Obstetricians and gynecologists' practice and opinions of expanded carrier testing and noninvasive prenatal testing.

OBJECTIVE: The objective of this study is to assess the opinions of Fellows of the American College of Obstetricians and Gynecologists on expanded carrier testing (molecular detection of >100 genetic diseases of variable severity) and noninvasive prenatal testing (NIPT). METHODS: A survey conducted between March and August 2012, assessed current use of testing, provision of genetic counseling, types of disorders that should be identified, preferences for future use, ethical aspects, and views on regulatory oversight. RESULTS: Expanded carrier testing was offered to all patients by 15% of the responders and 52.1% upon patient request. Most (67.3%) favored testing only for mutations of known significance. In this study, 79.1% supported the use of NIPT as a screen for Down syndrome for all women with 47.9% viewing NIPT as a complete substitution for invasive testing. Most supported expansion to other aneuploidies (97.5%) and severe early-onset Mendelian disorders (90.4%) but not for adult-onset disorders (29.8%) or nonmedical sex identification (15.7%). A majority (73.2%) believed that NIPT would increase pregnancy terminations for mild disease states. Respondents favored a role for professional societies in providing regulatory oversight. CONCLUSION: Rapid incorporation of new genetic technologies may be limited by the availability of genetic counseling, concerns regarding inclusion of clinically mild disorders, results of unknown significance, and costs.

Short-term neonatal outcomes in diamniotic twin pregnancies delivered after 32 weeks and indications of late preterm deliveries.

OBJECTIVE: We sought to compare neonatal outcomes in twin pregnancies following moderately preterm birth (MPTB), late preterm birth (LPTB), and term birth and determine the indications of LPTB. STUDY DESIGN: We performed a retrospective cohort study. MPTB was defined as delivery between 32(0/7) and 33(6/7) weeks and LPTB between 34(0/7) and 36(6/7) weeks. The composite neonatal adverse respiratory outcome was defined as respiratory distress syndrome and/or bronchopulmonary dysplasia. The composite neonatal adverse nonrespiratory outcome included early onset culture-proven sepsis, necrotizing enterocolitis, retinopathy of prematurity, intraventricular hemorrhage, or periventricular leukomalacia. LPTB cases were categorized as spontaneous (noniatrogenic), evidence-based iatrogenic, and non-evidence-based (NEB) iatrogenic. RESULTS: Of the 747 twin deliveries during the study period, 453 sets met the inclusion criteria with 22.7% (n = 145) MPTB, 32.1% (n = 206) LPTB, and 15.9% (n = 102) term births. Compared with term neonates, the composite neonatal adverse respiratory outcome was increased following MPTB (relative risk [RR] 24; 95% confidence interval [CI] 3.0 to 193.6) and LPTB (RR 13.7; 95% CI 1.8 to 101.8). Compared with term neonates, the composite neonatal adverse nonrespiratory outcome was increased following MPTB (RR 22.3; 95% CI 3.9 to 127.8) and LPTB (RR 5.5; 95% CI 1.1 to 27.6). Spontaneous delivery of LPTB was 63.6% (n = 131/206) and the rate of iatrogenic delivery was 36.4% (n = 75/206). The majority, 66.6% (n = 50/75), of these iatrogenic deliveries were deemed NEB, giving a total of 24.2% (50/206) NEB deliveries in LPTB group. CONCLUSION: Our data demonstrate a high rate of late preterm birth among twin pregnancies, with over half of nonspontaneous early deliveries due to NEB indications. Although our morbidity data will be helpful to providers in counseling patients, our finding of high NEB indications underscores the need for systematic evaluation of indications for delivery in LPTB twin deliveries. Furthermore, this may lead to more effective LPTB rate reduction efforts.

