Information preferences of high literacy pregnant women regarding informed consent models for genetic carrier screening.

OBJECTIVE: With the increasing carrier screening options being offered to pregnant women, it is critical to consider what information women want in an informed consent process, and how they make decisions regarding screening. METHODS: We surveyed 201 pregnant women. RESULTS: Subjects prefer "to have as much information as possible" (84%), and valued their physician's recommendations (82%) regarding screening. After reviewing two hypothetical scenarios, 71% of participants preferred more information about genetic carrier screening; however, some participants expressed concern that too much information can also lead to anxiety. When specifically asked about components of a potential informed consent process, the highest preferences were to include: the chance of having a child with the disorder (97%), the options for carriers (93%), the value and purpose of testing (91%), and the prognosis if a child has the disease (94%); preference for "symptoms" information differed based on scenario preference (p<0.001). CONCLUSION: This study is the first to document variation in patients' views regarding the information desired as part of the informed consent process. PRACTICE IMPLICATIONS: Providers should consider ways to ascertain their patients' preferred informational style, and how to provide information in the amount and style that patients find useful in making decisions.

Antipicornavirus activity of SCH 47802 and analogs: in vitro and in vivo studies.

SCH 47802 and its derivatives are potent inhibitors of enteroviruses in vitro. The IC50 for SCH 47802 ranges from 0.03 to 10 micrograms/ml when tested against a spectrum of enteroviruses in plaque reduction assays. The compounds have in vitro therapeutic indices of at least 81 based on viral cytopathic effect (CPE) assays. The in vitro activity of SCH 47802 translates into in vivo activity in the murine model of poliovirus encephalitis. In an oral dosing regimen, SCH 47802 protects mice from mortality at 60 mg/kg per day. Consistent with the in vivo efficacy, pharmacokinetic analyses after oral dosing with SCH 47802 demonstrate serum levels of the compound above the in vitro IC50 for poliovirus for at least 4 h. SCH 47802 and its active analogs stabilize poliovirus to thermal inactivation indicating that the compounds bind to the virus capsid. Mechanistic studies with poliovirus indicate that SCH 47802 acts early in viral infection. This series of molecules represents potential candidates for the treatment of human enterovirus infections.

SCH 43478 and analogs: in vitro activity and in vivo efficacy of novel agents for herpesvirus type 2.

SCH 43478 and analogs are a class of non-nucleoside antiviral agents that have potent and selective activity against herpes simplex virus type 2 (HSV-2). The IC50 for these compounds in plaque reduction analysis using Vero cells ranges from 0.8 to 2.0 microg/ml. All compounds have a LC50 > 100 microg/ml in cytotoxicity analysis. Mechanism of action studies suggest that these molecules have an effect on the transactivation of viral immediate early (alpha) gene expression. Time of addition studies indicate that antiviral activity of these analogs is limited to the initial 2-3 h after infection and is not due to inhibition of viral adsorption or penetration. Analysis of HSV protein expression demonstrates that SCH 49286 inhibits the accumulation of viral immediate early (alpha) gene products. SCH 43478 demonstrates statistically significant efficacy (P < 0.05) in the guinea pig genital model of HSV infection. Following subcutaneous administration in a therapeutic treatment regimen, SCH 43478 (90 mg/kg/day) is efficacious in reducing the number and severity of lesions and the neurological complications of acute HSV infection. Thus, SCH 43478 and analogs are anti-herpesvirus agents with a unique mechanism of action.

The role of fetal growth restriction and gestational age on length of hospital stay in twin infants.

