Circulating cell-free fetal DNA for the detection of RHD status and sex using reflex fetal identifiers.

OBJECTIVE: To determine the sensitivity and specificity of circulating cell-free fetal DNA in determining the fetal RHD status and fetal sex. METHODS: Maternal blood was collected in each trimester of pregnancy from RhD negative nonalloimmunized women. Whole blood was centrifuged, separated into plasma and buffy coat, and frozen at -80°C. DNA analysis was conducted via allele-specific primer extensions for exons 4, 5, and 7 of the RHD gene and for a 37-base pair insertion in exon 4 (RHD pseudogene; psi) three Y-chromosome sequences (SRY, DBY, and TTY2), and an extraction control (TGIFL-like X/Y). RhD serotyping on cord blood and gender assessment of the newborns were entered into a Web-based database. RESULTS: One hundred twenty women were enrolled. The median gestational age at the first venipuncture was 12.4 (range: 10.6-13.9) weeks with 120 samples drawn; 118 samples were drawn at 17.6 (16-20.9) weeks; and 113 samples at 28.7 (27.9-33.9) weeks. Overall accuracy for RHD was 99.1%, 99.1%, and 98.1% for each trimester and was 99.1%, 99.1%, and 100% for fetal sex determination. CONCLUSIONS: Fetal RHD genotyping and sex can be very accurately determined in all three trimesters using circulating cell-free fetal DNA in the maternal circulation.

Maintaining quality assurance for sonographic nuchal translucency measurement: lessons from the FASTER Trial.

OBJECTIVE: To evaluate nuchal translucency measurement quality assurance techniques in a large-scale study. METHODS: From 1999 to 2001, unselected patients with singleton gestations between 10 + 3 weeks and 13 + 6 weeks were recruited from 15 centers. Sonographic nuchal translucency measurement was performed by trained technicians. Four levels of quality assurance were employed: (1) a standardized protocol utilized by each sonographer; (2) local-image review by a second sonographer; (3) central-image scoring by a single physician; and (4) epidemiological monitoring of all accepted nuchal translucency measurements cross-sectionally and over time. RESULTS: Detailed quality assessment was available for 37 018 patients. Nuchal translucency measurement was successful in 96.3% of women. Local reviewers rejected 0.8% of images, and the single central physician reviewer rejected a further 2.9%. Multivariate analysis indicated that higher body mass index, earlier gestational age and transvaginal probe use were predictors of failure of nuchal translucency measurement and central image rejection (P = 0.001). Epidemiological monitoring identified a drift in measurements over time. CONCLUSION: Despite initial training and continuous image review, changes in nuchal translucency measurements occur over time. To maintain screening accuracy, ongoing quality assessment is needed.

Cocaine abuse is associated with abruptio placentae and decreased birth weight, but not shorter labor.

Many of our patients report having ingested cocaine hoping to decrease the duration of labor. We reviewed the computerized records of 592 women who abused cocaine. Compared with 4687 controls, women who ingested cocaine were older and had higher parity. Birth weight, birth weight percentile, and gestational age at delivery were significantly decreased among their neonates, and the incidence of abruptio placentae was nearly doubled among these women. Although these factors tend to shorten labor, the total duration of labor was not significantly different between the two groups. These data add to the accumulating evidence that cocaine abuse is associated with increased obstetric morbidity, but do not support the belief that cocaine shortens labor.

Fetal hemorrhage from umbilical cord hemangioma.

Hemangiomas of the umbilical cord are rare. In this case, an acute, massive fetal hemorrhage from a ruptured umbilical hemangioma occurred after spontaneous rupture of membranes. Ectopic small intestinal mucosa covered the proximal surface of the umbilical cord. Fetal anomalies included a patent vitellointestinal duct remnant and distal ileal atresia. Fetal hemorrhage appears to be another previously unreported and potentially life-threatening complication of umbilical hemangiomas.

Determinants of morbidity in obese women delivered by cesarean.

