Faculty Bibliography

OBJECTIVE:The objective was to perform a systematic review of prospective randomized trials evaluating the efficacy of oral tocolytics in the prevention of recurrent preterm labor and its associated complications. METHODS:A MEDLINE search of English language articles published since 1966 was performed to identify studies of maintenance oral tocolytic therapy. Studies were included in the review which: 1) randomized patients to an oral tocolytic after stabilization with parenteral therapy; 2) reported results for either a placebo or a control group; and 3) included patients with intact membranes only. These studies were analyzed for nine outcomes, including incidence of preterm delivery, incidence of recurrent preterm labor, latency from treatment to delivery, gestational age, birthweight, admission to an intensive care nursery (ICN), incidence of respiratory distress syndrome (RDS), incidence of intraventricular hemorrhage (IVH), and perinatal mortality. RESULTS:Seven studies met the inclusion criteria, four of which used oral terbutaline for the treatment arm (two had a control group, and two had a placebo group), and one used oral ritodrine (with a placebo group). Of the remaining two, one used oral ritodrine and oral magnesium chloride (with a control group), and the other used oral terbutaline and oral magnesium chloride (with a placebo group). The results of the individual studies suggest that there was no beneficial effect of oral tocolytic therapy on the incidence of preterm delivery (odds ratio (OR) range: 0.7-2.0), incidence of preterm labor recurrence (OR range: 0.6-3.2), ICN admission (OR range: 1.3-2.0), incidence of RDS (OR range 0.1-4.3), incidence of IVH (OR range 0.3-2.0), perinatal mortality (OR range: 1.6-4.3), or gestational age at delivery. CONCLUSIONS:We concluded that a meta-analysis based on the available studies is not possible due to the fact that there is little that these seven studies have in common with respect to treatment comparisons. In addition, inconsistent definitions of outcome variables makes pooling this data inappropriate and invalid. Therefore, well-designed, large, randomized trials are needed to evaluate the efficacy of oral tocolytics in improving perinatal outcome.

OBJECTIVE: To determine sonographic findings in Down syndrome fetuses in the third trimester. METHODS: Down syndrome fetuses who had third-trimester ultrasound examinations between 25 and 41 weeks' gestation were matched for gestational age with three controls each. Fetal structural anomalies, Down syndrome dysmorphology markers (abnormal facial profile, sandal gap, tongue thrusting, clinodactyly, or hypoplastic middle phalanx of the fifth finger), and abnormal long-bone biometry (femur, humerus, tibia, and fibula; femur length to biparietal diameter ratio; and femur length to abdominal circumference ratio were abstracted from the ultrasound reports. The fetal face, hands, feet, profile, and cardiac outflow tracts are routinely evaluated in our center. RESULTS: Seventeen fetuses with Down syndrome who had third-trimester ultrasound evaluations were identified. Anomalies included cardiac defects (five), tongue thrusting (three), clinodactyly (three), abnormal profile (three), sandal gap (two), and duodenal atresia (two). Of the 17 fetuses, at least one long-bone abnormality was found in 13, at least one structural or biometric anomaly was found in 15, and at least two abnormal findings existed in 11. Abnormal ultrasound findings, including structural anomalies, short bones, and Down syndrome dysmorphology markers, were more common in cases than in matched controls. CONCLUSION: At least one abnormal ultrasound finding was present in 15 of 17 fetuses, and abnormal bone measurements or ratios were discovered in 13 of 17. Abnormal long-bone biometry at third-trimester ultrasound should raise the suspicion of fetal Down syndrome

