Preeclampsia: What Does the Father Have to Do with It?

Preeclampsia (PE) is one of the leading causes of maternal and fetal morbidity and mortality, with incidence rates ranging between 2 and 5 % in the Western World. The exact causes of the disease remain largely unknown, because of the complex pathophysiologic mechanisms involved in the process. Genetic, environmental, and epigenetic parameters have been implicated by various authors as culprits for the pathogenesis of PE. Recent reports in the literature highlight the paternal role. Still, the exact extent and mechanism remain elusive. In this systematic review, we attempt to present data regarding the paternal role in a concise and comprehensive manner.

Homeopathy for infertility treatment: a case series.

Homeopathy has been used in the past for treating a broad aspect of diseases. In gynecology, its use remains limited. Taking under consideration its clinical aspects, the authors attempted to use it for treating female sub fertility problems. With this study, the authors present five cases of female infertility treated successfully with the use of homeopathic treatment in a large obstetrics-gynecology Hospital in Athens.

Corticotropin-releasing hormone and progesterone plasma levels association with the onset and progression of labor.

UNLABELLED: PURPOSE OF LNVESTIGATION: To examine the relationship between maternal plasma progesterone along with corticotropin- releasing hormone (CRH) plasma levels and the progression of labor. MATERIALS AND METHODS: Maternal serum CRH and progesterone were measured during the latent phase of labor, active labor, and 24 hours postpartum in women who went into spontaneous labor and delivered vaginally at term. Progesterone (P) levels in women delivered by an elective cesarean section at term were also measured as baseline. RESULTS: Mean maternal plasma P was 18% higher in the active phase than in the latent phase of labor (p < 0.01), and declined significantly by 24 hours postpartum (p < 0.001). Mean level of serum CRH was 24% higher in the active phase than in the latent phase of labor (p < 0.01), and subsequently declined significantly by 24 hours postpartum (p < 0.001). CONCLUSIONS: As labor progresses, P and CRH increase and subsequently decrease precipitously in the immediate postpartal period. P levels tend to drop in women who are in early labor compared with non-laboring full-term women.

Asynchronous delivery of twins and triplets with an interval period ranging from 48 hours to 19 weeks.

OBJECTIVE: To improve perinatal survival rates by prolonging the rest of the pregnancy after an abortion or extremely premature birth of one fetus in multiple pregnancies, especially in women with low fertility potential. METHODS: Following the expulsion of one fetus a cervical cerclage was applied to all patients. The placenta of the expelled fetus including a small portion of its cord after it was ligated close to the external os, was left in situ. The patients were invariably kept on bed rest until the pregnancy was completed under close observation, tocolysis and preventive antibiosis. After the 24th week of gestation corticosteroids were administered. RESULTS: The delivery interval achieved ranged between two and 135 days, the longest reported. Although the survival rate was relatively low (40%) all but one of the women (83%) managed eventually to have a live child, one with twins. CONCLUSIONS: In selected multiple pregnancies the attempt to prolong the rest or the pregnancy, following the abortion or the extremely premature birth of one fetus, seems efficacious and justified especially in women with a history of long-term infertility.

Uterine artery Doppler velocimetry with leiomyomas.

The study was conducted to establish a correlation between Doppler velocimetry in relation to uterine weight in any phase of the menstrual cycle and symptoms in women who have leiomyomas. Doppler velocimetry was carried out on both uterine arteries in 18 pre-menopausal women and one post-menopausal woman prior to undergoing abdominal hysterectomy at Winthrop University Hospital in Mineola, NY and at Ioannina University Hospital. The t-test was used for statistical analysis. Changes in flow velocity correlated directly with uterine size. When a division at 500 g was used, S/D ratio was 2.74 +/- 0.53 for larger uteri vs. 4.2 +/- 1.24 for smaller uteri, p < 0.006. Eight women presented heavy bleeding and the mean S/D ratio was 3.75 +/- 1.36 while eleven women presented mild bleeding and the mean S/D ratio was 3.51 +/- 1.2 (p > 0.5). Thus the study has demonstrated that in cases of uterine leiomyomas, the uterine artery flow increases although angiography had previously shown decreased vascularity within the tumor.

