Twin pregnancy in a woman on long-term epoprostenol therapy for primary pulmonary hypertension. A case report.

BACKGROUND: Pregnancy associated with primary pulmonary hypertension is an uncommon observation, with maternal mortality > 50%. Experience treating this condition is limited. Past reports have emphasized the need for pregnancy termination. In the last few years there has been considerable interest in long-term intravenous use of epoprostenol (prostacyclin) in patients with primary pulmonary hypertension. CASE: A woman with severe primary pulmonary hypertension who was on long-term epoprostenol therapy became pregnant with twins and was treated with high doses of epoprostenol and nitric oxide during delivery and the postpartum period. She was well six months later on continuous epoprostenol therapy. The one viable infant was alive and still hospitalized at this writing. CONCLUSION: Epoprostenol therapy may be continued during pregnancy in patients with severe primary pulmonary hypertension for long-term pulmonary vasodilatation.

Patterns of fetal perinasal fluid flow in cases of congenital diaphragmatic hernia.

OBJECTIVE(S): Our purpose was to expand the previous reported series of observations of fetal perinasal fluid flow in cases of antenatally diagnosed congenital diaphragmatic hernia, characterize the timing parameters of the fetal breath cycle, and define the relationship of fetal perinasal fluid flow and the diaphragmatic component of fetal breathing movements. Our hypothesis was that characteristics of diaphragm-related and nondiaphragm-related perinasal fluid flow and other breath cycle characteristics differ in cases of congenital diaphragmatic hernia compared with controls. STUDY DESIGN: Fetal perinasal fluid flow velocity and fetal chest wall movements were studied in 24 cases of uncomplicated pregnancy, and flow was studied in 24 cases of antenatally diagnosed congenital diaphragmatic hernia at gestational ages ranging from 30 to 41 weeks. The examination of fetal perinasal fluid flow velocity was performed with use of an ultrasonography system applying color flow and spectral Doppler analysis. Breath-to-breath interval, time of inspiration, time of expiration, and peak inspiratory and expiratory velocities were determined for each type of perinasal flow. RESULTS: The study revealed that the time of expiration in cases of congenital diaphragmatic hernia at 30 to 36 and 37 to 41 weeks of gestation was significantly shorter than in cases of uncomplicated pregnancy. The ratio of time of inspiration and breath-to-breath interval in cases of diaphragmatic hernia was approximately 30% higher (p = 0.001) at 30 to 36 weeks of gestation than in cases of uncomplicated pregnancy. The study also showed that in cases of congenital diaphragmatic hernia the expiratory peak velocity ratio at 30 to 36 weeks of gestation was significantly lower than in cases of uncomplicated pregnancy. CONCLUSIONS: We conclude that by Doppler ultrasonography measurements of fetal perinasal fluid flow, in cases of congenital diaphragmatic hernia, we can evaluate the timing parameters of fetal diaphragm-related breath cycles, the relationship of intraalveolar and intraamniotic pressures, and fetal upper respiratory tract resistance. Fetuses with diaphragmatic hernia spent significantly more time with diaphragm-nonrelated perinasal flow than did fetuses in cases of uncomplicated pregnancy, which can cause the increased loss of lung liquid and consequently be associated with pulmonary insufficiency in the early neonatal period.

Patterns of perinasal fluid flow and contractions of the diaphragm in the human fetus.

