Transition to adult diabetes care in Germany-High risk for acute complications and declining metabolic control during the transition phase.

OBJECTIVE: There is evidence that transition from pediatric to adult health care is frequently associated with deterioration of health in youths with type 1 diabetes (T1D). The aim of this study was to compare metabolic control, acute complications and microvascular complications in adolescents and young adults before and after transfer to an adult treatment center with respect to the time between first visit in the adult center and last visit in pediatric treatment. METHODS: All data were collected during routine care and retrieved from the German/Austrian DPV database. We analyzed data as of March 2017. RESULTS: We found 1283 young adults with available data of the last pediatric treatment year and the first year after transition to adult care. HbA1c increased significantly from 8.95% (74 mmol/mol) before to 9.20% (77 mmol/mol) in the first year after transition. Frequency of DKA with hospitalization (0.10-0.191 per annum, P < .0001) and severe hypoglycemia (0.23-0.46 per annum, P = .013) doubled during transition. Microvascular complications increased dramatically depending on the time between first visit in adult treatment and last visit in pediatric care. We could not find a significant correlation of this rise of microvascular complications to the duration of transition (short or long). CONCLUSION: This phase of life bears a high risk for detrimental outcome in young adults with T1D. Structured transition programs with case management are therefore needed to improve the transition process and outcomes.

Blood pressure regulation determined by ambulatory blood pressure profiles in children and adolescents with type 1 diabetes mellitus: Impact on diabetic complications.

BACKGROUND: The combination of high blood pressure and hyperglycemia contributes to the development of diabetic complications. Ambulatory monitoring of blood pressure (ABPM) is seen as standard to assess blood pressure (BP) regulation. OBJECTIVE: We evaluated 24-hour BP regulation in 3529 children with type 1 diabetes, representing 5.6% of the patients <20 years of age documented in the DPV registry, and studied the influence of BP parameters including pulse pressure (PP) and blood pressure variability (BPV) on microalbuminuria (MA) and diabetic retinopathy (DR). RESULTS: BP was increased in this selected cohort of children with diabetes compared to healthy German controls (standard deviation score (SDS) day: systolic BP (SBP) +0.06, mean arterial pressure (MAP) +0.08, PP +0.3; night: SBP +0.6, diastolic BP +0.6, MAP +0.8), while daytime diastolic BP (SDS -0.2) and dipping of SBP and MAP were reduced (SBP -1.1 SDS, MAP 12.4% vs 19.4%), PP showed reverse dipping (-0.7 SDS). Children with microvascular complications had by +0.1 to +0.75 SDS higher BP parameters, except of nocturnal PP in MA and diurnal and nocturnal PP in DR. Reverse dipping of PP was more pronounced in the children with MA (-5.1% vs -0.8%) and DR (-2.6% vs -1.0%). BP alteration was stronger in girls and increased with age. CONCLUSION: There is an early and close link between 24-hour blood pressure regulation and the development of diabetic complications not only for systolic, diastolic, and mean arterial BP but also for the derived BP parameter PP and BPV in our selected patients.

Overweight and Obesity Based on Four Reference Systems in 18,382 Paediatric Patients with Type 1 Diabetes from Germany and Austria.

AIM: To evaluate the prevalence of overweight and obesity in paediatric type 1 diabetes (T1D) subjects, based on four commonly used reference populations. METHODS: Using WHO, IOTF, AGA (German pediatric obesity), and KiGGS (German Health Interview and Examination Survey for Children and Adolescents) reference populations, prevalence of overweight (≥90th percentile) and obesity (≥97th percentile) and time trend between 2000 (n = 9,461) and 2013 (n = 18,382) were determined in 2-18-year-old T1D patients documented in the German/Austrian DPV database. RESULTS: In 2000, the overweight prevalence was the highest according to IOTF (22.3%), followed by WHO (20.8%), AGA (15.5%), and KiGGS (9.4%). The respective rates in 2013 were IOTF (24.8%), WHO (22.9%), AGA (18.2%), and KiGGS (11.7%). Obesity prevalence in 2000 was the highest according to WHO (7.9%), followed by AGA (4.5%), IOTF (3.1%), and KiGGS (1.8%). In 2013, the respective rates were WHO (9.6%), AGA (6.2%), IOTF (4.5%), and KiGGS (2.6%). Overall, the prevalence of overweight and obesity increased from 2000 to 2006 (p < 0.001) but showed stabilization thereafter in girls and overweight in boys. CONCLUSION: Overweight and obesity prevalence in T1D subjects differs significantly if it is assessed by four separate reference populations. More detailed assessment of each child is required to determine obesity-related risks.

