Infertility case management: improving both short-term and long-term outcomes while reducing costs.

PURPOSE/OBJECTIVES: Infertility is a growing medical condition as more women are desirous of having children at an older age. It is estimated to be a $3 billion business, and, while infertility treatment is a for-profit commercial endeavor, the product is noncommercial (baby or babies). The treatment process may be complicated with overutilization, drug wastage, and adverse outcomes. High-order multiple gestations may result in preterm births, chronic adult diseases, and lifelong neurological impairments (such as cerebral palsy). The total national cost of infertility treatment unfortunately equals the cost of providing care to these babies in the nursery and neonatal intensive care unit. This article explores the potential benefit of the integration of information technology with clinical case management to reduce overall cost and improve provider accuracy. PRIMARY PRACTICE SETTING(S): Office-based telephonic nurse case management and pharmacology management practice. FINDINGS/CONCLUSIONS: The article demonstrates that the challenging integration of information technology with clinical case management is very effective and improves provider accuracy, resulting in the best transfer of real-time information. The case management program at Women's Integrated Network Healthcare has been shown to lower infertility treatment costs by 30% to 40% and lower the numbers of high-order multiple gestations. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Eighty-one percent of the cost reduction is related directly to case management, not reduction in physician fees or unit pharmaceutical costs. Case management can improve effectiveness and quality of conception, and there is a reduction in high-order multiple gestations. It was also found that, by expanding infertility benefits and including case management as the pivotal element, payers and employers could recognize significant savings and, more importantly, the women and families would benefit.

Defining the relationship between obstetricians and maternal-fetal medicine specialists.

OBJECTIVE: The purpose of this study was to determine how frequently general obstetricians refer pregnant patients to maternal-fetal medicine specialists in the presence of the clinical indications specified as appropriate for referral or consultation by the 1996 statement of the Society of Perinatal Obstetricians. STUDY DESIGN: A questionnaire was mailed to 400 randomly selected general obstetricians across the United States. The obstetricians were asked how often they refer their high-risk pregnant patients to maternal-fetal medicine specialists in the presence of (1) a need for diagnostic or therapeutic procedures, (2) medical/surgical disorders, (3) healthy gravid women with high-risk fetuses, and (4) conditions that necessitate admission for reasons other than delivery. Response categories for each individual procedure/high-risk condition included "always," "frequently," "infrequently," "never," and "not applicable." RESULTS: Overall, 55% of the responses indicated referral (always or frequently) to maternal-fetal medicine specialists for procedures or in the presence of high-risk conditions. More than 75% of the obstetricians always or frequently refer to maternal-fetal medicine specialists for most diagnostic/therapeutic procedures and for the following high-risk conditions: acute fatty liver, portal hypertension, pulmonary hypertension, transplantations, fetal hydrops, fetal anomaly/cytogenetic abnormality, fetal supraventricular tachycardia or congenital heart block, isoimmunization, and twin-to-twin transfusion syndrome. CONCLUSION: Most of the conditions for which >75% of the obstetricians refer to maternal-fetal medicine are rarely seen in practice. Comprehensive ultrasound examination is the only commonly encountered clinical situation that >75% of the general obstetricians refer to maternal-fetal medicine specialists.

Do maternal-fetal medicine practice characteristics influence high-risk referral decisions by general obstetrician-gynecologists?

OBJECTIVE: To determine whether the decision of the general obstetrician-gynecologist to refer high-risk obstetric patients depends on the type of practice of the maternal-fetal medicine (MFM) specialist. METHODS: A questionnaire was mailed to 935 general obstetrician-gynecologists who were asked whether the MFM specialist's practice characteristics would influence their decision to refer their high-risk obstetric patients. Potential MFM practice components presented in the survey included: MFM, high-risk obstetrics, low-risk obstetrics or general obstetrics and gynecology. RESULTS: A total of 140 (15%) general obstetrician-gynecologists responded, 110 of whom were practicing obstetrics. Of the practicing responders, 77% stated that they were more likely to refer their high-risk obstetric patients if the MFM specialist practiced only MFM and high-risk obstetrics; 69% were less likely to refer their patients when the MFM specialist, in addition to MFM, practiced general obstetrics; and 75% were less likely to refer their patients when the MFM specialist also practiced general obstetrics and gynecology. The MFM practice setting (university vs. community hospital vs. private practice), as well as the geographic location and years of practice of the respondents, did not influence the general obstetrician-gynecologists' decision to refer their high-risk obstetric patients. CONCLUSION: General obstetrician-gynecologists are more likely to refer high-risk obstetric patients if the MFM specialist practiced only MFM and high-risk obstetrics.

