Lawrence D. Platt

Antepartum fetal evaluation: Development of a fetal biophysical profile

Five fetal biophysical variables, fetal breathing movements, fetal movements, fetal tone, qualitative amniotic fluid volume, and the nonstress test, were measured in the same observation period in 216 patients with high-risk pregnancies. All delivered within one week of the last observation. The relationship between individual biophysical variables and combinations of variables to the outcome of pregnancy as judged by five-minute Apgar score, fetal distress in labor, and perinatal mortality rate (PMN) was determined. For any single test, the false negative rate was low and was similar between tests, but the false positive rate was high (greater than 50%) and varied significantly between tests. Combining tests resulted in a significant change in both the false negative and false positive rates as compared to any single test. The most accurate differentiation of the normal from the compromised fetus was obtained when all five variables were studied. The PNM ranged from 0 when all variables were normal to 600 per 1,000 when all were abnormal. These data suggest that combined fetal biophysical testing is a more accurate method of antepartum fetal evaluation than any single method.

Genome-Wide Fetal Aneuploidy Detection by Maternal Plasma DNA Sequencing

OBJECTIVE: To prospectively determine the diagnostic accuracy of massively parallel sequencing to detect whole chromosome fetal aneuploidy from maternal plasma. METHODS: Blood samples were collected in a prospective, blinded study from 2,882 women undergoing prenatal diagnostic procedures at 60 U.S. sites. An independent biostatistician selected all singleton pregnancies with any abnormal karyotype and a balanced number of randomly selected pregnancies with euploid karyotypes. Chromosome classifications were made for each sample by massively parallel sequencing and compared with fetal karyotype. RESULTS: Within an analysis cohort of 532 samples, the following were classified correctly: 89 of 89 trisomy 21 cases (sensitivity 100%, 95% [confidence interval] CI 95.9–100), 35 of 36 trisomy 18 cases (sensitivity 97.2%, 95% CI 85.5–99.9), 11 of 14 trisomy 13 cases (sensitivity 78.6%, 95% CI 49.2–99.9), 232 of 233 females (sensitivity 99.6%, 95% CI 97.6 to more than 99.9), 184 of 184 males (sensitivity 100%, 95% CI 98.0–100), and 15 of 16 monosomy X cases (sensitivity 93.8%, 95% CI 69.8–99.8). There were no false-positive results for autosomal aneuploidies (100% specificity, 95% CI more than 98.5 to 100). In addition, fetuses with mosaicism for trisomy 21 (3/3), trisomy 18 (1/1), and monosomy X (2/7), three cases of translocation trisomy, two cases of other autosomal trisomies (20 and 16), and other sex chromosome aneuploidies (XXX, XXY, and XYY) were classified correctly. CONCLUSION: This prospective study demonstrates the efficacy of massively parallel sequencing of maternal plasma DNA to detect fetal aneuploidy for multiple chromosomes across the genome. The high sensitivity and specificity for the detection of trisomies 21, 18, 13, and monosomy X suggest that massively parallel sequencing can be incorporated into existing aneuploidy screening algorithms to reduce unnecessary invasive procedures. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01122524. LEVEL OF EVIDENCE: II

Exercise in pregnancy

We investigated cardiovascular and metabolic responses in 23 healthy pregnant volunteers in their third trimester prior to, during, and after a 15-minute period of treadmill exercise. The energy utilization of this exercise was 2.33 MET with an oxygen consumption under 0.5 L/minute. Exercise induced a significant increase in maternal heart rate and a shortening of the R time intervals; both returned to baseline by 30 minutes of recovery. This light exercise also induced a significant increase in glucagon, norepinephrine, and epinephrine concentrations, all of which were transitory and reversed within 30 minutes of the recovery period. No change in glucose or cortisol concentration resulted from this exercise. We conclude that light exercise of brief duration elicits appropriate and transitory cardiovascular and metabolic responses in normal pregnancy.

Qualitative amniotic fluid volume determination by ultrasound: Antepartum detection of intrauterine growth retardation

Qualitative amniotic fluid volume (AFV) was determined by a linear array ultrasound method in 120 patients referred with a diagnosis of intrauterine growth retardation (IUGR). Eighty-nine of these patients were delivered of a normal infant; the false positive rate by clinical methods alone was 74.2%. Qualitative AFV was termed normal if at least one pocket of amniotic fluid measuring 1 cm in its broadest diameter was identified. Qualitative AFV was normal in 91 patients, and 86 were delivered of a normal fetus (93.4%). In contrast, qualitative AFV was decreased in 29 patients, and 26 were delivered of a fetus with IUGR (89.9%). These differences were highly significant. Perinatal morbidity was increased tenfold in patients with decreased AFV. Overall, 26 of 31 IUGR fetuses (83.4%) demonstrated decreased qualitative AFV.

Management of asymptomatic ovarian and other adnexal cysts imaged at US: Society of Radiologists in Ultrasound Consensus Conference Statement.

The Society of Radiologists in Ultrasound convened a panel of specialists from gynecology, radiology, and pathology to arrive at a consensus regarding the management of ovarian and other adnexal cysts imaged sonographically in asymptomatic women. The panel met in Chicago, Ill, on October 27-28, 2009, and drafted this consensus statement. The recommendations in this statement are based on analysis of current literature and common practice strategies, and are thought to represent a reasonable approach to asymptomatic ovarian and other adnexal cysts imaged at ultrasonography.

