[Acute or expectant management in premature labour with preterm premature rupture of the membranes?]. / Akutní, nebo expektacní prístup u predcasného porodu s predcasne odteklou plodovou vodou?

OBJECTIVE: To evaluate current knowledge about the management of preterm premature rupture of the membranes (PPROM). DESIGN: Review article. SETTING: Perinatological center, Department of Gynecology and Obstetrics, General Faculty Hospital and 1st Medical School of Charles University, Prague. METHODS AND RESULTS: Expectant management in case of PPROM increases the incidence of infection/ inflammation but does not statistically increase mortality and serious morbidity of the infants. The incidence of infants morbidity corresponds with gestational age. The most serious complications occur in the lower gestational age. It is necessary to take an individual approach. The acute management increases the number of operative deliveries and respiratory distress syndrome (RDS) in the infants. The combination of RDS, extremely prematurity and hypoxia during the labour decreases the infants survival rate. CONCLUSIONS: The prolongation of the latency period in pregnancies above 28th week does not deteriorate the neonatal mortality or morbidity.

Five-year survival without major disability of extremely preterm infants born at 22-27 weeks' gestation admitted to a NICU.

AIM: To compare the 5-year survival without major disability in infants born at the threshold of viability at 22-25 weeks who were actively treated in the delivery room and admitted to a NICU to that of those born at 26-27 weeks of gestation. METHODS: All infants between 22(+0) and 27(+6) weeks of gestation admitted to a regional intensive care unit during 1999-2003 were enrolled prospectively. The survival and major disability at 5 years of age were analysed by gestational age. RESULTS: Of 242 treated infants, 202 survived (83.5%). Although the overall survival rate was significantly higher in the 25-27 weeks' gestation infants than the 22-24 weeks' gestation infants (p < 0.001), the survival rate among infants 22-24 weeks (63.6%, 63.6%, and 70%) did not significantly differ, likewise infants 25-27 weeks (88.7%, 90.6%, and 92%) had similar results. Overall, 28 children (14.4% of assessed) had major disability. Both survival and survival without major disability were positively influenced by increasing gestational age, increasing birth weight, being born at 25-27 weeks and being female child. CONCLUSION: With an active approach in treatment, the outcome of infants born at 25 weeks is comparable to those born at 26-27 weeks. Thus, the 'grey zone' in which the risk of adverse outcome is high narrows to 22-24 weeks.

Activities of respiratory chain complexes and pyruvate dehydrogenase in isolated muscle mitochondria in premature neonates.

BACKGROUND AND AIMS: Most diseases in premature neonates are secondary to immaturity of various organ systems. Also the inadequate capacity of mitochondrial energy production may play an important role in the neonatal morbidity. SUBJECTS AND METHODS: The activities and amount of respiratory chain (RC) complexes, pyruvate dehydrogenase (PDH) and citrate synthase (CS) were analysed in isolated muscle mitochondria obtained at autopsy in 19 premature neonates using spectrophotometric and radioenzymatic methods and blue-native electrophoresis and Western blotting. Two groups of children recommended for muscle biopsy at the age of 0.5-2 and 3-18 years served as controls. RESULTS: In premature neonates, the activities of RC complexes III, IV, PDH and CS were markedly lower in comparison with older children. On the contrary, the activity of complex I was higher in premature neonates than in older children. The ratios between RC complexes I, II and III and CS were significantly higher in premature neonates in comparison with older children. In addition, the protein amount of RC complexes and PDH subunits were lower in premature neonates in comparison with older children. CONCLUSION: The results of our study document the age-dependent differences in activities of PDH and respiratory chain complexes in early childhood. Lower functional capacity of mitochondrial energy-providing system in critically ill neonates may be explained by combination of various factors including the delay in maturation of PDH and respiratory chain complexes in very premature neonates and increased degradation of mitochondrial proteins in connection with sepsis, tissue hypoperfusion or hypoxemia.

Carnitine concentrations in term and preterm newborns at birth and during the first days of life.