Medium-chain acyl-CoA dehydrogenase deficiency associated with a novel splice mutation in the ACADM gene missed by newborn screening.

BACKGROUND: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common disorder of mitochondrial fatty acid ß-oxidation and a target disease of newborn screening in many countries. CASE PRESENTATION: We report on two siblings with mild MCAD deficiency associated with a novel splice site mutation in the ACADM gene. The younger sibling was detected by newborn screening, while the older sister was missed, but diagnosed later on by genetic family testing. Both children were found to be compound heterozygous for the common c.985A > G (p.K329E) mutation and a novel splice site mutation, c.600-18G > A, in the ACADM gene. To determine the biological consequence of the c.600-18G > A mutation putative missplicing was investigated at RNA level in granulocytes and monocytes of one of the patients. The splice site mutation was shown to lead to partial missplicing of the ACADM pre-mRNA. Of three detected transcripts two result in truncated, non-functional MCAD proteins as reflected by the reduced octanoyl-CoA oxidation rate in both patients. In one patient a decrease of the octanoyl-CoA oxidation rate was found during a febrile infection indicating that missplicing may be temperature-sensitive. CONCLUSIONS: Our data indicate that the c.600-18G > A variant activates a cryptic splice site, which competes with the natural splice site. Due to only partial missplicing sufficient functional MCAD protein remains to result in mild MCADD that may be missed by newborn screening.

Long-term Surveillance of Children with Congenital Hypothyroidism: Data from the German Registry for Congenital Hypothyroidism (AQUAPE "Hypo Dok").

BACKGROUND: The German study group for quality assurance in pediatric endocrinology and the University of Ulm have established a software ("Hypo Dok") for the documentation of longitudinal data of patients with congenital primary hypothyroidism (CH). Aim of this study was to analyse the long-term follow-up of patients with CH and to compare treatment with current guidelines. METHODS/PATIENTS: Anonymised data of 1,080 patients from 46 centres were statistically analysed. RESULTS: Newborn screening result was available at a mean age of 7.3 days. Confirmation of the diagnosis was established at 8.4 days and therapy was started at 11 days. The average screening TSH was 180.0 mIU/L. During the first 3 months mean levothyroxine (LT4) dose was 10.7 µg/kg/day or 186.0 µg/m²/day. Weight-, BMI- and height-SDS did not differ significantly from the normal population. Only 25% of the patients (n=262) underwent formal EQ/IQ-testing. Their average IQ was 98.8 ± 13.2 points. DISCUSSION: In Germany screening, confirmation and start of treatment of CH are within the recommended time frame of 14 days. Initial LT4-doses are adequate. The auxological longterm outcome of young CH patients is normal. The implementation of standardized IQ testing has to be improved in routine patient care. CONCLUSION: Longitudinal data of patients with CH was analysed and compared to current guidelines. Confirmation and start of treatment are according to the recommendations. However standardised IQ testing requires improvement.

Introducing excess body weight in childhood and adolescence and comparison with body mass index and waist-to-height ratio.

BACKGROUND: Weight status in children and adolescents is commonly defined using age- and gender-corrected standard deviation scores for body mass index (BMI-SDS, also called z-scores). Values are not reliable for the extremely obese however. Moreover, paediatricians and parents may have difficulties understanding z-scores, and while percentiles are easier to gauge, the very obese have values above the 99th percentile, making distinction difficult. The notion of excess body weight (EBW) is increasingly applied in adult patients, mainly in the context of bariatric surgery. However, a clear definition is not available to date for the paediatric population. METHODS: A simple definition of EBW for children and adolescents is introduced, with median weight as a function of height, age and gender (characterized by an asterisk): EBW (%) = 100x(weight-median weight*)/median weight*. EBW is compared with BMI-SDS and waist-to-height ratio (WHtR). Using two data sources (APV registry and German Health Interview and Examination Survey for Children and Adolescents (KiGGS)) including more than 14,000 children, the relationships between these anthropometric and various metabolic parameters are analysed for a group of overweight/obese children who have sought obesity therapy (APV), for the general paediatric population and for the subset of overweight/obese children from the general population (KiGGS). RESULTS: The three anthropometric parameters are strongly correlated, with the linear correlation coefficients exceeding 0.8 in the general population and 0.75 in those seeking obesity therapy. Moreover, their relationship to metabolic parameters is quite similar regarding correlations and area under the curve from receiver operating characteristic analyses. CONCLUSIONS: EBW has similar predictive value for metabolic or cardiovascular comorbidities compared with BMI and WHtR. As it is reliable at the extreme end of the obesity spectrum, easily communicable and simple to use in daily practice, it would make a very useful addition to existing tools for working with obese children and adolescents. Its usefulness in assessing weight change needs to be studied however.

