Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes.

OBJECTIVE: Increased advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) have been implicated in the pathogenesis of pre-eclampsia (PE). However, this association has not been elucidated in pregnancies complicated by diabetes. We aimed to investigate the serum levels of these factors in pregnant women with Type 1 diabetes mellitus (T1DM), a condition associated with a four-fold increase in PE. DESIGN: Prospective study in women with T1DM at 12.2 ± 1.9, 21.6 ± 1.5 and 31.5 ± 1.7 weeks of gestation [mean ± standard deviation (SD); no overlap] before PE onset. SETTING: Antenatal clinics. POPULATION: Pregnant women with T1DM (n = 118; 26 developed PE) and healthy nondiabetic pregnant controls (n = 21). METHODS: Maternal serum levels of sRAGE (total circulating pool), N(ε)-(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays. MAIN OUTCOME MEASURES: Serum sRAGE and AGEs in pregnant women with T1DM who subsequently developed PE (DM PE+) versus those who remained normotensive (DM PE-). RESULTS: In DM PE+ versus DM PE-, sRAGE was significantly lower in the first and second trimesters, prior to the clinical manifestation of PE (P < 0.05). Further, reflecting the net sRAGE scavenger capacity, sRAGE:hydroimidazolone was significantly lower in the second trimester (P < 0.05) and sRAGE:AGE and sRAGE:CML tended to be lower in the first trimester (P < 0.1) in women with T1DM who subsequently developed PE versus those who did not. These conclusions persisted after adjusting for prandial status, glycated haemoglobin (HbA1c), duration of diabetes, parity and mean arterial pressure as covariates. CONCLUSIONS: In the early stages of pregnancy, lower circulating sRAGE levels, and the ratio of sRAGE to AGEs, may be associated with the subsequent development of PE in women with T1DM.

Detection of fetal growth restriction in patients with chronic hypertension: is it feasible?

OBJECTIVE: To determine the utility of sonographic estimated fetal weight (EFW) in diagnosing intrauterine growth restriction (IUGR, birth weight < 10% for gestational age) in patients with chronic hypertension. METHODS: All pregnant patients with hypertension delivered during a 5-year period at three centers were identified retrospectively. Patients with gestational hypertension, pre-eclampsia, diabetes mellitus, fetal anomalies and absence of a sonographic examination within 3 weeks of delivery were excluded. Likelihood ratio (LR) and guidelines established by the Evidence-Based Medicine Working Group were used to determine whether sonographic EFW is a reliable diagnostic test to detect IUGR. RESULTS: At the three centers, there were 264 patients with chronic hypertension (122, 77 and 65 at centers I, II and III, respectively). The incidence of IUGR ranged from 13% to 27% but was similar at the three locations (p = 0.064). The LR (with 95% confidence interval (CI)) of detecting IUGR was 4.4 (95% CI 2.5, 7.7), 2.3 (95% CI 1.4, 3.7) and 6.1 (95% CI 2.7, 13.7) at centers I, II and III, respectively. Based on the proportions of abnormal growth, we required 253 and 71 newborns with fetal growth restriction at centers I and II, respectively, to have narrow confidence intervals around the clinically important LR of 10. The extremely low incidence of IUGR at center III (13%) precluded the estimation of required sample size. CONCLUSION: Use of Evidence-Based Medicine Working Group guidelines indicates that sonographic EFW is slightly to moderately useful in detecting fetal growth restriction in patients with chronic hypertension.

Sonographic estimate of birth weight: relative accuracy of sonographers versus maternal-fetal medicine specialists.

OBJECTIVE: To compare the relative accuracy of predicting birth weight among registered diagnostic medical sonographers versus maternal-fetal medicine specialists. STUDY DESIGN: Over 7 months all patients who delivered within 2 weeks and had sonographic measurements of femur length and head and abdominal circumferences by sonographers and physicians were included in the analysis. The exclusion criteria were multiple gestation and anomalous fetuses. Receiver operating-characteristic curves (ROC) were constructed to determine the ability to detect intrauterine growth restriction (IUGR; birth weight < 2,500 g) and macrosomia (birth weight > or = 4,000 g) among term (gestational age > or = 37 weeks) parturients. A level of p < 0.05 was considered significant. RESULTS: Among 365 patients recruited, the mean gestational age was 37.3 +/- 2.4 weeks with a mean birth weight of 3,083 +/- 72.5 g. Among term patients the prevalence of IUGR was 7.5% (18/238) and of macrosomia 12% (29/238). A significantly higher percentage of predictions were within 10% of the birth weight when obtained by sonographers (70%) than physicians (54%; p < 0.0001). Registered sonographers were significantly more likely to detect IUGR than the specialists (area under the ROC curves 0.97 +/- 0.02 vs. 0.92 +/- 0.02, respectively; p = 0.02). Both groups had similar accuracy in detecting macrosomic fetuses (area under the ROC curves 0.92 +/- 0.02 for sonographers and 0.90 +/- 0.02 for physicians; p = 0.40). CONCLUSIONS: Prediction of birth weight is significantly more accurate when sonographers rather than maternal-fetal medicine specialists perform the ultrasonographic examination.

