Estradiol and hemodynamics during ovulation induction.

Left ventricular size and stroke volume increase in human pregnancy and during estrogen administration in laboratory animals. In order to determine if elevated levels of endogenous estrogens in humans produce hemodynamic changes similar to those that occur during pregnancy, 14 patients were studied during ovulation induction at day 8 +/- 2 (SD) (proliferative phase) and at day 14 +/- 4 (midcycle) of their cycles. M-mode echocardiography was carried out with the patient in the left lateral decubitus, head down and head up positions. The mean serum estradiol level was 294 +/- 234 (SD) pg ml-1 at day 8 +/- 2 (treatment day) and it increased to 1503 +/- 531 pg ml-1 at day 14 +/- 4 (cycle day) of the same cycle. This change in serum estradiol was significant (P less than 0.001), associated with an increase in left ventricle diastolic dimension of 2.3 +/- 1.1 mm (P less than 0.001). During the same time period stroke volume and cardiac index correspondingly increased. Heart rate, fractional shortening, and blood pressure did not change and systemic vascular resistance decreased. Many of the cardiovascular adaptations of pregnancy are duplicated by high levels of endogenous estrogens and these changes are evident in as few as 6 days. Thus, we conclude that changes in endogenous estrogen correlate with certain cardiovascular parameters, the most striking of which is the left ventricular size. This may be one of the adaptive mechanisms by which the maternal circulation adapts to pregnancy.

Unbalanced mosaic karyotypes with different structural abnormalities involving a common chromosome region: report of two cases.

We report on 2 cases with different de novo unbalanced mosaic karyotypes in which each cell line had a different structural abnormality involving a common chromosome region: 46,XX,del(11)(q23.3)/46,XX.-11, + der(11)t(11;?)(q23.3;?) and 46,X,idic(Xq)/46,X,idic(Xq),-12, + der(12)t(X;12)(p11.2;p13.3). Molecular-cytogenetic analysis confirmed the origin of the derivative 12 chromosome in the latter. We present a literature review of reports with mosaic cell lines of structural chromosome abnormalities that share the same chromosome breakpoint.

Chronic granulomatous disease in pregnancy.

The ability of phagocytes to kill certain bacteria is impaired in chronic granulomatous disease. This results in frequent infection in the childhood period and frequent death in the early teens. Survival beyond this period is rare and often occurs in patients who have a mild variant of the disease. Reported herein is the obstetric course of a patient with chronic granulomatous disease.

Fetal echocardiographic signs of congenital endocardial fibroelastosis.

Endocardial fibroelastosis is characterized by a porcelain-like thickening of the endocardium, resulting in a marked increase in echodensity of the endocardium, as well as ventricular dilatation and aortic atresia. With improvement in prenatal ultrasound, this condition can be suspected in utero on the basis of ventricular enlargement, poor ventricular contractility, and marked echodensity of the endocardial surface. We present two cases in which such conditions were found on prenatal M-mode echocardiography and two-dimensional directed pulsed Doppler. Ventriculomegaly and hypocontractility of the ventricle are, however, nonspecific for such conditions; the diagnosis can be made accurately only by pathology. When such findings appear on ultrasound, all efforts should be made to deliver the patient in a perinatal center for optimal neonatal surgery to improve the survival of the newborn.

Ethical dilemmas in fetal echocardiography.

Recent technology permits detection of congenital heart diseases as early as the 17th or 18th week of gestation. These detectable defects include hypoplastic left heart syndrome, Ebstein anomaly, and atrioventricular canal malformation. Surgical treatments for these problems raise ethical as well as medical questions regarding patients whose prenatal diagnosis reveals congenital heart disease. We report six cases of in utero diagnosis of hypoplastic left heart syndrome and other complex congenital heart anomalies. Empirical factors relevant to our management were gestational age, severity of the anomaly, degree of certainty of diagnosis and prognosis, possibilities for treatment, and parental wishes regarding the fetus or newborn. Each of these factors was examined in the context of the reported cases and correlated with ethical principles applicable to obstetrics and neonatology: 1) respect for parental autonomy, 2) promotion of the infant's welfare, and 3) fairness in distributing scarce medical resources. We maintain that the first two principles are paramount in ethical decisions regarding individual patients, while the third is foremost in policy decisions affecting others as well.