Studies examining the increased surgical morbidity among obese gravidas have focused mainly on differences in outcome between obese and nonobese mothers. Little is known, however, about the cause for worsened operative outcome in obese mothers or the potential impact of perioperative interventions. To define more precisely the clinical determinants of postoperative morbidity, multivariate analysis was used to relate antepartum and intrapartum variables to three measures of morbidity in 107 consecutively delivered obese women undergoing cesarean. Although obesity is clearly an operative risk factor, this study suggested that among obese gravidas, varying degrees of maternal obesity and accompanying medical complications, such as diabetes and hypertension, were not associated with greater operative morbidity. Furthermore, neither choice of skin incision nor type of anesthesia appeared to be related to operative morbidity. However, two factors potentially under the control of the clinician, increased length of surgery and operative blood loss, were associated significantly with measures of operative morbidity. A finding of worsened outcome with prophylactic antibiotics and heparin requires further study.

Maternal obesity: a potential source of error in sonographic prenatal diagnosis.

Sonograms from 1622 consecutively scanned singleton pregnancies at a mean gestational age of 28.5 weeks were analyzed to determine whether maternal obesity affected visualization of fetal anatomy. Fetal head (cerebral ventricles), heart (four-chamber view), stomach, kidneys, bladder, diaphragm, intestines, spinal column, extremities, and umbilical cord were classified as visualized or suboptimally visualized. Maternal body mass index was used as a measure of relative leanness. No significant impairment of ultrasound visualization was noted until a body mass index above the 90th percentile, when visualization fell by an average of 14.5%. Reduction in visualization was most marked for the fetal heart, umbilical cord, and spine. Among non-obese women, advancing gestation and decreasing body mass index were the most important determinants of visualization. However, among obese women, body mass index was the best predictor of visualization, with no improvement seen with advancing gestation or duration of examination.

Vaginal birth after cesarean in the diabetic gravida.

OBJECTIVE: To compare the delivery outcomes in term diabetic patients without a prior cesarean delivery to those attempting vaginal birth after cesarean (VBAC). STUDY DESIGN: A retrospective chart review study was performed of singleton pregnancies complicated by class A-2-R diabetes who delivered at > or = 37 weeks from 1991 to 1997. Exclusion criteria were prior classical or low vertical cesarean, more than one prior cesarean delivery, fetal structural defects or any contraindications to labor. Outcome measures were compared for patients without prior cesarean (group 1) to those with a VBAC attempt (group 2). RESULTS: One hundred fifty-nine patients, 127 patients without a prior cesarean delivery and 32 patients with a VBAC attempt, met all the study criteria. The cesarean delivery rate was 26.3% (34/127) in group 1 and 56.3% (18/32) in group 2 (VBAC success rate, 43.7%). There were no cases of uterine rupture. There were no differences in the frequency of endometritis rates or neonatal intensive care unit admission, whether vaginal or cesarean delivery occurred. CONCLUSION: VBAC success rates appeared to be lower for diabetic gravidas as compared to those for nondiabetic women reported in the literature. Although maternal and neonatal complication rates were low, further studies are necessary to determine the safety of VBAC in this population.

Maternal thrombocytopenia. Predicting neonatal thrombocytopenia with cordocentesis.

OBJECTIVE: To evaluate the efficacy of cordocentesis for predicting fetal thrombocytopenia in the presence of maternal thrombocytopenia. STUDY DESIGN: We studied platelet counts obtained by cordocentesis from 42 consecutive immune thrombocytopenia purpura patients. Platelet counts were obtained on 36 neonates, and the statistical analysis included only these infants. Presence of maternal antiplatelet antibodies, interval from fetal sampling to delivery, neonatal platelet counts and outcome were evaluated. Thrombocytopenia was defined as a platelet count < or = 150,000/microL, with < or = 50,000 microL considered severe. RESULTS: No procedure-related complications occurred. A moderate correlation existed between fetal and neonatal platelet counts (r = .48, P = .003), unrelated to the interval between sampling and delivery. Eight of 36 fetuses had thrombocytopenia, and 4 were confirmed at delivery. Two neonates had thrombocytopenia at birth but not at cordocentesis. Two neonatal thrombocytopenia cases were severe. Neither was categorized as severe antenatally. The sensitivity, specificity, and positive and negative value for predicting severe neonatal thrombocytopenia were 0%, 100%, 0%, and 94%, respectively. Grade 1 intraventricular hemorrhages occurred in two neonates delivered at 35 weeks' with normal platelet counts. CONCLUSION: Cordocentesis was not reliable in predicting severe neonatal thrombocytopenia; however, the high negative predictive value was reassuring. The clinical utility of the technique and the population in which it should be used remain to be defined.