Our aim was to identify patterns of fetal perinasal fluid flow, and to determine the relationship of pattern of flow to the diaphragmatic component of fetal breathing movements. Twenty-four fetuses were studied with the use of two ultrasound systems simultaneously. Continuous video-tape records of the color and spectral Doppler imaging of fluid flow velocity in the nose and of the movements of the fetal diaphragm were made on two video recorders during 30-min study sessions. Two different patterns of fetal perinasal flow were recognized. One type had a rapid rate and low amplitude, and was independent of ultrasonographically observed movements of the fetal diaphragm. The other type had a lower rate and higher amplitude, and was uniformly related to diaphragmatic contractions. The breath-to-breath interval, time of inspiration, time of expiration and peak inspiratory and expiratory velocities were determined for each type of perinasal flow. Two ratios were used to quantify the change of peak flow velocity. There were significant differences in the values of all timing parameters between diaphragm-related perinasal flow velocities and those not related to the diaphragm, at both 30-36 and 37-41 weeks of gestation. The rate of perinasal flow related to diaphragmatic contraction cycles was one-third that of the flow cycles not related to diaphragmatic contraction (approximately 50 vs. 148 cycles/min). For both patterns of perinasal flow velocity, the expiratory peak velocity ratio was about 1.6 times higher than the inspiratory peak velocity ratio. We conclude that, in uncomplicated pregnancy, one pattern of fetal perinasal fluid flow reflects activity of the diaphragm. We speculate that the contractions of the fetal airway smooth muscle or oropharyngeal-laryngeal muscle groups are the origin of the second pattern of perinasal flow.

Doppler ultrasound characteristics of fetal nasal flow in pregnancies complicated by diabetes mellitus.

The purpose of our study was to determine the Doppler ultrasound characteristics of fetal breathing-related nasal fluid flow velocity in pregnancies complicated by diabetes mellitus and to examine any changes in the timing parameters of fetal breath cycle relative to maternal blood glucose level. Fetal nasal fluid flow velocity was studied in 67 women at 30-41 weeks of gestation. In 37 cases, the pregnancy was uncomplicated; in 13 cases, the pregnancy was complicated by type I diabetes mellitus; and in 17 cases, the pregnancy was complicated by gestational diabetes. At the examination, subjects with diabetes mellitus were grouped by glucose control (normoglycemic and hyperglycemic) and by gestational age: 30-36 weeks and 37-41 weeks. Maternal hyperglycemia was defined as a plasma glucose value ranging from 140 to 205 mg per 100 ml. A continuous videotape record of the spectral Doppler imaging of fluid flow velocity in the nose was made during each study session. Based on a sample of 25 consecutive fetal breaths, the timing components of breath cycles were determined: time of inspiration (Ti), time of expiration (Te), breath-to-breath interval (Ttotal), and ratio of Ti and Te (Ti/Te). There was a statistically significant difference between the Ttotal (msec) at 30-36 weeks' gestation in the cases of diabetes mellitus with maternal normoglycemia (1,050 +/- 68 SEM) and uncomplicated pregnancy with maternal normal carbohydrate intolerance (1,221 +/- 52). There was a similar difference in the values of Te (552 +/- 37 and 660 +/- 29, respectively) at 30-36 weeks. In cases of maternal hyperglycemia at 30-36 weeks' gestation, the value of Te (689 +/- 84) was significantly higher than in cases of normoglycemia (552 +/- 37). At 37-41 weeks' gestation, only the fetal Ti/Te ratio in normoglycemic diabetic patients was significantly lower than in an uncomplicated pregnancy. No differences were found in the other timing parameters at this gestational age group in cases of diabetes mellitus relative to maternal blood glucose level. No relationship was found between the value of maternal blood glucose and either fetal Ttotal (r2 = 0.003), or Ti/Te ratio (r2 = 0.0001) in cases of diabetes mellitus. Expiratory phase of fetal breath cycle even in well-controlled normoglycemic diabetic women, is significantly shorter than in uncomplicated pregnancies before 37 weeks of gestation. Maternal hyperglycemia in these cases prolonged the duration of expiratory phase of fetal breath cycle and significantly decreased the Ti/Te ratio more than 15% at 30-36 weeks of gestation. It is suggested that blood glucose level is involved in the regulation of fetal respiratory center in pregnancies complicated by diabetes mellitus.

Fetal breathing characteristics and postnatal outcome in cases of congenital diaphragmatic hernia.