Maternal left ventricular dimension in pregnancies complicated by fetal growth retardation.

Previous studies using two-dimensional chest radiographs have found a significant correlation between prematurity, fetal growth retardation, and the size of the maternal heart. Accordingly, we evaluated maternal left ventricular size and function by M-mode echocardiography near the end of gestation in 42 women with suspected fetal growth retardation and in 79 women whose pregnancies were normal. No significant differences were found between the two groups, implying that maternal left ventricular size and function is adequate in pregnancies complicated by "idiopathic" fetal growth retardation.

Human umbilical artery flow velocity waveforms before and after regional anesthesia for cesarean section.

The umbilical artery waveform was assessed in 18 normal nonlaboring patients before and after full surgical epidural anesthesia for repeat cesarean section. Using range-gated pulsed Doppler ultrasound, we found that the waveform analysis of the umbilical artery close to its placental insertion did not change significantly. These results suggest that no deleterious effect on fetoplacental circulation occurs with this form of anesthesia as long as maternal blood pressure is normal.

Interventricular septal thickness in fetuses of diabetic mothers.

Sixty-four diabetic women had their fetuses studied by M-mode echocardiogram between 20-41 weeks of gestation. The mean septal size during both diastole and systole increased in a linear fashion with advancing gestational age in both the normal and diabetic groups. Ventricular septal hypertrophy (ie, more than 2 standard deviations above the normal mean) was present in 48 of 64 (75%) of the fetuses of diabetic women. The ratio of septal size to the anteroposterior cardiac dimension was significantly greater in the diabetic than in the normal group (12 versus 8%; P less than .05). The anteroposterior cardiac dimension indexed to the estimated fetal weight was also greater in the diabetic group. Because both septum and cardiac dimension are larger with maternal diabetes, there may be a specific diabetic cardiomyopathy that originates in utero.

Effect of maternal carbon dioxide inhalation on human fetal breathing movements in term and preterm labor.

Induced maternal hypercapnia is a potent stimulus to fetal breathing movements in nonlaboring pregnant women. To determine the effect of maternal CO2 administration on fetal breathing movements during spontaneous labor, 14 healthy pregnant volunteers at term and 34 in preterm labor were recruited. If fetal breathing movements were markedly decreased or absent, the subjects were administered a prepared gas mixture of 3% CO2 in air. In term labor and in true preterm labor, fetal breathing movements were markedly decreased and could not be induced by maternal hypercapnia. Among women with suspected preterm labor, initial absence of fetal breathing movements and failure to evoke this response by maternal hypercapnia predicted delivery within 48 hours with a sensitivity of 80% and specificity of 95.5%. Induced maternal hypercapnia fails to stimulate fetal breathing movements in true term and preterm labor and may assist in distinguishing between true and false preterm labor.

Umbilical artery waveform during bicycle exercise in normal pregnancy.

Eighteen healthy pregnant women in the last half of gestation exercised to 85% of their predicted maximum heart rate on a bicycle ergometer. Pulsed Doppler flow studies before the exercise and during the recovery period were taken close to the umbilical artery's placental insertion site. The systolic-to-diastolic ratio (S/D) of the umbilical artery waveform did not change significantly during the period of observation. In three women, however, a significant increase in the S/D ratio occurred in the first few minutes post-exercise; this was due to a transient fetal bradycardia. In one woman, the S/D ratio remained high despite return of a normal fetal heart rate.

Chlamydia in pregnancy: a randomized trial of azithromycin and erythromycin.