First- and second-trimester Down syndrome screening markers in pregnancies achieved through assisted reproductive technologies (ART): a FASTER trial study.

OBJECTIVE: To determine whether first- and second-trimester Down syndrome screening markers and screen-positive rates are altered in pregnancies conceived using assisted reproductive technologies (ARTs). METHODS: ART pregnancies in the multicenter FASTER trial were identified. Marker levels were evaluated for five types of ART: in vitro fertilization with ovulation induction (IVF-OI), IVF with OI and egg donation (IVF-OI-ED), IVF with ED (IVF-ED), and intrauterine insemination with OI (IUI-OI) or without OI (IUI). Each group was compared to non-ART controls using Mann-Whitney U analysis. RESULTS: First-trimester marker levels were not significantly different between ART and control pregnancies, with the exception of reduced PAPP-A levels in the IUI-OI group. In contrast, second-trimester inhibin A levels were increased in all ART pregnancies, estriol was reduced and human chorionic gonadotropin (hCG) was increased in IVF and IUI pregnancies without ED, and alpha-fetoprotein (AFP) was increased in ED pregnancies. Second-trimester screen-positive rates were significantly higher than expected for ART pregnancies, except when ED was used. CONCLUSIONS: These data show that ART significantly impacts second-, but not first-, trimester markers and screen-positive rates. The type of adjustment needed in second-trimester screening depends on the particular type of ART used.

Biparietal diameter and femur length discrepancies: are maternal characteristics important?

We examined whether gestational age, maternal race or height can be used to explain discrepancies between biparietal diameter- and femur length-derived gestational ages by analyzing ultrasound scans from 8041 consecutively scanned, singleton pregnancies, using multiple regression analysis. While a consistent association was noted between differences of more than 3 weeks and less than 3 weeks and advancing gestational age, neither maternal height nor race were significantly related. We conclude that, first, discrepancies between gestational age by biparietal diameter and femur length are rare (5%) and, second, the presence of discrepancies should not be dismissed on the basis of maternal stature or race and should alert the clinician to possible abnormal fetal growth or development.

Recurrent small for gestational age birth: perinatal risks and outcomes.

The risk of recurrent small for gestational age birth, as well as maternal and fetal-neonatal characteristics associated with recurrence, was examined in 174 mothers of consecutively delivered small for gestational age infants followed through an additional 240 livebirths. There was a twofold and fourfold increase in the risk for small for gestational age birth after one and two small for gestational age births, respectively. Although an intervening average for gestational age birth decreased the risk of recurrence, these women remained at increased risk over the general population. Given the history of a previous small for gestational age birth, perinatal risks and outcomes considered individually would not improve the prediction of recurrence. However, the significantly higher frequency of these variables, considered as a group, among mothers with recurrent small for gestational age birth suggests an association with underlying maternal disease, for example, chronic hypertension, substance use and abuse, more severe fetal-neonatal compromise, and recurrent small for gestational age birth. Recurrent small for gestational age birth should initiate a search for persistent, underlying maternal disease.

Ultrasound findings in gestations destined for unanticipated fetal demise.

There are few reports of ultrasound findings in the second and third trimesters preceding intrauterine fetal demise. To describe these findings, the ultrasound assessments of 36 structurally normal singleton fetuses with subsequent intrauterine fetal demise were compared to gestational age-matched controls. Compared to controls, it was found that biparietal diameter, head circumference, femur length and estimated fetal weight were all decreased, abnormalities of amniotic fluid volume were more frequent, but the cephalic index was not different. Upon delivery, the group with subsequent intrauterine fetal demise was not found to have any major anomalies, but had a high incidence of abnormal umbilical cord position, abruptio placentae, chorioamnionitis and meconium aspiration.