OBJECTIVE: To evaluate the association between length of gestation and fetal growth restriction (FGR) and the role of FGR in neonatal morbidity as determined by length of hospital stay among newborn twins. METHODS: Using a race-, gender-, and gestational age-specific birth weight and length of hospital stay singleton standard, 490 twin infants were classified as FGR (at or below the tenth percentile) or non-FGR (above the tenth percentile). Length of stay and length-of-stay ratio (twin stay divided by the 50th percentile singleton stay) were calculated for each twin. Analysis included stepwise multiple regression for length of stay and length-of-stay ratio, and analysis of variance with main effects and second-order interactions for the length-of-stay measures using factors significant in the multiple regression models. RESULTS: For length of stay, significant factors in the multiple regression model included respiratory distress syndrome (RDS), gestation category, FGR, sepsis, time of birth (1979-1984 versus 1985-1989), and cesarean delivery. For length-of-stay ratio, significant factors included FGR, gestation category, sepsis, period of birth, cesarean delivery, and hyperbilirubinemia. The analysis of variance showed that RDS had the greatest effect on length of stay, whereas FGR had the greatest effect on length-of-stay ratio. For both dependent variables, the effect of FGR was magnified when compounded by significant neonatal complications (RDS, sepsis, hyperbilirubinemia) or gestation category. CONCLUSIONS: Fetal growth restriction is a major factor in the neonatal morbidity of twins. Early recognition of and interventions for FGR in twin gestations should be a primary goal for reducing both immediate and long-term adverse outcomes.

Underestimation of gestational age by conventional crown-rump length dating curves.

Inaccuracies in gestational age assignment based on published crown-rump length data were noted in patients with known ovulation dates. In this study, we tested the hypothesis that crown-rump length data derived from pregnancies with known ovulation dates differ from those of menstrually timed pregnancies. Seventy-two previously infertile women with known dates of ovulation had crown-rump length measurements from 35-79 days postovulation. We transformed the data to menstrual age (gestational age) by adding 14 days to the date of ovulation and compared our crown-rump length values with those of two previous reports. At corresponding crown-rump length values, the gestational ages from our data differed from those in the previous studies. We suggest using crown-rump length dating curves based on ovulation-timed pregnancies because crown-rump length data derived from menstrually dated pregnancies underestimate true gestational age.

Sonographic diagnosis of congenital heart disease: comparison between the four-chamber view and multiple cardiac views.

OBJECTIVE: To report our experience in the detection of congenital heart disease using both the four-chamber view of the heart as part of the standard obstetric ultrasound examination and multiple cardiac views as part of the detailed targeted examination. METHODS: All admissions to Children's Memorial Hospital of Northwestern University Medical Center with the diagnosis of congenital heart disease between June 1988 and April 1992 were identified (N = 1947). These admissions were matched to deliveries (N = 19,321) that occurred at Prentice Women's Hospital during the same period; of these, 10,004 had at least one obstetric ultrasound examination. All fetuses were scanned either with the standard obstetric ultrasound type of examination, featuring only the four-chamber view of the heart, or by the detailed targeted imaging type of study, featuring multiple cardiac views. The type of examination performed was based on the specific request of the attending obstetrician or gynecologist. RESULTS: Thirty-three neonates who had at least one obstetric ultrasound examination were treated for congenital heart disease. An additional five pregnancies were terminated secondary to serious fetal heart defects. When only the four-chamber view was visualized, 11 of 33 fetuses (33.3%) with confirmed congenital heart disease were detected. CONCLUSIONS: Assessment of the outflow tracts is crucial for detection of many forms of congenital heart disease. However, before this is accepted as the standard of care, both the obstetric and radiologic communities should develop their skills in cardiac imaging. Only then can this sophisticated type of cardiac examination be offered to pregnant women.

The changing pattern of infant mortality in the US: the role of prenatal factors and their obstetrical implications.

