Ferdinand Pulzer

Thyroid gland development and defects.

During the functional ontogenesis of the thyroid gland an increasing number of transcription factors play fundamental roles in thyroid-cell differentiation, maintenance of the differentiated state, and thyroid-cell proliferation. The early growth and development of the fetal thyroid appears to be generally independent of thyroid-stimulating hormone (TSH). TSH and thyroxine (T4) levels increase from the 12th week of gestation until delivery, whereas triiodothyronine (T3) levels remain relatively low. At birth, a cold-stimulated short-lived TSH surge is observed, followed by a TSH decrease until day 3 or 4 of life by T4 feedback inhibition. Disorders of thyroid gland development and/or function are relatively common, affecting approximately one newborn infant in 2000-4000. The most prevalent disease, congenital hypothyroidism, is frequently caused by genetic defects of transcription factors involved in the development of the thyroid or pituitary gland. A major cause of congenital hyperthyroidism is the transplacental passage of stimulating thyrotropin antibodies from the mother to the fetus. Hypothyroxinaemia or hypotriiodthyroninaemia is frequently observed in preterm infants with or without severe non-thyroidal illness. Whereas congenital hypo- and hyperthyroidism may be treated successfully with T4 or thyrostatic drugs, there is still insufficient evidence on whether the use of T4 for treatment of the latter condition results in changes in neonatal morbidity or reductions in neurodevelopmental impairment.

Hemodynamics among neonates with hypoxic-ischemic encephalopathy during whole-body hypothermia and passive rewarming.

OBJECTIVE. To assess changes in cardiac performance, with Doppler echocardiography, among newborns with hypoxic-ischemic encephalopathy during mild therapeutic hypothermia and during rewarming. METHODS. For 7 asphyxiated neonates (birth weight: 1840–3850 g; umbilical artery pH: 6.70–6.95) who received mild whole-body hypothermia, the following hemodynamic parameters were determined immediately before rewarming (33°C) and during passive rewarming (35°C and 37°C): heart rate, systolic and diastolic blood pressure, core and peripheral temperatures, left ventricular ejection time, mean velocity of aortic flow, stroke volume, and cardiac output. RESULTS. Heart rate decreased during hypothermia. Bradycardia, with heart rates below 80 beats per minute, did not occur. The median difference between core and peripheral temperatures decreased from 2.0°C (range: 0–6.2°C) during hypothermia to 0.7°C (range: 0.4–1.9°C) at normothermia. Cardiac output was reduced to 67% and stroke volume to 77% of the posthypothermic level. The median heart rate was 129 beats per minute before rewarming and increased to 148 beats per minute during complete rewarming. Before and during passive rewarming, hypotension was not observed. Before, during, and at the end of rewarming, the following parameters increased: mean velocity of aortic flow (median: 44, 55, and 58 cm/second, respectively), stroke volume (median: 1.42, 1.55, and 1.94 mL/kg, respectively), and cardiac output (median: 169, 216, and 254 mL/kg per minute, respectively). Left ventricular ejection time remained unchanged. CONCLUSIONS. Whole-body hypothermia resulted in reduced cardiac output, which reached normal levels at the end of passive rewarming, at normothermia. Physiologic cardiovascular mechanisms seemed to be intact to provide sufficient tissue perfusion, with normal blood lactate levels.

Transcutaneous bilirubinometry in preterm infants

The aim of this study was to evaluate the accuracy and safety of transcutaneous bilirubinometry in preterm infants using the new bilirubin analyser BiliCheck±. The study included 145 preterm children (23–36 wk gestation). Capillary blood sampling for determination of serum bilirubin (BS) was combined with transcutaneous bilirubin measurement (BTc) every morning until the sixth postnatal day and related to several clinical data (phototherapy (PT), infection signs, breathing disturbances, skin bleeding, etc.). Overall bilirubin concentration ranged from 17 to 371 μmol/l, and from 21 to 325 μmol/l for BS and BTc, respectively. Mean values obtained by BTc were significantly higher than BS values. The correlation coefficient between BS and BTc was r= 0.64 for the whole group, and r= 0.73 in infants without PT. As demonstrated by multiple regression analysis, BS‐BTc correlations were related only to gestational age (beta ‐0.32) and breathing disturbances (beta 0.29), indicating that the lower the gestational age and the more seriously ill the baby, the higher the incoherence between BS and BTc.