Comparison of somatomedin-C (SMC/IGF-I), human placental lactogen and Doppler velocimetry between appropriate and small-for-gestational-age pregnancies.

Thirty-two pregnant women with small-for-gestational-age (SGA) fetuses and 45 pregnant women with appropriate-for-gestional-age (AGA) fetuses (controls) were recruited after the 32nd week of gestation. Blood samples were collected for estimation of somatomedin-C (SMC/IGF-I) and hPL in the maternal serum and in the umbilical cord serum. The systolic/diastolic (S/D) ratio of the umbilical artery was also recorded. The results showed somatomedin-C and hPL levels in the maternal serum and in the umbilical cord to be significantly decreased and the Doppler S/D ratio to be significantly increased in the SGA group. In this group, using the multivariable regression analysis, we found significant correlations between maternal hPL, somatomedin-C, Doppler S/D ratio and birth weight.

Fetal heart rate patterns in pregnancies complicated by maternal diabetes.

OBJECTIVE: To compare the fetal heart rate (FHR) pattern between fetuses of well controlled diabetic and non diabetic mothers using a computerized analysis of FHR. STUDY DESIGN: Weekly fetal surveillance was performed in 99 fetuses of mothers with diabetes class A, 21 fetuses of mothers with diabetes class B-R, and 55 fetuses of non-diabetic women, starting at 30 weeks' gestation. All diabetic patients were well controlled. Fetal surveillance included a computerized analysis of the FHR, umbilical and uterine Doppler velocimetry, and a biophysical profile. Changes of FHR variation, frequency of FHR accelerations, and umbilical and uterine Doppler velocimetry were calculated using a regression analysis for each patient. The average slopes and the intercept at 30, 34, and 38 weeks' gestation of these variables were compared among the three groups. RESULTS: The slope of FHR variation and the frequency of accelerations had a lower rate of increase during the third trimester in fetuses of mothers with diabetes class A (0.84 +/- 0.25 ms/week and 0.06 +/- 0.02/20 min/week, respectively) compared with fetuses of non-diabetic mothers (1.34 +/- 0.55 ms/week and 0.5 +/- 0.1/20 min/week, respectively). In fetuses of mothers with diabetes class B-R, FHR variation did not change with gestation (-0.011 +/- 0.2 ms/week) with a small increase in the frequency of accelerations (0.02 +/- 0.004/20 min/week). While no differences were observed at 30 weeks' gestation, FHR variation and the frequency of accelerations were significantly reduced at 34 weeks' gestation in fetuses of mothers with diabetes class B-R compared with fetuses of non-diabetic mothers (P < 0.01). At 38 weeks' gestation, fetuses of mothers with diabetes class B-R and diabetes class A had both significantly reduced FHR variation as well as frequency of accelerations compared with fetuses of non-diabetic mothers (P < 0.01). The rate of decrease of the umbilical and uterine artery S/D ratios were similar among the three groups. CONCLUSIONS: The FHR pattern appears to be different in fetuses of well controlled diabetic mothers when related to fetuses of non-diabetic mothers. Disease specific standards should be considered for interpretation of FHR patterns in diabetic pregnancies.

Computerized analysis of fetal heart rate changes after antepartum external cephalic version.

OBJECTIVE: To assess the fetal heart rate (FHR) changes following external cephalic version using a computerized FHR monitor. STUDY DESIGN: We performed 116 external cephalic versions on 106 pregnant women at 36-40 weeks' gestation. Tocolysis (magnesium sulfate) was given to 39 patients (34%). Computerized FHR monitoring was performed for 20-30 minutes before and for 20-30 minutes after the procedure. In addition, we analyzed the results of the FHR tracing obtained during the first 10 minutes following the procedure. RESULTS: External cephalic version was successful in 40% of the patients. In the group of patients who were not treated with magnesium sulfate, FHR variation and the number of accelerations per 10 minutes were significantly reduced during the first 10 minutes following the procedure as compared with those factors on the FHR tracings obtained before or 20-30 minutes following the procedure (P < .05). In the group of patients who were treated with magnesium sulfate, FHR variation and the number of accelerations per 10 minutes were significantly reduced before and 10 minutes after the procedure as compared with the FHR tracings obtained 20-30 minutes following the procedure (P < .05). In both groups the basal FHR was significantly lower during the first 20-30 minutes following the procedure (P < .05). FHR decelerations were observed following the procedure in only two patients. None of the 106 fetuses had a low Apgar score or were admitted to the neonatal intensive care unit. CONCLUSION: External cephalic version appears to be safe for the mother and fetus, although transient FHR changes may occur following the procedure.