OBJECTIVE: Our purpose was to determine characteristics of fetal breathing activity by recording fetal nasal fluid flow velocity in cases of congenital diaphragmatic hernia. STUDY DESIGN: Fetal breathing-related nasal fluid flow was studied in 47 patients at 34 to 41 weeks of gestation, 16 cases of antenatally diagnosed congenital diaphragmatic hernia and 31 cases of uncomplicated pregnancy. The examination was performed by ultrasonography combined with color-flow and spectral Doppler analysis. An average of 25 breath cycles from each case was determined for each of the following timing parameters: breath-to-breath interval, time of inspiration, time of expiration, and ratio of time of inspiration and time of expiration. RESULTS: In all cases with uncomplicated pregnancy fetal breathing-related nasal fluid flow was seen at the level of the nose, and the timing components of this flow were determined as control values. In two cases with diaphragmatic hernia no perinasal flow was demonstrated, although fetal breathing movements observed as chest wall movements were present. The other 14 cases with congenital diaphragmatic hernia who demonstrated perinasal flow had the following postnatal outcome: one stillbirth, five neonatal deaths (group I), and eight survived and were discharged (group II). The study revealed that the time of expiration (in milliseconds) in group II (493.2 +/- 34.3 SEM) was significantly (p = 0.0030) shorter than in group I (653.4 +/- 38.4) and in cases of uncomplicated pregnancy (633.6 +/- 18.5). The value of the time of inspiration/time of expiration ratio in group II was approximately 15% higher than in group I and approximately 30% higher than in cases of uncomplicated pregnancies. CONCLUSIONS: Observation of fetal breathing-related nasal fluid flow velocity in cases of antenatally diagnosed congenital diaphragmatic hernia provides a rationale for the hypothesis that time of expiration and the time of inspiration/time of expiration ratio may be useful in the prediction of postnatal outcome. We speculate that the changes in the group of survivors may represent a compensatory phenomenon by causing intermittent changes in the volume of fluid within the lungs.

Ultrasound prediction of fetal pulmonary hypoplasia in pregnancies complicated by oligohydramnios and in cases of congenital diaphragmatic hernia: a review.

The objective of this review is to discuss the current knowledge of fetal pulmonary hypoplasia and to summarize the clinical significance of the many ultrasound methods for predicting pulmonary hypoplasia in pregnancies complicated by oligohydramnios due to spontaneous rupture of the fetal membranes and in cases complicated by fetal congenital diaphragmatic hernia. We concluded that the presence or absence of polyhydramnios, fetal breathing movements, mediastinal shift, thoracic position of the stomach, fetal breathing-related nasal and oropharyngeal fluid flow, ductal flow velocity modulation, and gestational age at onset and severity of ventricular disproportion as useful markers for predicting fetal pulmonary hypoplasia is a productive area for continued research. All studies show that there is a clear association between most of these markers and pulmonary hypoplasia. However, these markers have not been studied together in a large number of cases, and comparisons between each of the markers is unknown.

Fetal movement in response to vibroacoustic stimulation: a review.

Fetal movement in response to vibroacoustic stimulation (VAST) depends on functional maturation of the fetal central nervous system and related to changes in fetal behavior. Researchers have associated the presence of fetal movement with fetal well-being. Use of the maternal perception of sound-provoked fetal movement as a test for predicting fetal health is questionable and may suggest further research. All studies show that there is a clear association between this test and favorable neonatal outcomes. This test is inexpensive and easily obtainable. However, because the test has not been studied on large numbers of patients and maternal reporting at times is biased, its adaptation for clinical use should cautiously wait for clear theoretical advantages.

Fetal breathing-related nasal fluid flow velocity in uncomplicated pregnancies.