OBJECTIVE: To determine side effect profiles and cure rates of azithromycin compared with erythromycin in the treatment of chlamydial cervicitis complicating pregnancy. METHODS: Pregnant patients with positive DNA antigen assays for Chlamydia trachomatis were randomized to either azithromycin, 1 g oral slurry in a single dose, or erythromycin, 500 mg every 6 hours for 7 days. Repeat assays were planned for 3 weeks after therapy. Side effects, compliance, and treatment efficacy were assessed. RESULTS: One hundred six women were enrolled, and eighty-five women completed the protocol. Significantly fewer gastrointestinal side effects were noted in the azithromycin group than in the erythromycin group (11.9% versus 58.1%, P < or = .01). Enhanced compliance was noted with azithromycin, because it was given in a single observed dose. Similar treatment efficacy was noted between azithromycin and erythromycin (88.1% versus 93.0%, P > .05). CONCLUSION: Compared with erythromycin, azithromycin is associated with significantly fewer gastrointestinal side effects in pregnancy. This association, along with the ease of administration and similar efficacy, suggests that azithromycin should be considered for the initial treatment of chlamydial cervicitis in pregnancy.

Meconium-stained amniotic fluid-associated infectious morbidity: a randomized, double-blind trial of ampicillin-sulbactam prophylaxis.

OBJECTIVE: To evaluate the efficacy of intrapartum prophylactic administration of ampicillin-sulbactam in reducing intraamniotic infection and postpartum endometritis in patients with meconium-stained amniotic fluid (AF). METHODS: Patients with intrapartum meconium-stained AF were randomized to receive either ampicillin-sulbactam or normal saline (placebo) intravenously at the time of diagnosis of meconium and every 6 hours until delivery. The outcomes of the two groups were compared with respect to intra-amniotic infection and postpartum endometritis. RESULTS: During the study period, 332 patients with meconium-stained AF were approached for participation, and 120 patients met inclusion criteria and were enrolled. Patient demographics, labor, and delivery characteristics were similar. Ampicillin-sulbactam reduced the incidence of intra-amniotic infection from 23.3 to 6.7%, (P = .02; relative risk [RR] 0.48, 95% confidence interval [CI] 0.22-0.98). The incidence of postpartum endometritis was also reduced, but the difference was statistically nonsignificant (8.3 versus 16.7%, P = .16; RR 0.64, 95% CI 0.30-1.33). CONCLUSION: Prophylactic intravenous ampicillin-sulbactam significantly reduces intra-amniotic infection in patients with meconium-stained AF.

Maternal and fetal cardiovascular response to exercise during pregnancy.

With the two-dimensional Doppler echocardiogram and M-mode echocardiogram, one can study maternal and fetal cardiovascular physiology during rest and exercise. Using such noninvasive techniques, studies indicate that left ventricular function is maintained even during vigorous bicycle exercise in healthy pregnant subjects during the second half of pregnancy. In early pregnancy, the left ventricle adapts to strenuous bicycle exercise by increasing its contractile reserve, enhancing ventricular emptying, whereas in late pregnancy, the left ventricle increases its preload reserve without significantly increasing its contractile reserve. Thus, women are "cardiovascularly" disadvantaged early in pregnancy. Using Doppler signals, early (E-passive) flow and late peak (A-active) flow reflect left ventricular diastolic filling properties. Using such techniques, we found that diastolic filling patterns are significantly influenced by pregnancy and that each trimester influences these diastolic filling patterns during upright bicycle exercise. Doppler studies of uteroplacental circulation during or after exercise have yielded conflicting results. Some have described an increase in "the vascular resistance" of this pelvic bed during strenuous exercise, whereas others have not. It seems safe to conclude that more studies are needed to elucidate this problem. Exercise does not seem to influence the resistivity index of the umbilical artery in either singleton or twins, and may even cause it to decrease. Ventricular diastolic filling properties of the fetal heart do not seem to be influenced by maternal bicycle exercise. Further studies are needed to determine if less active pregnant subjects, women with chronic hypertensive disorders, women with sickle cell anemia, or women with insulin-dependent diabetes adapt to exercise as well as their "normal" counterparts.

Maternal right hypogastric artery blood flow during normal pregnancy and 6 weeks postpartum.