Doppler study of the fetal cardiac function in prolonged pregnancies.

OBJECTIVE: To evaluate the association between fetal cardiac function and amniotic fluid index (AFI) in postterm fetuses, and to determine if changes in fetal cardiac function precede the occurrence of nonreassuring intrapartum fetal heart rate (FHR) patterns. METHODS: Forty-five otherwise low-risk pregnant women between 41 and 43 weeks' gestation were studied longitudinally. Gestational age was confirmed in all patients by ultrasound before 20 weeks' gestation. Each subject had two or three tests performed every 3-4 days, including a non-stress test, a biophysical profile, and Doppler studies of the aortic and pulmonic outflow tracts. Aortic and pulmonic artery flow velocity waveforms were recorded slightly distal to the valves. Peak velocity, velocity time integral, and heart rate were calculated from the flow velocity waveforms we obtained. The change in AFI and aortic and pulmonic peak velocity and [velocity time integral] x [heart rate] were calculated for each fetus. RESULTS: Labor was induced at 42 weeks' gestation in 20 patients, and 17 entered labor spontaneously. Changes in AFI, observed during the follow-up period, correlated significantly with changes in aortic peak velocity (r = 0.54, P < .01) and with aortic outflow [velocity time integral] x [heart rate] (r = 0.60, P < .001) but not with pulmonic peak velocity and [velocity time integral] x [heart rate]. The decrease in aortic peak velocity and aortic and pulmonic [velocity time integral] x [heart rate] was significantly higher (P < .01) in eight fetuses that developed a nonreassuring intrapartum FHR (reduced FHR variability, late decelerations, and severe variable decelerations) than in those who had an uneventful labor. CONCLUSION: In prolonged pregnancies, cardiac function deteriorates in fetuses that develop a nonreassuring intrapartum FHR, and the changes in the left cardiac function correlate with changes in AFI.

Central and peripheral haemodynamic changes in post-term fetuses: correlation with oligohydramnios and abnormal fetal heart rate pattern.

OBJECTIVE: To assess the hypothesis that the occurrence of oligohydramnios and abnormal fetal heart rate (FHR) pattern in post-term fetuses is associated with impaired fetal cardiac function. DESIGN: A cross sectional study was performed on post-term and term fetuses. Fetal tests included a computerised analysis of the FHR, a biophysical profile and Doppler studies of the abdominal aorta, umbilical artery, middle cerebral artery and the fetal heart. Pulsatility index (PI) was calculated from the abdominal aorta, umbilical and middle cerebral artery flow velocity waveforms. Peak velocity, velocity time integral (VTI), E:A ratio, and heart rate (HR) were calculated from the flow velocity waveforms obtained from the aortic and pulmonic outflow, and from the mitral and tricuspid valves. SETTING: Maternal fetal laboratory, Department of Obstetrics. SAMPLE: One hundred and twenty post-term and 42 term fetuses. RESULTS: Only the tricuspid E:A ratio was significantly higher (P < 0.05) in post-term fetuses with a normal amniotic fluid index compared with term fetuses. Post-term fetuses with an abnormal amniotic fluid index had a significantly lower aortic peak velocity (P < 0.01), aortic VTI x HR (P < 0.01), and mitral VTI x HR (P < 0.05) compared with post-term fetuses with a normal amniotic fluid index or compared with term fetuses. Post-term fetuses with reduced FHR variation had a significantly lower aortic peak velocity (P < 0.01), pulmonic peak velocity (P < 0.05), aortic VTI x HR (P < 0.01), pulmonic VTI x HR (P < 0.05) and a significantly lower mitral VTI x HR (P < 0.05) when compared with post-term fetuses with normal FHR variation. Similar results were obtained in comparing fetuses with normal and adverse perinatal outcome. CONCLUSION: The occurrence of oligohydramnios and abnormal FHR pattern in post-term fetuses appears to be associated with impaired fetal cardiac function. This finding should allow further investigations of post-term fetuses.