OBJECTIVE:The purpose of this study was to determine whether elevated levels of umbilical vein IL-6 would be a better marker for early neonatal sepsis than the clinical signs of maternal chorioamnionitis. METHODS:Patients delivering preterm because of spontaneous preterm labor or premature rupture of the membranes were evaluated for clinical signs of chorioamnionitis, which was defined as a temperature of > or =100.4 degrees F along with > or =2 of the following: significant maternal tachycardia (> or = 120 bpm), fetal tachycardia (> or =160 bpm), purulent discharge, uterine tenderness, and leukocytosis (WBC > or =18,000 cells/mm3). Umbilical vein blood was assayed for interleukin-6. An elevated interleukin-6 level was determined to be 25 pg/mL. Infants were evaluated for evidence of early neonatal sepsis. The abilities of clinical chorioamnionitis and interleukin-6 levels > or =25 pg/mL to predict early neonatal sepsis were compared. RESULTS:There were 28 patients delivering 14 (50%) neonates with evidence for early neonatal sepsis. The incidence of suspected neonatal sepsis in women with and without clinical chorioamnionitis was 6/10 (60%) vs. 8/18 (44.4%), P = 0.43. Using receiver operator characteristic curves, the best cutoff for interleukin-6 was found to be 25 pg/mL. The compared sensitivity, specificity, and positive and negative predictive values of clinical chorioamnionitis vs. interleukin-6 levels > or =25 pg/mL for predicting early neonatal sepsis were 42.9% vs. 92.9%, 71.4% vs. 92.9%, 60% vs. 92.9%, and 55.6% vs. 92.9%, respectively. CONCLUSIONS:Elevated umbilical vein levels of interleukin-6 predict those preterm infants with early sepsis better than the presence of clinical chorioamnionitis.

OBJECTIVE:To compare the accuracy of three different sonographic circumference measurement techniques in predicting birth weight in term fetuses, using a standard equation for estimating fetal weight. METHODS:Fifty-three singleton, term fetuses were examined sonographically within 24 hours of scheduled elective cesarean delivery. The biparietal diameter (BPD) and femur length (FL) were measured using standard techniques, and head circumference (HC) and abdominal circumference (AC) were measured using three separate circumference measurement techniques (Two-diameter, ellipse, and trace). With the use of each circumference method, estimated fetal weights were determined for each fetus according to a weight-estimation formula incorporating BPD, HC, AC, and FL. The accuracy of the formula using each circumference measurement technique for predicting actual birth weight was calculated. RESULTS:The mean (+/- standard deviation [SD]) gestational age was 38.1 +/- 0.9 weeks and the mean actual birth weight was 3536 +/- 472 g. The two-diameter and ellipse circumference measurements allowed more accurate birth weight prediction than did the trace method, with mean (+/- SD) percent deviations from the actual birth weight of -0.5 +/- 7.8%, 1.9 +/- 8.0%, and 8.2 +/- 11.6% (P < .05), respectively. The trace method was the least accurate, with a mean birth weight overestimation of 266 g and measurements within 10% of the actual birth weight only 49.1% of the time. The two-diameter and ellipse method yielded predicted birth weights within 10% of actual birth weights in 77.4 and 79.2% of cases, respectively. CONCLUSION/CONCLUSIONS:Two-diameter and ellipse circumference measurement techniques are similarly accurate in predicting birth weight and both are significantly better than the trace technique.

