Dirk Faas

Percutaneous minimal-access fetoscopic surgery for spina bifida aperta. Part II: maternal management and outcome

To assess maternal morbidity and outcome in women undergoing minimal‐access fetoscopic surgery for spina bifida aperta.

Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial

BACKGROUND Tolerating higher partial pressure of carbon dioxide (pCO2) in mechanically ventilated, extremely low birthweight infants might reduce ventilator-induced lung injury and bronchopulmonary dysplasia. We aimed to test the hypothesis that higher target ranges for pCO2 decrease the rate of bronchopulmonary dysplasia or death. METHODS In this randomised multicentre trial, we recruited infants from 16 tertiary care perinatal centres in Germany with birthweight between 400 g and 1000 g and gestational age 23-28 weeks plus 6 days, who needed endotracheal intubation and mechanical ventilation within 24 h of birth. Infants were randomly assigned to either a high target or control group. The high target group aimed at pCO2 values of 55-65 mm Hg on postnatal days 1-3, 60-70 mm Hg on days 4-6, and 65-75 mm Hg on days 7-14, and the control target at pCO2 40-50 mmHg on days 1-3, 45-55 mm Hg on days 4-6, and 50-60 mm Hg on days 7-14. The primary outcome was death or moderate to severe bronchopulmonary dysplasia, defined as need for mechanical pressure support or supplemental oxygen at 36 weeks postmenstrual age. Cranial ultrasonograms were assessed centrally by a masked paediatric radiologist. This trial is registered with the ISRCTN registry, number ISRCTN56143743. RESULTS Between March 1, 2008, and July 31, 2012, we recruited 362 patients of whom three dropped out, leaving 179 patients in the high target and 180 in the control group. The trial was stopped after an interim analysis (n=359). The rate of bronchopulmonary dysplasia or death in the high target group (65/179 [36%]) did not differ significantly from the control group (54/180 [30%]; p=0·18). Mortality was 25 (14%) in the high target group and 19 (11%; p=0·32) in the control group, grade 3-4 intraventricular haemorrhage was 26 (15%) and 21 (12%; p=0·30), and the rate of severe retinopathy recorded was 20 (11%) and 26 (14%; p=0·36). INTERPRETATION Targeting a higher pCO2 did not decrease the rate of bronchopulmonary dysplasia or death in ventilated preterm infants. The rates of mortality, intraventricular haemorrhage, and retinopathy did not differ between groups. These results suggest that higher pCO2 targets than in the slightly hypercapnic control group do not confer increased benefits such as lung protection. FUNDING Deutsche Forschungsgemeinschaft.

Percutaneous minimally invasive fetoscopic surgery for spina bifida aperta. Part III: neurosurgical intervention in the first postnatal year

To evaluate the need for postnatal neurosurgical intervention after fetoscopic patch coverage of spina bifida aperta (SBA).

Percutaneous minimally‐invasive fetoscopic surgery for spina bifida aperta ‐ Part III ‐ Postnatal neurosurgical interventions in the first year of life

To evaluate the need for postnatal neurosurgical intervention after fetoscopic patch coverage of spina bifida aperta (SBA).

Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO2 targets: the PHELBI follow-up study

Background Tolerating higher partial pressures of carbon dioxide (PCO2) in mechanically ventilated extremely low birthweight infants to reduce ventilator-induced lung injury may have long-term neurodevelopmental side effects. This study analyses the results of neurodevelopmental follow-up of infants enrolled in a randomised multicentre trial. Methods Infants (n=359) between 400 and 1000 g birth weight and 23 0/7–28 6/7 weeks gestational age who required endotracheal intubation and mechanical ventilation within 24 hours of birth were randomly assigned to high PCO2 or to a control group with mildly elevated PCO2 targets. Neurodevelopmental follow-up examinations were available for 85% of enrolled infants using the Bayley Scales of Infant Development II, the Gross Motor Function Classification System (GMFCS) and the Child Development Inventory (CDI). Results There were no differences in body weight, length and head circumference between the two PCO2 target groups. Median Mental Developmental Index (MDI) values were 82 (60–96, high target) and 84 (58–96, p=0.79). Psychomotor Developmental Index (PDI) values were 84 (57–100) and 84 (65–96, p=0.73), respectively. Moreover, there was no difference in the number of infants with MDI or PDI <70 or <85 and the number of infants with a combined outcome of death or MDI<70 and death or PDI<70. No differences were found between results for GMFCS and CDI. The risk factors for MDI<70 or PDI<70 were intracranial haemorrhage, bronchopulmonary dysplasia, periventricular leukomalacia, necrotising enterocolitis and hydrocortisone treatment. Conclusions A higher PCO2 target did not influence neurodevelopmental outcomes in mechanically ventilated extremely preterm infants. Adjusting PCO2 targets to optimise short-term outcomes is a safe option. Trial registration number ISRCTN56143743.