Carnitine plays an important role in energetic metabolism. The aim of the study was to characterize the carnitine status in term and preterm newborns with respect to gestational age, birth weight, haematocrit and red blood cell count (RBC). The effect of nutrition on carnitine levels in the first week of life was also studied. Total blood pool of free carnitine (FC), acylcarnitines (AC) and total carnitine (TC) were analysed in whole cord blood and postnatally in capillary blood obtained at the day 4-6 in 33 term newborns and at the day 7-10 in 27 preterm newborns using tandem mass spectrometry. Plasma level of carnitine in the cord blood was measured using radioenzymatic method. Cord plasma levels of FC, AC and TC were higher in preterm newborns in comparison with term newborns (p < 0.01), but the total blood pool of FC and TC in whole cord blood was lower in preterm newborns than in term newborns (p < 0.01) and positive correlation was found between FC and gestational age or birth weight (p < 0.05). In addition, positive correlation was found between AC and red blood cell count or haematocrit (p < 0.05). During the first week of life, blood pool of FC and TC in term newborns and AC and TC in preterm newborns decreased regardless of the type of enteral or parenteral nutrition. Our results indicate that preterm newborns are born with limited carnitine store. Interpretation of carnitine analyses in whole blood relies in addition to gestational age and birth weight on the haematocrit, especially in newborns with anaemia or blood hyperviscosity.

[Does the decreasing rate of neonatal mortality increase severe neonatal neurosensory morbidity?]. / Zvysuje klesající mortalita závaznou neonatální neurosenzorickou morbiditu?

OBJECTIVE: To investigate relation between the mortality and the incidence of serious neonatal neurosensoric morbidity in very low birth weight newborns (VLBWN, birth weigh < or = 1499 g) during the three periods as defined by different quality of the parinatal and neonatal care. DESIGN: Retrospective analysis. SETTING: Perinatal center of the General Faculty Hospital. 1st Medical Faculty Charles University, Prague. SUBJECT AND METHODS: All live-born VLBWN in 1987-2001 were divided according to their birth-date to three five-year periods characterized by different quality of the perinatal and neonatal care. Ist period 1987-1991: the presurfactant area with no standard use of antenatal steroids and without defined border of the fetus viability; IInd period 1992-1996: the transient aera; IIIrd period 1997-2001: the surfactant aera with standard use of the antenatal steroids, and defined border of the fetus viability. VLBWN were divided according to birth weight to three subgroups (p. h. < 750 g, p. h. = 750-999 g, p. h. = 1000-1499 g). Mortality was defined by a death in our department until the discharge. VLBW newborns classified as newborns with serious neonatal neurosensoric morbidity (NNsM) had to have one of the following diagnoses at least: severe intraventricular haemorrhage (IVH gr. 3-4), posthemorhagic hydrocephaly (PHH), cystic periventricular leukomalacia (cPVL), meningitis, ventriculitis, encephalitis (M/E), retinopathy of prematurity > or = stage III (ROP > or = III st.). The chi 2 test was used for statistic evaluation. RESULTS: There were 873 VLBWN born and 208 of them died in the whole period (1987-2001). Mortality decreased in 5 year periods gradually: 1st period 111/226 (49%); IInd period 55/217 (25%); IIIrd period 42/430 (10%). The decrease of mortality was significant in all weight categories (p < 0.001). The incidence of NNsM was evaluated in 612 newborns and was similar in all periods regarding weight subcategories < 1000 g, but decreased significantly in the weight category 1000-1499 g (14/215 (6%) vs 13/73 (18%), p < 0.01). CONCLUSION: Improvement in survival of extremely low birth-weight infants did not increase the incidence of serious neurosensoric morbidity and evenmore NNsM was reduced in haevier very premature newborns during the nineties.

Fast decline of hematopoiesis and uncoupling protein 2 content in human liver after birth: location of the protein in Kupffer cells.