The sonographically thick placenta: a predictor of increased perinatal morbidity and mortality.

In order to determine the prevalence and significance of sonographically thick placentas, we reviewed the computerized records of 18 827 viable, singleton pregnancies. Of these, 116 (0.6%) had thick placentas diagnosed by ultrasound examination. Perinatal mortality was markedly increased among pregnancies with thick placentas (odds ratio = 13.1, 95% confidence limits (CL) = 8.3-20.8), accounting for 6.2%; of the total. The rates of abruptio placentae (odds ratio = 2.9, CL = 1.1-8.1), neonatal intensive care unit admissions (odds ratio = 4.6, CL = 3.1-6.9) and anomalies (odds ratio = 8.4, CL = 4.9-14.4) were also significantly increased among the thick placenta cohort compared to controls. The 106 liveborn neonates with thick placentas had lower Apgar scores, were delivered at an earlier gestational age, and weighed less than controls. Anomalies, hydrops fetalis and abruptio placentae complicated 16 of the 24 cases of perinatal mortalities. Sonographically thick placentas should alert the clinician to the possibility of compromised perinatal outcome.

Benefits associated with harmonic tissue imaging in the obstetric patient.

OBJECTIVE: We sought to determine the impact of harmonic tissue imaging on image resolution and visualization of fetal structures during obstetric ultrasonography. STUDY DESIGN: Patients with singleton second- or third-trimester fetuses were recruited. Prospective comparisons of conventional fundamental imaging and harmonic tissue imaging were made. Visualization rates and frequencies of improvement in resolution were calculated. Discriminate function analysis evaluated determinants of improved visualization. RESULTS: Harmonic tissue imaging improved resolution of at least one fetal structure in 51.4% of patients studied. Differences were most marked for 4-chamber views of the heart with improvement in resolution in 30.5% of patients and change in ability to visualize in 9.5%. Maternal weight and gestational age had a significant influence on whether improvements were noted with harmonic tissue imaging, accounting for 27% of the variance. CONCLUSIONS: Harmonic tissue imaging offers significant improvements over fundamental imaging in image resolution and structure visualization in obese patients during the second trimester of pregnancy.

Limited clinical utility of midtrimester fetal morphometric percentile rankings in screening for birth weight abnormalities.

OBJECTIVE: Our purpose was to determine whether midtrimester fetal ultrasonographic morphometric percentile rankings are sensitive screening tests for preterm labor or birth weight abnormalities. STUDY DESIGN: Stepwise multiple regression and chi 2 analysis were used to identify midtrimester fetal measurements predicting birth weight and gestational age. Receiver-operator characteristics curves were used to evaluate abdominal circumference percentiles as a test for large-for-gestational-age and small-for-gestational-age infants. RESULTS: Extremes in abdominal circumference and head measurement percentiles were associated with large- and small-for gestational-age infants but not with preterm delivery. Abdominal circumference predicted birth weight in regression analysis; however, receiver-operator characteristic curves showed abdominal circumference percentiles to be poor screening tests for large- or small-for-gestational-age infants. The positive predictive value of 10th and 90th abdominal circumference percentiles for small- and large-for-gestational-age infants was < 20%. CONCLUSION: Midtrimester percentile rankings offer no clear benefit in targeting fetuses with potential birth weight abnormalities or risk of preterm delivery and may provide clinically misleading information.

Delivery of the marginally preterm infant: what are the minor morbidities?

