[Late first-trimester invasive prenatal diagnosis--secondary publication. An international randomized trial].
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Abortion, Induced↗
Biomedical subjects
R J Wapner
Publications and source records attributed to R J Wapner.
Late first-trimester invasive prenatal diagnosis: results of an international randomized trial.
OBJECTIVE: To assess, in a randomized trial, the safety and accuracy of amniocentesis and transabdominal chorionic villus sampling (CVS) performed at 11-14 weeks of gestation, given that this time frame is increasingly relevant to early trisomy screening. METHODS: We compared amniocentesis with CVS from 77 to 104 days of gestation in a randomized trial in a predominantly advanced maternal age population. Before randomization, the feasibility of both procedures was confirmed by ultrasonography, and experienced operators performed sampling under ultrasound guidance; conventional cytogenetic analysis was employed. The primary outcome measure was a composite of fetal loss plus preterm delivery before 28 weeks of gestation in cytogenetically normal pregnancies. RESULTS: We randomized 3,775 women into 2 groups (1,914 to CVS; 1,861 to amniocentesis), which were comparable at baseline. More than 99.6% had the assigned procedure, and 99.9% were followed through delivery. In contrast to previous thinking, in the cytogenetically normal cohort (n = 3,698), no difference in primary study outcome was observed: 2.1% (95% confidence interval 1.5, 2.8) for CVS and 2.3% (95% confidence interval, 1.7, 3.1) for amniocentesis. However, spontaneous losses before 20 weeks and procedure-related, indicated terminations combined were increased in the amniocentesis group (P =.07, relative risk 1.74). We found a 4-fold increase in the rate of talipes equinovarus after amniocentesis (P =.02) overall and in week 13 (P =.03, relative risk = 4.65), but data were insufficient to determine this risk in week 14. CONCLUSION: Amniocentesis at 13 weeks carries a significantly increased risk of talipes equinovarus compared with CVS and also suggests an increase in early, unintended pregnancy loss. LEVEL OF EVIDENCE: I
Abortion, Induced↗
Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. National Institute of Child Health and Development Fetal Cell Isolation Study.
OBJECTIVES: The National Institute of Child Health and Human Development Fetal Cell Isolation Study (NIFTY) is a prospective, multicenter clinical project to develop non-invasive methods of prenatal diagnosis. The initial objective was to assess the utility of fetal cells in the peripheral blood of pregnant women to diagnose or screen for fetal chromosome abnormalities. METHODS: Results of fluorescence in situ hybridization (FISH) analysis on interphase nuclei of fetal cells recovered from maternal blood were compared to metaphase karyotypes of fetal cells obtained by amniocentesis or chorionic villus sampling (CVS). After the first 5 years of the study we performed a planned analysis of the data. We report here the data from 2744 fully processed pre-procedural blood samples; 1292 samples were from women carrying singleton male fetuses. RESULTS: Target cell recovery and fetal cell detection were better using magnetic-based separation systems (MACS) than with flow-sorting (FACS). Blinded FISH assessment of samples from women carrying singleton male fetuses found at least one cell with an X and Y signal in 41.4% of cases (95% CI: 37.4%, 45.5%). The false-positive rate of gender detection was 11.1% (95% CI: 6.1,16.1%). This was higher than expected due to the use of indirectly labeled FISH probes in one center. The detection rate of finding at least one aneuploid cell in cases of fetal aneuploidy was 74.4% (95% CI: 76.0%, 99.0%), with a false-positive rate estimated to be between 0.6% and 4.1%. CONCLUSIONS: The sensitivity of aneuploidy detection using fetal cell analysis from maternal blood is comparable to single marker prenatal serum screening, but technological advances are needed before fetal cell analysis has clinical application as part of a multiple marker method for non-invasive prenatal screening. The limitations of the present study, i.e. multiple processing protocols, are being addressed in the ongoing study.
Adult↗
First-trimester trisomy screening: nuchal translucency measurement training and quality assurance to correct and unify technique.
