Faculty Bibliography

The object was to determine whether there is a correlation between the obstetric history and the ultrasonographically determined endocervical canal length between 15 and 24 weeks gestation. A retrospective cohort study was performed in singleton pregnancies of multigravidas with normal and abnormal obstetric histories. They underwent sonographic evaluation for the determination of the endocervical canal length between 15 and 24 weeks gestation. The shortest endocervical canal length measurements between 15 and 20 weeks and also between 21 and 24 weeks of gestation were recorded. An ultrasound diagnosis of cervical incompetence was defined as progressive shortening of the endocervical canal length to <2 cm or a single endocervical canal length measurement <2 cm. A multivariable general linear regression model was used to correlate the relationship between endocervical canal lengths at 15-20 weeks and 21-24 weeks gestation in the current pregnancy with the earliest gestational age at delivery of prior pregnancies. Chi-square test was used to determine the relationship between the development of an ultrasound diagnosis of cervical incompetence and the earliest gestational age at delivery of prior pregnancies. A total of 155 pregnancies were studied. The number of women according to the obstetric history categories were: 57 had delivered <24 weeks, 12 between 24 and 26 weeks, 16 between 27 and 32 weeks, 16 between 33 and 36 weeks, and 54 delivered > or =37 weeks. There was a significant correlation between the endocervical canal length measurements between 15-20 (P < 0.0001) weeks and 21-24 weeks (P < 0.0001) in the studied pregnancy and the earliest gestational age at delivery of prior pregnancies. A significant relationship between the ultrasound diagnosis of cervical incompetence and the obstetric history category (P = 0.0026) was observed. There were 36 cases of ultrasound diagnosed cervical incompetence with 91.7% (33/36) occurring in women who had a prior <27 weeks' gestation delivery. These data provide further evidence that cervical incompetence is a relative condition and not an 'all or none' phenomenon. In addition, women with a prior delivery <30 weeks gestation should be followed with second trimester serial cervical sonography to rule out cervical incompetence

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/METHODS: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.

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/METHODS: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%.

OBJECTIVE: To determine the weekly cervical shortening rates of the endocervical canal between 15 and 24 weeks' gestation in women at risk for pregnancy loss or spontaneous preterm birth. METHODS: We performed a retrospective cohort study of transvaginal sonographic measurements of the endocervical canal length done at least twice between 15 and 24 weeks' gestation in women at risk for pregnancy loss and spontaneous preterm birth. The ultrasound diagnosis of cervical incompetence was defined as progressive shortening of the endocervical canal length to 2 cm or less either spontaneously or after application of transfundal pressure. Multivariable linear regression models were developed to determine the weekly crude rate of endocervical canal length shortening rates in cases of competent cervices and incompetent cervices, with incompetent cervices further stratified as those diagnosed at 15-19 weeks' and 20-24 weeks' gestation. Comparisons of the models for weekly rate of endocervical canal length shortening were performed. RESULTS: The endocervical canal lengths were measured in 61 women (180 measurements) who did not develop ultrasound evidence of cervical incompetence and 28 women (103 measurements) who had ultrasound evidence of cervical incompetence. Between 15 and 24 weeks' gestation, competent cervices had a nonsignificant rate of endocervical canal length shortening (-0.03 cm/week). During this period in gestation, incompetent cervices had significantly greater endocervical canal length shortening (-0.41 cm/week, P < .001). The rate of endocervical canal length shortening of incompetent cervices diagnosed between 15 and 19 weeks' gestation was -0.52 cm/week (P < .001). The rate of endocervical canal length shortening in incompetent cervices diagnosed between 20 and 24 weeks' gestation was significant and varied from -0.49 cm/week to -0.80 cm/week at 20 and 24 weeks' gestation, respectively (P < .001). The models describing the rate of cervical shortening in the two groups of incompetent cervices were significantly different (P < .001). The sonographic detection of endocervical canal length shortening in the 28 cases of cervical incompetence was identified at a median (range) gestational age of 20 (16-24) weeks. CONCLUSION: Weekly rates of endocervical canal length shortening were established, which may be useful for detecting and managing cervical incompetence in high-risk women examined with cervical sonography

OBJECTIVE:To establish fetal growth nomograms for twin gestations, categorized by placental chorionicity, and to compare them with those of published singleton and twin nomograms. METHODS:Computerized data files of live births of all twins delivered between January 1990 and October 1996 at Saint Peter's Medical Center were used. Birth weight curves corresponding to the fifth, tenth, 50th, 90th, and 95th percentiles were derived separately for twins with monochorionic and dichorionic placentation. We generated the curves by applying the method of generalized estimating equations, after adjusting for the potential intracluster correlation due to twinning. The curves were then smoothed on the basis of nonparametric restricted cubic splines to derive (smoothed) birth weight percentiles. We then compared our twin birth weight nomogram to six previously published singleton and two twin nomograms published previously for predicting small for gestational age infants (defined as birth weight below the tenth percentile). RESULTS:Among 1302 twin fetuses, 272 (21%) were monochorionic. Twins from monochorionic gestations weighed, on average, 66.1 g (standard deviation 28.4 g, P = .02) less than twins from dichorionic gestations after correcting for gestational age. Twin curves based on parity (nulliparity versus multiparity) were not different from each other. Analyses indicate that all previously published singleton nomograms approximate twin growth reasonably well between 32 and 34 weeks, but they underestimate twin growth at earlier gestational ages (between 25 and 32 weeks) and overestimate twin growth beyond 34 weeks' gestation. Similarly, a comparison of previously published twin nomograms with those of ours indicates that the growth standards in our population were similar to those in other published twin nomograms. CONCLUSION/CONCLUSIONS:We recommend that future epidemiologic and clinical studies use twin nomograms to identify growth-restricted twin fetuses. Moreover, because fetal growth is influenced by placental chorionicity, we recommend that fetal growth assessment in twin gestations consider placental chorionicity, whenever the information is available.