New Jersey's electronic birth certificate program: variations in data sources.

OBJECTIVES: This study sought to determine primary sources of data for electronic birth certificates. METHODS: A survey was administered from 1997 through 1998 to maternity facilities in New Jersey requesting information about what primary information sources were used for 53 electronic birth certificate variables. Potential information sources included the facilities' maternal and infant medical records, the prenatal record, and a parent-completed birth certificate worksheet. RESULTS: Among the 66 maternity facilities responding, there was significant variation in the choice of primary data sources for the electronic birth certificate variables examined. CONCLUSIONS: The variability of primary sources for electronic birth certificate data acquisition represents a potential cause of systematic error in reported vital statistics information.

Placental abruption among singleton and twin births in the United States: risk factor profiles.

The authors performed a population-based epidemiologic study to evaluate and contrast risk factor profiles for placental abruption among singleton and twin gestations. Data were derived from linked US birth/infant death files for 1995 and 1996, comprising 7,465,858 singleton births and 193,266 twin births. The authors also evaluated effect modification between smoking and hypertension and the effect of a dose-response relation with number of cigarettes smoked daily on abruption risk. Abruption was recorded in 5.9 per 1,000 singleton births and 12.2 per 1,000 twin births. Risk factors for abruption among singleton and twin births, respectively, included preterm premature rupture of membranes (adjusted relative risks (RRs) = 4.89 and 2.01), eclampsia (RRs = 3.58 and 1.67), anemia (RRs = 2.23 and 2.33), hydramnios (RRs = 2.04 and 1.66), renal disorders (RRs = 1.54 and 2.56), and intrapartum fever (>100 degrees F) (RRs = 1.17 and 1.69). Chronic hypertension (RR = 2.38) and pregnancy-induced hypertension (RR = 2.34) were risk factors for abruption in singleton births but not in twin births. Number of cigarettes smoked daily demonstrated a dose-response trend for abruption risk in singletons and twins. Abruption was more likely to occur among smokers with chronic hypertension (RRs = 4.66 and 3.15) and eclampsia (RRs = 6.28 and 5.08). The authors conclude that abruption is twice as likely to occur in twins as in singletons with differing risk factor profiles. This suggests that abruption in twins may result from different pathophysiologic processes.

A multicenter controlled trial of fetal pulse oximetry in the intrapartum management of nonreassuring fetal heart rate patterns.

OBJECTIVE: Recent developments permit the use of pulse oximetry to evaluate fetal oxygenation in labor. We tested the hypothesis that the addition of fetal pulse oximetry in the evaluation of abnormal fetal heart rate patterns in labor improves the accuracy of fetal assessment and allows safe reduction of cesarean deliveries performed because of nonreassuring fetal status. STUDY DESIGN: A randomized, controlled trial was conducted concurrently in 9 centers. The patients had term pregnancies and were in active labor when abnormal fetal heart rate patterns developed. The patients were randomized to electronic fetal heart rate monitoring alone (control group) or to the combination of electronic fetal monitoring and continuous fetal pulse oximetry (study group). The primary outcome was a reduction in cesarean deliveries for nonreassuring fetal status as a measure of improved accuracy of assessment of fetal oxygenation. RESULTS: A total of 1010 patients were randomized, 502 to the control group and 508 to the study group. There was a reduction of >50% in the number of cesarean deliveries performed because of nonreassuring fetal status in the study group (study, 4. 5%; vs. control, 10.2%; P =.007). However, there was no net difference in overall cesarean delivery rates (study, n = 147 [29%]; vs. control, 130 [26%]; P = .49) because of an increase in cesarean deliveries performed because of dystocia in the study group. In a blinded partogram analysis 89% of the study patients and 91% of the control patients who had a cesarean delivery because of dystocia met defined criteria for actual dystocia. There was no difference between the 2 groups in adverse maternal or neonatal outcomes. In terms of the operative intervention for nonreassuring fetal status, there was an improvement in both the sensitivity and the specificity for the study group compared with the control group for the end points of metabolic acidosis and need for resuscitation. CONCLUSION: The study confirmed its primary hypothesis of a safe reduction in cesarean deliveries performed because of nonreassuring fetal status. However, the addition of fetal pulse oximetry did not result in an overall reduction in cesarean deliveries. The increase in cesarean deliveries because of dystocia in the study group did appear to result from a well-documented arrest of labor. Fetal pulse oximetry improved the obstetrician's ability to more appropriately intervene by cesarean or operative vaginal delivery for fetuses who were actually depressed and acidotic. The unexpected increase in operative delivery for dystocia in the study group is of concern and remains to be explained.