Eating problems in very low birthweight children are highest during the first year and independent risk factors include duration of invasive ventilation.

This study aimed to investigate the incidence and time course of eating problems in children born with a very low birthweight (VLBW) and to identify the perinatal risk factors.

Prenatal immunomodulation treatment in neonatal myasthenia gravis.

Neonatal mysthenia gravis (NMG) is a rare cause of arthrogryposis multiplex congenita (AMC) due to diaplacental transfer of maternal acetylcholine receptors (AChR) antibodies. 2 cases of severe NMG complicated by chronic lung disease and pulmonary arterial hypertension are reported. With respect to the severe course of the index patient, prenatal diagnosis and immunomodulation treatment were offered during the 2nd pregnancy. The combination of prenatal immunoadsorption (IA) therapy, administration of intravenous immunoglobulin (IVIG) and prednisolone failed. Failure may be partly explained by immaturity of the infant. However, considering the successful treatment of fetal/neonatal alloimmune thrombocytopenia (AIT) reported in literature, a treatment approach with IVIG doses up to 1-2 g/kg per week plus prednisone/prednisolone at a higher dose up to 1 mg/kg/d might be more effective.

Prophylactic prenatal therapy with intravenous immunoglobulins for patients at risk for neonatal haemochromatosis

Neonatal haemochromatosis (NH) is a connatal hepatopathy that is lethal in 32% and necessitates liver transplantation in 63% of the survivors. The classical diagnostic criteria of extrahepatic siderosis do not apply in all patients who are suspected to have NH. The hypothesis of NH as an alloimmune disease is supported by the quantitative immunohistochemical proof of C5b-9 complement complexes on the hepatocytes of liver biopsy material. This has opened a new perspective in the therapy and prophylaxis for this severe disease. Prophylactic therapy with intravenous immunoglobulins (IVIG) for mothers at risk can prevent a relevant NH in most cases.

Correlation of maternal age and migration on IHPS epidemiology in Germany 2000-2008.

A decline in the incidence of infantile hypertrophic pyloric stenosis (IHPS) was recently reported in Sweden, the US, Denmark, Scotland, and Germany. Data to explain this phenomenon, however, are scarce. Given our previous epidemiologic data showing a decline in the incidence of IHPS, we collected data on maternal age and history of migration from regional administrative centers to obtain data that might support an explanation for our previous findings. We examined the correlation between these factors and the incidence of IHPS. Data were extracted from the public report of health (Gesundheitsberichterstattung des Bundes) and population data from federal state governments. We obtained the numbers of IHPS (ICD-10 code 40.0) and live births in each federal state for the period 2000-2008. Further data were collected from federal state administrative agencies on age of the mother at the birth of their first child and history of migration for all mothers at first birth. There were significant differences in the regional distribution of both variables and the variability of these factors over time. Average maternal age and the percentage of mothers with a history of migration showed a negative correlation with the regional incidence of infantile hypertrophic pyloric stenosis. Conclusion: The wide variation in the incidence of infantile hypertrophic pyloric stenosis over time and for different regions is significantly inversely correlated with rising maternal age and the percentage of mothers with a history of migration.

Lung volume reduction surgery in preterm infants with bronchopulmonary dysplasia. A case report

A preterm infant at the age of 9 months with severe bronchopulmonary dysplasia (BPD) and large lobar emphysema, compromising ventilation into adjacent lobes with respiratory failure under maximal conservative treatment and pulmonary arterial hypertension recovered initially well after bilateral lung volume reduction surgery, but progressed 2 years later into respiratory failure. The initial imaging with Magnetic‐Resonance‐Imaging (MRI)‐Angiography and decision‐making was difficult and interdisciplinary treatment was essential.