Efficacy of the genetic sonogram in a stepwise sequential protocol for down syndrome screening.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of the genetic sonogram in Down syndrome screening for women who have received the stepwise sequential test. METHODS: This retrospective cohort study included women with singleton pregnancies who underwent stepwise sequential (first-trimester combined and second-trimester serum) screening and then had a genetic sonogram between March 2005 and January 2010. Stepwise sequential Down syndrome risks were multiplied by either a positive or negative likelihood ratio based on the second-trimester sonographic findings to determine the final Down syndrome risk. A final Down syndrome risk of 1:270 or higher was considered screen positive. RESULTS: A total of 6286 women fulfilled our criteria, including 17 with Down syndrome-affected fetuses. After stepwise sequential testing, the Down syndrome detection rate was 88.2% (15 of 17), and after the genetic sonogram, there was a non-significant reduction in detection to 82.4% (14 of 17; P > .05). For the 6269 unaffected pregnancies, the genetic sonogram converted 58 screen-negative results (1%) to positive and 183 screen-positive results (3.1%) to negative. The net effect was a change in the false-positive rate from 6.2% (390 of 6269) after stepwise sequential screening to 4.2% (266 of 6269) after the genetic sonogram. CONCLUSIONS: The genetic sonogram should be applied cautiously for women who have received prior prenatal screening tests. Women with screen-positive results need to be counseled that a negative sonographic result can be falsely reassuring. Conversely, for women with screen-negative results who have a risk close to the cutoff, a sonographic examination could assist in the decision of whether to accept or reject amniocentesis.

The ObGyn clerkship: are students denied the opportunity to provide patient care and what is the role of gender?

OBJECTIVE: We sought to study the frequency, and reasons that third-year medical students on an ObGyn clerkship are denied the opportunity to be involved in patient care. METHODS: Students from four hospitals affiliated with the University of Connecticut Medical School completed an anonymous postclerkship survey. RESULTS: Among the 157 students studied (66 males and 91 females), 51% (n = 80) were denied the opportunity to participate in a gynecologic examination and 47% (n = 73) were denied the opportunity for routine ObGyn care by patients. Among these students, 55% (n = 44) and 38% (n = 28) stated that being male was the reason they were excluded from gynecologic and routine care, respectively. Of the 80 students who were denied involvement in a gynecologic examination, 81% (n = 65) were denied involvement by clinic patients. Of the 44 males who stated they were denied the opportunity to be involved in a gynecologic examination due to their gender, 89% (n = 39) were refused by clinic patients. Compared with female students, male students are statistically more likely to be denied the opportunity to be involved in gynecologic examinations (RR = 1.69 [1.24-2.29]), especially by clinic patients (RR = 2.07 [1.41-3.03]). CONCLUSION: A significant number of students were denied the opportunity to be involved in ObGyn care experiences. More frequently male students were denied involvement in care, with a higher incidence among clinic patients. We hypothesize that being denied involvement provides a negative perception of the ObGyn specialty, especially to male students, possibly affecting their decision to choose ObGyn training. PRECIS: A significant number of medical students, particularly males, were denied involvement in patient care, primarily by clinic patients, during the ObGyn clerkships.

Reported experiences with prenatal care: is there a difference in patient satisfaction based on racial and ethnic background?

Pregnant women were queried to determine if racial and ethnic disparities exist in prenatal care by assessing their satisfaction in private and clinic practices. An anonymous survey was distributed in both English and Spanish and focused on demographics, satisfaction and cultural sensitivity. A total of 273 surveys were collected. Demographics of clinic patients (Hispanic 62%, Black 26.4%, and Caucasian 5%) varied significantly (P < 0.001) from private patients (Caucasian 62.5%, Black 14.1%, and Hispanic 18.8%). Significant differences were noted between clinic and private patients' in their country of birth, education, income, insurance, employment status, home ownership, and planned pregnancies. Patients reported that their prenatal care was influenced by race (27% clinic vs 5% private, P < 0.001) and language (24.9% clinic vs 4.9% private, P = 0.004). Race andlanguagewere morelikelyto influence clinic patients' perceptions of the prenatal care received as compared to those seeking care in private practices.

Demographic differences in Down syndrome livebirths in the US from 1989 to 2006.

OBJECTIVE: To explore demographic differences in Down syndrome livebirths in the United States. METHODS: Using National Center for Health Statistics (NCHS) birth certificate data from 1989 to 2006 we analyzed Down syndrome livebirths after correcting for under-reporting. We created six subsets based on maternal age (15-34 and 35-49 years old); US regions, that is, Northeast, Midwest, South and West; marital status, (married, unmarried); education, ( ≤ 12 years, ≥ 13 years); race, (white, black); and Hispanic ethnicity, (non-Hispanic, Hispanic). We estimated expected Down syndrome livebirths assuming no change in birth certificate reporting. The percentage of expected Down syndrome livebirths actually born was calculated by year. RESULTS: There were 72 613 424 livebirths from 1989 to 2006. There were 122 519 Down syndrome livebirths expected and 65 492 were actually born. The Midwest had the most expected Down syndrome livebirths actually born (67.6%); the West was lowest (44.4%). More expected Down syndrome livebirths were born to women who were 15 to 34 years old (61 vs 43.8%) and to those with ≤ 12 years education (60.4 vs 46.9%), white race (56.6 vs 37%), unmarried (56.0 vs 52.5%), and of Hispanic ethnicity (55.0 vs 53.3%). CONCLUSION: The percentage of expected Down syndrome livebirths actually born varies by demographics.