OBJECTIVE: To document and quantify the temporal hemodynamic changes occurring in the pelvic circulation in normal human pregnancy, and to compare these changes with those found 6 weeks postpartum. METHODS: Thirty-three patients had color pulsed Doppler evaluation of the right hypogastric artery six times during pregnancy and once 6 weeks postpartum. Pulsed Doppler waveforms were digitized to assess the time velocity integral (area under the Doppler curve = TVI) and the peak flow velocity (maximum velocity = PFV). The diameter of the vessel was determined during systole using high-resolution two-dimensional ultrasound from a longitudinal plane. A quantitative estimate of the blood flow through this vessel was calculated by multiplying the TVI by the calculated cross-sectional area of the vessel. RESULTS: The cross-sectional area and the indexed volume of blood flow per minute of the hypogastric artery were significantly greater during pregnancy compared with the postpartum value. The estimated vascular resistance index was significantly decreased during pregnancy. Time velocity integral was significantly lower at the initial study compared with the postpartum value. CONCLUSION: The hypogastric artery undergoes significant hemodynamic changes during pregnancy when compared to the postpartum period. Furthermore, the pelvic circulation displays these changes early in gestation.

Hyperemic response of the brachial artery during the second half of pregnancy.

OBJECTIVE: To determine if women who developed preeclampsia had measurable differences in the vascular response postrelease of a 1-minute blood flow occlusion. METHODS: A total of 33 nulliparous patients were enrolled in this study during the second half of the pregnancy. All had baseline Doppler flow velocities while resting in the left lateral decubitus. Subsequently, a blood pressure cuff was inflated for 60 seconds in the forearm so as to occlude blood flow. Doppler waveforms were analyzed immediately after the release of the blood pressure cuff and on a single beat occurring at 15 second intervals for a total of five readings. After a rest period, patients were asked to squeeze a handheld manometer at maximum strength as long as possible. Doppler waveforms were analyzed as above. The Doppler waveforms of all enrolled patients who subsequently developed preeclampsia any time after the study were compared to those who remained normotensive. RESULTS: 1) The "hyperemic response" that occurred immediately after release of the blood pressure occlusion of the forearm was significantly different between patients who subsequently developed preeclampsia compared with those who remained normotensive, 2) the hyperemic response that occurred after the isometric handgrip exercise was not significantly different between the two groups, and 3) sensitivity, specificity, and negative predictive values were high, but positive predictive values were low. CONCLUSION: There was a significant difference in the hyperemic response of the brachial artery to a short period of ischemia of the forearm (blood pressure occlusion) between normotensive patients and a group of patients who subsequently developed preeclampsia.

Gaucher's disease in pregnancy.

Gaucher's disease is an autosomal recessive lysosomal storage disease, resulting from a deficiency of the enzyme glucocerebrosidase, important for the physiologic recycling of cell membrane lipids. The clinical symptoms and disease presentations of Gaucher's disease are heterogeneous, including hepatosplenomegaly, bone "crisis" and fracture, anemia, thrombocytopenia and in some forms, rapid neurological decompensation. Similarly, the genetic variability of Gaucher's disease is diverse, and in some aspects affects phenotypic expression. Type 1 Gaucher's disease, however, usually present with less severe symptoms, at more advanced age, and is particularly amenable to enzyme replacement therapy with alglucerase. In type 1 patients with Gaucher's disease reproductive age is commonly reached and childbearing frequently desired with need for appropriate prenatal diagnosis, counseling and careful obstetrical surveillance. Although pregnancy concurrent with Gaucher's disease has been reported in the medical literature, only one small series of alglucerase treated Gaucher's disease during pregnancy exists. Without treatment, pregnancy concurrent with Gaucher's disease has several risks including an increased severity of anemia and thrombocytopenia that can potentiate postpartum bleeding, significant increases in organomegaly and possibly an increased spontaneous abortion rate. It is yet to be shown whether alglucerase reduces the risk of these complications during pregnancy and whether its use has any adverse effect on fetal development.

Management of preterm premature rupture of membranes.

