fentanyl‐induced chest wall rigidity in 4% of neonates after fentanyl administration. Conclusion: Even low doses of fentanyl can lead to thoracic rigidity in neonates. Additionally, we observed laryngospasm in two patients and speculate that it might be a variant of muscle rigidity.

Prenatal Contact with Inhalant Allergens

Pollen contact in early infancy may enhance the risk for subsequent pollen allergy. In this study likelihood of a prenatal antigen contact, as a result of inhalation of pollen allergens by the mother, was investigated. Due to the seasonal occurrence of allergens studied, the date of priming can be estimated, and this can supply data about the maturation of the fetal immune system. Proliferative responses of umbilical cord blood mononuclear cells (UCB MNCs) to the recombinant major allergens of birch (rBet v 1) and timothy grass(rPhl p 1) were analyzed throughout the whole year. A positive proliferative response was regarded as the criterion for a prenatal contact of the immune system with the allergen. Prenatal priming with both allergens was observed. Timothy grass pollen displayed considerably higher antigenicity than did birch pollen. The susceptibility of the fetal immune system to be primed by these allergens varies during the gestation period. The majority of positive responses to rPhl p 1 and rBet v 1 were found in UCB samples in which antigen contact (the respective pollen season) took place in the first 6 mo of pregnancy. Our results offer indirect evidence that, shortly after migration of T cell precursors to the epithelial thymus, T cells are mature enough for priming with antigens. No relationship was found between the susceptibility of the fetal immune system to be primed by these allergens and the clinical history of the family concerning type I allergy.

Long term cardiac follow up of severe twin to twin transfusion syndrome after intrauterine laser coagulation

Objective: To assess long term changes in cardiac morphology and function in survivors of severe twin to twin transfusion syndrome (TTTS) after intrauterine laser coagulation of placental anastomoses. Design: Prospective follow up of fetuses with severe TTTS treated by laser coagulation of intrauterine placental anastomoses. Fetal echocardiography and Doppler studies of feto-placental haemodynamic function were performed at the time of laser coagulation (median gestational age of 21.7 weeks). Postnatal cardiac follow up included a detailed echocardiographic study of systolic and diastolic cardiac function at a median age of 21.1 months. Setting: Paediatric cardiology unit. Patients: 89 survivors from 73 consecutive pregnancies with severe TTTS. Results: Before laser treatment, 28 of 51 (54.9%) recipient twins had typical signs of cardiac dysfunction due to volume overload and 9 of 38 (23.7%) donors had absent or reversed end diastolic flow in the umbilical artery. Echocardiography was normal in 87.6% of the survivors (34 of 38 donors, 44 of 51 recipients). The prevalence of congenital heart disease and particularly of pulmonary stenosis, which was recorded only in recipients, was increased in comparison with the general population (congenital heart disease, 10 of 89 (11.2%) v 0.3%; pulmonary stenosis, 4 of 51 (7.8%) v 0.03%). Findings before laser treatment were not correlated with the development of structural heart disease. Conclusions: Despite the high rate and severity of prenatal cardiac overload in recipients, the majority of cases of TTTS are normalised after laser treatment. However, given the increased prevalence of congenital heart disease and in particular pulmonary stenosis, intrauterine and postnatal follow up is warranted.

Erythropoietin gene expression in different areas of the developing human central nervous system

UNLABELLED Evidence from cell culture and animal experiments suggests a neuroprotective and neurotrophic function of erythropoietin (EPO). We have quantitated the distribution of EPO mRNA expression in the developing human central nervous system (CNS). PATIENTS AND METHODS Up to seven biopsies from different areas of the CNS of four preterm fetuses (gestational age 23-37 weeks) were obtained at routine postmortem examinations. EPO mRNA was quantitated by competitive PCR in samples from the CNS, the kidneys, and the liver where the EPO gene is predominantly expressed at this gestational age. RESULTS EPO mRNA was most abundant in one sample from the cerebellum (0.29 amol/microg total RNA [amol=10(-18)mol]) and two from the pituitary gland (0.23 amol/microg total RNA), but levels varied considerably. EPO mRNA in the cortex cerebri (median 0.12 amol/microg total RNA; n=4) dominated over the expression in the corpora amygdala (median 0.05 amol/microg total RNA; n=4), the hippocampus (median 0.03 amol/microg total RNA; n=4), or the basal ganglia (median 0.01 amol/microg total RNA; n=3). Only little EPO mRNA (<0.01 and 0.06 amol/microg total RNA) was found in the spinal cord. EPO mRNA levels in the cerebellum, pituitary gland, or the cerebral cortex were within the same range as in the liver (0.03-1.67 amol/microg total RNA; n=4), or the kidneys (0.06-0.79 amol/microg total RNA; n=4). CONCLUSION We found the EPO gene expressed throughout the fetal human CNS. Our data provide the basis to discuss a function for EPO in the brain of humans as well.

Percutaneous Fetoscopic Patch Coverage of Spina Bifida Aperta in the Human – Early Clinical Experience and Potential

Objective: The current operative approach for fetal repair of spina bifida aperta requires maternal laparotomy and hysterotomy. Following technical feasibility studies in sheep, we performed percutaneous fetoscopic patch coverage of this lesion in 3 human fetuses between 23 + 4 and 25 + 3 weeks of gestation. Methods and Results: Whereas the patch detached in the first case 3 weeks after the procedure, it covered the exposed neural tissue in the 2 other fetuses beyond their delivery. Two of the three children survived, but 1 unexpectedly died from a ventilation problem in its 3rd week of life. In 1 of the 2 survivors, ventriculoperitoneal shunt insertion was delayed. Conclusions: Percutaneous fetoscopic patch coverage of spina bifida aperta is feasible in human fetuses and offers a substantial reduction of maternal trauma compared to open fetal repair. Further clinical experience is now required before the efficacy of the new approach to protect the exposed neural tissue from mechanical and chemical damage and to improve hindbrain herniation can be evaluated.