Distortions of sex ratios at birth in the United States; evidence for prenatal gender selection.

OBJECTIVE: The normal male to female livebirth sex ratio ranges from 1.03 to 1.07. Higher ratios in China, India and Korea reflect prenatal sex selection. We reviewed sex ratios for US births to investigate potential prenatal sex selection. METHODS: We reviewed all US livebirths from 1975 to 2002 using National Center for Health Statistics birth certificates in 4-year intervals. We compared the sex ratios of Blacks, Chinese, Filipinos, Asian Indians and Koreans relative to Whites. We also compared the sex ratios by birth order for first, second and third and more births (third+) from 1991 to 2002. RESULTS: The male to female sex ratio from 1975 to 2002 was 1.053 for Whites, 1.030 (p < 0.01) for Blacks, 1.074 (p < 0.01) for Chinese and 1.073 (p < 0.01) for Filipinos. From 1991 to 2002, the sex ratio increased from 1.071 to 1.086 for Chinese, 1.060 to 1.074 for Filipinos, 1.043 to 1.087 for Asian Indians and 1.069 to 1.088 for Koreans. The highest sex ratios were seen for third+ births to Asian Indians (1.126), Chinese (1.111) and Koreans (1.109). CONCLUSION: The male to female livebirth sex ratio in the United States exceeded expected biological variation for third+ births to Chinese, Asian Indians and Koreans strongly suggesting prenatal sex selection.

Characteristics of nulliparous women who would consider cesarean delivery on maternal request.

INTRODUCTION/HYPOTHESIS: To identify factors that influence nulliparous women to choose cesarean delivery on maternal request (CDMR). METHODS: Nulliparous women at > or = 34 weeks completed a 76-item survey about concerns during labor, delivery and postpartum. RESULTS: Mean age of the 294 respondents was 28.4 years (+/- 6.13 years SD) and mean gestational age was 35.4 weeks (+/- 2.8 weeks). Sixteen patients (5.4%) would request CDMR if offered. Women who would request CDMR were more likely to plan breastfeeding (OR 5.1, P=0.02), have a mother who delivered by C-section (OR 5.1, P= 0.01), and be concerned about the number of family members present (OR 1.75, P=0.002). Pelvic muscle damage, urinary incontinence, fecal incontinence, or need for prolapse surgery were notcited by any patient as her top concern. CONCLUSIONS: Few women in our sample desire CDMR. Concern for pelvic-floor problems was low.

Down syndrome screening in the United States in 2001 and 2007: a survey of maternal-fetal medicine specialists.

OBJECTIVE: The purpose of this study was to determine changes in screening and performance of invasive diagnostic procedures for Down syndrome between 2001 and 2007. STUDY DESIGN: The Society for Maternal-Fetal Medicine members completed a survey in 2007 regarding screening tests and diagnostic procedures for Down syndrome. With the use of descriptive statistics, the chi(2) test, and the Student t test, responses from 2007 were compared with responses from a similar 2001 survey. RESULTS: Performance of first-trimester screening more than doubled from 2001-2007 (43.1% in 2001, 97.3% in 2007; P < .0001). Between 2001 and 2007, the use of the quad screen increased 10-fold (8.5% in 2001, 85.6% in 2007; P < .0001). There was an estimated 20% decrease in invasive diagnostic procedures that were performed in risk-positive women (53.7% in 2001, 34.2% in 2007; P < .0001). In 2007, the average fetal loss rates that were quoted by maternal-fetal medicine specialists after chorionic villous sampling was 1:160 and after an amniocentesis was 1:493. CONCLUSION: Down syndrome screening evolved from 2001-2007, with an increasing emphasis on first-trimester screening. With more efficacious screening, the number of invasive procedures has declined.

Perinatal and neonatal outcomes of triplet gestations based on placental chorionicity.