In conclusion, the suggested management for PROM follows two general principles. The first principle, which is accepted by most, consists of searching for a positive history of PROM, confirming PROM (by speculum examination, pooling, positive Nitrazine testing, and ferning), and obtaining cervical and vaginal cultures (for group B streptococcus/gonococcus and chlamydia). If free-flowing fluid from the cervix is seen, or if pooling is present, a sample should be sent for L-S and PG analysis. The cervix is assessed (for position, dilatation, and abnormalities), monitoring of maternal vital signs and fetal heart rate is done, white blood cell and differentials are obtained, and finally, immediate ultrasonogrpahy should be performed to document fetal position and viability, the number of fetuses, the amount of amniotic fluid, fetal anatomy, gestational age, and estimated weight. The other principle is a controversial one. It involves the use of amniocentesis for determination of fetal lung maturity and the presence of bacteria (if technically feasible); the use of a short course of tocolysis (terbutaline, 0.250 mg subcutaneously, or a similar medication for patient evaluation) if patient has contractions and all information is not yet available; the administration of steroids to accelerate fetal lung maturity; and finally, the administration of prophylactic antibiotics. In any event, delivery is indicated if there is clinical evidence of chorioamnionitis, as evidenced by maternal fever and tachycardia, tender uterus, fetal tachycardia, elevated white blood cell count with bands or left shift, and a positive Gram stain on examination of amniotic fluid. Antibiotic prophylaxis or treatment is only used if group B streptococcus or N. gonorrhea, or both, are present. Cesarean sections are reserved for obstetrical indications only. Furthermore, delivery is also indicated if there is evidence of lung maturity, fetal distress, active labor or advanced cervical dilatation (greater than or equal to 4 cm), PROM before the 20th to 22nd week of gestation, advanced gestational age of more than 36 weeks, or hemorrhage. In all circumstances, monitoring of the fetus with PROM is essential, with a nonstress test performed every other day to assess variable decelerations or a daily biophysical profile performed, as previously recommended. Even though no absolute recommendation exists as to the frequency of intrapartum testing, evaluation of the fetus with PROM should be done frequently, even on a daily basis.(ABSTRACT TRUNCATED AT 400 WORDS)

The modified Mueller-Hillis maneuver in predicting abnormalities in second stage labor.

OBJECTIVE: To assess prospectively the utility of a modification of the Mueller-Hillis maneuver in predicting abnormalities of the second stage of labor. METHODS: The Mueller-Hillis maneuver was modified by limiting its use to the second stage of labor during a contraction. The maneuver was performed by one examiner; descent of 1 cm or more was deemed a positive maneuver. Descent less than 1 cm was deemed a negative maneuver. Labor outcomes were analyzed according to the results of this maneuver. RESULTS: Seventy patients were enrolled in this study. Fifty-one (72.9%) had > or = 1 cm descent maneuver and 19 (27.1%) had < or = 1 cm descent. A descent > or = 1 cm was significantly predictive of vaginal delivery (100%) and a descent < or = 1 cm was significantly associated with an increased cesarean section rate (P = 0.001), prolonged second stage of labor (P = 0.001), abnormal position (P = 0.01) and higher station (P = 0.001). CONCLUSIONS: A positive modified Mueller-Hillis maneuver in second stage labor had a high predictive value for vaginal delivery, whereas a negative maneuver was significantly associated with high operative delivery rate, prolonged second stage labor and abnormal position. These results indicate that this modification of the Mueller-Hillis maneuver needs to be considered for its utility in second stage labor.

The role of antepartum surveillance in the management of gastroschisis.

OBJECTIVE: To evaluate the perinatal morbidity and mortality of fetuses diagnosed with gastroschisis at our Fetal Diagnosis and Treatment Center. METHODS: A retrospective review of a regional prenatal diagnostic center. Twenty-nine cases of gastroschisis which were diagnosed, managed, delivered and had corrective surgeries through the Fetal Diagnosis and Treatment Center were identified from 1985 to 1994. Perinatal morbidity and mortality were reviewed. Antepartum testing schemes were reviewed when available to determine whether morbidity or mortality could have potentially been prevented. RESULTS: Meconium occurrence, intrauterine growth retardation (IUGR) and oligohydramnios complicated 79%, 41% and 36% of the cases, respectively. The perinatal mortality of this series was 241/1000. Significant differences in perinatal mortality were noted when fetal testing was incorporated (200/1000 vs. 286/1000, P < or = 0.001). CONCLUSION: Gastroschisis is associated with a high incidence of IUGR, meconium, oligohydramnios and high perinatal mortality. Antenatal testing appears to significantly lower perinatal mortality in pregnancies complicated by gastroschisis.