OBJECTIVE:To examine the cost-effectiveness of prenatal carrier screening for cystic fibrosis. METHODS:A cost-benefit equation was developed that was based on the hypothesis that the cost of prenatal diagnosis required to diagnose and prevent one case of cystic fibrosis should be equal to or less than the lifetime cost generated from the birth of a neonate with cystic fibrosis. The formula was adjusted because a woman's positive or negative carrier status remains unchanged, thus eliminating the need for testing in subsequent pregnancies. The formula was manipulated to identify the optimal cost per screening test, as well as the net cost savings per prenatally diagnosed case of cystic fibrosis for various racial or ethnic groups. Sensitivity analyses included some key assumptions regarding the cost per screening test ($50-150), patient screening acceptance rates (25-100%), and therapeutic abortion rates (50-100%). RESULTS:Assuming therapeutic abortion rates of 50-100%, the net savings per prenatally diagnosed case of cystic fibrosis are $58,369-$382,369 among whites. Given the previously reported patient screening acceptance rates of 50-78%, the overall annual cost savings in the United States for whites are $161-251 million. However, the screening program was not found to be cost-effective for blacks, Asians, or Hispanics. CONCLUSION/CONCLUSIONS:Under most assumptions and sensitivity analyses, a prenatal cystic fibrosis-carrier screening program appears to be cost-effective.

OBJECTIVE:To determine 1) the diagnostic accuracy requirements of first-trimester genetic sonography from the cost-benefit point of view and 2) the economic impact of first-trimester genetic sonography for the United States on the basis of the accuracy of previously published studies. METHODS:A cost-benefit equation was developed on the basis of the hypothesis that the cost of chorionic villus sampling (CVS) in pregnant women with advanced maternal age (at least 35 years old) should be at least equal to the cost of genetic sonography with CVS used only for those with abnormal ultrasound results. The components of the equation included the diagnostic accuracy of genetic ultrasound (sensitivity and specificity for detecting Down syndrome), the costs of the CVS package and genetic ultrasound, and the lifetime cost of Down syndrome cases. RESULTS:First-trimester genetic sonography was found to be beneficial if the overall sensitivity for detecting Down syndrome was greater than 70%, and even then, the cost-benefit ratio depended on the corresponding false-positive rate. The required minimum ultrasound sensitivity varied according to the maternal age-specific prevalence of Down syndrome and ranged between 40% (for women 35 years old) to 96% (for women 44 years old). Of eight published cohorts using nuchal translucency thickness for genetic sonography, five had accuracies of genetic ultrasound compatible with net benefits. CONCLUSION/CONCLUSIONS:The benefits of first-trimester genetic sonography depend on its diagnostic accuracy. First-trimester genetic sonography has the potential for annual savings of 22 million dollars in the United States.

We tested the accuracy of a mathematical model based on computer analysis of the fetal heart rate tracing in predicting umbilical artery pH at birth. In a previous report based on data on 38 growth-restricted fetuses, the second-order polynomial regression equation, umbilical artery pH = 7.28 + 0.002 (duration of episodes of low variation in minutes) + 0.00009 (duration of episodes of low variation in minutes), was retrospectively found to be the best model for the prediction of umbilical artery pH at birth. In the present study, this formula was prospectively tested in 29 growth restricted fetuses between 26 and 37 weeks of gestation from pregnancies with abnormal uterine and/or umbilical artery Doppler velocimetry. Computer analysis of the fetal heart rate tracing of 1 hour duration was performed within 1.5-6 hours of cesarean birth prior to the onset of labor. Umbilical artery cord blood was collected at birth with pH determined within 5 minutes of collection. Acidemia was defined as umbilical artery pH < 7.20, preacidemia pH 7.20-7.25 and nonacidemia pH > 7.25. Then, the data on all 67 growth-restricted fetuses were pooled to generate a new formula that was retrospectively assessed against the entire group. Values are reported as median (range). In the 29 prospectively evaluated cases, there was no statistical difference between the predicted and actual umbilical artery pH at birth [7.28 (7.1-7.29) vs. 7.28 (7.18-7.37), P = 0.57]. The median difference between the paired predicted and actual umbilical artery pH values was -0.001 (-0.10-0.08). The difference between the predicted and actual umbilical artery pH was zero and within +/- 0.04 in 17% (5/29) and 76% (22/29) of the cases, respectively. When the data on the 67 growth-restricted fetuses were pooled together the formula did not change. There was no difference between the predicted and actual umbilical artery pH at birth when the formula was applied to all 67 growth-restricted fetuses [7.28 (7.08-7.29) vs. 7.27 (6.97-7.37), P = 0.41]. The median difference between the paired predicted and actual pH values was -0.001 (-0.12-0.12). The difference between the predicted and actual umbilical artery pH was zero and within +/- 0.04 in 15% (10/67) and 74% (49/67) of the cases, respectively. The accuracy of the formula in correctly categorizing the umbilical artery pH at birth was: acidemia 67% (8/12), preacidemia 28% (8/29) and nonacidemia 80% (37/46), P < 0.0001. A mathematical formula using the computer analysis index of duration of episodes of low variation reliably predicted umbilical artery pH at birth. This type of noninvasive monitoring may allow for the antepartum estimation and continuous tracking of fetal pH