[Evidence-based procedures for the treatment of diseases associated with childhood obesity]. / Evidenzbasierung von Maßnahmen zur Behandlung der Folgeerkrankungen kindlicher Adipositas.

Childhood obesity is associated with cardiovascular events in adulthood. Multidisciplinary conventional obesity treatment programmes may reduce the body mass index standard deviation score at any age. However, over the years they lose their effectiveness especially during childhood. Only one study dealing with adult type 2 diabetic patients could show persistent weight reduction over the period of 4 years. Therefore, these conventional programmes may have short-term but no long-term influence on cardiovascular events. Bariatric surgery in childhood is exclusively performed in cases of morbid obesity. In adults, experience with regard to persistent weight loss has existed for over 20 years now and has reached good therapeutic results in type 2 diabetes. However, randomized and controlled long-term studies as to cardiovascular events and death do not exist. The Swedish Obese Subjects (SOS) study showed a significant decrease of cardiovascular events and death in the bariatric surgery study group compared to the conventional therapy group, but the groups were not randomized. The surgery group was younger and healthier compared to the conservatively treated group. The late start of therapy probably also had an unfavourable influence on cardiovascular events.

Mutation analysis in 54 propionic acidemia patients.

Deficiency of propionyl CoA carboxylase (PCC), a dodecamer of alpha and beta subunits, causes inherited propionic acidemia. We have studied, at the molecular level, PCC in 54 patients from 48 families comprised of 96 independent alleles. These patients of various ethnic backgrounds came from research centers and hospitals in Germany, Austria and Switzerland. The thorough clinical characterization of these patients was described in the accompanying paper (Grünert et al. 2012). In all 54 patients, many of whom originated from consanguineous families, the entire PCCB gene was examined by genomic DNA sequencing and in 39 individuals the PCCA gene was also studied. In three patients we found mutations in both PCC genes. In addition, in many patients RT-PCR analysis of lymphoblast RNA, lymphoblast enzyme assays, and expression of new mutations in E.coli were carried out. Eight new and eight previously detected mutations were identified in the PCCA gene while 15 new and 13 previously detected mutations were found in the PCCB gene. One missense mutation, p.V288I in the PCCB gene, when expressed in E.coli, yielded 134% of control activity and was consequently classified as a polymorphism in the coding region. Numerous new intronic polymorphisms in both PCC genes were identified. This study adds a considerable amount of new molecular data to the studies of this disease.

Propionic acidemia: neonatal versus selective metabolic screening.

BACKGROUND: Whereas propionic acidemia (PA) is a target disease of newborn screening (NBS) in many countries, it is not in others. Data on the benefit of NBS for PA are sparse. STUDY DESIGN: Twenty PA patients diagnosed through NBS were compared to 35 patients diagnosed by selective metabolic screening (SMS) prompted by clinical findings, family history, or routine laboratory test results. Clinical and biochemical data of patients from 16 metabolic centers in Germany, Austria, and Switzerland were evaluated retrospectively. Additionally, assessment of the intelligent quotient (IQ) was performed. In a second step, the number of PA patients who have died within the past 20 years was estimated based on information provided by the participating metabolic centers. RESULTS: Patients diagnosed through NBS had neither a milder clinical course regarding the number of metabolic crises nor a better neurological outcome. Among NBS patients, 63% were already symptomatic at the time of diagnosis, and <10% of all patients remained asymptomatic. Among all PA patients, 76% were found to be at least mildly mentally retarded, with an IQ <69. IQ was negatively correlated with the number of metabolic decompensations, but not simply with the patients' age. Physical development was also impaired in the majority of patients. Mortality rates tended to be lower in NBS patients compared with patients diagnosed by SMS. CONCLUSION: Early diagnosis of PA through NBS seems to be associated with a lower mortality rate. However, no significant benefit could be shown for surviving patients with regard to their clinical course, including the number of metabolic crises, physical and neurocognitive development, and long-term complications.