Infant mortality is one of the leading public health problems in the United States today. During the first half of this century the decline in infant mortality resulted largely from a reduction in postneonatal deaths (2-11 months after birth). Since 1950, two-thirds of all infant deaths have occurred in the neonatal period (1st month after birth). Since 1981, the rate of decline in the infant mortality rate has slowed due to a deterioration in the distribution of birthweights and a slowed improvement in birthweight-specific mortality rates. The role of birthweight is central to this issue, because low birthweight (LBW, < 2500 g) is a major determinant of death in the first year of life, particularly during the neonatal period. Stated another way, less than 0.5% of infants with birthweights > 2500 g die during the first year of life compared to 10.2% of infants with birthweights < 2500 g and 45.3% with birthweights < 1500 g (very low birthweight, VLBW). These effects are magnified when evaluated on a race-specific basis: the rate of LBW is twice as high and the rate of VLBW is three times as high for black infants compared to white infants. Reducing the rates of VLBW and LBW, particularly among blacks, holds the greatest potential for future reductions in infant mortality in the United States. The important role of maternal factors in the antecedents of infant mortality (VLBW, LBW, intrauterine growth retardation, preterm birth) have been clearly and repeatedly demonstrated. Some of these factors, such as maternal race, adverse obstetrical history and low level of education, are not amenable to change during pregnancy. Other factors, such as cessation of smoking, higher maternal weight gain and the initiation of early prenatal care have been shown to improve the course and outcome of pregnancy and subsequently result in reduced infant mortality.

What do patients prefer: informed consent models for genetic carrier testing.

The recent increased number of conditions for which patients can undergo genetic carrier testing raises the question of how best to obtain pre-test informed consent. Clinical approaches vary from a minimalist model to a model where patients are given detailed information about all conditions to be screened for. Few data exist as to patient preferences, or how information impacts decision-making. Eight high-literacy focus groups were conducted to assess the knowledge and preferences of pregnant patients and their male partners. Most groups indicated that some balance between details and brevity was optimal, recognizing that anxiety can occur when patients are provided with too much information and that the wide range of tests offered during pregnancy often led to confusion. Critical areas for the informed consent process included (1) details about the conditions and risk of being a carrier, (2) logistics of testing, (3) next steps if the test is positive, and (4) prognosis, options and resources if the child were to be affected with a disorder. It will be useful to develop model consent programs and prospectively assess their impact on informed consent and patient satisfaction, both when positive and negative results are received.

When does a statistical fact become an ethical imperative?

Trial of labor is a safe and effective management alternative but remains underused in current clinical practice. To explore whether this underuse is justified, decision analysis is developed to compare a trial of labor with elective repeat cesarean section. With the use of available probability estimates and outcome scoring based on a survey of perinatologists, decision analysis identifies trial of labor as superior to elective repeat cesarean section for both the mother and the neonate. Going beyond the simple comparisons of management options and outcomes, the ethical implications of such results are discussed in terms of "utility ethics," "informed consent," and "universal equality." Such considerations suggest that there is a professional (ethical) responsibility to increase the application of trial of labor.

The Northwestern University Twin Study. XV: Rationales for a standard of care in compromised twin pregnancies.

Current antenatal technologies have improved the obstetrician's ability to assess fetal well-being as well as to diagnose fetal compromise. These technologies have given rise to very difficult ethical issues in the management of compromised twin pregnancies: for example, a choice must be made between putting a healthy twin at risk due to preterm delivery for the sake of a compromised cotwin or of allowing the compromised twin to die in order to buy time for the healthy twin. Though each case is unique, good medical practice requires a standard of care by which consistent patient management can be proposed. In the pluralistic environment of Northwestern Memorial Hospital, our staff has favored a standard of care based on patient autonomy. This approach demands: 1) a practitioner who offers a thorough explanation of the diagnosis and possible treatment approaches; 2) time for the patient and her partner to assimilate this information and test treatment options against their personal value system; 3) a third, but disinterested, party to facilitate patient understanding and value clarification; 4) a practitioner either willing to support the patient's decisions or refer her to another practitioner who will.

Vaginal birth after cesarean section for arrest of labor: is success determined by maximum cervical dilatation during the prior labor?