The purpose of our study was to evaluate perinatal and neonatal outcomes in triplet gestations in relation to placental chorionicity. We hypothesized that triplets containing a monochorionic pair (dichorionic triamniotic) would have increased morbidity compared with triplets without a monochorionic pair (trichorionic triamniotic). We retrospectively analyzed all triplet sets > or =20 weeks delivering at our institutions from January 1995 through April 2007. Data were collected via perinatal and neonatal databases, chart review, and placental pathology. Individuals in dichorionic triamniotic triplet sets (N = 75), when compared with trichorionic triamniotic triplets (N = 309), were more likely to have a lower mean birth weight (P < 0.001) and lower gestational age at delivery (P < 0.001), spend more days in the neonatal intensive care unit (P = 0.045), have culture-proven sepsis (P = 0.02), and require intubation (P = 0.05). Multivariate analysis demonstrated that dichorionicity is not an independent cause of morbidity, but results in earlier delivery and lower birth weight. Dichorionic triamniotic triplets are at increased risk for earlier deliveries and lower birth weight at delivery compared with trichorionic triamniotic triplets.

A comparison of reasons for choosing obstetrician/gynecologist subspecialty training.

Recently, applications for subspecialty fellowship positions in obstetrics and gynecology have increased dramatically. A survey completed by fellows in Maternal-Fetal Medicine (MFM), Reproductive Endocrinology (REI), Gynecologic Oncology (Gyn Onc), and Urogynecology (Urogyn) training programs in the United States between January and March 2006 was aimed at determining why this trend was occuring. Of 449 fellows in 2006, 192 (42.8%) responded. The two most influential factors in all four subspecialties were interest and lifestyle (P < .001). Although these factors were similar throughout all subspecialties, variations exist in how fellows rated each factor by subspecialty. An overwhelming majority (99%) of fellows were either "very satisfied" or "satisfied" with their decisions to pursue fellowship training. The majority of fellows believe that when compared to a generalist Obstetrician/Gynecologist (OB/GYN) they will have a reduced workload, decreased liability, and a higher salary. The recent increase in the number of fellowship applicants is most likely due to a complex interplay of multiple factors.

Use of the genetic sonogram in the United States in 2001 and 2007.

OBJECTIVE: The purpose of this study was to determine whether there have been changes in the use of second-trimester genetic sonograms and in the second-trimester sonographic markers used to screen for fetal aneuploidy by maternal-fetal medicine specialists in the United States from 2001 to 2007. METHODS: A survey was mailed to Society for Maternal-Fetal Medicine members in the United States in April 2007 inquiring about their practice patterns regarding the genetic sonogram. Specific sonographic markers used for risk adjustment as part of the genetic sonogram were also assessed. The responses from 2007 were compared with responses from a similar survey administered in 2001 (Am J Obstet Gynecol 2002; 187:1230-1234) using descriptive statistics, the chi(2) test, and the Wilcoxon rank sum test. RESULTS: A total of 991 responses were analyzed: 543 of 1638 (32%) in 2001 and 448 of 1756 (26%) in 2007. Significant increases (P < .0001) were noted in the number of specialists who used the genetic sonogram as a screening tool for Down syndrome and for every single sonographic marker used to adjust a woman's risk for having a fetus with Down syndrome during a genetic sonogram, except for choroid plexus cyst, clinodactyly, sandal gap toes, and widened pelvic angle. CONCLUSIONS: Practitioners in the United States are using an increasing number of second-trimester sonographic markers to help identify aneuploid fetuses. The growing acceptance of sonography to screen for fetal aneuploidy and the recommendation by the American College of Obstetricians and Gynecologists for universal screening suggest that more resources may be necessary to meet the growing demand for second-trimester sonograms.

Prevalence of the human papillomavirus in an inner-city indigent population with previously normal Pap tests.

OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) in our inner-city indigent population (clinic population) of women with previously normal Pap tests and to identify any associated risk factors. MATERIALS AND METHODS: A prospective cohort of 187 women between the ages of 15 and 49 years, with previously normal Pap tests, was recruited from a university affiliated outpatient clinic. A demographic questionnaire of social and sexual history was elicited, and ThinPrep cytology (Cytyc, Marlborough, MA) and HPV Digene Hybrid Capture II results (Digine, Gaithersburg, MD) were obtained. RESULTS: The prevalence of HPV in our primarily Hispanic clinic population was 21%. The mean age of women with HPV was 28.9 years and those without were 32.1 years (p <.046). In women with HPV, 24% had abnormal Pap tests, whereas in those without HPV, 5% had abnormal Pap tests (p <.001). Women who were older and parous were less likely to have HPV (7.5%; p <.024). The presence of HPV was not influenced by sexual behaviors, sexually transmitted diseases, smoking, race, or contraceptive use. CONCLUSIONS: The prevalence of HPV in an inner-city indigent population, despite previously normal cytology, was consistent with earlier reported rates of HPV. Our data suggest that younger, nulliparous women have a high prevalence of HPV.