Reference intervals for TSH and thyroid hormones are mainly affected by age, body mass index and number of blood leucocytes, but hardly by gender and thyroid autoantibodies during the first decades of life

OBJECTIVES The purpose of our study was to establish reference intervals for thyroid function tests in children and adolescents and to identify factors that may influence the limits of these intervals. METHODS TSH, FT3, FT4, T3, T4, t-uptake, TPO-antibody (TPO-Ab) and TG-antibody (TG-Ab) levels were determined in blood of 1004 infants, children and adolescents by the Elecsys system (Roche). RESULTS A distinct overall age-dependent decrease of analyte levels was found for all parameters investigated. Puberty was accompanied by an increase of TSH, FT3 and T3 levels. Results of T4 and t-uptake were significantly higher in girls compared to boys. The exclusion of children with increased TPO-Ab and TG-Ab had no significant effect on the limits of the reference interval. We found that besides age, BMI-SDS but also white blood cells count and gender played a role in the prediction of analyte variation. CONCLUSIONS Covariates like BMI-SDS and white blood cell count should be taken into consideration when interpreting TSH and thyroid hormone measurements as well whereas gender and TPO-Ab or TG-Ab play a minor role.

The effect of maturation and sedation on amplitude‐integrated electroencephalogram of the preterm neonate: Results of a prospective study

Background and aim: Amplitude‐integrated electroencephalogram (aEEG) is becoming more common in NICUs for monitoring infants after perinatal asphyxia. We used aEEGs for preterm infants, and analysed the influence of sedation and maturation on their aEEG, focusing on continuous activity. Methods: Weekly or biweekly aEEGs were performed in preterm infants and evaluated by visual analysis. Results: We analysed 92 aEEGs of 56 preterm infants (gestational age (GA) 24 + 6 to 34 + 0 wk, median 30 + 0 wk). In their first week of life, children with higher GA had a higher percentage of continuous activity: with a GA ≤ 28 + 0 wk it was 8.1%, 33.5% with a GA from 28 + 1 to 30 + 0 wk (p= 0.02), 85.9% with a GA from 30 + 1 to 32 + 0 wk (p= 0.005), and 89.1% with a GA from 32 + 1 to 34 + 0 wk. Continuous activity increased with growing postnatal age. With a GA ≤ 28 + 0 wk, it rose from 8.1% (first week) to 55.3% (second week) and reached 96.8% (week 6/7) (p= 0.017). With GA from 28 + 1 to 30 + 0 wk, continuous activity was 33.5% (first week) and 86.6% (second week) (p= 0.03).

Unusual presentation of congenital disorder of glycosylation type 1a: congenital persistent thrombocytopenia, hypertrophic cardiomyopathy and hydrops-like aspect due to marked peripheral oedema

Of the congenital disorder of glycosylation (CDG) syndromes, type 1a is the most common. CDG 1a is a multisystem disorder with a wide clinical spectrum. We report on a term newborn with a severe and fatal clinical course of CDG 1a syndrome. Skin fibroblasts showed a reduced activity of phosphomannomutase 2 (PMM2) and mutation analysis revealed a compound heterozygous PMM2gene mutation (F119L/F157S). Presenting features at birth were hypertrophic non-obstructive cardiomyopathy, “orange-peel” skin, inverted nipples and a hydrops-like aspect due to marked peripheral oedema. Suspected hydrops fetalis was not confirmed due to lack of ascites and pleural effusions. Striking clinical problems were therapy-resistant arterial hypertension, recurrent pericardial and pleural effusions and feeding difficulties with failure to thrive. Persistent congenital thrombocytopenia and hyperferritinaemia in the absence of infection were noted. Bone marrow cytology revealed a macrophage activation of unknown aetiology. Conclusion:Congenital thrombocytopenia, unspecific macrophage activation and a hydrops-like aspect without a real hydrops fetalis broaden the already wide phenotypic spectrum of congenital disorder of glycosylation syndrome type 1a.

Metabolic syndrome in children and adolescents--risk for sleep-disordered breathing and obstructive sleep-apnoea syndrome?