OBJECTIVE: To describe the process of training for measuring nuchal translucency at five clinical centers in North America and to evaluate methods of quality assurance and feedback. DESIGN: Throughout a period of 18 months, the performance of sonographers in measuring fetal nuchal translucency was monitored using qualitative and quantitative methods of review. After 12 months, different approaches (written and personal feedback) were used to inform sonographers of technical aspects that needed to or could be improved. RESULTS: On initial qualitative review, discrepancies in judgment from different reviewers coincided with suboptimal magnification, failure to visualize the amniotic membrane and/or use of cross-shaped calipers. At subsequent global review, 13 (29%) images of nuchal translucency measurements were considered unacceptable. Quantitative assessment revealed that, during the first part of the study, the means from four sonographers were significantly smaller and the mean from the fifth sonographer was significantly larger than expected on the basis of findings from The Fetal Medicine Foundation (P < 0.0001). Following feedback, sonographers who underestimated nuchal translucency and who received a written report only did not change measurements overall (P = 0.9759). In contrast, those who received additional intervention showed a marked difference (P < 0.0001). CONCLUSIONS: Global qualitative review of images from one sonographer may be preferable to assessment of individual aspects of images. Results from global qualitative review correspond well with findings from quantitative analysis, indicating that the latter can be applied for ongoing audit. Observation of divergent results should prompt extensive personal feedback, rather than a written report, to prevent sonographers from settling in their own, inappropriate technique.
Allied Health Personnel↗
Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection.
BACKGROUND: Infection with Trichomonas vaginalis during pregnancy has been associated with preterm delivery. It is uncertain whether treatment of asymptomatic trichomoniasis in pregnant women reduces the occurrence of preterm delivery. METHODS: We screened pregnant women for trichomoniasis by culture of vaginal secretions. We randomly assigned 617 women with asymptomatic trichomoniasis who were 16 to 23 weeks pregnant to receive two 2-g doses of metronidazole (320 women) or placebo (297 women) 48 hours apart. We treated women again with the same two-dose regimen at 24 to 29 weeks of gestation. The primary outcome was delivery before 37 weeks of gestation. RESULTS: Between randomization and follow-up, trichomoniasis resolved in 249 of 269 women for whom follow-up cultures were available in the metronidazole group (92.6 percent) and 92 of 260 women with follow-up cultures in the placebo group (35.4 percent). Data on the time and characteristics of delivery were available for 315 women in the metronidazole group and 289 women in the placebo group. Delivery occurred before 37 weeks of gestation in 60 women in the metronidazole group (19.0 percent) and 31 women in the placebo group (10.7 percent) (relative risk, 1.8; 95 percent confidence interval, 1.2 to 2.7; P=0.004). The difference was attributable primarily to an increase in preterm delivery resulting from spontaneous preterm labor (10.2 percent vs. 3.5 percent; relative risk, 3.0; 95 percent confidence interval, 1.5 to 5.9). CONCLUSIONS: Treatment of pregnant women with asymptomatic trichomoniasis does not prevent preterm delivery. Routine screening and treatment of asymptomatic pregnant women for this condition cannot be recommended.
Adult↗
Prenatal diagnosis of congenital nephrosis by in utero kidney biopsy.
The diagnosis of congenital nephrosis is difficult during the antepartum period. The combination of an elevated amniotic fluid alpha-fetoprotein, a negative acetylcholinesterase, and a negative ultrasound examination is highly indicative of congenital nephrosis; however, these findings can also be associated with a normal gestation. This is the first report of pathologic confirmation of congenital nephrosis from an in utero fetal kidney biopsy.
Acetylcholinesterase↗
Future directions.
With the continued explosion of genetic technology, the number of disorders amenable to screening is expanding geometrically. Historically, most genetic screening has been in the newborn period. Much more can be done for the fetus if genetic screening and diagnosis are accomplished early in the pregnancy rather than after birth. The principal requirements to make neonatal screening disorders possible in the first trimester center around those tests that can be one on a molecular basis, and the development of fetal cell isolation from the maternal circulation. Over the course of the next decade, it is likely that many of the tests currently performed in the newborn period will be accomplished in the early or mid-gestational period.
Forecasting↗
Does transvaginal ultrasound of the cervix predict preterm premature rupture of membranes in a high-risk population?