Absent or shortened nasal bone length and the detection of Down Syndrome in second-trimester fetuses.

OBJECTIVE: To estimate the accuracy of evaluating nasal bone length, expressed as multiples of the median (MoM), for the detection of Down syndrome in second- trimester fetuses. METHODS: Expected normal median nasal bone measurements were established for an initial cohort of women receiving fetal ultrasound examinations at 15-24 weeks of gestation. Nasal bone lengths were converted to MoM with adjustment for maternal race and ethnicity using whites as the referent group. Nasal bone MoM were compared in euploid and Down syndrome fetuses. The sensitivity and specificity were evaluated in this initial cohort and in a second cohort in which all ultrasound measurements were carried out prospectively. RESULTS: For the combined data set, 10 of 21 affected pregnancies had an absence of the nasal bone (sensitivity 47.6%), but absence was noted in only 1 of 2,515 unaffected pregnancies (false-positive rate 0.04%). Using less than 0.80 MoM as a cutoff, the sensitivity was 20 of 21 (95.2%), and the false-positive rate was 185 of 2,515 (7.4%). Changing the cutoff to 0.75 MoM resulted in 18 of 21 (85.7%) sensitivity and 74 of 2,515 (2.9%) false-positive rate. Using medians derived from whites to calculate MoM for the entire population resulted in higher false-positive rates. CONCLUSION: Nasal bone length expressed as MoM seems to be an useful ultrasound marker for Down syndrome in second-trimester fetuses with a high sensitivity and a low false-positive rate. LEVEL OF EVIDENCE: III.

Stepwise sequential screening for fetal aneuploidy.

OBJECTIVE: The purpose of this study was to evaluate stepwise sequential screening for fetal aneuploidy. STUDY DESIGN: Women who received first-trimester screening were also offered second-trimester tests with second-trimester risks that were based on both sets of markers. Screen-positive rates, use of second-trimester testing and invasive testing, sensitivity, and changes in risks were evaluated. RESULTS: Of 1528 women who received first-trimester screening, 133 women (8.7%) had an indication for invasive testing that was based on first-trimester results alone; 1173 women (76.8%) received second-trimester tests, which reduced the net number of women with an indication for invasive testing to 105 (6.9%). In unaffected pregnancies, the addition of the second-trimester testing reduced the median Down syndrome risk from 1:2368 to 1:10,301. Six of 10 chromosome abnormalities (60%) were identified by first-trimester screening, and 9 of 10 chromosome abnormalities (90%) were identified by sequential screening. CONCLUSION: Sequential screening can be introduced successfully into clinical practice, is effective, and can reduce the number of invasive tests that are performed.

The relationship between utilization of prenatal care and Down syndrome live births.

OBJECTIVE: This study evaluated whether utilization of prenatal care, as measured by the Kessner index, affects the number of Down syndrome live births. METHODS: A retrospective analysis of birth certificate data of Down syndrome live births comparing 1989 to 2001 by year, maternal age, gestational age at first prenatal visit, and adequacy of prenatal care according to Kessner categories of adequacy of prenatal care. RESULTS: Down syndrome live births were inversely correlated with adequacy of prenatal care. Reductions in Down syndrome live births were seen in all categories of prenatal care in all age groups. In 2001 a minimum 30% reduction was seen in any category rising to a 58% reduction in women > or =35 years with adequate prenatal care. The largest reductions were seen in women > or =35 years of age. CONCLUSIONS: Reductions in Down syndrome live births occurred in all age groups between 1989 and 2001. Utilization of prenatal care as measured by the Kessner index was associated with reductions in Down syndrome live births, with a greater reduction in women > or =35 years of age.

The influence of body mass index on pregnancy outcomes.