Defining Normal and Abnormal Fetal Growth: Promises and Challenges

Normal fetal growth is a critical component of a healthy pregnancy and influences the long-term health of the offspring. However, defining normal and abnormal fetal growth has been a long-standing challenge in clinical practice and research. We review various references and standards that are used widely to evaluate fetal growth and discuss common pitfalls of current definitions of abnormal fetal growth. Pros and cons of different approaches to customize fetal growth standards are described. We further discuss recent advances toward an integrated definition for fetal growth restriction. Such a definition may incorporate fetal size with the status of placental health that is measured by maternal and fetal Doppler velocimetry and biomarkers, biophysical findings, and genetics. Although the concept of an integrated definition appears promising, further development and testing are required. An improved definition of abnormal fetal growth should benefit both research and clinical practice.

Fetal echocardiography. IV. M-mode assessment of ventricular size and contractility during the second and third trimesters of pregnancy in the normal fetus.

M-mode echocardiographic examination of the right and left ventricles was performed on 82 normal fetuses between 18 and 41 weeks of gestation. The diameter of the right and left ventricles correlated with the biparietal diameter. The right/left ratio of the ventricular diameters remained constant (1:1) throughout gestation. Fractional shortening and mean circumferential shortening of both ventricles were independent of gestational age. The data presented in this paper will allow the clinician to evaluate abnormal fetal conditions that might affect cardiovascular structure and/or function.

Reverse end-diastolic flow velocity on umbilical artery velocimetry in high-risk pregnancies: An ominous finding with adverse pregnancy outcome

Systolic/diastolic ratios of umbilical velocimetry have been used to assess downstream placental vascular resistance. Reverse end-diastolic flow velocity during end diastole suggests extreme abnormality in waveform and resistance. We reviewed our experience of patients showing reverse end-diastolic flow velocity over a 2 1/2-year period. Out of 550 high-risk patients studied with umbilical velocimetry over this period, 12 patients showed the finding. All patients were delivered of small for gestational age fetuses and the perinatal mortality in this group was 50%. There was also significant perinatal morbidity as judged by cesarean section performed because of fetal distress, low Apgar scores, days in neonatal intensive care, prematurity, placental infarcts, and lethal anomalies. These findings suggest that reverse end-diastolic velocity on umbilical velocimetry is associated with catastrophic perinatal outcome, and aggressive perinatal management may be advised in this group of patients.

Peritoneal serous papillary carcinoma, a phenotypic variant of familial ovarian cancer: implications for ovarian cancer screening.

OBJECTIVE Our purpose was to report the cancers arising during a familial ovarian cancer screening program and investigate the tumors clonality and association with BRCA1 and BRCA2 mutations. STUDY DESIGN Program participants with a diagnosis of ovarian cancer or peritoneal serous papillary carcinoma were identified and their demographic characteristics, ultrasonographic findings, CA 125 results, operative reports, and pathology slides reviewed. Immunohistochemical analysis of p53, bcl-2, HER-2/neu, and nm23 H1 expression was performed on tumor tissues from multiple metastatic sites, and germline BRCA1 and BRCA2 mutations were identified. RESULTS Three stage I ovarian cancers and 7 cases of peritoneal serous papillary carcinoma were diagnosed from among 1261 program participants. Ultrasonographic abnormalities triggered surgical exploration in all 3 cases of stage I disease. Elevated levels of CA 125 were the harbinger in 2 of 7 cases of peritoneal serous papillary carcinoma, abnormal ultrasonographic findings prompted diagnosis in 2 of 7 cases, and 3 of 7 women had abdominal symptoms 5, 6, and 16 months after screening. Results of immunohistochemical studies suggested multifocal disease in 5 of 7 patients with peritoneal serous papillary carcinoma. At least 3 of the patients with peritoneal serous papillary carcinoma carry BRCA1 185delAG mutations. CONCLUSION Multifocal peritoneal serous papillary carcinoma may be a phenotypic variant of familial ovarian cancer, and screening strategies for these women cannot rely on ultrasonography and CA 125 testing to detect early disease.

Maternal and infant complications in high and normal weight infants by method of delivery

Objective To estimate the population risks of maternal and infant complications with the birth of macrosomic (at least 4000 g) compared with normal weight infants. Methods Term, singleton infants were identified from the state of Washingtons birth event records database for 1990. Diagnosis codes from the Internal Classification of Diseases (9th revision) were used to identify delivery method and previously defined complications. We adjusted for maternal demographic and clinical factors using multivariable logistic regression to derive the risk of each maternal and infant complication. Results The incidence of macrosomia was 13% (8815 of 66,086). Vaginal birth of macrosomic infants was associated with low incidence of complications except for shoulder dystocia (11%) and postpartum hemorrhage (5%). Postpartum infection was the most common complication for women who had cesarean delivery after labor (5%), and complications for women who had cesarean without labor were rare (less than 3%). Neonatal complications were rare. Among infants with shoulder dystocia, the risks of asphyxia (adjusted relative risk [RR] 1.2, 95% confidence interval [CI] 0.6, 2.3), birth trauma (RR 0.6, 95% CI 0.2, 1.6), long-bone injury (RR 1.2, 95% CI 0.6, 2.4), seizures (RR 1.0, 95% CI 0.0, 25.0), and facial palsy (RR 2.2, 95% CI 0.2, 44.4) were not significantly different for macrosomic and normal weight infants; however, macrosomic infants had a significantly increased risk of Erb palsy (RR 3.5, 95% CI 1.8, 7.5). Conclusion This population-based study showed that most macrosomic infants are delivered vaginally with low rates of maternal and neonatal complications. Macrosomic infants have higher rates of Erb palsy, but similar rates of other serious complications of shoulder dystocia when compared with normal weight infants.