OBJECTIVES: To determine in patients with a cervical length < 25 mm on transvaginal ultrasound if the severity of cervical length shortening can be used to predict preterm premature rupture of membranes (PPROM) and the contribution of PPROM to preterm delivery in these patients. METHODS: We retrospectively reviewed asymptomatic singleton pregnancies between 14 and 24 weeks at high risk of preterm delivery by obstetric history and transvaginal cervical length < 25 mm. Cases developing subsequent PPROM were compared with controls for transvaginal sonographic cervical characteristics. RESULTS: Of 69 patients identified to have a cervical length < 25 mm, 27 (39%) had PPROM, and 42 (61%) did not. Mean +/- standard deviation (SD) cervical length was 12.7 +/- 8.7 mm and 17.0 +/- 7.6 mm in the two groups, respectively (P = 0.04). Mean +/- SD cervical funneling was 57.4 +/- 31.4% and 40.0 +/- 28.1%, respectively (P = 0.01). The characteristics most predictive of PPROM were: cervical length of < 10 mm (sensitivity, specificity, positive and negative predictive values of 33, 90, 69, and 68%, respectively; odds ratio, 4.8; 95% confidence interval, 1.3-17.5) and cervical funneling > 75% (sensitivity, specificity, positive and negative predictive values of 33, 93, 75 and 68%, respectively; odds ratio, 6.5; 95% confidence interval, 1.6-26.9). Stepwise logistic regression revealed cervical length to be a significant predictor of PPROM (odds ratio, 4.0; 95% confidence interval, 1.1-14.2). CONCLUSION: In patients at high risk for preterm delivery because of obstetric history and transvaginal sonographic cervical length < 25 mm, a cervical length < 10 mm and cervical funneling > 75% were most predictive of PPROM. PPROM was the major contributor to preterm delivery in these patients.
Adult↗
Improvement in outcomes of multifetal pregnancy reduction with increased experience.
OBJECTIVE: This study was undertaken to evaluate a decade of data on multifetal pregnancy reductions at centers with extensive experiences. STUDY DESIGN: A total of 3513 completed cases from 11 centers in 5 countries were analyzed according to year (before 1990, 1991-1994, and 1995-1998), starting and finishing numbers of embryos or fetuses, and outcomes. RESULTS: With increasing experience there has been a considerable improvement in outcomes, with decreases in rates of both pregnancy loss and prematurity. Overall loss rates in the last few years were correlated strongly with starting and finishing numbers (starting number > or =6, 15.4%; starting number 5, 11.4%; starting number 4, 7.3%; starting number 3, 4.5%; starting number 2, 6.2%: finishing number 3, 18.4%; finishing number 2, 6.0%; finishing number 1, 6.7%). Birth weight discordance between surviving twins was increased with greater starting number. The proportion of cases with starting number > or =5 diminished from 23.4% to 15.9% to 12.2%. The proportion of patients >40 years old increased in the last 6 years to 9.3%. Gestational age at delivery did not vary with increasing maternal age but was inversely correlated with starting number. CONCLUSION: Multifetal pregnancy reduction outcomes at our centers for both losses and early prematurity have improved considerably with experience. Reductions from triplets to twins and now from quadruplets to twins carry outcomes as good as those of unreduced twin gestations. Patient demographic characteristics continues to change as more older women use assisted reproductive technologies. In terms of losses, prematurity, and growth, higher starting numbers carry worse outcomes.
Abortion, Spontaneous↗
Fetal reduction procedures for triplets.
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Female↗
In vitro sealing of punctured fetal membranes: potential treatment for midtrimester premature rupture of membranes.
OBJECTIVE: Midtrimester premature rupture of membranes causes significant perinatal morbidity and death. No effective treatment exists. We investigated (1) whether a needle puncture in the fetal membranes could be sealed in vitro and (2) the optimal composition of the sealant to be used. STUDY DESIGN: Membranes from second trimester pregnancies (16-24 weeks of gestation) were stretched over a modified syringe with a 2.5-cm open diameter. The syringe was filled with 20 mL of second trimester amniotic fluid, and the membrane was punctured with a 20-gauge needle. Sealants were injected into the amniotic fluid. The primary outcome variable was time for leakage of amniotic fluid. Median times for leakage for the formulations were compared by Wilcoxon exact rank sum test. RESULTS: Platelets alone failed to seal the puncture site. All other formulations stopped leakage temporarily. Tisseel (Baxter Corp, Glendale, Calif) and cryoprecipitate/thrombin preparations led to more prolonged sealing of punctured amniotic membranes than platelets (P <.01) and were not significantly different from each other. CONCLUSION: Of the sealants tested in vitro, amniotic membranes are best sealed by a fibrin/thrombin-based sealant.
Amnion↗
Vaginal fetal fibronectin measurements from 8 to 22 weeks' gestation and subsequent spontaneous preterm birth.