Mode of delivery for the morbidly obese with prior cesarean delivery: vaginal versus repeat cesarean section.

OBJECTIVE: We sought to describe the peripartum outcome of women weighing >300 pounds (135 kg) who were candidates for trial of labor after a prior cesarean delivery. STUDY DESIGN: All pregnant women who weighed in excess of 300 pounds and had a prior cesarean delivery were included in this prospective investigation. Student t test, chi(2) analysis, or Fisher exact tests were used. Odds ratios and 95% confidence intervals were calculated. P <.05 was considered significant. RESULTS: During a 2-year period, 69 patients met the inclusion criteria; 39 (57%) underwent an elective repeat cesarean delivery, and 30 (43%) women attempted a vaginal delivery after prior cesarean delivery. The demographics of age, race, gravidity, maternal weight, and preexisting medical conditions were similar for the two groups. Vaginal birth after prior cesarean delivery occurred in 13% (4/30). Reasons for failure included a labor arrest disorder in 46%, fetal distress in 38%, and failed induction in 15%. The rates of endometritis and wound breakdown were higher in the women undergoing trial of labor (30% and 23%, respectively) than in those undergoing repeat elective cesarean delivery (20% and 8%). The combined infectious morbidity rate was significantly higher for women attempting trial of labor (53%) than those undergoing elective repeat cesarean delivery (28%; odds ratio 1.78, 95% confidence intervals 1.05, 3.02). CONCLUSION: The success rate for a vaginal delivery in the morbidly obese woman with a prior cesarean delivery is less than 15%, and more than half of the patients undergoing a trial of labor have infectious morbidity.

Validation of bioimpedance estimates of cardiac output in preeclampsia.

OBJECTIVE: We sought to evaluate the capacity of a new thoracic electric bioimpedance system to estimate cardiac output in patients with preeclampsia. STUDY DESIGN: We performed a prospective comparison of thoracic electric bioimpedance and echocardiographic M-mode volumetric estimates of cardiac output (in liters per minute) in preeclampsia. Subjects with preeclampsia who were chosen by means of strict criteria (either a systolic blood pressure >/=140 mm Hg or a diastolic blood pressure 90 mm Hg, or both, and proteinuria >/=300 mg in 24 hours or >/=+1 on repeat dipstick measurement 6 hours apart) were asked to participate in an institutional review board-approved study. Thoracic electric bioimpedance and echocardiography were performed with the patients in the left lateral recumbent position. Thoracic electric bioimpedance estimates were recorded at bedside; investigators were blinded to 3 simultaneously obtained echocardiographic M-mode estimates of cardiac output. Means were entered as the estimate for each patient. To satisfy the assumption of independent samples, only 1 estimate from each technique was used for each patient. Data were analyzed by Bland-Altman comparison. Hemodynamic and demographic variables are presented as mean +/- SD. RESULTS: Fifteen patients were enrolled. Mean maternal age was 25.9 +/- 4.8 years, and mean gestational age was 34.0 +/- 3.5 weeks. Mean arterial pressure was 112 +/- 14 mm Hg. There was good agreement of thoracic electric bioimpedance-derived and M-mode-derived cardiac output estimates. CONCLUSIONS: In patients with preeclampsia, thoracic electric bioimpedance estimates of cardiac output compare well with echocardiographic M-mode estimates.

Predicting the success of a trial of labor with a simple scoring system.

