Stanley S. Grant

Normal values for human umbilical venous and amniotic fluid pressures and their alteration by fetal disease

Umbilical venous and amniotic fluid pressures were measured in 68 human pregnancies at the time that cordocentesis was performed. Normal umbilical venous pressure was unrelated to gestational age and remained within a tight range (5.3 +/- 2.3 mm Hg, mean +/- SD). Fetuses with an elevated umbilical venous pressure had disorders consistent with either hepatomegaly or congestive heart failure. Umbilical venous pressure was significantly increased before treatment in two fetuses with immune hydrops; it rapidly declined with treatment. Neither gestational age nor umbilical venous pressure was significantly different in the groups that received and did not receive pancuronium. There was a strong relationship between amniotic fluid pressure and gestational age in normal pregnancy (r = 0.54, p less than 0.0001). Women with hydramnios had amniotic fluid pressures greater than control subjects (p = 0.0007). This investigation documents normal human amniotic fluid and fetal umbilical venous pressures. These measurements are altered by disease and may prove to be of diagnostic and therapeutic value in the future.

Evaluation of multiple-marker screening for Down syndrome in a statewide population

OBJECTIVE Our purpose was to evaluate our experience with a statewide, multiple-marker Down syndrome screening program. STUDY DESIGN The results of 18,712 screening tests performed from July 1, 1991, to Oct. 31, 1992, were reviewed. Amniocentesis and aneuploidy detection rates were compared with the experience of a previous year (1989-1990) in which material serum alpha-fetoprotein was used for detection of Down syndrome. RESULTS Positive screening tests (Down syndrome risk > or = 1/190) occurred in 665 of 18,712 (3.5%) patients; 516 of 665 (78%) patients accepted amniocentesis. Fifteen aneuploidies were identified: 12 trisomy 21, one trisomy 18, one trisomy 13, and one 48,XXXY. The overall detection rate was one in 34 amniocenteses performed; for trisomy 21 it was one in 43. In a previous year in which maternal serum alpha-fetoprotein alone was used, 3.6% had positive screening tests (Down syndrome risk > or = 270); the detection rate for all aneuploidies was one in 57 amniocenteses, and for trisomy 21 it was one in 114. The expanded maternal serum alpha-fetoprotein test was well accepted by clinicians, with 36% of gravid state residents undergoing screening. CONCLUSION The multiple marker test is a good screening tool and is superior to material serum alpha-fetoprotein alone.

Detection of fetal Turner syndrome with multiple-marker screening

OBJECTIVE Our purpose was to examine the ability of the multiple-marker screening test (maternal serum alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and maternal age) to detect fetal Turner syndrome. STUDY DESIGN We reviewed 27,282 screening tests performed at our institution between July 1, 1990, and June 30, 1992. All cases in which fetal Turner syndrome was detected as a result of a positive Down syndrome screening test (Down syndrome risk > or = 1:190) or in which a positive screening test was obtained before an amniocentesis scheduled for other reasons were included. Serum marker levels, Down syndrome risk, and ultrasonographic findings were reviewed. To clarify the relative contributions of estriol and human chorionic gonadotropin to the positive screen, the risks were recalculated using only maternal serum alpha-fetoprotein and hCG or maternal serum alpha-fetoprotein and estriol. RESULTS Eight cases were identified. Four fetuses had cystic hygroma and hydrops, two had hygroma only, and two had no abnormality on ultrasonography. Both human chorionic gonadotropin and estriol contributed to the positive screen. CONCLUSION The multiple-marker screening test appears to detect Turner syndrome, as well as trisomies 21 and 18.

Midtrimester amniocentesis. An analysis of 923 cases with neonatal follow-up

Maternal, fetal, and neonatal results and complications were analyzed after 923 genetic amniocenteses. Maternal age of 35 years and beyond was associated with a 2.0% risk of fetal trisomy 21 and a 3.0% risk of all major chromosome abnormalities. Comparable rates for women aged 40 and beyond were 4.8% and 7.2%. Neural tube defects were detected in 0.15% of procedures done for maternal age and 3.4% of those done for a previous involved child. The risk of spontaneous abortion as a result of amniocentesis was 0.2% to 1.4%. Mahogany or green fluid was associated with a 29% rate of fetal loss. Unexplained midtrimester elevations of maternal serum alpha-fetoprotein were associated with a 38% risk of a subsequent low-birth weight infant. The only neonatal complication associated with amniocentesis was an apparent marked increase in the incidence of lower-extremity orthopedic abnormalities.