OBJECTIVE: We sought to determine the range of fetal fibronectin values in the vagina from 8 to 22 weeks' gestation, the factors associated with both low and high values, and whether high values are associated with gestational age at birth. STUDY DESIGN: Vaginal fetal fibronectin was quantitatively determined in a prospective cohort study of 13,360 women being evaluated for participation in the National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit treatment trials for bacterial vaginosis and Trichomonas vaginalis. Fetal fibronectin values were correlated with gestational age at screening, race, the presence of bacterial vaginosis and Trichomonas vaginalis, and gestational age at delivery. RESULTS: Vaginal fetal fibronectin values at each gestational age ranged from unmeasurable to >1000 ng/mL, with median values always being <10 ng/mL. Fetal fibronectin values declined progressively with increasing gestational age at sampling. Bacterial vaginosis and black race were associated with higher values, whereas nulliparity was associated with lower values. High values after 13 weeks' gestation were associated with a 2- to 3-fold increased risk of subsequent spontaneous preterm birth overall and a 4-fold increased risk of very early preterm birth. CONCLUSION: Elevated vaginal fetal fibronectin levels from 13 to 22 weeks' gestation are associated with a significantly increased risk of spontaneous preterm birth.
Black People↗
Patients with a prior failed transvaginal cerclage: a comparison of obstetric outcomes with either transabdominal or transvaginal cerclage.
OBJECTIVE: Our purpose was to compare the incidence of preterm birth after a prior failed vaginal cerclage in patients who had a subsequent transabdominal or a transvaginal cerclage. STUDY DESIGN: We conducted a retrospective cohort study of singleton pregnancies in women who had undergone (9-14 weeks) either a transabdominal or a transvaginal prophylactic cerclage after >/=1 prior failed transvaginal cerclage. Prior failed transvaginal cerclage was defined as a preterm birth at <33 weeks' gestation in the immediate prior pregnancy despite a transvaginal cerclage. All transabdominal cerclage procedures were performed by a single attending physician (George Davis, DO). Patients with a cervix too short for transvaginal cerclage placement, placenta previa, or major fetal anomalies were excluded. Primary outcome was preterm birth at <35 weeks' gestation. RESULTS: Forty transabdominal and 24 transvaginal cerclage pregnancies were analyzed. These 2 groups were similar in race and payer status but differed in age (34.0 +/- 4.2 vs 31.3 +/- 4.6 years, respectively; P =.01). The transabdominal cerclage group had more prior failed cerclage procedures per patient (1.8 +/- 1.0 vs 1.1 +/- 0.3; P =.02) and more prior 14- to 24-week spontaneous abortions per patient (2.4 +/- 1.3 vs 1.5 +/- 1.0; P =.02) than the transvaginal cerclage group. Preterm delivery at both <35 and <33 weeks' gestation was less common in the transabdominal cerclage group (18% vs 42%, P =.04; 10% vs 38%, P =.01; respectively) than in the transvaginal cerclage group. Gestational age at delivery was 36. 3 +/- 4.1 weeks in the transabdominal cerclage group and 32.8 +/- 8. 6 weeks in the transvaginal cerclage group (P =.03). Preterm premature rupture of membranes also occurred less often in the transabdominal cerclage group than in the transvaginal cerclage group (8% vs 29%, P =.03). CONCLUSION: In patients with a prior failed transvaginal cerclage, transabdominal cerclage is associated with a lower incidence of preterm delivery and preterm premature rupture of membranes in comparison with transvaginal cerclage.
Abdomen↗
Timing of cerclage removal after preterm premature rupture of membranes: maternal and neonatal outcomes.
OBJECTIVE: Our aim was to evaluate immediate versus delayed removal of cerclage for women with preterm premature rupture of membranes with respect to maternal and neonatal outcomes. STUDY DESIGN: We retrospectively analyzed women with preterm premature rupture of membranes at <34 weeks' gestation with prior cerclage placement. Exclusion criteria included presentation with chorioamnionitis, active labor, or nonreassuring fetal status. Timing of cerclage removal, immediate (<24 hours) or delayed (>24 hours), was compared. RESULTS: There were 25 women in the delayed-removal group and 37 in the immediate-removal group. Average times to removal were 206.8 +/- 7.4 and 5.4 +/- 0.2 hours, respectively. Use of betamethasone was similar for both groups; however, antenatal antibiotic use (100% vs 80%; P =.03) and short-term tocolytic use (20% vs 3%; P =.04) were higher in the delayed-removal group. Duration of latency was significantly longer with delayed removal (10.1 vs 5.0 days; P <. 001). Delivery occurred >48 hours from preterm premature rupture of membranes in 96% (24/25) versus 54% (20/37; P <.001) and >7 days from rupture in 56% (14/25) versus 24% (9/37; P =.02), respectively. Rates of neonatal sepsis (at <10 days) and maternal infection were not statistically different. Neonatal outcomes did not significantly differ regarding mortality, respiratory distress syndrome, birth weight, or duration of stay in the intensive care nursery. CONCLUSION: With the current management scheme for preterm premature rupture of membranes, cerclage retention significantly increases duration of latency without significantly altering maternal or neonatal outcomes.