After-hours telephone calls to obstetrician-gynecologists.

OBJECTIVE: To characterize the pattern, content, and management of after-hours telephone interactions between obstetrician-gynecologists and patients. METHODS: In a prospective observational study, 12 resident and nine private physicians practicing obstetrics and gynecology completed data cards for after-hours telephone interactions with patients. Chief complaints were categorized as related to either women's health or primary care and on whether women were pregnant, postpartum, or not pregnant. Triage dispositions (evaluate now, office follow-up, or home care) were compared between groups. Women also were asked what they would have done if they had been unable to contact their physicians by telephone. RESULTS: One hundred ninety-two of 276 calls evaluated (69. 6%) were from pregnant women, 20 (7.2%) were from postpartum women, and 64 (23.3%) were from nonpregnant women. Calls were related to primary care health issues in 24.1% (n = 45) of pregnant women, 40% (n = 8) of postpartum women, and 28.1% (n = 18) of nonpregnant women. There were no differences between residents and private physicians in the proportion of women triaged to immediate evaluation for pregnancy (35.1% [n = 40] versus 41.9% [n = 31], P =.74) or postpartum (11.1% [n = 1] versus 10% [n = 1],P =.96) problems. Among 139 women triaged to office follow-up, 41% (n = 57) would have come to the hospital for emergency evaluation if they had been unable to reach their physicians. CONCLUSION: Resident and private obstetrician-gynecologists provide primary care and women's health care advice during after-hours telephone calls from patients. More than one third of after-hours telephone calls from pregnant women are triaged to immediate evaluation.

Routine second-trimester ultrasonography in the United States: a cost-benefit analysis.

OBJECTIVE: The objective of this study was to perform a cost-benefit analysis of routine second-trimester screening ultrasonography in the United States as compared with performing ultrasonography only in the presence of indications. STUDY DESIGN: It was assumed that 1 million pregnant women are available annually who otherwise would not have an indication for an ultrasonographic examination. Cost savings from early detection and therapeutic abortion were considered only for fetal conditions for which lifetime cost estimates are available, including spina bifida, major cardiac disease, cleft lip or palate, renal agenesis or dysgenesis, urinary obstruction, lower or upper limb reduction, omphalocele, gastroschisis, and diaphragmatic hernia. Two separate cost-benefit analyses were considered with the range of fetal anomaly detection rates before 24 weeks' gestation as reported by tertiary and non-tertiary centers in the Routine Antenatal Diagnostic Imaging with Ultrasound (RADIUS) trial. Potential cost savings from averting treatment for preterm labor and postdate gestations were also considered. RESULTS: The ratio of savings to cost was between 1.35 and 1.70 (savings of $1.35-$1.70 per $1 spent) if the ultrasonographic examinations were performed in tertiary care centers. The ratio of savings to cost was between 0.40 and 0.74 (loss of $0.26-$0.60 per $1 spent) if the examinations were performed in nontertiary centers. If the screening ultrasonography was performed in tertiary centers, the expected annual net benefits were estimated at $97 to 189 million. If ultrasonographic screening was performed in nontertiary centers, the expected annual net losses were estimated at $69 to 161 million. CONCLUSION: Routine second-trimester ultrasonographic screening appears to be associated with net benefits only if the ultrasonography is performed in tertiary care centers.

Cost-benefit analysis of prenatal diagnosis for Down syndrome using the British or the American approach.

OBJECTIVE: To compare the cost and benefits of prenatal diagnosis for Down syndrome using the British and American approaches. METHODS: This cost-benefit analysis was based on a decision-analytic approach. The British strategy included screening by a first-trimester ultrasound at 10-14 weeks for nuchal translucency thickness, and the American strategy included only second-trimester screening by using maternal age and maternal serum screening. The key probabilities of the decision-tree analysis and all cost estimates were based on American standards. The best scenario of the British strategy assumed ultrasound nuchal translucency thickness sensitivity (for detecting Down syndrome) of 80% and a false-positive rate of 5% and the worst scenario assumed a sensitivity of 50% and a false-positive rate of 10%. The results were expressed in annual costs based on approximately 4 million births per year in the United States. RESULTS: As compared with do-nothing, the American strategy was found to allow savings of approximately $96 million per year and the best scenario for the British strategy was savings of approximately $5 million per year. The financial costs of the British and American strategies would be comparable only if the first-trimester ultrasound had a sensitivity of 80% and a false-positive rate of 5% in detecting Down syndrome. CONCLUSION: The British strategy does not appear to be economically beneficial in the United States even under the most ideal scenarios of ultrasound accuracy.

