Marta Szymankiewicz

Usefulness of cardiac troponin T and echocardiography in the diagnosis of hypoxic myocardial injury of full-term neonates.

Background: Perinatal asphyxia constitutes a significant problem influencing neonatal mortality and morbidity. Objectives: The aim of the present work was to provide evidence of the usefulness of cardiac troponin T (cTnT) and echocardiographic investigations in the diagnosis of heart damage in full-term infants after intrauterine hypoxia. Material and Methods: The subjects were 39 asphyxiated and 44 term infants without fetal anoxia. Quantitative determinations of cTnT were performed between 12 and 24 h of life. Two-dimensional Doppler and color Doppler studies were performed at the bedside. We evaluated fractional shortening (FS), cardiac output (CO), cardiac index (CI), tricuspid (TI) and mitral (MI) insufficiency. Results: Asphyxiated infants presented increased cTnT (mean 0.141 ± 0.226 vs. 0.087 ± 0.111ng/ml; p < 0.01) and TI (38.5 vs. 11.4% of population; p < 0.05) compared to healthy infants. CO, CI and FS remained in the same range. Conclusions: We found cTnT to be the most useful among accessible diagnostic tools used in post-hypoxic heart damage in neonates. The data from our relatively small population study suggest a cTnT value of >0.1 ng/ml as a reliable marker of myocardial injury in neonates. Further study should be performed to generate a receiver-operator characteristic curve to discover what the cut-off level should be.

Mechanics of Breathing after Surgical Ligation of Patent Ductus arteriosus in Newborns with Respiratory Distress Syndrome

The aim of the study was to detect changes in pulmonary function following ligation of a patent ductus arteriosus (PDA). Pulmonary function was recorded in 16 newborns (birth weight 1,081 ± 166 g, gestational age 27.6 ± 1.7 weeks) before and after ligation. No change in resistance of airways or mean airway pressure was observed. We found an increase in dynamic compliance (Cdyn) of 77% (p < 0.01), in tidal volume (TV) of 29% (p = 0.004), and in minute ventilation (MV) of 17% (p < 0.01) after the procedure. We demonstrated that pulmonary function improves after surgical ligation of the PDA. Because of considerable variation in intubated and spontaneously breathing premature newborns, we recommend the analysis of three main parameters: Cdyn, TV and MV for estimation of pulmonary mechanics in these infants.

Predictors of successful extubation of preterm low-birth-weight infants with respiratory distress syndrome.

Objective: The aim of the study was to measure pulmonary mechanics in infants with respiratory distress syndrome before extubation and to correlate pulmonary function values with successful extubation. Design: Clinical study. Setting: Neonatal intensive care unit. Patients: Fifty-one infants (birth weight, 1158.6 ± 150.6 g; gestational age, 29.1 ± 2.0 wks). Interventions: Ventilation and daily ventilatory management. Measurements and Main Results: Of the 51 infants studied, 35 (60.8%) were successfully extubated, whereas 16 (39.2%) required reintubation and mechanical ventilation within 72 hrs after extubation. All patients met the clinical and biochemical criteria for extubation. Variables of artificial ventilation before extubation were minimal in all the studied cases (Fio2 ≤0.4, inspiratory pressure ≤20 cm H2O, ventilatory rate, ≤10/min). Pulmonary mechanics were measured before extubation using a noninvasive, mobile VenTrak measuring station. Results: Significant differences in pulmonary function values between the groups were found. Lower resistance of airways and work of breathing and higher dynamic compliance, tidal volume, and minute ventilation before extubation were associated with successful extubation. Conclusion: On the average, tidal volume values of >6 mL/kg, minute ventilation of >309 mL/kg/min, work of breathing of <0.172 J/L, dynamic compliance of ≥1 mL/cm H2O/kg, and resistance of airways of ≤176 cm H2O/L/sec predicted successful extubation. We recommend measurement of pulmonary function as an assessment tool in determining readiness for extubation.