Impact of overweight on effectiveness of treatment with human growth hormone in growth hormone deficient children: analysis of German KIGS data.

BACKGROUND: We hypothesized that overweight children with growth hormone deficiency (GHD) demonstrate a lower response to growth hormone (GH) as a result of a misclassification since obesity is associated with lower GH peaks in stimulation tests. METHODS: Anthropometric data, response, and responsiveness to GH in the first year of treatment were compared in 1.712 prepubertal children with GHD from the German KIGS database according to BMI (underweight=group A, normal weight=group B, overweight=group C) (median age: group A, B, C: 7.3, 7.28, and 8.4 years). RESULTS: Maximum GH levels to tests (median: group A, B, C: 5.8, 5.8, and 4.0 µg/ml) were significantly lower in group C. IGF-I SDS levels were not different between the groups. Growth velocity in the first year of GH treatment was significantly lower in the underweight cohort (median: group A, B, C: 8.2, 8.8, and 9.0 cm/yr), while the gain in height was not different between groups. The difference between observed and predicted growth velocity expressed as Studentized residuals was not significantly different between groups. Separating the 164 overweight children into obese children (BMI>97th centile; n=71) and moderate overweight children (BMI>90th to 97th centile, n=93) demonstrated no significant difference in any parameter. CONCLUSIONS: Overweight prepubertal children with idiopathic GHD demonstrated similar levels of responsiveness to GH treatment compared to normal weight children. Furthermore, the IGF-I levels were low in overweight children. Therefore, a misclassification of GHD in overweight prepubertal children within the KIGS database seems unlikely. The first year growth prediction models can be applied to overweight and obese GHD children.

Treatment recommendations in long-chain fatty acid oxidation defects: consensus from a workshop.

Published data on treatment of fatty acid oxidation defects are scarce. Treatment recommendations have been developed on the basis of observations in 75 patients with long-chain fatty acid oxidation defects from 18 metabolic centres in Central Europe. Recommendations are based on expert practice and are suggested to be the basis for further multicentre prospective studies and the development of approved treatment guidelines. Considering that disease complications and prognosis differ between different disorders of long-chain fatty acid oxidation and also depend on the severity of the underlying enzyme deficiency, treatment recommendations have to be disease-specific and depend on individual disease severity. Disorders of the mitochondrial trifunctional protein are associated with the most severe clinical picture and require a strict fat-reduced and fat-modified (medium-chain triglyceride-supplemented) diet. Many patients still suffer acute life-threatening events or long-term neuropathic symptoms despite adequate treatment, and newborn screening has not significantly changed the prognosis for these severe phenotypes. Very long-chain acyl-CoA dehydrogenase deficiency recognized in neonatal screening, in contrast, frequently has a less severe disease course and dietary restrictions in many patients may be loosened. On the basis of the collected data, recommendations are given with regard to the fat and carbohydrate content of the diet, the maximal length of fasting periods and the use of l-carnitine in long-chain fatty acid oxidation defects.

Management and outcome in 75 individuals with long-chain fatty acid oxidation defects: results from a workshop.

At present, long-chain fatty acid oxidation (FAO) defects are diagnosed in a number of countries by newborn screening using tandem mass spectrometry. In the majority of cases, affected newborns are asymptomatic at time of diagnosis and acute clinical presentations can be avoided by early preventive measures. Because evidence-based studies on management of long-chain FAO defects are lacking, we carried out a retrospective analysis of 75 patients from 18 metabolic centres in Germany, Switzerland, Austria and the Netherlands with special regard to treatment and disease outcome. Dietary treatment is effective in many patients and can prevent acute metabolic derangements and prevent or reverse severe long-term complications such as cardiomyopathy. However, 38% of patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency had intermittent muscle weakness and pain despite adhering to therapy. Seventy-six per cent of patients with disorders of the mitochondrial trifunctional protein (TFP)-complex including long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, had long-term myopathic symptoms. Of these, 21% had irreversible peripheral neuropathy and 43% had retinopathy. The main principle of treatment was a fat-reduced and fat-modified diet. Fat restriction differed among patients with different enzyme defects and was strictest in disorders of the TFP-complex. Patients with a medium-chain fat-based diet received supplementation of essential long-chain fatty acids. l-Carnitine was supplemented in about half of the patients, but in none of the patients with VLCAD deficiency identified by newborn screening. In summary, in this cohort the treatment regimen was adapted to the severity of the underlying enzyme defect and thus differed among the group of long-chain FAO defects.