Indication-specific accuracy of second-trimester genetic ultrasonography for the detection of trisomy 21.

OBJECTIVE: The object of this study was to determine whether there are any clinically significant indication-specific variations in the accuracy of second-trimester genetic ultrasonography and to provide a risk adjustment for fetal trisomy 21 according to the results of genetic ultrasonography. STUDY DESIGN: From November 1, 1992, to September 30, 1998, a second-trimester genetic sonogram was offered to all pregnant women who were at an increased risk for fetal trisomy 21 (>/=1:274) because of either advanced maternal age (>/=35 years) or abnormal serum biochemical profile or both of these. Outcome information included the results of genetic amniocentesis if performed and the results of pediatric assessment and follow-up after birth. In determining diagnostic accuracy of the genetic sonogram the presence of >/=1 abnormal ultrasonographic marker was considered an abnormal test result. RESULTS: A total of 1835 fetuses with known outcomes underwent genetic ultrasonography between 15 and 24 weeks' gestation; of these 1792 had normal results, 34 had trisomy 21, and 9 had other chromosomal abnormalities. The likelihood of fetal trisomy 21 was reduced by 80% after a normal result of genetic ultrasonography. The overall sensitivity, specificity, and positive and negative predictive values of genetic ultrasonography for the detection of trisomy 21 were 82%, 91%, 15%, and 99.6%, respectively. There were no significant indication-specific variations in the accuracy of second-trimester ultrasonography. The sensitivity for the detection of fetal trisomy 21 ranged from 80% among women with advanced maternal age to 100% among women with both an abnormal biochemical profile and advanced maternal age. CONCLUSIONS: The likelihood of fetal trisomy 21 risk was reduced 80% after a normal result of genetic ultrasonography. In addition there were no significant indication-specific variations in the detection rate of genetic ultrasonography.

Economic evaluation of prenatal carrier screening for fragile X syndrome.

OBJECTIVE: The objective of this study was to conduct an economic evaluation of routine prenatal carrier testing for fragile X syndrome. METHODS: This economic analysis was conducted from the societal perspective. A cost-benefit equation was developed based on the premise that the cost of routinely offering prenatal carrier testing for fragile X syndrome should be at least equal to, or less than, the cost of the current practice of not offering such testing. Sensitivity analyses included key assumptions regarding therapeutic abortion rates (50-100%) and patient screening acceptance rates (50-80%). RESULTS: A policy of routinely offering prenatal carrier testing for fragile X syndrome may be beneficial only if the cost per screening test is less than $120 during the first year of the screening program, or less than $240 when the program reaches its full maturity. Given the current cost per screening test of $250, prenatal screening for carrier status for fragile X syndrome carries the potential for annual losses of approximately $10 to $195 million in the United States. In addition, approximately 46-115 fetal lives may be lost due to invasive genetic procedures. CONCLUSIONS: Prenatal screening for fragile X syndrome may be economically beneficial only if the cost of the prenatal screening test for carrier identification is considerably less than the current cost.

Cost-benefit analysis of targeted ultrasonography for prenatal detection of spina bifida in patients with an elevated concentration of second-trimester maternal serum alpha-fetoprotein.

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: 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: 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.

An economic evaluation of second-trimester genetic ultrasonography for prenatal detection of down syndrome.

