Diazepam and its metabolites in the mothers' and newborns' hair as a biomarker of prenatal exposure.

UNLABELLED: Pregnant women are exposed to benzodiazepines for therapeutic purposes during gestation. The goal of this study was to evaluate prenatal exposure to benzodiazepines. Time of exposure during course of pregnancy is a significant aspect of fetal exposure to drugs. Benzodiazepine concentration assay in hair of mothers and newborns exposed prenatally to these drugs was performed in the studies. Development, validation and evaluation of benzodiazepine determination method in mothers and their newborns enables assessment of health risks for the child and implementation of adequate therapeutic procedures. We used A LC-ESI-MS/MS method that allowed determination of diazepam (the main benzodiazepine used by pregnant women was diazepam) and its metabolites (nordazepam, oxazepam) in hair of mothers and newborns. LOQ 10 pg/mg of hair was used in the study. RESULTS: concentration of nordazepam was higher than parent drug (diazepam) and higher in newborns' hair when compared to mothers'. The mean concentrations of diazepam in mothers' hair were 31.6±36.0 and 34.1±42.4 pg/mg in the second and third trimester of pregnancy respectively. The mean concentration of diazepam in newborns' hair was higher and reached levels of 53.3±36.5 pg/mg. The mean concentration of nordazepam in the mothers' hair corresponding to the second and third trimester was 52.9±48.1 and 89.9±122.8 pg/mg, respectively. Nordazepam in the newborns' hair was detected at the mean level of 108.1±144.2 pg/mg. It was concluded that diazepam and nordazepam are permanently incorporated into the hair structure. Presence of diazepam and its metabolites in newborn's hair confirms that these benzodiazepines permeate placental barrier. Segmental analysis of mothers' hair enabled the assessment of drug administration time. Diazepam and its metabolites determined in hair of newborns may serve as biomarkers of prenatal exposure to these drugs. The performed LC-MS/MS analysis was accurate enough to determine even low concentrations of benzodiazepines, at the level of few pg/mg of hair. Levels of diazepam detected in hair of newborns were higher than levels determined in mothers. This may confirm the fact, that fetus's ability to metabolize diazepam is scarce. Nordazepam was found in higher concentrations in hair of newborns than in hair of mothers, which may suggest that it is cumulated in child's organism. Other metabolites of diazepam--oxazepam and temazepam--were detected in very few cases, in low concentrations.

[Analysis of pulmonary venous blood flow in growth retarded fetuses above 30 weeks of gestation]. / Ocena przeplywu krwi w zylach plucnych plodu po 30 tygodniu ciazy powiklanej wewnatrzmacicznym ograniczeniem wzrostu plodu.

Abnormal spectra of blood flow are observed in many fetal vessels in pregnancy complicated by intrauterine growth restriction. Redistribution of blood flow to the most important organs causes a diminished perfusion of the others. The disturbances of lung perfusion in utero are related to abnormal growth and development of the fetal lung. The aim of this study was to describe blood flow velocity waveforms in fetal pulmonary veins in normally grown and growth restricted fetuses above 30 weeks of gestation. Doppler studies were performed in 53 normally grown and 39 growth restricted fetuses. The subjects of analysis were: peak systolic (VS), peak diastolic (VD), end-diastolic (VA), and pulsatility index for veins (PIV). Analysis was performed for two gestational intervals: 31-36, 37-41 wks. The pulmonary venous flow in growth retarded fetuses demonstrates the similar pattern to that observed in normally grown fetuses above 30 weeks of gestation. There were no statistically significant differences between normally grown and growth restricted fetuses in all analyzed indices in both gestational intervals.

[Lung hypoplasia and the application of Doppler ultrasonography in the assessment of fetal pulmonary circulation]. / Hipoplazja pluc a mozliwosci zastosowania technik dopplerowskich w ocenie plodowego krazenia plucnego.

The paper presents a review of literature concerning the use of Doppler technique in the evaluation of pulmonary blood flow. Especially, it is important to monitor the development of lung in suspicion of lung hypoplasia that closely correlates with abnormal development of pulmonary vessels. In the literature there are single reports pointing on its usefulness in the detection of lethal lung hypoplasia. It has been suggested that this technique may provide valuable information of the development of vascular bed in lung. Recent data concerning Doppler blood flow velocimetry in hypoplastic lung stimulate to further studies suggesting their significant value in the diagnosis and distinguishing the lethal form of pulmonary hypoplasia.

[Fetal breathing movements and onset of delivery at term]. / Ruchy oddechowe plodu a czas wystapienia porodu w ciazy donoszonej.