The charts of 229 patients who attempted a vaginal birth after a cesarean section were reviewed. A total of 103 patients had a prior cesarean section for either failure to progress or cephalopelvic disproportion. On the basis of the maximum cervical dilatation in the prior labor, the patients were categorized into three groups: 0 to 5 cm, 6 to 9 cm, and 10 cm. The success rates for vaginal delivery of 61%, 80%, and 69%, respectively, were not significantly different among groups (p = 0.31). When arrest of labor was not the indication for primary cesarean section, 78% of the patients were subsequently delivered of their infants vaginally. This was not significantly different from the 70% overall success rate achieved by the group with failure to progress or cephalopelvic disproportion (p = 0.17). Similarly, when the success rate for a trial of labor was plotted against neonatal birth weight, the trends were comparable in the groups with and without failure to progress or cephalopelvic disproportion. These data suggest that patients with a prior cesarean section for arrest of labor are good candidates for a trial of labor and that the cervical dilatation previously reached does not determine the likelihood of success.

Fetal heart rate changes after fetal intravascular treatment with pancuronium bromide.

Because of recurrent needle dislodgement secondary to fetal movement, we have altered our intravascular transfusion technique by replacing maternal premedication (meperidine and diazepam [group 1]) with fetal intravascular infusion of pancuronium bromide (Pavulon [group 2]), a nondepolarizing neuromuscular blocking agent. Baseline fetal heart rate, number of accelerations, and variability were assessed before and after transfusion in both groups. Whereas there were no changes after transfusion in the former group, those fetuses who received pancuronium bromide demonstrated a dramatic abolishment of accelerations and decrease in variability, with the heart rate pattern often appearing "sinusoidal-like." These alterations in fetal heart rate were temporary changes that reverted to normal once the fetus "awakened" from the neuromuscular blockade. We speculate that these changes in fetal heart rate are secondary to the interaction of the reported hypertensive and vagolytic effects of pancuronium bromide.

Factors that influence route of delivery--active versus traditional labor management.

OBJECTIVE: Our purpose was to compare maternal and fetal factors that influence the route of delivery with active management of labor and a traditional labor management protocol. STUDY DESIGN: Data were collected prospectively on 346 consecutive patients receiving active management of labor and 354 patients who were managed traditionally. Within each group demographic and labor characteristics of patients undergoing cesarean section were compared with those of patients having vaginal deliveries by means of the Student t test, chi 2 analysis, and stepwise logistic regression. RESULTS: With both active management of labor and traditional labor management success in achieving vaginal delivery was related to the station of the fetal vertex at admission, the need for oxytocin augmentation of labor, the uterine response to oxytocin, the use of epidural anesthesia, and the development of chorioamnionitis. By means of multiple logistic regression analysis maternal age, height, payor status, and birth weight were also identified as risk factors for cesarean section with traditional labor management but not with active management of labor. CONCLUSIONS: Differences were identified in risk factors for cesarean section between active management and traditional labor management. Active management of labor may diminish or eliminate some patient characteristics as risk factors for cesarean birth.

The efficacy of oral terbutaline after intravenous tocolysis.

OBJECTIVE: Our purpose was to investigate in a prospective, randomized study the efficacy of oral terbutaline after successful intravenous tocolysis in reducing preterm birth. STUDY DESIGN: Patients between 28 and 35 weeks' gestation with uterine contractions and change in cervical examination were treated with intravenous magnesium sulfate for 12 to 24 hours. After successful tocolysis patients were approached for study participation and randomized to receive either oral terbutaline or no therapy. The dose of terbutaline was individualized to achieve a maternal pulse > 100 beats/min, and terbutaline was continued until 36 completed weeks of gestation. Recurrent preterm labor (contractions with change in cervical examination) for either group was treated with intravenous magnesium sulfate, and subsequent treatment was based on the previous randomization. RESULTS: Fifty-five patients were enrolled (28 terbutaline, 27 no oral tocolytic). No difference was found between groups with respect to time gained (4.0 +/- 2.7 vs 4.6 +/- 3.1 weeks, p = 0.412), gestational age at delivery (35.6 +/- 2.7 vs 36.1 +/- 2.4 weeks, p = 0.562), > or = 37 weeks at delivery (nine vs 13, p = 0.291), recurrent preterm labor (10 vs four, p = 0.104), recurrent uterine contractions alone (five vs eight, p = 0.527), birth weight (2616 +/- 633 gm vs 2645 +/- 599 gm, p = 0.785), special care nursery admissions (eight vs six, p = 0.759), or neonatal respiratory distress syndrome (three vs two, p = 0.965). CONCLUSION: The use of oral terbutaline after successful parenteral tocolysis failed to reduce the rate of preterm birth.