Candida infection in very low birth-weight infants: outcome and nephrotoxicity of treatment with liposomal amphotericin B (AmBisome).

SummarySystemic fungal infection occurs in 2 to 4.5% of very low birth-weight (VLBW) infants (<1,500 g) and may be fatal in 25 to 54%.Candida sp. is the major pathogen and amphotericin B the treatment of choice. To reduce side effects and optimize drug action, a formulation of amphotericin B encapsulated in liposomes (AmBisome®) has been introduced. Data on 21 VLBW infants who received a full course of AmBisome® was collected and its toxic effects with emphasis on nephrotoxicity and hypokalemia assessed. The median gestational age was 25 weeks (range 23–31) with a median birth-weight of 730 g (range 450–1,370). Antifungal therapy was started at a median age of 13 days (range 1–49). The median dose given was 2.6 mg/kg/day (range 1–5), and the median duration of therapy was 28 days (range 11–79), corresponding to a median cumulative dose of 71 mg/kg (range 12–271). Hypokalemia (<3.0 mmol/l) was observed in 30% before, and 15% during AmBisome® treatment. Twenty-one days after the termination of therapy, hypokalemia was not present in any patient. Median maximum daily potassium supplementation did not exceed doses usually recommended for VLBW infants. The median of the maximum creatinine levels before treatment was 121 μmol/l (range 71–221) and fell to 68 μmol/l (range 31–171) during treatment and 46 μmol/l (range 26–62) 21 days after the termination of therapy. All patients treated with AmBisome® eradicated fungi and recovered clinically. AmBisome® showed no certain nephrotoxicity in VLBW infants in this study.

Mutations are involved in emergence of aminoglycoside-induced small colony variants of Staphylococcus aureus

Staphylococcus aureus small colony variants (SCVs) occur frequently after local treatment with aminoglycosides and cause persistent as well as recurrent infections. So far, the molecular mechanism of the emergence of SCVs is not understood and regulatory as well as genetic mechanisms seem conceivable. To screen for possible mutations, the hemin biosynthetic gene cluster of a gentamicin-induced SCV was sequenced and was found to contain a deletion in the gene hemH. To further assess the influence of a high mutation rate on the development of SCVs, we tested the emergence of SCVs in a strain that had been inactivated in the DNA proofreading enzyme MutS. In the mutant, spontaneous SCVs emerged 556-fold more frequently than in the parent strain. By incubation in the presence of subinhibitory concentrations of gentamicin, the SCV frequency in the parent strain could be increased to 9.7 x 10(-6), whereas it remained rather stable in the mutant (1.8 x 10(-5)). Eighty percent of the gentamicin-induced SCVs were hemin auxotrophic in contrast to only 20% of the spontaneous SCVs which may explain the large proportion of hemin auxotrophs among clinical SCVs from patients previously treated with aminoglycosides. Additionally, a clinical S. aureus SCV isolate with a mutator phenotype, indicated by the generation of rifampicin-resistant mutants at a 16-fold higher frequency than in the reference strain S. aureus NCTC 8325, was characterized. The results demonstrate that a high mutation rate favours the emergence of SCVs, and suggest that mutations in general play an important role in the development of SCVs.

Neurodevelopmental outcome after intrauterine red cell transfusion for Parvovirus B19‐induced fetal hydrops

Objective To assess long term neurodevelopmental outcome of children after intrauterine intravascular red cell transfusion (IUT) for Parvovirus B19‐induced fetal hydrops.

Congenital chylothorax: lymphopenia and high risk of neonatal infections

Aim: To describe the clinical course of patients with congenital chylothorax focusing on infectious complications. Congenital chylothorax is a common manifestation of non‐immune hydrops fetalis (NIHF). The drainage of chyle leads to loss of cellular and plasmatic factors that influence the patients immune response and increase the risk of infections. Methods: In a retrospective analysis of 24 preterm infants with NIHF treated between 1998 and 2002, congenital chylothorax was diagnosed in 7 patients. Results: All 7 patients were treated conservatively with pleural drainage over a median period of 22 d (range 10–36 d). Lymphopenia was found in all patients (median of minimal lymphocyte counts 285/μl, range 80–770). The nadir was on day 5 (2‐6 d). Lymphopenia lasted for 12 d median (range 4–39 d) and was significantly correlated with the duration of lymph drainage (p= 0.001). Cell‐surface analysis of peripheral blood lymphocytes was performed in two patients. Both patients had a decreased number of total T cells. Four out of seven (57%) patients developed nosocomial infections. This incidence of nosocomial infections in patients with congenital chylothorax is about three times higher than that in other neonatal patients. None of the children suffered from fungal or viral infection. Although there was a very high incidence of infections, no correlation between lymphopenia and the occurrence of infections could be shown.

Fetoscopic and ultrasound‐guided decompression of the fetal trachea in a human fetus with Fraser syndrome and congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia

Congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia bears a poor prognosis for hydropic fetuses owing to cardiac failure. We attempted percutaneous fetoscopic and ultrasound‐guided tracheal decompression in a hydropic human fetus with CHAOS associated with Fraser syndrome.