OBJECTIVE: To determine the applicability of a simple scoring system, by Troyer and Parisi, in predicting the success of a trial of labor among parturients with prior cesarean delivery. STUDY DESIGN: Retrospectively, all patients who underwent a trial of labor over six consecutive years were reviewed. chi 2, Fisher's exact test and analysis of variance followed by the Turkey or Dunn test were used when appropriate. P < .05 was considered significant. RESULTS: There were 263 trials of labor, of which 63% (167) ended in vaginal delivery. While 21% had a score of 0, 40%, 28% and 11% had a score of 1, 2 and at least 3, respectively. The frequency of vaginal birth was significantly different between the four groups (P < .001): 98% for a score of 0, 69% for 1, 40% for 2 and 33% for 3-4. Occurrence of cesarean delivery for cephalopelvic disproportion (2%, 24%, 39%, 56%; P < .001) or for a nonreassuring fetal heart rate tracing (0%, 7%, 21%, 11%; P < .001) was significantly different between the four groups. CONCLUSION: In our population, we confirmed the inverse relationship between the Troyer-Parisi scoring system and a successful trial of labor.

Antepartum detection of macrosomic fetus: clinical versus sonographic, including soft-tissue measurements.

OBJECTIVE: To compare clinical and sonographic estimates of birth weights with five new estimation techniques that involve measurements of soft tissue, for identifying newborns with birth weights of at least 4000 g. METHODS: Over 1 year, each woman at or after 36 weeks' gestation and suspected of having a macrosomic fetus had clinical and sonographic estimates of fetal weight (EFW) based on femur length (FL) and head and abdominal circumference, followed by five additional ways to identify excessive growth: cheek-to-cheek diameter, thigh soft tissue, ratio of thigh soft tissue to FL, upper arm subcutaneous tissue, and EFW derived from it. Areas (+/- standard error) of receiver operating characteristic (ROC) curves were calculated and compared with the area under the nondiagnostic line. P <.05 was considered statistically significant. RESULTS: Among 100 women recruited, 28 newborns weighed 4000 g or more. The areas under the ROC curves with clinical (0.72 +/- 0.06) and sonographic predictions using biometric characteristics (0.73 +/- 0.06) had the highest but similar accuracies (P.05). Three of the five newer methods (upper arm or thigh subcutaneous tissue and ratio of thigh subcutaneous tissue to FL) were poor diagnostic tests (range of areas under ROC 0.52 +/- 0.06 to 0.58 +/- 0.07). Estimated fetal weight based on upper arm soft tissue thickness and cheek-to-cheek diameter (areas 0.70 +/- 0.06 and 0.67 +/- 0.06, respectively) were not significantly better than clinical predictions (P.05) for detecting macrosomic fetuses. About 110 macrosomic and nonmacrosomic infants combined would be needed to have 80% power to detect a difference between ROC curves with areas of 0.58 (thigh subcutaneous tissue) and 0.72 (clinical estimate). CONCLUSION: ROC curves indicated that measurements of soft tissue are not superior to clinical or sonographic predictions in identifying fetuses with weights of at least 4000 g.

Neonatal acidemia with trial of labor among parturients with prior cesarean delivery: a case-control study.

OBJECTIVE: To determine the risk factors for neonatal acidemia with trial of labor among parturients with a prior cesarean delivery. METHODS: From a prospectively collected database on all parturients attempting a trial of labor, newborns with umbilical arterial pH < 7.15 were selected as cases and the controls (1:4) were the next four patients who delivered nonacidotic (pH > or = 7.15) neonates. Exclusion criteria were no prior cesarean delivery, anomalous fetus, and nonavailability of umbilical arterial blood gas analysis. Student's t-test, chi2, and Fisher's exact tests were utilized and odds ratio (OR) and 95% confidence intervals (CI) were calculated. P < 0.05 was considered significant. RESULTS: The frequency of neonatal acidemia among patients undergoing trial of labor was 12% (28/234). The cases and controls (n = 112) were similar (P > 0.05) with regards to maternal age, frequency of more than one prior cesarean delivery (11% vs. 8%), gestational age, cervical exam on admission (3.0 +/- 1.5 vs. 3.4 +/- 1.7 cm), usage of oxytocin, and duration of first or second stage of labor. The mean birthweight was significantly higher among acidotic (3,758 +/- 670 g) than nonacidotic (3,470 +/- 545 g; P = 0.018) newborns. Compared to the controls, the cases had a significantly higher frequency of unsuccessful trial of labor (19% vs. 50%; OR: 4.09; 95% CI: 1.70, 9.82) and separation of the uterine scar (0.8% vs. 14%; OR: 18.50; 95% CI: 1.98, 173.05). CONCLUSIONS: Acidotic newborns with trial of labor tend to be heavier. Parturients have a failed attempt at vaginal birth after cesarean, and have separation of the uterine scar during labor.