Elevated umbilical erythropoietin levels during labor in newborns of smoking mothers.

Umbilical cord blood erythropoietin levels and hematocrit are significantly higher in smoking mothers than those nonsmoking ones. In addition, the incidence of newborns with low birthweight is higher in women who smoke. We conclude that in addition to other parameters, cord blood erythropoietin might be used as a valuable indicator of fetal distress in smokers.

Surveillance of growth-retarded fetuses with computerized fetal heart rate monitoring combined with Doppler velocimetry of the umbilical and uterine arteries.

OBJECTIVE: To define guidelines for surveillance of growth-retarded fetuses with a computerized fetal heart rate (FHR) monitor and Doppler device. STUDY DESIGN: Eighty-one growth-retarded fetuses with birth weights < 10th percentile and lacking major anomalies were studied. One hundred ninety-two tests (one to six per patient), including computerized FHR monitoring and Doppler studies of the umbilical and uterine arteries, were performed. The relationship between Doppler velocimetry or FHR variation and fetal outcome was examined. RESULTS: Fetuses with an abnormal FHR variation or abnormal Doppler velocimetry had a significantly higher rate of cesarean deliveries for fetal distress and a higher number of admissions to the neonatal intensive care unit (NICU) as compared with fetuses with normal results on both tests. The best distinction was noted when the growth-retarded fetuses were partitioned into four analytic groups based on the presence of normal or abnormal FHR variation or Doppler velocimetry. The group with the poorest results was composed of fetuses with abnormal umbilical flow velocity and reduced FHR variation. These fetuses had significantly lower birth weights (1,250 g) and significantly higher rates of cesarean deliveries for fetal distress (92%) and admission to the NICU (100%). Thirty percent of these fetuses died. CONCLUSION: Fetal surveillance with Doppler and computerized FHR monitoring allows better understanding of the management of fetuses that are small for gestational age.

Successful pregnancy after treatment of cervical pregnancy with methotrexate and curettage. A case report.

Cervical pregnancy was diagnosed in a nulliparous, 28-year-old woman who presented with intermittent vaginal spotting at 12 weeks of gestation. Sonographic evaluation revealed a cervical gestational sac with a fetus with cardiac activity. Methotrexate was instilled intraamniotically, followed by an intramuscular injection with folinic acid rescue. On the seventh day of treatment an uneventful curettage was performed because of persistent fetal viability. Five months later pregnancy occurred. The patient vaginally delivered a healthy, 3,080-g neonate at 40 weeks of gestation. To our knowledge, only nine other cervical pregnancies have been managed medically with either methotrexate or etoposide. It seems that first-trimester cervical pregnancies, especially those at less than nine weeks of gestation, can be effectively treated with methotrexate. Successful medical therapy must be considered, not only for regression of the gestation but also for preservation of anatomic integrity and fertility. Four of the above patients, including ours, had a subsequent intrauterine pregnancy, and one of those pregnancies terminated in spontaneous abortion.

Corpus luteum blood flow in normal and abnormal early pregnancy: evaluation with transvaginal color and pulsed Doppler sonography.

One hundred and thirteen (66.5%) women in this study had a normal intrauterine pregnancy with ages ranging 6 to 12 weeks of gestation. Fifty-seven (33.5%) patients were admitted to the hospital owing to clinically suspected abnormal early pregnancy. Dilatation and curettage were done on all women and tissue sample sent to the pathologist for a final diagnostic. Diagnosis of ectopic pregnancy was made on laparoscopy. Both ovaries were examined carefully by color Doppler in sonography in all patients. Color flow was used as a guide for pulsed Doppler exploration. Corpus luteum blood flow was defined as random, usually semilunar in appearance, dispersed vessels with very low impedance to blood flow. The resistive index and pulsatility index were calculated. Overall detection rate of corpus luteum blood flow in normal pregnancies was higher for the left ovary (62.6%) than for the right ovary (37.4%) (P < 0.01). The mean resistive and pulsatility indices from corpus luteum blood flow were not influenced by gestational age in normal pregnancy. The overall mean value for for resistive index was 0.452 +/- 0.04 and for pulsatility index 0.636 +/- 0.09. The overall detection rate of corpus luteum in abnormal pregnancies also was higher for the left ovary (56.7%) than for the right ovary (43.4%) (P < 0.01). The mean resistive indices from corpus luteum blood flow in patients with missed abortion was higher than in women with normal pregnancy (P < 0.01). Both resistive and pulsatility indices were higher in patients with incomplete or threatened abortion in comparison with normal pregnancy (P < 0.01). No statistically significant difference was seen in the case of anembryonic, molar, or ectopic pregnancy.