It has been studied the relation between fetal breathing activity and labor among 216 patients in uncomplicated pregnancies at term. It has been also described the value of fetal breathing movements in the evaluation of fetal well-being. Among patients where fetal breathing movements were absent 81.9% women delivered within 3 days since ultrasonographic examination. And among patients with visible fetal breathing activity only 25.0% delivered within this period. The analysis of newborn condition based on Apgar score in pregnant women with or without fetal breathing movements showed no significant statistical differences. The absence of fetal breathing movements has no prognostic value concerning the evaluation of fetal well-being in antepartum period. The cessation of fetal breathing activity facilitates to prognose the time of labor in mature pregnancies.

[Analysis of selected parameters of maternal and fetal status during stimulation of fetal lung maturation]. / Analiza wybranych parametrów stanu ciezarnej i plodu w trakcie stymulacji dojrzewania ukladu oddechowego.

At patients threatened with premature childbirth the influence of glicocorticoids on short and tong-term fetal heart rate variability and the occurrence of respiratory arrhythmia was evaluated. It has been ascertained statistical significant lowering of the incidence of fetal respiratory arrhythmia and short-term variability. Described changes had a temporary character and surrendered of normalization in the course 72 of hours after last use of glicocorticoids. The influence of glicocorticoids on select biochemical and biophysical parameters of state pregnant women was also studied. One specified occurrence of incidental symptoms in road drove of therapy. Pregnant women in road of treatment glicocorticoids have also observed a temporary weakness of feeling of fetal movements.

[Evaluation of fetal breathing movements in prognosis of preterm labor]. / Ocena aktywnosci oddechowej plodu w prognozowaniu porodu przedwczesnego.

The relationship between fetal breathing activity and preterm labor among patients with signs of preterm labor has been analyzed. The assessment concerned pregnant women admitted to the hospital because of regular uterine contractions, uterine contractility and bleeding or premature rupture of membranes. It has been found the significant correlation between the absence of fetal breathing movements and preterm labor.

[Twin-to-twin transfusion syndrome--case report]. / Zespól transfuzji plodowo-plodowej--opis przypadku.

Authors described a case of twin-to-twin transfusion syndrome that did not comply with a classic definition of syndrome. It has been presented possibilities of ultrasound screening regarding to Doppler blood flow velocimetry. It has been also shown the usefulness of these methods in the monitoring and assessment of fetal status. This is an example of Doppler blood flow velocimetry applying that yields information concerning fetal condition. This method seems to be very useful in these situations when fetal heart rate monitoring is difficult or even inapplicable.

[Intrauterine therapy of obstructive uropathy--case report]. / Terapia wewnatrzmaciczna uropatii zaporowej--opis przypadku.

The use of vesicoamniotic shunt in the case of obstructive uropathy was described. On the base of ultrasound screening it has been diagnosed urethral obstruction. This abnormality of urinary tract was found in male fetus. It has been diagnosed the posterior urethral valve. Qualification to intrauterine therapy was based on normal parameters of renal function. Under ultrasound guidance the vesicoamniotic shunt was installed. The normal drenage was observed within 6 weeks, until it was dislocated. In 36th week of gestation the cesarean section was performed. The indications were signs of urethral obstruction. The boy was born in whom posterior urethral valves were recognized. He was born in good condition without any biochemical features of renal damage as well as signs of hypoplastic lung.

[Fetal pulse oximetry in second stage of labor]. / Zastosowanie pulsoksymetrii plodowej w II okresie porodu.

OBJECTIVE: To compare the mean values of fetal oxygen saturation with fetal heart rate pattern in the second stage of labor (Melchior classification) MATERIAL AND METHODS: The study included 30 parturients in gestational age 37-41 weeks. Fetal oxygen saturation was recorded and averaged over the last 30 min of the second stage of labor Simultaneously, fetal heart rate and uterine contractions were monitoring. Fetal heart rate patterns were assessed according to Melchior's classification. At birth, the cord acid-base parameter (pH) was calculated. RESULTS: The lowest value of fetal oxygen saturation over the last 30 min of labor was 10%, the highest 60%, and the mean value 39.1 +/- 12.5%. Statistically, significant correlation between the mean value of oxygen saturation over the last 30 min of labor and pH arterial values (n = 25, p = 0.004, r = 0.42) was found. There was no statistically significant correlation between fetal oxygen saturation and pH venous values (n = 24, p. = 0.006, r = 0.49), but trend towards significance could be observed. Statistical analysis revealed that arterial pH was significantly correlated to Melchior's classification. The lowest pH and FSpO2 values coexisted with type 3 and 4 of FHR patterns according to Melchior's classification. CONCLUSIONS: The mean values of fetal oxygen saturation over the last 30 min of labor significantly correlate with arterial pH values. These values correlate with FHR abnormalities according to Melchior's classification. Fetal pulse oximetry seems to be an important, additional method assessing fetal well-being in the second stage of labor.

[Spectral analysis of fetal heart rate variability]. / Analiza spektralna zmiennosci czynnosci serca plodu.