Effect of diagnostic and therapeutic cordocentesis on maternal serum ac.-fetoprotein concentration

We investigated the affect of cordocentesis (n = 36) and intravascular transfusion (n = 14) performed with a fixed needle guide on maternal serum alpha-fetoprotein levels. In 50% of the procedures, the placenta was anterior and punctured. For all patients, maternal serum alpha-fetoprotein levels rose 70.8% +/- 28%. The magnitude of the rise was unrelated to the number of attempts necessary, gestational age, or the initial maternal serum alpha-fetoprotein levels concentration. The location of the placenta was the sole identified variable related to the rise. A total of 44% of the patients had a significant increase in maternal serum alpha-fetoprotein level when the placenta was anterior. In contrast, only 4% of the patients had a significant rise in maternal serum alpha-fetoprotein level when the placenta was other than anterior. There was no difference in the frequency of a significant rise in maternal serum alpha-fetoprotein level concentration between the patients who underwent cordocentesis and those who underwent intravascular transfusion. On the basis of these findings, we recommend that when maternal isoimmunization is a potential concern and the placenta is anterior, the umbilical cord should be approached either through a window or laterally from the placenta.

Options for Down Syndrome Screening: What Will Women Choose?

Down syndrome screening has been offered to pregnant women since the early 1980s. Protocols have changed as research confirmed improvements that result in higher detection rates and lower false-positive rates. Results from 2 clinical trials evaluating screening protocols that include ultrasound measurement of nuchal translucency and biochemical testing in the first and second trimester are now available. First-trimester screening is an option if there are adequate ultrasound, diagnostic, and counseling services available. Regional variation in the availability of these services may limit the implementation of first-trimester screening. Combining screening tests for Down syndrome from both trimesters as an integrated test offers the highest detection rate with the lowest false-positive rate. The possibility of avoiding a positive screen will make this an attractive option for some. Timing, detection rate, false-positive rates, and personal factors influence the decision women make regarding screening versus diagnostic testing. This article reviews the efficacy of current protocols for Down syndrome screening. Accurate information about available screening tests will facilitate informed decisions about screening and testing.

Prospective evaluation of prenatal maternal serum screening for trisomy 18

OBJECTIVE Our goal was to evaluate the performance of prenatal serum screening for trisomy 18. STUDY DESIGN All 40,762 samples for maternal serum testing (August 1991 to June 1994) with a trisomy 18-positive screen (n = 175, alpha-fetoprotein < or =0.75 multiples of the median, unconjugated estriol < or =0.60 multiples of the median, human chorionic gonadotropin < or =0.55 multiples of the median) were analyzed. Results of all amniocenteses, ultrasonographic studies, and birth or death certificate information were obtained from the Iowa Expanded Serum Screening Program, the Iowa Department of Public Health, and the Iowa Birth Defects Registry. RESULTS We obtained the expected screen-positive rate for trisomy 18 (0.43%, 175/40,762). Fourteen samples from outside the state were excluded, which left 161 cases with outcome data obtained through amniocentesis (n = 121), birth certificates (n = 34), telephone contact (n = 2), or a sonogram indicating a nonviable gestation (n = 4). Of 121 screen-positive women undergoing amniocentesis, 119 had a normal karyotype and 2 had an abnormal karyotype: 69,XXY and 47,XY,+18. Of 36 who declined amniocentesis, none had findings consistent with aneuploidy on clinical neonatal examination. Of the 103 patients who had a detailed ultrasonographic study at the University of Iowa, 27 had a subtle fetal abnormality or growth alteration. Both cases with aneuploidy were in this group. An additional 7 cases of trisomy 18 without the typical trisomy 18 maternal serum screening pattern were diagnosed during this period either at amniocentesis performed because of increased Down syndrome risk indicated by serum screening (n = 1), by elevated alpha-fetoprotein level (n = 1), or by advanced maternal age (n = 2) with serum for screening drawn coincidentally, or they were diagnosed postnatally (n = 3). Three of the 7 cases had early second-trimester ultrasonographic examinations, and all showed abnormalities. CONCLUSIONS The detection rate of trisomy 18 among patients offered amniocentesis was significantly lower (p < 0.05) than the expected rate (10/161 on the basis of published data). Combining serum screening with detailed ultrasonographic evaluations may improve predictive value by more precisely targeting amniocentesis toward those at highest risk.