Managing nonreassuring fetal heart rate patterns before cesarean delivery. Compliance with ACOG recommendations.

OBJECTIVE: To determine the rate of compliance with current American College of Obstetricians and Gynecologists (ACOG) recommendations for management of parturients undergoing cesarean delivery for persistent nonreassuring fetal heart rate (FHR) tracings. STUDY DESIGN: We performed a retrospective chart review (July 1995-June 1998) of all parturients who underwent cesarean delivery for nonreassuring FHR tracings. Outcome measures included maneuvers for fetal assessment (scalp stimulation or scalp blood pH) and therapeutic interventions (tocolytic agents for reducing uterine activity or amnioinfusion). Patients with multiple gestations and cesarean delivery for other indications were excluded. Student's t test, chi 2 and Fisher's exact tests were used; odds ratio and 95% confidence interval were calculated. P < .05 was considered significant. RESULTS: Cesarean delivery for persistent nonreassuring FHR patterns included 134 (3.6%) of the 3,671 deliveries during three years. Thirty patients produced intrapartum FHR tracings containing persistent variable decelerations; 12 (40%) of these patients received amnioinfusion. In only 37% (50/134) of cases was there a documented attempt at scalp or acoustic stimulation prior to delivery. Scalp pH was obtained in 15% (15/98) of patients whose cervix was at least 3 cm dilated. Tocolytic agents were used for intrauterine resuscitation in 25% (34/134) of cases; their use varied significantly (P = .006) with the type of FHR abnormality. CONCLUSION: At our tertiary center, ACOG recommendations for management of nonreassuring intrapartum FHR tracings were used in a limited number of cases.

Accuracy of sonographically estimated fetal weight with and without oligohydramnios. A case-control study.

OBJECTIVE: To determine the accuracy of sonographically estimated fetal weight among women with and without oligohydramnios (amniotic fluid index [AFI] < or = 5.0 cm) and to ascertain the ability to detect fetal growth restriction (FGR) (estimated birth weight < 10th percentile for gestational age [GA]) among patients in two groups. STUDY DESIGN: Assuming that 50% of sonographic predictions are within 10% of the birth weight in the study group, 300 parturients are necessary to show a difference of 15% among controls (alpha = .05, beta = .02). The study group consisted of parturients with a reliable GA of > or = 24, no known anomalies and known AFI of < or = 5.0 cm. The control (1:1) was the next patient with the same GA but AFI between 5.1 and 23.9 cm. The paired t test was used, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. P < .05 was considered significant. RESULTS: Among the study and control groups (N = 162 each), maternal demographics, mean estimate (P = .078) and actual birth weight (P = .091) were similar. Sonographic estimates within 10% of weight were not significantly different among those with (57%) and without oligohydramnios (59%; OR 0.92; 95% CI 0.59, 1.44). The frequency of FGR was higher among those with inadequate fluid (18%) than controls (9%; OR 2.13; 95% CI 1.10, 4.16). Sensitivity, positive predictive value and likelihood ratio were higher among those with oligohydramnios (76%, 78% and 16) than controls (53%, 42% and 7). CONCLUSION: The accuracy of sonographic estimates of fetal weight is not influenced by whether the parturient has oligohydramnios. Moreover, the accuracy of identifying FGR is not diminished among those with AFI < or = 5.0 versus > 5.0 cm.

Effect of fetal presentation on the amniotic fluid index.

OBJECTIVE: The aim of this study was to determine whether the amniotic fluid index differs according to whether a fetus is in breech or cephalic presentation. STUDY DESIGN: Between January 1995 and April 1996 the amniotic fluid index was measured both immediately before and after attempted external cephalic version. Amniotic fluid indexes were measured by a senior obstetric resident or attending physician. Preprocedure amniotic fluid indexes and change in amniotic fluid index after successful and failed external cephalic version were compared with unpaired and paired Student t tests, respectively. P <.05 was considered statistically significant. RESULTS: Thirty consecutive women between 36 and 40 weeks' gestation with breech presentations were evaluated before undergoing an attempt at external cephalic version. The preprocedure amniotic fluid index was not different (P =.61) between women who had success (12.1 cm) and failure (11.4 cm) of attempts at external cephalic version. Successful external cephalic version was associated with a statistically significant increase (P <.0001) in amniotic fluid index with respect to gestations with a persistent breech presentation (3.14 vs -0.35). CONCLUSION: Successful version from a breech to a cephalic presentation resulted in a significant increase in the amniotic fluid index. This should be considered when a breech presentation with a low normal amniotic fluid index is evaluated. Presentation of the fetus should be considered in evaluating amniotic fluid index distribution curves.