First description of three patients with multifocal lymphangiomatosis and protein-losing enteropathy following palliation of complex congenital heart disease with total cavo-pulmonary connection.

The objective was to identify abdominal lymphatic malformations in pediatric patients with protein-losing enteropathy after palliation of complex congenital heart disease with total cavo-pulmonary connection (TCPC). In 2006, we performed complete hemodynamic and laboratory workup and thoracic and abdominal MRT screens in three patients who newly presented with symptoms of protein-losing enteropathy. All three patients, aged 3, 5, and 7 years, showed excellent TCPC hemodynamics with central venous pressures of 10-13 mm Hg. None of the patients had right-to-left overflow. All three patients showed extensive thoracic and mesenterial lymphangiomatosis. One patient died after 18 months of therapy, which included long-term parenteral nutrition, somatostatin, subcutaneous heparin injections, and frequent albumin and immunoglobulin substitution. The other two patients are in stable condition. Lymphangiomatosis might play an unknown role in the pathogenesis of protein-losing enteropathy after TCPC. It remains unclear whether lymphangiomatosis is a primary congenital disease related to the cardiac disease or if it is triggered by repeated surgery or venous congestion. The presence of lymphangiomatosis should be given diagnostic and therapeutic consideration in TCPC patients in the future.

Moebius sequence: behaviour problems of preschool children and parental stress.

This study investigates behaviour problems of preschool children with Moebius sequence, and their primary caregivers' stress. To this end, parents of all preschool children with Moebius sequence known to the German Moebius foundation were anonymously asked to fill out questionnaires, e.g. the Child Behavior Checklist [CBCL] 1.5-5. The primary caregivers of 13/22 children (seven males, six females; mean age: 3;10 [2;1-5;11] years) sent back filled-out questionnaires. Two children were rated as clinical on the CBCL-1.5-5. Boys had significantly higher scores on the scales aggressive behavior and total problems than girls. Compared to the general population, but not to other parents of mentally and / or physically handicapped children, the primary caregivers experienced higher levels of stress. In conclusion, preschool children with Moebius sequence do not show essentially increased rates of clinical behaviour problems. Nevertheless, their primary caregivers experience increased stress and need early and adequate support.

22q11.2 deletion syndrome: behaviour problems of infants and parental stress.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2 DS) can be associated with a variety of somatic symptoms, developmental delays and psychiatric disorders. At present, there is little information on early behaviour problems, and nothing is known about parental stress and possible relations between these factors. Therefore, the aim of this study was to investigate behaviour problems of infants with 22q11.2 DS, and their primary caregivers' stress. METHODS: Parents of infants with 22q11.2 DS known to the German 22q11.2 deletion syndrome foundation were anonymously asked to fill out several questionnaires, e.g. the Child Behavior Checklist (CBCL) 1.5-5. RESULTS: The primary caregivers of 22/30 children [12 boys and 10 girls aged 1 year 8 months to 3 years 11 months (mean age: 2 years 9 months)] sent back filled-out questionnaires. Seventeen out of 21 children showed motor, and 15/21 language delay. Five out of 21 children were rated as clinical on at least one CBCL 1.5-5 scale. The patients' age was correlated with anxiety problems, and girls had significantly more sleep problems than boys. Compared with the general population, the primary caregivers did not experience higher levels of strain, and compared with parents of mentally and/or physically handicapped children, their parental stress was significantly lower. Parental stress and strain were correlated to a variety of child behaviour problems, e.g. externalizing and anxious/depressed behaviour. CONCLUSIONS: Longitudinal studies are required to show whether behaviour problems and parental stress worsen when 22q11.2 DS patients grow older.

Hypoglycemia-dependent beta2-adrenoceptor downregulation: a contributing factor to hypoglycemia unawareness in patients with Type-1 diabetes?