Hepatic hematopoiesis is prominent during fetal life and ceases around birth. In rodent liver, the decline of the hepatic hematopoiesis starts abruptly at birth being accompanied by a decrease of mitochondrial uncoupling protein 2 (UCP2) expression in monocytes/macrophages, whereas hepatocytes may express UCP2 only under pathologic situations. The goals of this study were to characterize hepatic hematopoiesis in humans around birth, and to identify cells expressing UCP2. Hematopoiesis was evaluated histologically in the liver of 22 newborns (mostly very premature neonates), who died between 45 min and 140 d after birth, and one fetus. UCP2 expression was characterized by Northern blots, immunoblotting, immunohistochemistry, and by in situ hybridization. The number of hematopoietic cells started to decrease rapidly at birth, irrespectively of the gestational age (23-40 wk) of neonates. A similar decline was observed for UCP2 expression, which was relatively high in fetal liver. UCP2 was detected only in myeloid cells (mainly in Kupffer cells), but not in hepatocytes, although sepsis or other pathologies occurred in the critically ill newborns. Kupffer cells represent the major site of mitochondrial UCP2 expression in the human newborn. UCP2 may be essential for the differentiation and function of macrophages and serve as a marker for these cells in human liver during the perinatal period.

Recurrent ACTH-independent Cushing's syndrome in multiple pregnancies and its treatment with metyrapone.

A 17-year-old primigravid woman presented with Cushing's syndrome. Typical clinical symptoms and signs developed at the beginning of pregnancy. By week 17 of gestation, plasma cortisol diurnal rhythm was absent and there was a paradoxical increase in plasma cortisol after a 1-mg dexamethasone overnight suppression test. Basal urinary free cortisol was 10 times above the upper limit (in pregnancy) and ACTH levels were suppressed. The diagnosis of ACTH--independent Cushing's syndrome was established. MRI scans revealed normal adrenal and pituitary glands. To control hypercortisolism, the patient was treated with metyrapone. At 34 weeks of gestation, the patient developed preeclampsia and underwent caesarean section. A female infant weighing 1070 g was delivered. No apparent metyrapone-induced teratogenic effects were observed. Cushing's syndrome in the patient resolved within three weeks of delivery. No corticosteroid replacement therapy either for child or mother was needed. Eight months after delivery the patient became pregnant again and rapidly developed Cushing's syndrome with typical clinical symptoms and signs and laboratory results (urinary free cortisol 6464 nmol/24 h). This second pregnancy was unwanted and terminated by artificial abortion that was followed by rapid resolution of hypercortisolism. A third pregnancy, 12 months after delivery was also accompanied by the rapid development of hypercortisolism which recovered after artificial termination. The mechanisms by which pregnancy-induced Cushing's syndrome occurred in this patient are unclear. Aberrant responsiveness or hyperresponsiveness of adrenocortical cells to a non-ACTH and non-CRH substance produced in excess in pregnancy should be considered. Metyrapone suppression of hypercortisolism currently represents the best treatment for these rare cases.

[Neonatal mortality in the Czech Republic 1998-1999]. / Novorozenecká úmrtnost v Ceské republice v letech 1998-1999.

OBJECTIVE: To evaluate neonatal mortality rate (NMR) in 1998 and 1999 years in the Czech Republic. DESIGN: Retrospective epidemiological study of all alive newborns born in 1998 and 1999 in the Czech Republic. SETTINGS: 12 perinatological centers of nine regions of Bohemia and Moravia. METHODS: All alive, died, died with congenital defects newborns were registered and results of neonatal mortality rate and specific neonatal mortality rate were calculated. The main causes of death were divided into four groups (intraventricular hemorrhage grade III-IV, infection, acute respiratory failure and others) and evaluated comparatively. In 1999 the NMR of newborns with birth weight below 500 g and their survival were introduced for the first time in the Czech Republic. RESULTS: The fluent decrease of NMR during nineties was stopped in 1999. Increase of NMR from 2.8@1000 in 1998 to 3.0@1000 in 1999 was mainly caused by arise of specific neonatal mortality rate in newborns weighing > or = 2000 g. Comparing 1998 and 1999 years, two times more these newborns without serious congenital defects died in 1999 (28 vs. 56). Specific neonatal mortality rate of extremely low birth weight newborns further decreased (359@1000 vs. 279@1000) especially in the newborns with birth weight between 500-749 g (543@1000 vs. 373@1000). The most frequent main causes of death still has been intraventicular haemorrhage grade III-IV and infection in very low birth weight newborns, and serious congenital defects and infection in newborns weighing > or = 1500 g. The concentration of very low birth weight newborns to perinatological centers by transfer in uterus was 81% in 1998 and 83% in 1999. The differences in neonatal mortality rates between nine regions of Bohemia and Moravia has been getting equal but has been still great in specific neonatal mortality rate of extremely low birth weight newborns between the best and worst regions (147@1000 vs. 458@1000). There were registered 19 newborns weighing < or = 500 g surviving more than 24 hours after delivery in the Czech republic. Specific neonatal mortality rate of these newborns was 316@1000 and 527@1000 survived. CONCLUSION: Reserves for further lowering of NMR are improving the care after extremely low birth weight newborns in the regions with below average results and decreasing the mortality of newborns with birth weight > or = 2000 g by introducing of group B streptococcus prophylaxis, improving prenatal diagnostics of serious congenital defects and early and more quality postnatal transport of newborns suffered from acute respiratory failure to centers disposing of the latest methods of treatment.