OBJECTIVES: To determine antenatal complications, mode of delivery, and birth outcomes for Saint Francis Hospital and Medical Center and Burgdorf Obstetric clinic patient population based on their body mass index (BMI). MATERIAL AND METHODS: This is a retrospective cohort study of 2,270 women who delivered at our institution from 1996 to 2002. Our patient population ranged from ages 23.8 to 26.6 years. The majority of the patients in the study were Black or Hispanic. BMI at delivery was calculated. Maternal data were obtained from our computerized obstetrical database. Exclusion criteria included: nonviable fetus, no recorded maternal height or other incomplete data. For statistical analysis we used a one-way analysis of variance (ANOVA) and a post-hoc Tukey's test, using a computer statistics program (Statmost, Datamost Crop., Salt Lake City, UT), with, P<0.05 considerd significant. RESULTS: This study revealed that those patients with a higher BMI had greater weight gain during pregnancy. Operative delivery rates were also higher with increasing BMI, as was the infant birth weight. Diabetes and hypertension were directly related to the BMI; the higher the BMI the higher their prevalence. The low number of events recorded did not allow a statistical comparison to determine any increase in shoulder dystocia. CONCLUSION: A statistically significant increase in rate of operative delivery, hypertension, diabetes and a trend toward higher birth weight are associated with increased maternal BMI.

Frequency of echogenic intracardiac focus by race/ethnicity in euploid fetuses.

OBJECTIVE: To determine the frequency of echogenic intracardiac focus (EIF) by race/ethnicity. METHODS: We performed a retrospective analysis from January 1996 through June 2003. We reviewed all initial sonograms from 14 to 23 weeks gestation in singleton pregnancies. Mothers on admission for delivery provided race/ethnicity. RESULTS: There were 8207 ultrasounds and deliveries that met study criteria. There were 4636 (56.5%) Caucasian, 2087 (25.4%) African-American, 1261 (15.4%) Hispanic and 223 (2.7 %) Asian subjects. There were 347 (4.2%) EIF detected. The frequency by race/ethnicity varied significantly (p < 0.0001). CONCLUSIONS: This large, population-based study showed that fetuses born to Asian mothers were significantly more likely to have an EIF. This racial difference should be taken into account when counseling patients about the potential for Down syndrome.

Combined second-trimester biochemical and ultrasound screening for Down syndrome.

OBJECTIVE: To evaluate the efficacy of a Down syndrome screening protocol that combines second-trimester maternal serum analytes and the continuous ultrasound measures of nuchal fold thickness and proximal long bone length. METHODS: Ultrasound measurements of nuchal fold, femur length, and humerus length were reviewed for 72 second-trimester Down syndrome and 7063 unaffected fetuses. Derived statistical variables for these parameters were entered into a multivariable Gaussian model together with the statistical variables used in the "quad" test (maternal serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin A). Maternal age-specific sensitivities, false-positive rates, and positive predictive values were generated together with receiver operating characteristic curves. Overall efficacy of ultrasound screening alone, the quad test, and the combination of the ultrasound and quad test were compared using a 1:270 second-trimester risk cutoff applied to 1999 US births. RESULTS: Using ultrasound, a sensitivity of 79.9% and false-positive rate of 6.7% may be achieved (positive predictive value: 1 in 42). The quad test has a sensitivity of 81.5% and false-positive rate of 6.9% (positive predictive value: 1 in 42). The combination of the quad test with nuchal fold and long bone measurements may achieve 90% sensitivity and a 3.1% false-positive rate (positive predictive value: 1 in 18). CONCLUSION: Combining second-trimester serum testing and fetal biometry is a feasible approach to Down syndrome screening, compatible with current obstetric practice. This modality is substantially more effective than either serum screening or ultrasound alone. Efficacy may be comparable to that reported for combined first- and second-trimester (integrated) screening.

Incorporation of inhibin-A in second-trimester screening for Down syndrome.

OBJECTIVE: To evaluate the efficacy of the second-trimester quadruple test (maternal serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin-A) in prenatal screening for Down syndrome. METHODS: All quadruple tests performed on singleton pregnancies over a 32-month period were reviewed. The sensitivity and false-positive rates were compared with the theoretic rates predicted by the screening model when applied to a population of women with the same maternal age distribution. RESULTS: Twenty-three thousand seven hundred four women with unaffected pregnancies and 45 women with Down syndrome-affected pregnancies received the quadruple test. Mean analyte values for both unaffected and affected pregnancies were similar to those expected. The sensitivity of the quadruple test, which was based on ascertainment of all viable affected pregnancies in the screened population, was 85.8%. This sensitivity did not significantly differ from an expected 83.8% (P =.8). The initial false-positive rate, 9.0%, was significantly below that expected (9.9%) (P =.002) and was further reduced to 8.2% after correction for major gestational age errors. The positive predictive value of the quadruple test was one in 51. Women with an affected pregnancy and a positive test result (true positives) generally had very high risks (median 1:22) relative to women with false-positive results (median risk 1:111). CONCLUSION: The quadruple test meets or exceeds performance expectations and appears to represent an improvement over the widely used triple test.