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.

The second-trimester fetus with isolated choroid plexus cysts: a meta-analysis of risk of trisomies 18 and 21.

OBJECTIVE: To assess the risk of trisomy 18 and trisomy 21 associated with isolated choroid plexus cysts diagnosed by ultrasound in the second trimester. METHODS OF STUDY SELECTION: We reviewed the unabridged PREMEDLINE and MEDLINE databases for articles written in the English language regarding second-trimester fetal isolated choroid plexus cysts and trisomies 18 and 21, published in the period 1987-1997. Selection criteria included only second-trimester, prospective studies in which the rate of fetal isolated choroid plexus cysts could be calculated, the number of fetuses with trisomy 18 and 21 was reported clearly, and pregnant women of all ages were included, rather than only those at high risk for aneuploidy due to advanced maternal age. TABULATION AND RESULTS: Thirteen prospective studies, comprising 246,545 second-trimester scans, were selected. Among 1346 fetuses with isolated choroid plexus cysts, seven had trisomy 18, and five had trisomy 21. For each study, a 2 x 2 table was constructed and the likelihood ratio of a positive test was computed. The likelihood ratios for trisomies 18 and 21 were found to be homogeneous (P = .08 for trisomy 18, and P = .16 for trisomy 21). The summary likelihood ratio and 95% confidence interval (CI) for each chromosomal abnormality were calculated using the Mantel-Haenszel fixed effects model of meta-analysis. The summary likelihood ratio for trisomy 18 was 13.8 (CI 7.72, 25.14, P < .001) and for trisomy 21 was 1.87 (CI 0.78, 4.46, P = .16). CONCLUSION: The likelihood of trisomy 18 was 13.8 times greater than the a priori risk in fetuses with isolated choroid plexus cysts diagnosed in the second trimester. However, the likelihood of trisomy 21 was not significantly greater than the a priori risk with isolated choroid plexus cysts. The data supported offering pregnant women karyotyping to rule out trisomy 18 when maternal age at delivery is 36 years or older, or when the risk for trisomy 18 detected by serum multiple-marker screen is more than one in 3000.

Isolated fetal pyelectasis: assessment of risk for postnatal uropathy and Down syndrome.

Eight-two consecutive fetuses with ultrasound evidence of isolated pyelectasis (defined as dilation in the antero-posterior renal pelvic dimension of > or = 4 mm) were prospectively followed to determine the risk of postnatal uropathy and Down syndrome. In 98 (60%) kidneys, isolated pyelectasis was shown to be the first manifestation of a pathophysiological process that evolved into a gamut of postnatal uropathies (defined as urological conditions requiring remedial surgery or extended medical surveillance). Data quantifying the risk for postnatal uropathy in fetuses with varying degrees of isolated pyelectasis, at different gestational ages, are presented in figure format to facilitate prenatal counselling. Bivariate analysis showed that the evolution of isolated pyelectasis to uropathy was statistically significant when in utero progression was noted or in conjunction with other findings including contralateral pyelectasis (p < 0.01), male gender (p < 0.01) and increased kidney length (p < 0.001). Importantly, 55% of the infants requiring corrective surgery demonstrated in utero progression of pyelectasis (p < 0.002). Serial ultrasound examinations were necessary to evaluate progression or regression in the extent of pyelectasis. Finally, isolated pyelectasis was associated with an increase risk for Down syndrome, beginning at maternal age of 31 years, in the interval of 16-20 week's gestation.

A prospective study of the association between isolated fetal pyelectasis and chromosomal abnormality.

OBJECTIVE: To determine the incidence of chromosomal abnormalities among fetuses with isolated pyelectasis. METHODS: Between March 1991 and March 1994, 121 cases of isolated fetal pyelectasis were identified at our institution. Pyelectasis was defined as a renal pelvis anteroposterior diameter of at least 4 mm before 33 weeks' gestation, and at least 7 mm at 33 weeks or thereafter. Once identified, women were offered antenatal genetic testing; if they declined, consent was sought for umbilical cord blood studies at delivery. RESULTS: Chromosomal evaluation was available in 99 women. Two chromosomal abnormalities were identified: one trisomy 21 and one mosaic 46, XY/47, XYY. The ages of the women were 32 and 28 years, respectively. Calculation of adjusted risks for Down syndrome and all chromosomal abnormalities indicated a 3.9-fold increase in Down syndrome risk and a 3.3-fold increase in risk for all chromosomal abnormalities in the presence of isolated fetal pyelectasis. CONCLUSION: Isolated fetal pyelectasis is associated with increased risk, over that related to age, for both Down syndrome and all chromosomal abnormalities. These factors may be valuable in counseling individual patients regarding the appropriateness of amniocentesis.