Abstract The clinical relevance of the term “metabolic syndrome”, the definition criteria, and predictive power are being disputed. Inclusion of sleep-disordered breathing and sleep apnoea into a definition of metabolic syndrome is also controversial once children and/or adolescents are affected. Nevertheless, along with the increasing prevalence of childhood obesity, the prevalence of the metabolic syndrome in obese children is reported at 30%, irrespective of the definition applied. Moreover, childhood obesity is associated with sleep-disordered breathing. Adipocytokines, cytokines secreted from adipose tissue, are thought to play a major role in the pathophysiology of metabolic syndrome. Leptin was initially suggested as a promising “anti-obesity” hormone. New concepts indicate that in humans leptin and its soluble receptor may be more important in states of energy deficiency rather than a predictor of the metabolic syndrome. Adiponectin, on the other hand, is not only related to obesity and insulin resistance, but appears to be the strongest predictor for metabolic syndrome, even in children. In newborns and infants, both adipocytokines occur in high concentrations, even though this cannot completely explain the increased risk for ensuing metabolic disease later in life. Finally, low-grade systemic inflammation may underlie the clustering of metabolic risk factors. Overall factors from the adipose tissue may constitute not only markers but also mediators of metabolic sequelae of obesity.

Gastric perforation in a newborn.

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Effects of anaemia on haemodynamic and clinical parameters in apparently stable preterm infants.

BACKGROUND The criteria for erythrocyte transfusion in stable premature infants are currently controversial. Haemodynamic measurements are not common in transfusion practice. The purpose of this study was to determine whether haemodynamic measurements could be helpful as objective criterion for transfusion decisions. We, therefore, evaluated clinical and haemodynamic changes in stable, anaemic, premature infants before and after transfusion using our current blood transfusion protocol based on a haematocrit threshold (<24%) and the neonatologists discretion. MATERIAL AND METHODS Stable premature infants with a haematocrit level ≤30% were prospectively enrolled into the study. Cerebral, intestinal and renal blood flow velocities, cardiac function parameters and vital signs were measured up to three times following every routine haematocrit analysis. Moreover, transfused infants were evaluated three more times: directly before transfusion, and 24 hours and 72 hours after transfusion. RESULTS Thirty-six infants were enrolled and 23 of them were transfused. Subgroup analysis of transfused infants showed a significant decrease in cerebral blood flow velocities, cardiac output and heart rate. These changes persisted after transfusion. In the entire cohort, the degree of anaemia correlated with the increase of cerebral blood flow velocities, heart rate and cardiac output. DISCUSSION Cerebral blood velocities in the anterior cerebral artery might represent an objective Doppler sonographic criterion indicating the need for transfusion. The measurement of these velocities is non-invasive and quick and easy to perform. However, a randomised, controlled trial is necessary before a formal recommendation can be made.

Predictive value of umbilical cord blood bilirubin for postnatal hyperbilirubinaemia: Umbilical cord blood bilirubin and hyperbilirubinaemia

Aim: The study investigated the predictive value of umbilical cord serum (UCS) bilirubin for the postnatal course of bilirubinaemia in healthy term and near‐term newborns. Methods: Term appropriate‐for‐gestational‐age (AGA; n=1100), small‐for‐gestational‐age (SGA; n=163) and near‐term infants (GA 34–36 wk; n=78) were included and separated according to their UCS bilirubin levels, starting from <20 (group 1), 20–<30 (2), 30–40 (3) and >40 (4) μmol/l. The newborns were followed for at least 5 postnatal days, and UCS bilirubin values were correlated with the development of hyperbilirubinaemia and phototherapy (PT) treatment. Results: A clear relation between UCS bilirubin and the development of hyperbilirubinaemia was found in all three patient populations. None of the 75 AGA patients of group 1 developed postnatal bilirubin values above 300 μmol/l, whereas 0.3, 3.4 and 8.6% of the patients in groups 2–4, respectively, did so. The frequency of PT increased from 0% in group 1 up to 9.6% in group 4. For the prediction of further need of PT using a UCS bilirubin cut‐off level of 30 μmol/l, we found a sensitivity of 90% and a negative predictive value of 99.1%, indicating that all patients with UCS bilirubin values below 30 μmol/l (443/1100 or 40.2%) were at a very low risk of developing dangerous hyperbilirubinaemia. Similar results were obtained in SGA children with a sensitivity of 94.1% and a negative predictive value of 98.6%. In comparison to term newborns, we generally found higher bilirubin values in preterms. A total of 6.4% of preterm children developed bilirubin values over 300 μmol/l, compared with 3% of term children, and 47.4% of preterms had to be treated with PT. Predicting the need of PT by using a UCS bilirubin cut‐off level of 30 μmol/l revealed a sensitivity of 70.3% and a negative predictive value of 65.6%.