OBJECTIVE:The objectives of this study were to examine (1) the diagnostic accuracy requirements (from the cost-benefit point of view) of targeted ultrasonography versus genetic amniocentesis for prenatal detection of spina bifida in women with an elevated level of maternal serum alpha-fetoprotein, (2) the ultrasonographic accuracy of previously published studies from the cost-benefit point of view, and (3) the possible economic impact for the United States of offering targeted ultrasonography instead of routine amniocentesis to this group of patients. STUDY DESIGN/METHODS:Our cost-benefit formula was based on the hypothesis that the cost of universal genetic amniocentesis in patients with an elevated concentration of maternal serum alpha-fetoprotein in the second trimester should be at least equal to the cost of universal targeted ultrasonography, with amniocentesis used only for those with abnormalities on a sonogram. The main components of the formula included the diagnostic accuracy of targeted ultrasonography (sensitivity and specificity for detecting spina bifida), the cost of the amniocentesis package, the cost of targeted ultrasonography, and the lifetime cost of spina bifida not detected by targeted ultrasonography. After appropriate manipulation of the formula, a graph was constructed to represent the balance between the sensitivity and false-positive rate of targeted ultrasonography and was used to examine the accuracy of previously published ultrasonographic studies from the cost-benefit point of view. Sensitivity analyses included a range of prevalences of spina bifida in women with elevated maternal serum alpha-fetoprotein from 1:50 to 1:200 and false-positive rates of targeted ultrasonography from 1% to 10%. RESULTS:Assuming overall prevalences of spina bifida of 1:50, 1:100, or 1:200 among women with elevated maternal serum alpha-fetoprotein, we found targeted ultrasonography to be beneficial only if the overall sensitivities for detecting fetal spina bifida were >88%, >76%, and >51%, respectively. All 17 studies published after the mid-1980s, which used the "cranial signs" for detecting spina bifida, had accuracies compatible with economic benefits (sensitivities, 92% to 100%; false-positive rates, 0% to 3%). CONCLUSION/CONCLUSIONS:The benefit of second-trimester targeted ultrasonography for fetal spina bifida depends on diagnostic accuracy (ie, sensitivity and false-positive rate). Currently achieved ultrasonographic accuracies are compatible with net benefits. Targeted ultrasonography in patients with an elevated level of second-trimester maternal serum alpha-fetoprotein in the United States has the potential for annual savings of approximately $36 million to $49 million and for avoiding 268 fetal deaths.

OBJECTIVE:To systematically review the literature and summarize the relationship between cigarette smoking and placental abruption, and to evaluate the joint influences of smoking and hypertensive disorders (chronic hypertension and preeclampsia) on the subsequent development of abruption. DATA SOURCES/METHODS:We reviewed studies identified through a MEDLINE literature search between 1966 and 1997 and through studies cited in the references of published reports. METHODS OF STUDY SELECTION/METHODS:A total of 13 observational (seven case-control and six cohort) studies were identified which included a total of 1,358,083 pregnancies. We excluded case reports on placental abruption, and restricted the literature search to studies published in English. A meta-analysis was performed by computing pooled odds ratios based on random-effects models describing the association between placental abruption, smoking, and hypertensive disorders. Potential sources of heterogeneity among these studies were explored in detail. TABULATION, INTEGRATION, AND RESULTS/RESULTS:The overall incidence of placental abruption was 0.64% (8724 of 1,358,623). Smoking was associated with a 90% increase in the risk of placental abruption (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.8, 2.0). This pattern was consistent by study design (case-control compared with cohort studies) and smoking prevalence (low compared with high prevalence, defined as less than 30% compared with 30% or more, respectively). However, the association was significantly (p < .001) stronger among the seven studies conducted outside the United States (OR 2.1, 95% CI 2.0, 2.2), compared with the six studies conducted in the United States (OR 1.6, 95% CI 1.5, 1.8). Pooled population attributable risk percentage for each stratum ranged between 15% and 25%, implying that 15-25% of placental abruption episodes are attributable to cigarette smoking. Data on the dose-response relationship between number of cigarettes smoked per day and the risk of abruption indicate that the OR increased with increasing number of cigarettes smoked. Furthermore, a meta-analysis of the joint effects of smoking and hypertension during pregnancy on the development of abruption identified two published studies, including 102,609 pregnancies. In the presence of smoking, the risk of abruption was further increased due to chronic hypertension, mild or severe preeclampsia, or chronic hypertension with superimposed preeclampsia. CONCLUSION/CONCLUSIONS:Our meta-analyses showed an increased risk for placental abruption in relation to both cigarette smoking and hypertensive disorders during pregnancy. Because cigarette smoking is a modifiable risk factor, and hypertensive disorders are potentially treatable if diagnosed early in pregnancy, patient education, smoking cessation programs, and early prenatal care may be important factors in the prevention of placental abruption.