To evaluate the influence of the incidence and unawareness of hypoglycemia on lymphocyte beta2-adrenoceptor densities, we measured beta2-adrenoceptor density using [125I]-iodocyanopindolol and CGP 12177 before and after 1 week of treatment optimization in 33 adults with type-1 diabetes mellitus. Diabetes treatment of all patients was modified to improve their glycemic control. During this week, all patients had to complete a protocol with 7 daily glucose measurements, one of which was at night. The subjective symptoms were evaluated in case of hypoglycemia. A significant correlation between a hypoglycemia incidence below (but not above) the threshold of 2.75 mmol/l (50 mg/dl) and beta2-adrenoceptor densities on lymphocytes was found after the study week (r = -0.72, p < 0.00001). Nine patients suffering from hypoglycemia unawareness had a significantly higher incidence of hypoglycemia (p < 0.002) and lower beta2-adrenoceptor densities on lymphocytes compared to 24 patients who recognized all of their hypoglycemic episodes (p < 0.004). We conclude that downregulation of beta2-adrenoceptor densities on lymphocytes occurs as a result of recurrent hypoglycemia defined as glucose levels of < 2.75 mmol/l. Beta2-adrenoceptor densities are decreased in patients with subjective hypoglycemia unawareness and might contribute to the reduced beta-adrenergic sensitivity in this subgroup of patients.

Guanidinoacetate methyltransferase deficiency: differences of creatine uptake in human brain and muscle.

Deficiency of guanidinoacetate methyltransferase (GAMT), the first described creatine biosynthesis defect, leads to depletion of creatine and phosphocreatine, and accumulation of guanidinoacetate in brain. This results in epilepsy, mental retardation, and extrapyramidal movement disorders. Investigation of skeletal muscle by proton and phosphorus magnetic resonance spectroscopy before therapy demonstrated the presence of considerable amounts of creatine and phosphocreatine, and accumulation of phosphorylated guanidinoacetate in a 7-year-old boy diagnosed with GAMT deficiency, suggesting separate mechanisms for creatine uptake and synthesis in brain and skeletal muscle. The combination of creatine supplementation and a guanidinoacetate-lowering therapeutic approach resulted in improvement of clinical symptoms and metabolite concentrations in brain, muscle, and body fluids.

Constitutively active germline mutation of the thyrotropin receptor gene as a cause of congenital hyperthyroidism.

Congenital hyperthyroidism is a rare, transient disease usually caused by transmission of thyrotropin receptor autoantibodies from the mother with Graves' disease to her child. We report a German women and her two sons who had congenital, but persistent hyperthyroidism without any signs of autoimmunity. Direct sequencing of the polymerase chain reaction-amplified exon 10 of the thyrotropin receptor genomic DNA revealed in the mother and both sons a transition of GCC to GTC, resulting in an exchange of alanine 623 to valine. This germline mutation in a highly conserved region of the thyrotropin receptor resulted in a constitutive activation of the cyclic adenosine monophosphate-generating cascade with resulting hyperthyroidism. Analysis of the family for a corresponding BstXI restriction-site polymorphism revealed heterozygosity for this mutation in the affected family members, but not in the father or other relatives. We conclude that whenever congenital hyperthyroidism is persistent and parameters of autoimmunity are absent, a constitutively active thyrotropin receptor mutation should be considered. Treatment appears to require aggressive means such as total thyroidectomy or ablation by 131iodine because two subtotal thyroidectomies in the mother were insufficient to control the disease.

Inappropriate secretion of umbilical plasma catecholamines in preterm compared to term neonates.

To investigate the gestation and stimulus related catecholamine secretion and degradation at birth free and sulfoconjugated adrenaline, noradrenaline and dopamine were analysed in the umbilical artery and vein of 35 preterm and 75 term neonates. A highly sensitive radioenzymatic assay was used for the determination of free catecholamine levels, sulfoconjugated catecholamines were analysed after addition of 25 mU arylsulfatase type VI. Levels of free catecholamines were significantly lower in preterm as compared to term newborns. Hereby, adrenaline levels significantly correlated with the gestational age, birth weight, and birth length. Sulfoconjugated catecholamine levels were similarly lower, but only sulfoconjugated noradrenaline reached differences of statistical significance. The placental extraction rate of adrenaline and noradrenaline was significantly lower in preterm as compared to term neonates. Only in term but not in preterm neonates, arterial pH- and pCO2-levels significantly correlated with arterial plasma catecholamine levels. Therefore, lower catecholamine levels in preterm compared to term neonates result from lower secretion of catecholamines rather than increased degradation and may contribute to their frequent surfactant deficiency. In addition, the inadequate and diminished catecholamine secretion of preterm neonates may play a significant part in their postnatal adaptation problems like hypoglycaemia, hypothermia and occurrence of wet lungs.