A randomized, double-blind trial of oral nifedipine and intravenous labetalol in hypertensive emergencies of pregnancy.

OBJECTIVE: We sought to compare the efficacies of oral nifedipine and intravenous labetalol in the acute management of hypertensive emergencies of pregnancy. STUDY DESIGN: We performed a randomized double-blind trial of oral nifedipine (10 mg) and intravenous labetalol (20 mg) in 50 peripartum patients with sustained systolic blood pressure of >/=170 mm Hg or diastolic blood pressure of >/=105 mm Hg. Both agents were repeated at sequentially escalating dosages every 20 minutes until a therapeutic goal of systolic blood pressure of <160 mm Hg and diastolic blood pressure of <100 mm Hg was achieved. Crossover occurred if the treatment goal was not achieved after 5 doses. Primary outcome was time to achievement of the therapeutic goal. Secondary outcome variables were agent failure, urinary output, and adverse effects. Data were analyzed by unpaired t test, Mann-Whitney U test, and analysis of variance for repeated measures. RESULTS: The time to achieve the blood pressure goal was significantly shorter with nifedipine (mean +/- SD, 25 +/- 13.6 minutes) than with labetalol (43.6 +/- 25.4 minutes; P =.002). No patients required crossover therapy. Urine output was significantly increased (P <.001) at 1 hour after nifedipine dosing (99 +/- 99 mL) compared with labetalol (44.8 +/- 19.1 mL) and remained significantly increased at 2, 6, 12, 18, and 24 hours after initial administration. Adverse effects were infrequent. There were no differences in maternal age, gestational age, number of antepartum patients, or enrollment blood pressures between groups. CONCLUSIONS: Both oral nifedipine and intravenous labetalol are effective in the management of acute hypertensive emergencies of pregnancy; however, nifedipine controls hypertension more rapidly and is associated with a significant increase in urinary output.

A randomized, double-blind, hemodynamic evaluation of nifedipine and labetalol in preeclamptic hypertensive emergencies.

OBJECTIVE: Our purpose was to compare the hemodynamic effects of orally administered nifedipine and intravenously administered labetalol in preeclamptic hypertensive emergencies. STUDY DESIGN: Our study was a randomized, double-blind evaluation of nifedipine and labetalol in women with preeclampsia and a systolic blood pressure >170 mm Hg or a diastolic blood pressure >105 mm Hg. Nifedipine or labetalol and placebo were given, so patients received both tablet and intravenous solution. Hemodynamic parameters at dosing and at 15, 30, 60, and 120 minutes were recorded. Outcome measures were cardiac index, systemic vascular resistance index, mean arterial pressure, and heart rate. Data were analyzed by repeated-measures analysis of variance (Friedman test) with Dunn posttests, the Mann-Whitney U test, and the chi(2) test with the Yates correction. Significance was set at P <.05. RESULTS: At dosing, the nifedipine group (n = 6) had a cardiac index of 3.08 +/- 0.51 L/min per square meter. There was a 43% increase in the cardiac index after nifedipine administration (P =.0008). There was no significant effect in the labetalol group (P =.697). There was a significant decrease in the systemic vascular resistance index after nifedipine dosing (P =.002) but no significant effect on this index after labetalol use (P =.479). The mean arterial pressure was significantly affected in both groups as follows: nifedipine, P =. 001; labetalol, P =.004. The postanalysis showed significance at 60 minutes for both. An insignificant increase in heart rate with nifedipine (P =.147) and a significant decrease with labetalol (P =. 034) were noted. CONCLUSIONS: Nifedipine increases cardiac index, whereas labetalol may not do so.

Fetal acoustic stimulation in early labor and pathological fetal acidemia: a preliminary report.