Prediction of pregnancy outcome with single versus serial maternal serum a-fetoprotein tests

OBJECTIVE The purpose of our study was to determine whether the trend of three maternal serum alpha-fetoprotein samples was more predictive of pregnancy outcome than the initial sample in the evaluation of patients with unexplained alpha-fetoprotein elevations. STUDY DESIGN A total of 432 patients with unexplained elevation of their first two maternal serum alpha-fetoprotein samples had a third sample drawn. Pregnancy outcomes were determined. Patients were grouped for analysis according to the level of the initial sample, the final sample, and the trend of three samples. Statistical analysis was by chi 2 and logistic regression, with p < 0.05 considered significant. RESULTS The initial maternal serum alpha-fetoprotein was most predictive of preterm delivery (p < 0.001), size small for gestational age (p < 0.001), and intrauterine fetal death (p = 0.009). Neither the final value nor the trend of three values was as prognostic. CONCLUSION The first maternal serum alpha-fetoprotein is the best predictor of pregnancy outcome. Obtaining a second sample to confirm the elevation is appropriate, but additional samples provide minimal information.

The Fetus as a Patient

A 19-WEEK PARTURIENT presented with a fetus with a lung mass. Magnetic resonance imaging (panel A) demonstrated a congenital cystic adenomatous malformation (CCAM) occupying the right chest causing mediastinal shift, cardiac compression (H heart), and displacement of the hemidiaphragm (arrow). Both lungs were compressed. Hydrops fetalis was present (A fetal ascites; B bowel; L liver). Echocardiography revealed a compressed but structurally normal heart. The hydrops improved after aspiration, but the macrocyst recurred and the solid component continued to enlarge. A thoracoamniotic shunt was placed for continuous drainage. Imaging at 36 weeks (panel B) demonstrates the right hemidiaphragm in the correct position and resolution of the fetal ascites. Lung hypoplasia and mediastinal shift necessitated mass resection during ex utero intrapartum therapy. A maternal laparotomy was performed, followed by hysterotomy allowing delivery of the fetal head, chest, and arm. High-dose volatile anesthetic (2 minimum alveolar concentration of desflurane) provided uterine relaxation and fetal anesthesia. Maternal blood pressure was maintained with phenylephrine. Intramuscular fetal injections included fentanyl (20 g/kg), vecuronium (200 g/kg), and atropine (20 g/kg). The fetus was intubated (not ventilated), and pulse oximeter and peripheral venous access were established. After pulmonary lobectomy, the fetus was ventilated and delivery and newborn resuscitation were completed. Congenital cystic adenomatous malformation results from overgrowth of terminal bronchial epithelium. Mass effect results in pulmonary hypoplasia. Cardiac compression with impaired venous return leads to lethal cardiac failure (hydrops). Maternal health is threatened, asa state similar topreeclampsia (maternalmirror syndrome)mayensue. Exutero intrapartumtherapyprocedure isa feasibleandpotentially a life-saving treatment for congenital cystic adenomatous malformation. It provides time on uteroplacental gas exchange for controlled resection of the large fetal lung mass. The anesthetic goals for ex utero intrapartum therapy procedure include achieving uterine hypotonia, usingdeepgeneralanesthesiaornitroglycerin, tomaintainuteroplacentalcirculation;avoidingpostpartumhemorrhage;maintainingnormal maternal blood pressure often requiring -adrenergic agonist support; and achieving surgical anesthesia for the fetus to avoid first breathing while avoiding fetal cardiac depression.

FeatureOptions for Down Syndrome Screening: What Will Women Choose?

Down syndrome screening has been offered to pregnant women since the early 1980s. Protocols have changed as research confirmed improvements that result in higher detection rates and lower false-positive rates. Results from 2 clinical trials evaluating screening protocols that include ultrasound measurement of nuchal translucency and biochemical testing in the first and second trimester are now available. First-trimester screening is an option if there are adequate ultrasound, diagnostic, and counseling services available. Regional variation in the availability of these services may limit the implementation of first-trimester screening. Combining screening tests for Down syndrome from both trimesters as an integrated test offers the highest detection rate with the lowest false-positive rate. The possibility of avoiding a positive screen will make this an attractive option for some. Timing, detection rate, false-positive rates, and personal factors influence the decision women make regarding screening versus diagnostic testing. This article reviews the efficacy of current protocols for Down syndrome screening. Accurate information about available screening tests will facilitate informed decisions about screening and testing.