[Cesarean section and perinatal mortality 1993-1996 in a regional perinatology center]. / Císarský rez a perinatální úmrtnost v letech 1993-1996 v regionálním perinatologickém centru.

During the period between 1993-96 the authors made at the Second Gynaecological and Obstetric Clinic 1099 caesarean sections. The investigated group was subjected to frequency analysis. The relationship with perinatal mortality and early neonatal mortality was assessed. In a group of 287 caesarean sections in 1996 the authors analyzed indication spectra and maternal morbidity. The results were compared with data in the literature. From the assembled data ensues that although the rate of caesarean sections practically does not change, perinatal mortality decreased significantly. This positive result is due mainly to better perinatal and neonatological care. In the indications for caesarean section the authors did not reveal statistically significant deviations from nationwide average figures.

A prospective randomized comparison of conventional mechanical ventilation and very early high frequency oscillatory ventilation in extremely premature newborns with respiratory distress syndrome.

OBJECTIVE: To compare the effectiveness and safety of very early high-frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) in treatment of the respiratory distress syndrome (RDS) and to evaluate their impact on the incidence of chronic pulmonary disease and early and late morbidity of very low-birthweight neonates. DESIGN: A prospective randomized clinical trial. SETTING: Tertiary neonatal intensive care unit in the Perinatology Center in Prague. PATIENTS: 43 premature newborns, delivered in the Department of Obstetrics in the Perinatology Center, were randomly divided into two groups (HFOV and CMV) immediately after delivery; 2 patients in each group died, 2 fulfilled crossover criteria from CMV to HFOV, and 2 were excluded because of congenital malformations. Nineteen patients treated with HFOV were therefore compared with 18 infants in the CMV group. METHODS: The two contrasting modes of ventilation were introduced immediately after intubation. Maintenance of optimal lung volume in HFOV to optimize oxygenation and the therapeutic administration of surfactant after fulfilling defined criteria are important points of the strategy and design of the study. MEASUREMENTS AND MAIN RESULTS: Except for a higher proportion of males in the HFOV group (p<0.02), the basic clinical characteristics (gestational age, birthweight, Apgar score at 5 min, umbilical arterial pH), the two groups were similar. In the acute stage of RDS, infants treated with HFOV had higher proximal airway distending pressure with HFOV for 6 h after delivery (p<0.05). For a period of 12 h after delivery lower values for the alveolar-arterial oxygen difference (p<0.03) were noted. The number of patients who did not require surfactant treatment was higher in the HFOV group (11 vs. 1, p<0.001). In the HFOV group the authors found a lower roentgenographic score at 30 days of age (p<0.03) and a lower clinical score in the 36th postconceptional week (p<0.05), using these two scoring systems for assessing chronic lung disease according to Toce scale. The incidence of pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage and retinopathy of prematurity in both groups was the same. CONCLUSIONS: HFOV, when applied early and when the clinical strategy of maintenance of optimal lung volume is used, improves oxygenation in the acute stage of RDS, reduces the need of surfactant administration, and can decrease the injury to lung tissue even in extremely immature newborns to whom surfactant is administered therapeutically.