The clinical significance of a single umbilical artery as an isolated finding on prenatal ultrasound.

OBJECTIVE: To evaluate the perinatal outcome in fetuses with single umbilical artery detected on targeted prenatal ultrasound without other anomalies. METHODS: During a 3.5-year period, an isolated single umbilical artery was suspected on prenatal ultrasound examination in 57 fetuses evaluated at two referral centers. Targeted imaging to rule out concurrent fetal anomalies was normal in all cases. Pregnancy and perinatal outcome data were retrieved by review of the medical records or from conversations with referring physicians. Complete follow-up was available in 50 cases. RESULTS: A two-vessel umbilical cord was confirmed at birth in 50 neonates. The mean gestational age at delivery was 38.6 +/- 2.8 weeks; the mean birth weight was 3202.8 +/- 835.8 g. Seventeen patients (34%) underwent genetic amniocentesis, and all fetuses had a normal karyotype. The only neonate ascertained to have a congenital anomaly after birth was diagnosed with total anomalous pulmonary venous return. This neonate underwent a corrective surgical procedure and is thriving with no apparent problems at 3.5 years of age. There were no perinatal deaths. CONCLUSION: In the absence of additional sonographically detectable anomalies, an isolated single umbilical artery does not seem to affect clinical outcome and therefore should not alter routine obstetric management.

A comparison of preoperative ultrasound images of surgically proven endometriomas scanned by both transabdominal and transvaginal techniques.

The echo patterns of endometriomas have been described by both transabdominal and transvaginal scanning. This retrospective study was undertaken to evaluate the degree of internal echogenicity in endometriomas preoperatively scanned by both techniques. Transvaginal ultrasound scanning should be added to the diagnostic armamentarium.

Isolated choroid plexus cyst(s): an indication for amniocentesis.

OBJECTIVE: Our purpose was to prospectively evaluate the risk of chromosomal abnormalities associated with isolated choroid plexus cyst(s) in gravid women undergoing second-trimester ultrasonographic examination. STUDY DESIGN: During a 24-month period 9100 pregnant women underwent midtrimester ultrasonographic evaluation. Women with a fetal diagnosis of choroid plexus cyst(s) were offered amniocentesis and a repeat examination in 4 to 6 weeks. RESULTS: A diagnosis of choroid plexus cyst(s) was made in 102 fetuses (1.1%). In four of these fetuses multiple congenital anomalies were noted. Three of the four fetuses had a chromosomal abnormality, two trisomy 18 and one unbalanced translocation, t(3;13). In the remaining 98 fetuses the choroid plexus cysts were isolated findings, that is, there were no other ultrasonographically detected anomalies. Seventy-five of these 98 fetuses underwent amniocentesis. An abnormal karyotype was identified in four fetuses: three had Down syndrome (two trisomy 21 and one unbalanced translocation, t[14;21]), and one trisomy 18. The offspring of the 23 patients in which amniocentesis was declined were phenotypically normal. CONCLUSIONS: In our prospective study the risk of chromosomal abnormality with isolated choroid plexus cyst(s) was 1:25, a risk that exceeds the 1:200 risk of pregnancy loss after amniocentesis and the 1:126 and 1:260 risk for aneuploidy and Down syndrome, respectively, in a 35-year-old pregnant women during the midtrimester. These findings indicate that amniocentesis should be offered to pregnant women in the presence of isolated fetal choroid plexus cyst(s).

Arteriovenous malformation of the uterus associated with a missed abortion.

Arteriovenous malformation of the uterus is a rare uterine abnormality. This entity is generally associated with the presence of molar disease, choriocarcinoma and uterine surgery, but may be congenitally acquired. The presence of an arteriovenous malformation generally leads to unexplained profuse uterine bleeding. The diagnosis of this entity has traditionally been made by arteriography, and the treatment is usually hysterectomy. We present a patient with an arteriovenous malformation of the uterus whose prior delivery was by Cesarean section. The patient experienced episodes of heavy vaginal bleeding in the first month following the procedure of suction curettage for a first-trimester pregnancy loss. Chorionic villus sampling performed prior to the procedure showed a chromosomally normal fetus. The diagnosis of an arteriovenous malformation was made by color Doppler velocimetry and confirmed with arteriography. The patient desired to maintain her fertility. Interventional radiological techniques were successfully utilized to obliterate the arteriovenous malformation with the use of polyvinyl alcohol particles (250 micro m) and gelfoam. Discussion includes the presenting signs and symptoms along with the method of both diagnosis and conservative management.