Retrospective diagnosis of hypoxic myocardial injury in premature newborns

Abstract Perinatal asphyxia has a high impact on neonatal mortality, morbidity, and neurological outcome. The hypoxic effects on brain, kidney and gastrointestinal system are well recognized in newborns. While it is known that hypoxia also effects cardiac function, there are few studies of quantitative myocardial injury in premature infants who suffered hypoxia. Aim: To investigate usefulness of cardiac troponin (cTnT) and creatinine kinase MB (CK-MB) in the diagnosis of myocardial injury due to birth hypoxia and to correlate these markers with cardiac functions as measured by echocardiogram. Methods: We studied 43 preterm infants: 21 with birth asphyxia and 22 controls. Echocardiographic studies and quantitative determination of cTnT and CK-MB in blood serum was performed between the 12th and the 24th h of life. Results: cTnT and CK-MB levels were higher in asphyxiated infants compared to controls (0.287±0.190 vs. 0.112±0.099 ng/mL, P<0.001) and (18.35±14.81 vs. 11.09±5.17 ng/L, P<0.05). Among controls, we observed an elevated value of cTnT in those with respiratory distress syndrome (RDS). We found a decrease in fractional shortening (P<0.05) and an increase in tricuspid insufficiency (P<0.01) in asphyxiated newborns. Conclusions: cTnT and CK-MB levels are strong indicators of myocardial injury due to perinatal hypoxia. The cTnT level was most strongly related to RDS.

Pulmonary function after surfactant lung lavage followed by surfactant administration in infants with severe meconium aspiration syndrome

OBJECTIVE The effect of surfactant lung lavage (SLL) on pulmonary function was examined in neonates with severe form of meconium aspiration syndrome (MAS) (mean +/- standard deviation: birth weight, 3178.1 +/- 237.6 g; gestational age, 37.7 +/- 1.8 weeks). METHODS The infants were on mechanical ventilation and were subjected to SLL with Survanta. Dynamic compliance (Cdyn), airway resistance (Raw) and mean airway pressure (MAP) were obtained with use of the pneumotachometric method. Measurements of Cdyn, Raw, MAP and time constant (Tc) were compared in the study and control groups and between the groups before SLL and 24 and 48 h after SLL. RESULTS A significant increase in Cdyn (from 1.06 +/- 0.23 to 2.12 +/- 0.99 (ml/cmH(2)O)/kg) (p < 0.05) and a drop in both Raw (from 264.7 +/- 41.5 to 146.6 +/- 39.4 (cmH(2)O/l)/s) and MAP (from 12.4 +/- 3.6 to 5.4 +/- 2.1 cmH(2)O) were observed 48 hours after SLL. CONCLUSIONS These data suggest that SLL is associated with a rapid and significant improvement in pulmonary mechanics, together with an improvement in oxygenation, in newborns with severe MAS. We found that the beneficial effects of SLL on pulmonary mechanics persisted for at least 48 h after introduction of the procedure.

Airway concentrations of angiopoietin-1 and endostatin in ventilated extremely premature infants are decreased after funisitis and unbalanced with bronchopulmonary dysplasia/death.

A systemic inflammatory response of the fetus, reflected by histologic funisitis, is a risk factor for bronchopulmonary dysplasia (BPD). Impaired pulmonary angiogenesis accompanied by simplification and rarification of alveoli is a histologic hallmark of BPD. Angiopoietin-1 mediates vascular development, maturation, and stabilization. Endostatin mainly acts as an angiostatic factor. We hypothesized that funisitis was associated with changes of endostatin and angiopoietin-1 concentrations in the airways and that an imbalance between the factors might be associated with BPD or death. We measured concentrations of angiopoietin-1 and endostatin by enzyme-linked immunosorbent assay in tracheobronchial aspirate fluid samples of 42 ventilated preterm infants during postnatal days 1 through 15. The secretory component for IgA served as reference protein. A standardized histologic examination was used to distinguish three groups: chorioamnionitis, funisitis, and controls without inflammation. Concentrations of the mediators steadily decreased. Funisitis was associated with lower concentrations of both proteins, which might impair their physiologic activities in pulmonary angiogenesis. An increase of the ratio angiopoietin-1/endostatin until day 7 of life indicated a shift of the mediators potentially favoring angiogenesis. However, infants, who developed BPD or died, had a decreased ratio on days 1, 3, and 15, suggesting an imbalance toward inhibition of pulmonary angiogenesis.

Airway angiopoietin-2 in ventilated very preterm infants: association with prenatal factors and neonatal outcome

Pulmonary angiogenesis is a prerequisite for lung development. Angiopoietin‐2 (Ang2) destabilizes endothelial cells through its endothelial receptor TIE‐2, enabling vascular sprouting. Ang1 stabilizes new blood vessels. Soluble TIE‐2 (sTIE‐2) modulates these effects. We hypothesized that histological funisitis is associated with alterations of Ang2 in airways and of the systemic angiopoietin‐TIE‐2 homeostasis in very low birth weight (VLBW) infants, contributing to pulmonary morbidity and mortality.

