Faculty Bibliography

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.

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: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%.

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

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 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

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

This study was designed to evaluate the relationship of suspected early neonatal sepsis to umbilical artery and vein levels of interleukin-6 (IL-6) and soluble intracellular adhesion molecule-1 (sICAM-1). Umbilical artery and vein samples from 17 preterm and 6 term pregnancies were assayed for IL-6 (pg/ml) and sICAM-1 (ng/ml). Neonates were categorized as having probable or suspected sepsis vs. no sepsis within 3 days of birth. Levels of IL-6 and sICAM-1 were evaluated based on sepsis status. Neonatal hematologic parameters were correlated with umbilical artery (ua) and vein (uv) levels of IL-6 and sICAM-1. Sensitivity, specificity, positive and negative predictive values for detecting neonates having probable or suspected early sepsis were calculated. There were significant differences of IL-6 levels between suspected sepsis and no infants in the umbilical artery (P < 0.002) and vein (P < 0.0001). The sensitivity, specificity, positive and negative predictive values for detection of suspected early neonatal sepsis using umbilical artery IL-6 levels > 7 pg/ml were 88.5%, 66.6%, 58.8%, 91%, and for umbilical vein levels > 7 pg/ml these values were 88.5%, 93.3%, 88.5%, and 93.3%. Umbilical artery and vein IL-6 levels correlated with both absolute band counts and immature/total neutrophil ratios. sICAM-1 levels were not affected by designated sepsis status. Umbilical cord blood IL-6 (but not sICAM-1) is potentially useful as a marker for suspected early neonatal sepsis.