Maternal serum screening for Down syndrome involves biochemical tests such as alpha-fetoprotein (alpha FP), human chorionic gonadotrophin (hCG) and unconjugated oestriol (uE3), either alone or in combination, that have variable detection and false-positive rates. Choosing a screening protocol requires a trade-off between a desired detection rate and an acceptable false-positive rate. Selecting a screening protocol that maximizes the net benefit to society provides one approach. We have developed a general formula for calculating the per case net social benefit of a screening test and have applied it to United States data. The maximum net benefit associated with each of the various screening options currently available is estimated and the model is further applied to determine the conditions under which the addition of a new marker to an existing protocol can be justified. For each test, or combination of tests, optimal net benefits occur at different detection and false-positive rates. Net benefits are strongly and positively dependent on maternal age; high net benefits are associated with older patients and low, or even negative, net benefits with younger patients. Also, net benefits are affected by the term risk cut-off rate. For triple testing, the 1:351 Down syndrome term risk cut-off appears to provide a higher net benefit than that obtained with 1:250 or 1:300. The optimization of societal net benefit provides a powerful approach to evaluating screening strategies, but the policies used must also consider individuals' freedom in decision making at each step of the prenatal diagnosis pathway.

OBJECTIVE: To compare pregnancy outcomes in women at risk for pregnancy loss treated with elective versus ultrasound-indicated placement of cerclage. METHODS: A retrospective cohort study was performed on two groups of patients with singleton gestations. The first group consisted of women at risk for pregnancy loss who were treated with an elective cerclage, while the second group was managed conservatively and followed with serial transvaginal cervical sonography and transfundal pressure. An emergency cerclage was placed in women in the second group when the endocervical canal length shortened to < 20 mm, either spontaneously or in response to transfundal pressure. The two groups were compared with respect to maternal demographics, obstetric and gynecological history, and gestational age, both at time of cerclage placement and delivery. RESULTS: A total of 138 patients were identified. Eighty-one patients were treated with an elective cerclage and 57 with an ultrasound-indicated cerclage. Patients treated with elective cerclages were older (32 versus 27 years, p = 0.0003), more commonly white (56.8% versus 38.6%, p = 0.0380), less commonly nulliparous (23.5% versus 43.9%, p = 0.0063), and more often private patients (92.6% versus 28.1%, p < 0.0001). A history of previous treatment with cerclage (45.7% versus 10.5%, odds ratio (OR) 0.2, 95% confidence interval (CI) 0.1-0.4) and one prior midtrimester loss (53.1% versus 33.3%, OR 0.4, 95% CI 0.2-0.9) were also more common in the elective versus ultrasound-indicated cerclage group. However, there was no difference in the rates of previous preterm delivery, two midtrimester losses, two terminations of pregnancy, in utero diethylstilbestrol exposure, uterine anomalies, history of cone biopsy or parity. As expected, gestational age at placement of cerclage was significantly earlier in the elective group (13.0 versus 20.0 weeks, p < 0.0001). The median (range) gestational age at delivery (37 (15-41) versus 37 (17-41) weeks, p = 0.90), the number of early (< 25 weeks) losses (9.9% versus 8.8%, OR 1.6, 95% CI 0.3-7.9), and preterm deliveries (< 37 weeks) (35.8% versus 36.8%, OR 1.1, 95% CI 0.4-3.2) were similar in the elective and ultrasound-indicated cerclage patients, respectively. CONCLUSION: In patients at risk for pregnancy loss, placement of cervical cerclages in response to ultrasonographically detected shortening of the endocervical canal length is a medically acceptable alternative to the use of elective cerclage

To date, the prenatal diagnosis of cerebellar hemorrhage has been limited to isolated case reports, which have demonstrated either a hyperechoic cerebellar hemisphere or a hyperechoic mass within the cerebellum in near-term fetuses. We demonstrate the ultrasonographic findings of intracerebellar hemorrhagic infarction in a fetus at approximately 21 weeks' gestation. In contrast to previous case reports, the hemorrhagic infarcts seen in our case were hypoechoic