Estimation of birth weight by use of ultrasonographic formulas targeted to large-, appropriate-, and small-for-gestational-age fetuses.

This report sought to determine whether estimates of fetal weight are enhanced by using ultrasonographic formulas targeted to the large-, appropriate-, and small-for-gestational-age fetus in both preterm and term pregnancies. Ultrasonographic fetal measurements from 575 singleton pregnancies were obtained within 7 days of delivery. The first 194 fetuses were classified into three groups on the basis of the growth percentile rank of the abdominal circumference (greater than or equal to 90%, greater than 5% and less than 90%, and less than or equal to 5%). Regression analyses were performed to generate three formulas for estimating fetal weight on the basis of the following: Gestational age (weeks) + Head circumference (cm) + 2 x Abdominal circumference (cm) + Femur length (cm). This mathematic model allowed formulation of accurate and concise tables relating the sum of these measurements to estimated birth weight. The accuracy of these formulas was then prospectively compared, first, with the formula published by Hadlock et al. (in 32 large-, 279 appropriate-, and 70 small-for-gestational-age fetuses) and second, with the formula of Weiner et al. (in 82 preterm fetuses). The difference between actual and estimated birth weights generated by the three study formulas had no systemic error (t test, p greater than 0.05). Cumulatively, there was a statistically significant reduction of random error in the birth weight estimates by use of the three study formulas versus the best single formulas of Hadlock et al. (2 SD reduced from 21.6% to 19.8% and absolute 2 SD reduced from 15.6% to 12.2%). Additionally, the three study formulas resulted in a statistically significant reduction in the absolute 2 SD error compared with the best formula by Weiner et al. in fetuses less than or equal to 34 weeks' gestation (2 SD reduced from 19.1% to 13.6%).

Cesarean section rates in low-risk private patients managed by certified nurse-midwives and obstetricians.

This study was designed to assess the impact of selected medical interventions during labor upon cesarean section rates by comparing the maternal and neonatal outcomes of obstetrician- and nurse-midwife-managed low-risk private patients. All patients who delivered at Prentice Women's Hospital in Chicago, Illinois, from January 1, 1987 through December 31, 1990 were evaluated for low-risk criteria to be included in the study. During that time, the nurse-midwives delivered 573 patients and the obstetricians delivered 12,077 patients. Patients with fetal and maternal complications known to increase the cesarean section rate were eliminated from both groups. Eight percent of the nurse-midwife patients and 32% of the physician patients were eliminated, leaving 529 nurse-midwife patients and 8,266 physician patients. These patients were compared for race, parity, age, and birth weight. Information was collected from a perinatal data base and hospital computerized statistics. The rates of cesarean section, administration of oxytocin, analgesia, anesthesia, and infant outcome data were compared by chi-square analysis. Multiple logistic regression analysis was used to assess factors that predicted cesarean section. Nurse-midwife-managed patients had a significantly lower rate of cesarean section (8.5% versus 12.9%; P < .005) and operative vaginal delivery (5.3% versus 17%, P = .0001) than the physician-managed patients. Epidural anesthesia and oxytocin for induction and augmentation were used significantly more frequently in the physician-managed patients. Both interventions were associated with an increased rate of cesarean section. Fetal outcomes in the two groups were not statistically different. Women cared for by nurse-midwives had a lower cesarean section rate, fewer interventions, and equally good maternal and infant outcomes when compared with those cared for by physicians.