OBJECTIVE: We sought to determine frequencies of minor morbidities associated with delivery between 32 and 36 weeks' gestation. STUDY DESIGN: The study population consisted of all infants delivered between 32 and 36 weeks' gestation at a tertiary care hospital during 1997. Maternal and neonatal charts were abstracted for maternal history, pregnancy complications, and neonatal demographics comparing complications present at each gestational week. The Student t test, chi(2) analysis, and stepwise regression analysis were used to assess statistical significance. Odds ratios were calculated. RESULTS: There were 553 patients eligible for study. There was increased risk of neonatal intensive care unit admission with delivery before 34 weeks' gestation (P <.04). An increased incidence of feeding difficulties was present before 35 weeks' gestation (P <.001). Hypothermia remained more frequent until 35 weeks' gestation (P <.05). Delivery at 35 weeks' gestation did not increase the mean number of neonatal hospital days. CONCLUSION: Although the incidences of major morbidities decline after 32 weeks' gestation, minor morbidities continue up to 35 to 36 weeks' gestation and may lengthen neonatal hospitalization.

Influence of maternal-fetal medicine subspecialization on the frequency of trial of labor in term pregnancies with breech presentation.

OBJECTIVE: To investigate the role of subspecialization in maternal-fetal medicine (MFM) on the frequency of a trial of labor in term pregnancies with breech presentation. METHODS: We conducted a retrospective study of 332 singleton pregnancies > or =37 weeks with nonfootling breech presentation that delivered over a 6-year period (1994-1998) at a university-based, tertiary care hospital. Patients were divided into two groups based on whether the delivery was attended by an MFM or non-MFM obstetrician-gynecologist. Demographic and clinical data were compared between groups and outcome variables included whether the patient had an attempt at vaginal delivery, cesarean delivery after a labor attempt, or vaginal breech delivery. RESULTS: The frequency of labor attempt (OR 1.4, 95% CI 0.9-2.3), vaginal breech success rate (OR 0.6, 95% CI 0.3-1.5), and overall cesarean rates (OR 0.9, 95% CI 0.5-1.7) were similar between groups. Using discriminant function analysis, only nulliparity (R2 = 1.6%, F = 6.0, P = 0.005) and birthweight (R2 = 2.0% F = 6.4, P = 0.01) were associated with trial of vaginal delivery. CONCLUSIONS: Subspecialization in MFM had no impact on the frequency of trial of labor in the term pregnancy with a breech presentation.

Trends in sonographic fetal organ visualization.

In order to assess changes in sonographic visualization over the last 6 years, 7092 second- and third-trimester ultrasound examinations from separate pregnancies in three individual years (1451 in 1985, 3016 in 1988, and 2625 in 1991) were compared. Overall, visualization across all gestational ages improved from 63.9% (1985) to 85.8% (1988) to 87.3% (1991), with the year in which the scan was performed explaining 19.6% of the variance in visualization. Maternal size (as determined by body mass index) remained the major determinant of ultrasound visualization in 1991 (r(2) = 11.2%), with gestational age explaining only 5.2% additional variance. Overall organ visualization was maximal at 21-23 weeks' gestation, with the decline in later gestation primarily accounted for by worsened visualization of fetal extremities and spine. Improved fetal visualization earlier in the second trimester and the advent of embryonic visualization in the first trimester may allow a continuum of prenatal sonographic diagnosis.

The clinical utility of maternal body mass index in pregnancy.

To describe maternal body mass index and to compare the use of maternal weight and body mass index for risk assessment at the initial prenatal visit, 6270 gravid women who were consecutively delivered of infants were studied. Body mass index increased with advancing maternal age, parity, and advancing gestational age and was significantly greater in black women than in nonblack women. Risks for the development of adverse outcome associated with maternal obesity, including development of gestational diabetes, preeclampsia, fetal macrosomia, and shoulder dystocia, were comparably predicted by either maternal weight or body mass index greater than 90th percentile. Maternal weight was as predictive of preeclampsia, macrosomia, and shoulder dystocia as was body mass index when these factors were analyzed as continuous variables, whereas increasing body mass index was more predictive of gestational diabetes. The prediction of factors associated with low maternal weights, small-for-gestational-age birth, prematurity, low birth weight, and perinatal death was equivalent for maternal weight and body mass index that was less than 10th percentile. This study indicates that in the initial risk assessment of outcomes related to maternal weight, the calculation of maternal body mass index offers no advantage over simply weighing the patient. This finding contrasts with results in nonpregnant women.