Clara Cell Secretory Protein in Tracheobronchial Aspirates and Umbilical Cord Serum of Extremely Premature Infants with Systemic Inflammation

Background: A systemic fetal inflammatory response, reflected by chorioamnionitis with funisitis, is a risk factor for bronchopulmonary dysplasia. Clara cell secretory protein (CC10), a product of pulmonary Clara cells, has anti-inflammatory properties. Local down-regulation of CC10 has been associated with inflammatory lung disease. Increased serum levels of CC10 can indicate injury to alveolar-capillary integrity. Objective: We hypothesized that extremely premature infants with a systemic fetal inflammatory response would have decreased concentrations of CC10 in tracheobronchial aspirates and that CC10 concentrations in umbilical cord serum of these infants would be increased, reflecting alveolar epithelial damage. Methods: We measured CC10 concentrations in tracheobronchial aspirates of 42 ventilated extremely premature infants during their first week of life and in umbilical cord serum of 24 of them by ELISA. Standardized histological examination of the placenta, membranes and umbilical cord was used to identify infants with funisitis. Results: Seventeen infants with funisitis had lower CC10 concentrations in tracheobronchial aspirates on days 1 (p < 0.01) and 3 (p < 0.05) than the remaining 25. Exogenous surfactant treatment was associated with higher CC10 concentrations on day 1 (p < 0.05). Initial leukocyte count correlated inversely with CC10 in tracheobronchial aspirates on days 1–5. Umbilical cord serum concentrations of CC10 did not differ between the infants with funisitis and the controls. Conclusions: Reduced anti-inflammatory CC10 concentrations in airways of extremely premature infants with a fetal inflammatory response might make their lungs susceptible for further postnatal injuries. Umbilical cord serum CC10 is not an indicator for a fetal systemic inflammatory reaction.

Role of selected cytokines in the etiopathogenesis of intraventricular hemorrhage in preterm newborns.

Proinflammatory cytokines are essential mediators and indicators of an inflammatory process occurring in the body. Their physiological role is to stimulate the immune response, yet their excessive propagation and interaction with cells outside the immune system may be linked to the risk of organ damage. This is specifically important in the case of immature tissues of fetuses and prematurely born infants. Analysis of the concentrations of specific cytokines in different compartments makes it possible to assess the risk of premature birth, preterm rupture of the membranes, and to determine an existing intrauterine infection. The purpose of this paper is to summarize the existing research concerning the relationships between the concentrations of specific proinflammatory cytokines in different compartments (maternal blood serum, amniotic fluid, umbilical cord blood, arterial and venous blood, and cerebrospinal fluid of the newborn) and the risk of intraventricular hemorrhage (IVH) and the degree of its severity. The paper takes also into account the assessment of the usefulness of cytokines as biomarkers for IVH and its complications (posthemorrhagic hydrocephalus, white matter injury).

Effect of Pentoxifylline, administered in Preterm Labour, on the Foetal–Placental Circulation and Neonatal Outcome: A Randomized, Prospective Pilot Study

The aim of the study was to evaluate the pentoxifylline administration on the foetal-placental circulation and neonatal outcome in women with threatened preterm labour. Pentoxifylline was given as a supplement to standard tocolytic therapy in a group of 43 patients (pentoxifylline group) as an intravenous infusion and oral supplementation in a total dosage of 800 mg/day. The drug was administered within 3 weeks after admission. No pentoxifylline was given in the control group (53 patients). Doppler velocimetry of pulsatility indices (PI) of the umbilical (UA) and middle cerebral (MCA) arteries as well as cerebro-placental ratio (CPR) were calculated. Also, the neonatal outcome was estimated in both groups. From the second week of therapy with pentoxifylline, the PI decreased in umbilical artery and increased in the MCA, whereas in the control group, there were no changes. The value of PIUA, evaluated after the third week of pentoxifylline administration, was statistically significantly lower when compared to data obtained on admission (mean: 0.99 ± 0.22 versus 0.82 ± 0.12; p =0.016). Pentoxifylline significantly increased CPR values calculated after third week of drug administration, which were statistically significantly higher in the pentoxifylline group when compared with respective data in the control group (mean: 2.30 versus 1.61; p = 0.001). The risk of severe neonatal complications was significantly lower in the pentoxifylline group (p = 0.026). Pentoxifylline changed foetal-placental blood circulation in patients with threatened preterm labour and improved neonatal outcome.