OBJECTIVE: To determine if a nonreactive response to fetal acoustic stimulation in early labor can predict a significantly higher risk of umbilical arterial pH <7.10 or <7.00. METHODS: Fetal acoustic stimulation was applied to the fetuses of term parturients (gestational age > or =37 weeks) with cervical dilation of < or =5 cm. The responses to stimulation were correlated with cesarean delivery for fetal distress and umbilical arterial pH. Student's t-test, Chi-square, and Fisher exact test were used; P < 0.05 was considered significant. Relative risks (RR) and 95% confidence intervals (CI) were calculated. RESULTS: The study population contained 271 subjects, of which 90% (244) had a reactive response following acoustic stimulation and 10% (27) a nonreactive response. The maternal demographics, time interval from stimulation to delivery (8.3 +/- 8.7 vs. 8.3 +/- 8.4 h; P = 1.00) were similar in the two groups. Compared to those with a reactive response, patients with a nonreactive response had a significantly greater risk for: 1) cesarean delivery for fetal distress (2.0% vs. 11.1%; P = 0.03, RR 4.1, 95% Cl 1.5, 60.5), 2) umbilical arterial pH <7.10 (2.0% vs. 14.8%; P = 0.007, RR 5.0, 95% CI 2.2, 11.6), and 3) umbilical arterial pH <7.00 (0.8% vs. 7%; P = 0.05, RR 5.0, 95% CI 1.8, 15.2). CONCLUSION: A nonreactive response to fetal acoustic stimulation in early labor is associated with a significantly increased risk for cesarean delivery for fetal distress and neonatal acidosis. This finding extends the potential value of acoustic stimulation as an intrapartum admission screening test.

Detection of growth-restricted fetuses in preeclampsia: a case-control study.

OBJECTIVE: To determine the diagnostic accuracy of detecting growth-restricted fetuses in women with and without preeclampsia. METHODS: Over 2 years, parturients with reliable gestational ages, preeclampsia, and sonographic estimates of birth weights were matched (1:1) for gestational age with women without preeclampsia. Paired and unpaired t tests were used; P < .05 was significant. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Two hundred eighty-seven preeclamptic women were identified and matched. In each group, mean (+/- standard deviation [SD]) gestational age was 34.9 +/- 4.2 weeks, and 166 (57.8%) infants were born preterm. Fetal growth restriction (FGR) was significantly more common among women with preeclampsia (14.9%) than among controls (5.6%; OR 2.98, 95% CI 1.64, 5.44). The percentage of sonographic estimates within 10% of actual birth weight (57.5% versus 53.6%) was similar in the two groups (OR 1.16; 95% CI 0.84,1.62). Compared with normal growth, the mean (+/- SD) standardized absolute error was significantly higher among those with FGR regardless of group (preeclampsia 109 +/- 100 versus 158 +/- 152 g/kg; P = .009; control 117 +/- 103 versus 233 +/- 206 g/kg; P < .001). Fetal growth restriction was detected more commonly among preeclamptic women than among controls (11.6% versus 0%; OR 4.74 95% CI 0.25, 90.31). The sensitivity and positive predictive value of FGR detection were 10% and 50%, respectively, among women with preeclampsia and 0% each among controls. CONCLUSION: Although FGR was detected more frequently in fetuses of women with preeclampsia than in those of controls, the ability to predict it with sonography remained poor.

The effect of indomethacin tocolysis on fetal ductus arteriosus constriction with advancing gestational age.

OBJECTIVE: Our purpose was to determine whether continuing exposure to indomethacin tocolysis is associated with an increased incidence of constriction of the human fetal ductus arteriosus with advancing gestational age. STUDY DESIGN: Fetal echocardiograms were reviewed in 61 cases in which the pregnant women were treated for preterm labor with indomethacin (25 mg orally every 6 hours). Density function analysis and regression analysis were used to assess the effect of indomethacin tocolysis on ductal constriction with advancing gestational age. RESULTS: A total of 193 fetal echocardiograms were obtained for 72 fetuses. Ductal constriction developed in 50% of the fetuses ranging from 24.7 to 35.0 weeks' gestation. Fetuses with indomethacin-induced ductal constriction demonstrated a greater increase in systolic flow velocities with advancing gestational age compared with the nonconstricted group (p < 0.05). Constriction was detected at a mean gestational age of 30.9 +/- 2.3 weeks at an average of 5.1 +/- 6.0 days after initiation of therapy. Ductal constriction occurred by 31 weeks' gestation in 70% of the affected fetuses. After discontinuation of indomethacin therapy, all follow-up echocardiograms demonstrated a return to nonconstricted ductal flow velocities. No significant adverse neonatal outcomes were attributed to indomethacin use. CONCLUSIONS: A dramatic yet reversible increase in the incidence of indomethacin-induced ductal constriction occurs at 31 weeks' gestation. However, ductal constriction can occur at any gestational age. With indomethacin tocolysis, weekly fetal echocardiography is warranted for the duration of therapy.