OBJECTIVE: To assess power spectral densities and power spectrum of FHR variability in two categories of fetal activity, quiescence and breathing movements, in pregnancies complicated by diabetes mellitus or intrauterine growth retardation. MATERIAL AND METHODS: The study group included 70 women, 35 in uncomplicated pregnancies and 35 with above-mentioned complications. The spectral analysis of FHR variability in fetal quiescence or breathing activity was performed. The power spectrum was analyzed at frequencies 0-1.0 Hz. Successively, the power spectral density was calculated. It has been presented the plots of spectral densities of beat-to-beat variabilities well during breathing episodes as "no breathing". Subsequently, the power spectra were calculated in both analyzed activities and groups. RESULTS: The highest values of power spectral densities (0.118 +/- 0.025) at 0.6-0.8 Hz were found in uncomplicated pregnancies. In pregnancies complicated by diabetes mellitus (0.048 +/- 0.049) or IUGR (0.042 +/- 0.041) these values were statistically significantly. At 0.6 Hz and 0.8 Hz power spectra of FHR variability were lower in quiescence comparing to breathing activity, as well in uncomplicated as complicated pregnancies. At these frequencies power spectra during breathing movements were significantly lower in complicated pregnancies comparing to uncomplicated. COMMENTS: The results of this study confirm the usefulness of spectral analysis in the assessment of FHR variability. The observed disturbances may reflect an abnormal fetal reactivity. The evaluation of breathing and cardiovascular systems interaction allows to study indirectly the central nervous system that coordinates both activities.

Ultrasound in the diagnosis of twin-to-twin transfusion syndrome--a preliminary report.

OBJECTIVE: The aim of this study was to show the diagnostic possibilities of ultrasound in twin-to-twin transfusion syndrome (TTTS), to demonstrate its usefulness in cases of hemoglobin difference < 5 g/dL in neonates as well as in cases complicated by intrauterine death of one or both twins. STUDY DESIGN: The study included 4 pairs of twins. In two cases 3 fetuses died in utero. In the other two the hemoglobin difference in newborn infants was < 5 g/dL. The ultrasound examination, evaluating the fetal anatomy and biometry, amniotic fluid volume, placentation, was performed. The special attention was paid to polyhydramnios/oligohydramnios, discordant fetal growth (fetal weight, abdominal circumference), the presence of fetal hydrops, ascites, pericardial effusion. Doppler blood flow velocimetry has been done in umbilical vessels, middle cerebral artery. The data was compared with normal reference values for singleton pregnancies. The waveforms from both uterine arteries were also evaluated to exclude placental insufficiency. Additionally the blood flow through the AV valves was measured to exclude or confirm its regurgitation. Postnatally the hemoglobin difference was evaluated if available and compared with sonographic findings. RESULTS: In all cases inter-twin difference in abdominal circumference was greater than 18 mm and inter-twin weight difference of more than 15%. We observed polyhydramnios/oligohydramnios in all twin pregnancies. It has been found decreased PI in middle cerebral artery in larger fetus (recipient) in all our cases (comparing to single pregnancy). PI values for this vessel in smaller fetuses were within normal range (for single pregnancy). PI values in umbilical arteries of recipients were abnormal (increased PI or absent end-diastolic flow). COMMENTS: The sonographic criteria seem to be very useful in diagnosis of twin-to-twin transfusion syndrome, especially in cases where the measurement of hemoglobin level is impossible. Doppler blood flow velocimetry in fetal vessels helps to explain the changes in fetal hemodynamics in TTTS.

[Predictive value of absent or reverse end-diastolic blood flow in the umbilical artery in the diagnosis of fetal distress]. / Wartosc prognostyczna zaniku lub odwrócenia koncowo-rozkurczowego przeplywu krwi w tetnicy pepowinowej w diagnostyce zagrozenia plodu.

To examine the significance of the absence of reverse of end-diastolic (ARED) velocity in umbilical artery, outcome of pregnancy in 24 women with this complication was evaluated. Acute or chronic hypoxia was evident in 87.5% fetuses with ARED. Such situation is a definable high-risk state that demands intensive surveillance.

[Phagocytosis and bactericidal capacity of polymorphonuclear neutrophils in neonates]. / Fagocytoza i zdolnosc bakteriobójcza granulocytów obojetnochlonnych noworodków.

Phagocytosis and bactericidal capacity of polymorphonuclear neutrophils (PMN) obtained from umbilical venous blood was estimated in 30 neonates and their mothers by the use of fluorochrome microassay of Pantazis and Kniker. Phagocytosis of Staphylococcus was similar in both groups and controls, while intracellular bacteria killing was significantly impaired in PMN obtained from the neonates. These results may indicate that increased susceptibility to infection observed in neonates may be partly caused by PMN function impairment.