OBJECTIVE: Our purpose was to determine the Doppler ultrasonographic characteristics of fetal breathing-related nasal fluid flow velocity in uncomplicated pregnancies. STUDY DESIGN: Fetal nasal flow velocity was studied in 52 uncomplicated pregnancies at gestational ages ranging from 22 to 41 weeks. The evaluation of fetal breathing-related nasal fluid flow velocity was performed with ultrasonography combined with color flow and spectral Doppler analysis. RESULTS: The study revealed that the breath-to-breath interval and duration of the inspiratory phase of the fetal breathing-related nasal flow increased from 22 to 35 weeks and decreased thereafter. The breath-to-breath interval (milliseconds) at 33 to 35 weeks (1203.9 +/- 295.7 SD) was approximately twice what it was in the earliest age group (22 to 25 weeks); subsequently it decreased by approximately 25% in the term group (38 to 41 weeks). A positive correlation existed between the mean breathing-related nasal peak inspiratory flow velocity and advancing gestational age (r = 0.56, p = 0.0008), and between the inspiratory flow velocity acceleration and advancing gestational age (r = 0.53, p = 0.0076). CONCLUSION: Changes in fetal breathing activity during uncomplicated pregnancies can be determined by measurement of fetal breathing-related nasal fluid flow velocity. Our observations in uncomplicated pregnancies may be useful in future studies of these parameters in complicated pregnancies such as those at risk for pulmonary hypoplasia.

Fetal upper respiratory tract function in cases of antenatally diagnosed congenital diaphragmatic hernia: preliminary observations.

Fetal upper respiratory tract function was studied in five cases of antenatally diagnosed congenital diaphragmatic hernia and in 16 cases of uncomplicated pregnancy at gestational ages ranging from 27 to 38 weeks. The evaluation of fetal upper respiratory tract function was performed using ultrasonography combined with color-flow and spectral Doppler analysis. In all cases with uncomplicated pregnancy, fetal breathing-related nasal and oropharyngeal fluid flow was seen at the level of the nose. The five cases with congenital diaphragmatic hernia all demonstrated fetal breathing activity by thoracic wall movement. In four of the fetuses, perinasal fluid flow was seen by the Doppler technique. The fetus with no demonstrated perinasal flow during breathing movements died in the early neonatal period and had pulmonary hypoplasia. Observation of the fetal breathing-related nasal and oropharyngeal fluid flow in cases of antenatally diagnosed congenital diaphragmatic hernia provides a rationale to hypothesize that the absence of this phenomenon is a useful marker for prenatal prediction of pulmonary hypoplasia.

[Characteristics of the renin-aldosterone system of the fetoplacental complex in fetal erythroblastosis]. / Osobennosti renin-al'dosteronovoi sistemy plodovo-platsentarnogo kompleksa pri gemoliticheskoi bolezni ploda.

Renin activity and aldosterone concentrations have been determined in amniocentesis samples and fetal plasma obtained by intrauterine umbilical vein puncture in 23 women at 25 to 34 weeks' gestation, normal or complicated by hemolytic disease of the fetus. Prior to the intrauterine interventions, Doppler studies of umbilical arterial circulation were done and 1-hour fetal diuresis was measured. Fetal plasma pH and fetoplacental flood volume were determined. Hemolytic disease was shown to increase renin activity and aldosterone concentration in the amniotic fluid and fetal plasma in parallel with reduction in the fetoplacental blood flow and 1-hour fetal diuresis, increase in vascular resistance of fetal placenta and hypoxia. The increase in renin-aldosterone activity of the fetoplacental unit may be a compensatory fetal and chorionic response to hemodynamic and water-mineral balance in the presence of impaired uteroplacental circulation.

[Nature and mechanism of hemodynamic changes in fetuses of mothers with various types of diabetes mellitus]. / Kharakter i mekhanizm izmenenii gemodinamiki u plodov pri razlichnykh tipakh sakharnogo diabeta u materei.

Doppler echocardiography of flow in the fetal aorta and the umbilical artery as well as fetal echocardiography performed in 61 pregnant females with diabetes mellitus revealed central intracardiac hemodynamic alterations as risk factors for the development of "diabetic" heart failure in newborns. Pregnancy--associated diabetes patients and females with diabetes of type I demonstrated a somewhat decrease in the fetal myocardial contractility which was evidently determined by metabolic alterations in the myocardium, macrosomia and disorders in the fetoplacental circulation.