[Diagnosis and therapy of erythrocyte alloimmunization in pregnancy]. / Diagnostika a lécba erytrocytární aloimunizace v tehotenství.

INTRODUCTION: By preventive administration of anti-D globulin the number of cases of Rh isoimmunization declines steadily. Severe untreated isoimmunization may lead via foetal hydrops to intrauterine death, sometimes already during the 18th-19th week of gestation. The purpose of prenatal diagnosis in pregnant women with isoimmunization is to assess the danger or affection of the foetus, its prognosis and the mode of monitoring of the foetus. It is necessary to decide in time on intrauterine therapy by transfusion of erythrocyte mass and to assess the optimal time of delivery with regard to the risk of prematurity and foetal erythroblastosis, as well as with regard to intrauterine therapy. The objective of the present work was to test the protocol in the treatment of erythrocytic isoimmunization of the foetus. METHOD: During the period between January 1991 and October 1997 the authors investigated two groups of pregnant women: with a hydropic (n = 5) and non-hydropic (n = 20) foetus at the onset of treatment. In both groups amniocentesis and umbilical puncture were indicated. The authors investigated the number of cordocenteses and the volume of transfused blood per pregnancy, the number of complications and their type, gestation age of the foetuses on delivery, their birth weight, the condition of the neonates after delivery and on discharge to home care. RESULTS: During the mentioned period the authors administered 70 intraumbilical transfusions to 25 foetuses. The transfusion was not repeated more than eight times. The baseline haematocrit of non-hydropic foetuses was 26 (14-34), treatment was started on average during the 28th week (23rd-33rd). Pregnancy in women with a non-hydropic foetus was terminated during the 35th (27th-40th) week, with a mean weight of the foetuses of 2439 g (870-3520). Of 25 treated foetuses 6 were hydropic (24%) at the onset of treatment. The initial haematocrit of hydropic foetuses was 10.7 (4-19.8), treatment was started on average during the 28th (23rd-33rd) week. Pregnancy of women with hydropic foetuses was terminated during the 30th (25th-36th) week, the mean birth weight being 1838 g (660-3500). DISCUSSION: The very favourable therapeutic results in non-hydropic foetuses are in great contrast with the therapeutic results of moribund hydropic foetuses. CONCLUSION: The basic prerequisite of successful treatment by intraumbilical transfusion is to concentrate risk pregnancies in specialized centres with a high standard neonatological team for intensive care of pathological neonates.

[Gestational diabetes--a model trial. The effect of alloxan diabetes on the spectrum of fatty acids in the blood, liver and brain in laboratory rats]. / Gestacní diabetes--modelová studie. (Vliv aloxanového diabetu na spektrum mastných kyselin v krevním séru, v játrech a v mozku u laboratorního potkana).

In alloxan-induced diabetic rats (Wistar, females, age 3-4 months of postnatal life) the large spectrum of fatty acids in blood serum, brain cortex, medulla oblongata and liver was studied. The fatty acids, using gas chromatography, were detected as methyl esters and the methods were published previously (Smídová and al. 1994). Alloxan (Merck) administered i.p., 140 mg/kg body weight, caused immediately elevation (three times) of blood sugar levels. On the 13th day the rats were killed. The results are as follows: a) In blood serum alloxan diabetes of cca two weeks duration caused a significantly increased participation of saturated FA and decreased participation of both polyunsaturated FA (n-3 and n-6). b) In brain cortex no differences between controls and diabetic rats in the indicated groups of FA were found. c) In the medulla oblongata an increased participation of polyunsaturated fatty acids n-6 was established. d) In hepatic tissue the increased participation of saturated FA as well as a decreased participation of FA n-6 was described. Analysing the main groups of FA we found especially in n-3 and n-6 FA several significant changes in single FA (a smaller pool of arachidonic acid in blood serum as well as in liver, decreased participation of docosahexaenoic acid in the brain cortex, etc.). The purpose and possible consequences of such changes are discussed.