Doppler velocimetry. Where does it belong in evaluation of fetal status?

Doppler velocimetry is very useful as an antepartum surveillance tool that is able to detect pathologies of the fetus and predict the development of acidosis and hypoxia. Appropriate use can help us to decrease the mortality and morbidity in identifying earlier compromised fetuses.

Erythropoietin umbilical serum levels during labor in women with preeclampsia, diabetes, and preterm labor.

In this study we determine the erythropoietin levels and hematocrit in 22 women with preterm labor, 21 with insulin-dependent diabetes, 22 with preeclampsia, and 20 with normal gestation. The erythropoietin level was higher in the preeclamptic group than in the diabetic group compared with the normal and premature groups. There were no hypoxic fetuses. From this study, we found that the mechanism of increased erythropoietin levels in neonates can be different from fetal hypoxia. Further studies are needed on this subject.

Computerized analysis of fetal heart rate variation in postterm pregnancy: prediction of intrapartum fetal distress and fetal acidosis.

OBJECTIVE: Our purpose was to evaluate whether computerized analysis of fetal heart rate variation may improve fetal surveillance in postterm pregnancy. STUDY DESIGN: Three hundred thirty-seven pregnant women who were delivered after 41 weeks' gestation and who had 610 antenatal tests were included in this study. Fetal tests included a nonstress test with a computerized analysis of the fetal heart rate, Doppler examination of the umbilical artery, and a biophysical profile, performed every 2 to 4 days. Induction of labor was performed when the fetal heart rate variation was reduced (< 30 msec), when fetal heart rate decelerations appeared, or when the amniotic fluid index was < or = 5. The results of the fetal surveillance tests were compared with the results of the intrapartum fetal heart rate monitoring and with the metabolic status of the babies at delivery. Sensitivity and specificity of the various tests in predicting intrapartum fetal distress and acidosis at delivery were described by means of the receiver-operator characteristic curve. RESULTS: Ten of 12 fetuses with reduced fetal heart rate variation had a trial of labor. Nine of these 10 fetuses had fetal distress during labor. Seven of the 12 fetuses with reduced fetal heart rate variation were acidotic at delivery (umbilical artery pH < 7.2). Overall, there were 10 acidotic fetuses at delivery in the study group. Only two of them had an umbilical systolic/diastolic ratio > 95th percentile, three had an amniotic fluid index < or = 5, and five had fetal heart rate decelerations before labor. Fetuses who demonstrated an abnormal intrapartum fetal heart rate tracing or who were acidotic at delivery had a significantly higher rate of reduced fetal heart rate variation or decelerations before labor. The largest area under the receiver-operator curve curve for predicting fetal acidosis at delivery or fetal distress during labor was achieved by means of computerized analysis of fetal heart rate variation. CONCLUSION: A computerized numeric analysis of fetal heart rate variation may improve fetal surveillance in postterm pregnancy.

Prevalence in a volunteer population of pelvic cancer detected with transvaginal ultrasound and color flow Doppler.