OBJECTIVE: The objective of this study was to perform an economic evaluation of second-trimester genetic ultrasonography for prenatal detection of Down syndrome. More specifically, we sought to determine the following: (1) the diagnostic accuracy requirements (from the cost-benefit point of view) of genetic ultrasonography versus genetic amniocentesis for women at increased risk for fetal Down syndrome and (2) the possible economic impact of second-trimester genetic ultrasonography for the US population on the basis of the ultrasonographic accuracies reported in previously published studies. STUDY DESIGN: A cost-benefit equation was developed from the hypothesis that the cost of universal genetic amniocentesis of patients at increased risk for carrying a fetus with Down syndrome should be at least equal to the cost of universal genetic ultrasonography with amniocentesis used only for those with abnormal ultrasonographic results. The main components of the equation included the diagnostic accuracy of genetic ultrasonography (sensitivity and specificity for detecting Down syndrome), the costs of the amniocentesis package and genetic ultrasonography, and the lifetime cost of Down syndrome cases not detected by the genetic ultrasonography. After appropriate manipulation of the equation a graph was constructed, representing the balance between sensitivity and false-positive rate of genetic ultrasonography; this was used to examine the accuracy of previously published studies from the cost-benefit point of view. Sensitivity analyses included individual risks for Down syndrome ranging from 1:261 (risk of a 35-year-old at 18 weeks' gestation) to 1:44 (risk of a 44-year-old at 18 weeks' gestation). This economic evaluation was conducted from the societal perspective. RESULTS: Genetic ultrasonography was found to be economically beneficial only if the overall sensitivity for detecting Down syndrome was >74%. Even then, the cost-benefit ratio depended on the corresponding false-positive rate. Of the 7 published studies that used multiple ultrasonographic markers for genetic ultrasonography, 6 had accuracies compatible with benefits. The required ultrasonographic accuracy (sensitivity and false-positive rate) varied according to the prevalence of Down syndrome in the population tested. CONCLUSIONS: The cost-benefit ratio of second-trimester genetic ultrasonography depends on its diagnostic accuracy, and it is beneficial only when its overall sensitivity for Down syndrome is >74%.

An economic evaluation of prenatal strategies for detection of trisomy 18.

OBJECTIVE: The objective of this study was to perform an economic evaluation of prenatal diagnostic strategies for women who are at increased risk for fetal trisomy 18 caused by either fetal choroid plexus cysts discovered in a conventional sonogram or an abnormal triple screen. STUDY DESIGN: The prevalence of trisomy 18 in the presence of second-trimester fetal choroid plexus cysts and also in the presence of abnormal triple screen were made on the basis of previously reported studies. A cost/benefit analysis and cost-effectiveness determination of 3 strategies were performed: (1) no prenatal diagnostic workup of at-risk patients, (2) universal genetic amniocentesis of all at-risk patients, and (3) universal second-trimester targeted genetic ultrasonography of all at-risk patients with amniocentesis (for fetal karyotyping) reserved only for those with abnormal ultrasonography results. RESULTS: The strategy of no prenatal diagnostic workup was the least expensive approach, costing $1,650,000 annually in the United States. The more costly approach was the strategy of universal amniocentesis for detecting fetal trisomy 18 in the presence of either second-trimester choroid plexus cysts or abnormal maternal serum screening, generating an annual cost of approximately $12 million and 40 fetal losses as a result of amniocenteses. The strategy of targeted genetic ultrasonography generated an annual cost of only $5 million and 8 fetal losses as a result of amniocenteses. CONCLUSIONS: Routine second-trimester amniocentesis in patients at increased risk for fetal trisomy 18 caused by either the presence of fetal choroid plexus cysts or abnormal triple screening is not justified from the cost/benefit point of view.

Clinical issues surrounding the use of terbutaline sulfate for preterm labor.

beta-mimetics have been prescribed by physicians to arrest or prevent premature labor for more than 20 years. Although not approved by the Food and Drug Administration (FDA) for tocolytic use, terbutaline sulfate has been the most widely prescribed beta-mimetic in the United States. Recently, the role of terbutaline in the treatment and prevention of preterm labor has been questioned by the FDA. Because the off-label use of drugs is a formally accepted practice in medicine when scientific studies support such use, we reviewed the currently available clinical literature on terbutaline use in various routes of delivery: intravenous, oral, and subcutaneous via infusion pump. This review describes the clinical evidence that supports the safe and effective use of terbutaline as a tocolytic agent in certain patient populations. Practicing physicians should continue to have unrestricted use of terbutaline for tocolysis as one of the few remaining therapeutic options remaining in the fight against preterm birth.

TRANSFAC, TRRD and COMPEL: towards a federated database system on transcriptional regulation.

Three databases that provide data on transcriptional regulation are described. TRANSFAC is a database on transcription factors and their DNA binding sites. TRRD (Transcription Regulatory Region Database) collects information about complete regulatory regions, their regulation properties and architecture. COMPEL comprises specific information on composite regulatory elements. Here, we describe the present status of these databases and the first steps towards their federation.

TRANSFAC database as a bridge between sequence data libraries and biological function.