[Effect of combined administration of TRH and dexamethasone in pregnant women and the course of their pregnancy]. / Vliv kombinovaného podávání TRH a dexametazonu na tehotné zeny a samotný prubeh jejich tehotenství.

UNLABELLED: Extremely immature neonates are threatened during the first days after delivery by many conditions which are due to incomplete development.--A key role is played during the first days of extrauterine life by the incidence and degree of the respiratory distress syndrome (RDS). Its incidence in neonates born before the completed 32nd week of gestation is very common. Causal treatment of RDS is not known. To overcome it the neonatologist must use in the majority of infants invasive techniques of controlled ventilation which are associated with the risk of further complications such as barotrauma, retinopathy and later the development of bronchopulmonary dysplasia. Attempts to influence intrauterine maturation of the lungs were started in the fifties. As a routine procedure nowadays corticoids are administered antenatally. Their limited effect divert the attention of perinatologists to other substances which could enhance maturation of pulmonary tissue. In human medicine ambroxol was introduced, in animals opiates are tested as well as beta-mimetics, aminophylline. The greatest hopes were aroused by trials with the use of T-hormones. T-hormones have a maturating regulating function in the foetal organism. They have an affinity for pneumocytes and in animal experiments they have a positive effect on surfactant formation. Moreover they act synergically when combined with corticoids. OBJECTIVE OF STUDY: a) to evaluate the safety of the method from the aspect of undesirable side-effects of hormone administration to the mother b) evaluation of hormone levels: TSH, total T4, total T3, TRH and prolactin in maternal serum.

[Complications of prevention and treatment of erythrocyte alloimmunization (case reports)]. / Komplikace prevence a lécby erytrocytární aloimunizace (Kazuistiky).

OBJECTIVES: The treatment of late recognized alloimunization with intraumbilical transfusions is more difficult and more often connected with complications. MATERIAL AND METHOD: Between 1991-1997 we performed 70 intraumbilical transfusions in 25 fetuses for erythrocyte alloimunization. Six fetuses (24%) were hydropic in the beginning of the treatment. Eleven fetuses were delivered before 36 weeks of pregnancy. Two immature neonates (660 g and 1320 g) had intraventricular hemorrhage with neurologic complications. In six cases the transfusion was complicated by severe bradycardia of the fetus, but only twice the pregnancy was to be terminated by cesarean sectio during 24 hours after the procedure. Two of the 25 fetuses died antenataly and one postnataly, all of them primary hydropic. Two neonates had severe late onset anemia. CONCLUSION: Fetal alloimune anemia should be treated before onset of hydrops. The study was supported by the grant of IGA Ministry of Health CR No. 3200-3.

Tissue metabolism and plasma levels of thyroid hormones in critically ill very premature infants.

Thyroid status was characterized in very preterm infants (gestational age < or =32 wk; n = 61) from birth through d 14, and in infants who died within 16 d after delivery (n = 10), where it was also correlated with metabolism of iodothyronines in peripheral tissues (brain, liver, kidney, skeletal muscle, and adipose tissue). At 3 d of life, mean plasma levels of thyroxine, triiodothyronine, and TSH started to decrease, being lower in the critically ill compared with healthy premature neonates. Activities of the three iodothyronine deiodinases enzymes (type I, II, and III, respectively) were detected in all postmortem tissue samples, except for absence of the type II activity in kidney. All activities were the highest in liver and differed in other tissues. Lack of correlation between the type I activity in liver (and kidney), and plasma levels of thyroid hormones suggested that the thyroid was the primary source of circulating triiodothyronine. On the other hand, namely in brain, correlations between activity of the deiodinases and plasma hormone levels were found which suggested a complex control by thyroid hormones of their own metabolism. High activity of type III in liver, adipose tissue, and skeletal muscle demonstrated a role of these tissues in thyroid hormones degradation. Results support the view that peripheral tissues of very preterm infants are engaged in local generation of triiodothyronine, and inactivation of thyroid hormones, but do not represent a major source of circulating triiodothyronine.