Our objective was to find the prevalence of non-symptomatic endometrial and ovarian neoplasms in a volunteer population of women, aged 40 and over. We offered a free volunteer screening program to asymptomatic women for a study using transvaginal ultrasound and color flow Doppler for the detection of pelvic cancer. In the first 2 years, 2117 women were examined, 51.3% post-menopausal. An ovarian cyst was defined as having a maximum diameter of more than 2.4 cm. Color flow was used to identify blood vessels feeding pelvic organs and adnexal enlargements. An abnormal Doppler flow velocity for the ovary was defined as a resistance index of less than 0.41. Ovarian cysts of less than 5 cm with normal Doppler indices were followed up in 6 months to 1 year. An adnexal morphology score was created to quantify the usefulness of this parameter, particularly in postmenopausal women. Indications for surgery were pre-defined as a persistent ovarian cyst of more than 5 cm, a persistent suspicious Doppler and a total endometrial thickness of greater than 0.59 cm in postmenopausal women not taking hormones.A total of 202 women (9.5%) had ovarian cysts. Fourteen women were operated upon because of size criteria, one because of family history and three for persistent abnormal flow. By Doppler study, 15 cysts were predicted to be benign and histology was confirmatory. There were two false positives and one true positive, a stage Ib ovarian cancer. There were no false negatives, although a stage I endometrioid cancer of the ovary was detected 8 months after a negative scan. In those cases in which follow-up data were available, 56% of the cysts regressed in premenopausal women. In postmenopausal women, 28% regressed. Twenty of 1086 postmenopausal women had endometrial biopsies. Three had endometrial cancer, two stage I and one stage IIA. Five had atypical or adenomatous hyperplasia, and seven had benign polyps. So many women have small asymptomatic cysts of the ovary that a major reorientation of physicians' attitudes towards the ovary will have to be introduced to adapt to this new information. In this population, the prevalence of benign epithelial ovarian neoplasms was 7/1000, and of malignancy was 05/1000. In postmenopausal women, the prevalence rate for endometrial cancer was 5/1000, with 5/1000 hyperplasias and 7/1000 benign polyps. When endometrial and ovarian cancer screening are combined, the yield is comparable to that seen in breast and cervical cancer screening.

Central and peripheral hemodynamic changes in fetuses with absent end-diastolic velocity in umbilical artery: correlation with computerized fetal heart rate pattern.

OBJECTIVES: Our purpose was to study hemodynamic changes in peripheral and central blood vessels and to correlate these changes with the computerized fetal heart rate pattern in fetuses with absent end-diastolic velocity in the umbilical artery. STUDY DESIGN: Doppler studies of the umbilical artery, the middle cerebral artery, and aortic and pulmonic outflow, together with computerized fetal heart rate monitoring, were performed every 2 to 4 days until delivery in 13 fetuses with absent end-diastolic velocity in the umbilical artery. The pulsatility index was calculated from the flow velocity waveforms obtained from the umbilical and middle cerebral arteries. The velocity time integral (an index of cardiac output) and the heart rate were calculated from the flow velocity waveforms obtained from the aortic and pulmonic outflow. RESULTS: Two fetuses were delivered immediately after the first examination because of repetitive fetal heart rate decelerations. One fetus was excluded from the study because of major malformations. Ten had three to eight tests each. Six had a biphasic change of the middle cerebral artery, which consisted of a decrease (p < 0.001) followed by an increase in the pulsatility index (p < 0.05). When the middle cerebral artery lost its vasodilation, there was an increase in the middle cerebral artery/umbilical artery pulsatility index ratio (p < 0.05). Left cardiac output decreased (p < 0.05), resulting in an increase in the pulmonary/aortic velocity time integral x heart rate ratio (p < 0.05). Reduced fetal heart rate variation (< 30 msec) developed in all six fetuses, and they were delivered because of repetitive fetal heart rate decelerations. Four fetuses with only a decrease in the middle cerebral artery pulsatility index did not have reduced fetal heart rate variation or decelerations, the aortic velocity time integral x heart rate didn't decrease, and the pulmonic/aortic velocity time integral x heart rate ratio didn't increase. These fetuses were delivered for reasons other than fetal distress. The middle cerebral artery pulsatility index correlated with the aortic velocity time integral x heart rate (r = -0.53, p < 0.0001), and the middle cerebral artery/umbilical artery pulsatility index correlated with the pulmonic/aortic velocity time integral x heart rate (r = 0.56, p < 0.0001). CONCLUSION: Abnormal fetal heart rate patterns occur in fetuses with absent end-diastolic velocity in the umbilical artery when the middle cerebral artery begins to lose its compensatory maximal dilation. The increase in the middle cerebral artery pulsatility index is associated with a significant reduction in left ventricular output without significant changes in right ventricular function. Thus it appears that a loss of autonomic reactivity occurs in the brain first and is followed within a few days by a similar response in the heart, as shown by the decreased fetal heart rate variation.