The TRANSFAC database contains information about regulatory DNA sequences and the proteins (transcription factors) binding to and acting through them. It may thus serve as a dictionary for the biological meaning of these sequence elements. Moreover, the TRANSFAC data can be used to describe these elements, to define consensi and matrices for elements of certain function, and thus to provide means of identifying regulatory signals in newly unravelled genomic sequences.

Combining structural analysis of DNA with search routines for the detection of transcription regulatory elements.

MOTIVATION: Analysis of unannotated genomic sequences for regulatory regions depends on a reliable recognition of individual cis-acting elements. Since some of them have a very low conserved sequence pattern, additional criteria are required. RESULTS: Using molecular modelling techniques, we have created a complete database for the conversion of base sequences into profiles of structural parameters of DNA. On this basis, search routines can be developed that scan for profile matches. They may be used instead of or, probably most appropriate in most cases, in combination with conventional sequence pattern searches.

The effect of specific hormones on fibrinolysis in pregnancy.

OBJECTIVE: Plasminogen activator inhibitor-1, the major serum protease inhibitor of fibrinolysis, increases steadily during pregnancy. The study objective was to examine four hormones, namely, estradiol-17 beta, progesterone, prolactin, and hydrocortisone to determine their individual contributions in the production of tissue plasminogen activator antigen, plasminogen activator inhibitor-1 antigen, and plasminogen activator inhibitor-1 activity. STUDY DESIGN: Human umbilical vein endothelial cells were grown with physiologic third-trimester concentrations of the above hormones, and fibrinolytic parameters were measured. RESULTS: Of the four hormones evaluated, only hydrocortisone significantly increased plasminogen activator inhibitor-1 antigen and activity at both concentrations tested (p < 0.001). Estradiol-17 beta significantly increased tissue plasminogen activator antigen and progesterone significantly decreased tissue plasminogen activator antigen, but neither affected the overall fibrinolytic balance. CONCLUSION: Hydrocortisone demonstrated antifibrinolytic properties at physiologic concentrations in pregnancy, suggesting that there may be a role for hydrocortisone in the prothrombotic tendency associated with pregnancy. The overall process of fibrinolysis was unaffected by estradiol-17 beta, progesterone, or prolactin.

The use of second-trimester genetic sonogram in guiding clinical management of patients at increased risk for fetal trisomy 21.

OBJECTIVE: To test the efficacy of ultrasound in detecting fetuses with trisomy 21. METHODS: From November 1, 1992, to December 31, 1995, a second-trimester genetic sonogram was offered to all women with singleton fetuses at increased risk (at least 1:274) for trisomy 21, who had either declined genetic amniocentesis or chose to have a sonogram before deciding whether to undergo an amniocentesis. In addition to standard fetal biometry, the following ultrasound markers for aneuploidy were evaluated: structural anomalies (including face, hands, and cardiac [four-chamber view and outflow tracts]), short femur, short humerus, pyelectasis, nuchal fold thickening, echogenic bowel, choroid plexus cysts, hypoplastic middle phalanx of the fifth digit, wide space between the first and second toes, and two-vessel umbilical cord. Outcome information included the results of genetic amniocentesis, if performed, or the results of postnatal pediatric assessment and follow-up. RESULTS: Five hundred seventy-three patients had a genetic sonogram between 15 and 23 weeks' gestation: 378 patients had advanced maternal age (at least 35 years), 141 had abnormal serum biochemistry, and 54 had both. The majority (495, or 86.3%) had a normal genetic sonogram (absence of abnormal ultrasound markers); 51 (9%) had one marker present, and 27 (4.7%) had two or more markers present. Outcome was obtained on 422 patients (the remaining were ongoing pregnancies or were lost to follow-up). Twelve of 14 fetuses with trisomy 21, one fetus with trisomy 13, and one fetus with triploidy had two or more abnormal ultrasound markers present; one fetus with trisomy 21 had one abnormal marker and one had a completely normal ultrasound. When one or more abnormal ultrasound markers were present, the sensitivity, specificity, and positive and negative predictive values for trisomy 21 were 92.8%, 86.7%, 19.4%, and 99.7%, respectively. When two or more abnormal ultrasound markers were present, the corresponding values were 85.7%, 96.8%, 48%, and 99.5%. In the study population, the amniocentesis rate was 12.7% overall and 17.3% in cases with known outcome. CONCLUSION: Second-trimester genetic sonogram may be a reasonable alternative for patients at increased risk for fetal trisomy 21 who wish to avoid amniocentesis. In experienced hands, this approach may result in a high detection rate of trisomy 21 (93%), with an amniocentesis rate of less than 20%.