Diphenhydramine overdose during pregnancy: lessons from the past.

A primigravid woman was seen for the first time in a disoriented and combative state, with regular, painful uterine contractions. Evaluation revealed a negative illicit drug screen, no evidence of preeclampsia, and a nonfocal neurologic examination. Further workup revealed urinary diphenhydramine levels suggesting drug overdose. This case serves as a reminder of the oxytocin-like effects of diphenhydramine.

Hemodynamic effects of oral nifedipine in preeclamptic hypertensive emergencies.

OBJECTIVE: Our purpose was to evaluate the hemodynamic effects of oral nifedipine in preeclamptic hypertensive emergencies. STUDY DESIGN: A prospective observational study of the hemodynamic effects of oral nifedipine was conducted with severely preeclamptic patients receiving magnesium sulfate infusion during a hypertensive emergency. Patients were eligible for the study if systolic blood pressure was > or = 170 m Hg or the diastolic blood pressure was > or = 105 mm Hg on repeat measurements 15 minutes apart at > or = 24 weeks' gestation. Nifedipine was given with an initial dose of 10 mg orally followed by 20 mg orally every 20 minutes until systolic blood pressure was > 160 mm Hg and the diastolic blood pressure was < 100 mm Hg, or for a total of five doses. Patients were hemodynamically monitored in the lateral recumbent position by thoracic electrical bioimpedance before during, and after oral nifedipine dosing. Cardiac index, systemic vascular resistance index, mean arterial pressure, heart rate, and stroke index were all recorded at baseline and during treatment. Data were analyzed by analysis of variance for repeated measures (alpha 0.05) and paired t tests, baseline versus 15 minutes (alpha 0.01). RESULTS: Ten severely preeclamptic patients at 33.2 +/- 3.0 (mean +/- SD) weeks' gestation were enrolled in the study. Mean arterial pressure measurements taken at baseline, 0.25, 0.5, 1, and 4 hours were 133 +/- 10, 119 +/- 8, 109 +/- 8 89 +/- 12, and 100 +/- 13 mm Hg (mean +/- SD, p < 0.0001, analysis of variance repeated measures). Cardiac index increased over time (p = 0.0011, analysis of variance repeated measures). There was no significant effect on maternal heart rate or stroke index. No periodic fetal heart rate changes were noted. One patient had nausea. CONCLUSION: Oral nifedipine appears to be an effective antihypertensive agent in preeclamptic hypertensive emergencies. A steady decrease in mean arterial pressure, systemic vascular resistance, and a mirrored increase in cardiac index are noted.

Prospective determination of chorionicity, amnionicity, and zygosity in twin gestations.

OBJECTIVE: Our purpose was to determine the predictive accuracy of a composite ultrasonographic evaluation for chorionicity, amnionicity, and zygosity in a consecutive series of twins. STUDY DESIGN: One hundred ten consecutive twins were seen for ultrasonography beginning January 1992. Chorionicity, amnionicity, and, zygosity were prospectively assessed with a composite of ultrasonographic findings (placental number, fetal sex, membrane thickness, and "twin peak" sign). Clinical and pathologic confirmation of chorionicity, amnionicity, and zygosity was available on 100 of these twins. RESULTS: The 100 twins had 3.6 +/- 1.6 ultrasonographic scans each (mean +/- SD) with the first performed at 22.6 +/- 6.9 weeks. Chorionicity, amnionicity, and zygosity were each predicted with > or = 91% sensitivity and specificity. In 35 (35%) cases zygosity could not be determined by either ultrasonographic or clinical or pathologic assessment at delivery. CONCLUSION: Chorionicity, amnionicity, and zygosity have important implications for antepartum management and prognosis of twins. By use of a composite of ultrasonographic findings, chorionicity, amnionicity, and zygosity were predicted with excellent reliability when they were prospectively tested in a heterogeneous consecutive series of twins.