The ideal twin pregnancy: patterns of weight gain, discordancy, and length of gestation.

OBJECTIVE: Our purpose was to evaluate factors associated with the best intrauterine growth and lowest morbidity among twins ("ideal twin pregnancy"). STUDY DESIGN: A historic prospective study of 163 twin births was performed. Ten models were formulated with multiple regression and multivariate logistic regression. RESULTS: In the models of birth weight, gestations of 28 to 36 and 39 to 41 weeks, black race, > or = 15% discordancy, and smoking were all significant negative factors. The pattern of early low weight gain (< 0.85 pounds per week before 24 weeks) and late low weight gain (< 1.0 pound per week after 24 weeks) was negatively associated with all eight models of intrauterine growth. CONCLUSIONS: The best intrauterine growth and lowest morbidity is achieved earlier for twins than for singletons. Using length of stay and growth retardation criteria, nearly 70% of "ideal" twin pregnancies were between 35 and 38 weeks. In addition, poor weight gain and poor patterns of weight gain were associated with all measures of intrauterine growth and adverse pregnancy outcomes.

Severe acidosis and subsequent neurologic status.

To examine the relationship between severe acidosis at birth and evidence of subsequent neurologic dysfunction, a 4-year review was performed encompassing 15,528 neonates. One hundred forty-two (0.91%) of these neonates had an umbilical cord arterial pH less than or equal to 7.05 with a base deficit greater than or equal to mEq/L. Neurologic assessments found 101 of 110 term neonates (91.8%) and 17 of 32 preterm neonates (53.1%) with severe acidosis to be free of neurologic deficits at the time of hospital discharge. Follow-up developmental evaluation data were available for 7 of 9 term neonates and 8 of 15 preterm neonates with abnormal examinations. Although 5 term and 6 preterm infants demonstrated mild developmental delays or mild tone abnormalities in the first year of life, none exhibited a major motor or cognitive abnormality at 12 to 24 months of age. Consequently, acidosis in umbilical cord blood, even when severe, is a poor predictor of subsequent neurologic dysfunction.

Factors influencing hemostasis after umbilical vein puncture in vitro.

Bleeding from the site of cordocentesis can be detected by ultrasound examination, but significant hemorrhage into the amniotic fluid rarely occurs. To evaluate the relative contribution of amniotic fluid thromboplastins and the quantity of Wharton's jelly in facilitating coagulation at the puncture site, amniotic fluid samples and umbilical cord segments were obtained at cesarean section from 20 patients. After puncture of the umbilical vein, bleeding times were measured in amniotic fluid and 0.9% sodium chloride. The quantity of Wharton's jelly was assessed by measuring umbilical cord circumference. Mean bleeding times were significantly shorter in amniotic fluid compared with saline solution, but there was no consistent relationship between bleeding times and umbilical cord circumference. We conclude that properties of amniotic fluid facilitate coagulation at the site of umbilical vein puncture.

Prediction of fetoplacental blood volume in isoimmunized pregnancy.

Direct intravascular fetal transfusion under ultrasound guidance allows precise evaluation of both fetal anemia and adequacy of therapy. In addition, the change in hematocrit after transfusion may be used to estimate the circulatory fetoplacental blood volume. In this study we present the estimates of fetoplacental blood volume calculated at the time of intravascular fetal transfusions. Between March 1986 and March 1988, 60 intravascular fetal transfusions were performed in 20 patients. The 56 procedures in which fetal hematocrits were obtained both before and after transfusion were analyzed. The mean fetoplacental blood volume before transfusion was 94.0 ml/kg. Furthermore, the fetoplacental blood volume per kilogram fetal weight decreased with advancing gestation. These estimates of fetoplacental blood volume and changes relative to gestational age may be useful in the treatment of the severely isoimmunized fetus. Reliance on the more recently generated fetoplacental blood volumes may allow more accurate predictions of transfusion volumes and estimation of the hematocrit after transfusion.