Delivery, Obstetric↗
Population adjustment of the definition of the vaginal birth after cesarean rate.
OBJECTIVE: The vaginal birth after cesarean delivery rate is calculated with a denominator equal to the number of all women who give birth after a previous cesarean delivery, including those who are not candidates for a trial of labor. We evaluated the impact of adjustment for noncandidates for a trial of labor on vaginal birth after cesarean delivery rates. STUDY DESIGN: All women with a previous cesarean delivery who were delivered during 1998 were classified as either candidates or noncandidates for a trial of labor. An adjusted vaginal birth after cesarean delivery rate was calculated by eliminating noncandidates for a trial of labor from the denominator. The percentage of noncandidates for a trial of labor, the vaginal birth after cesarean delivery rate, and the adjusted vaginal birth after cesarean delivery rate were compared among 3 clinical services. RESULTS: The maternal-fetal medicine service had a significantly higher percentage of noncandidates for a trial of labor than did either the low-risk resident clinic or the low-risk private service. The maternal-fetal medicine service had a significantly lower vaginal birth after cesarean delivery rate than did the private service, but this difference was no longer present after application of an adjusted vaginal birth after cesarean delivery definition. CONCLUSION: For accurate comparison of vaginal birth after cesarean delivery rates among providers it is essential to account for patient risk status in the vaginal birth after cesarean delivery definition through the elimination of noncandidates for a trial of labor.
Female↗
The challenge of prenatal diagnosis in twin pregnancies.
Prenatal diagnosis in multiple gestations poses unique problems. The use of screening modalities is limited, diagnostic procedures are more complicated, and the management of discordant results may be required. This article reviews work, both past and present, regarding these issues.
Amniocentesis↗
Integrated screening for Down's syndrome.
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Down Syndrome↗
Prediction of preterm delivery with transvaginal ultrasonography of the cervix in patients with high-risk pregnancies: does cerclage prevent prematurity?
OBJECTIVES: We sought to determine the predictive accuracy for preterm delivery of transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation in high-risk patients and to determine whether cerclage prevents preterm delivery in patients with ultrasonographic cervical changes. STUDY DESIGN: Patients with asymptomatic singleton pregnancies at high risk for preterm delivery were followed prospectively from 14 weeks' to 23 weeks 6 days' gestation with transvaginal ultrasonography of the cervix. The subgroup of patients with either a cervical length of <25 mm or funneling of >25% or both was offered McDonald salvage cerclage, which was performed at the discretion of the patient and the obstetrician. The 2 groups (with and without cerclage) were compared for the primary outcome of preterm delivery at <35 weeks' gestation. RESULTS: One hundred sixty-eight women were followed, including 97 (58%) with >/=1 prior 14- to 34-week preterm deliveries. Of 63 (37. 5%) patients identified as having cervical changes, 23 (37%) had preterm delivery; of 105 patients with no cervical changes, 8 (8%) had preterm delivery (relative risk, 4.8; 95% confidence interval, 2. 3-10.1). The sensitivity, specificity, and positive and negative predictive values of either a short cervix of <25 mm or funneling of >25% or both were 74%, 70%, 37%, and 92%, respectively. Of 63 pregnancies in which there were cervical changes, 39 underwent cerclage and 24 did not. These 2 groups were similar for demographic characteristics, risk factors, and transvaginal ultrasonographic cervical length and funneling but dissimilar for gestational age at identification of cervical changes (18.3 vs 21.2 weeks' gestation in the groups with and without cerclage, respectively; P <.001). Multivariate logistic regression analysis after adjustment for gestational age at cervical changes showed no difference in the rate of preterm delivery between the groups with and without cerclage (odds ratio, 1.1; 95% confidence interval, 0.3-4.6). Stratified analysis of patients identified between 18 and 24 weeks revealed 22 pregnancies with cerclage and 22 pregnancies without cerclage, which was similar for all characteristics studied. The incidence of preterm delivery remained similar (27% vs 23%, respectively; P =.7), as did days from cervical changes to delivery (111 vs 96, respectively; P =.2). CONCLUSIONS: Transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation is a good predictor of preterm delivery in high-risk pregnancies. Cerclage may not prevent preterm delivery in patients identified to be at high risk for this outcome by transvaginal ultrasonography.
Cervix Uteri↗