Sonographic diagnosis of congenital heart disease: comparison between the four-chamber view and multiple cardiac views.

OBJECTIVE: To report our experience in the detection of congenital heart disease using both the four-chamber view of the heart as part of the standard obstetric ultrasound examination and multiple cardiac views as part of the detailed targeted examination. METHODS: All admissions to Children's Memorial Hospital of Northwestern University Medical Center with the diagnosis of congenital heart disease between June 1988 and April 1992 were identified (N = 1947). These admissions were matched to deliveries (N = 19,321) that occurred at Prentice Women's Hospital during the same period; of these, 10,004 had at least one obstetric ultrasound examination. All fetuses were scanned either with the standard obstetric ultrasound type of examination, featuring only the four-chamber view of the heart, or by the detailed targeted imaging type of study, featuring multiple cardiac views. The type of examination performed was based on the specific request of the attending obstetrician or gynecologist. RESULTS: Thirty-three neonates who had at least one obstetric ultrasound examination were treated for congenital heart disease. An additional five pregnancies were terminated secondary to serious fetal heart defects. When only the four-chamber view was visualized, 11 of 33 fetuses (33.3%) with confirmed congenital heart disease were detected. CONCLUSIONS: Assessment of the outflow tracts is crucial for detection of many forms of congenital heart disease. However, before this is accepted as the standard of care, both the obstetric and radiologic communities should develop their skills in cardiac imaging. Only then can this sophisticated type of cardiac examination be offered to pregnant women.

Fetal reduction: is this the appropriate answer to multiple gestation?

PIP: Fetal reduction techniques, experiences at Northwestern University of Evanston, Illinois, USA, and ethical issues are discussed. The use of fetal reduction pertains to higher order multiple pregnancies due to successful fertility treatments. The risk associated with multifetal pregnancy is preterm delivery i.e., 29-31 weeks for quadruplets. In addition, survivors often have a high risk of congenital abnormalities and complications related to prematurity. 1978 marked the 1st time selective termination was possible. Other terms include "selective" birth, reduction, feticide, abortion, and multiple pregnancy reduction. The procedure takes place in the 1st or 2nd trimester, and procedures are similar to an elective abortion but with different techniques. Although there are many techniques, the preferred one is transabdominal cardiac puncture and injection of potassium chloride. A highly skilled ultrasonographer is essential for a successful technique. The complexity of the technique is one where the physician from a 2-dimensional screen must envision a 3-dimensional picture of the uterus and contents. Accurate needle placement is important. The reports from 7 clinical trials using the intracardiac potassium chloride technique are presented. The Northwestern experience includes 25 reductions between 1987-91 using fentanyl and midazolidocaine analgesia and general anesthesia with 1% lidocaine. Gestational age ranged from 9 to 13 weeks. There was total loss in 2 cases and deliveries in 8 cases including neonatal death of a very preterm set of twins. At or = 37 weeks, there were 11 pregnancies. 11 patients were or = 35 years, and 4 of the 20 30 years. In 33% of cases, only 1 pregnancy was left, which is dissimilar to other studies. Many difficulties may be faced with a complete pregnancy loss where there is a lack of support for the decision for fetal reduction. 2 concerns are mentioned in the ethical debate: the adequacy of counseling and the criteria for determining how many reductions per pregnancy. Difficulties arise in physician counseling when patients are unable to assimilate complex and detailed information, and physicians may not accurately convey information. Institutions may bias patient counseling. When an abnormality exists, the decision is easy; but with multiple normal development, the recommendation is twins. The Northwestern recommendation involves patient and family decisions and joint discussion of risk. The likelihood of severely premature delivery and maternal morbidity should also be considered, as well as the medical cost incurred with delivery and care of preterm multiple infants i.e., 1.2 million dollars for delivery of quads at 27 weeks. Science should be directed to reducing multiple pregnancies by refining technique and using fetal reduction as an interim technique. Fetal reduction is not appropriate for all multiple pregnancies.^ieng

Sister chromatid exchange analysis of human cells exposed to diagnostic levels of ultrasound.

Lymphocyte and lymphoblastoid cells were exposed in vitro to diagnostic levels of ultrasonic beams delivered by a Hewlett-Packard CE 30001 and a GE system with a 5 MHz linear transducer for 20 sec, 1 min, 5 min, and 20 min. Temperature and cavitation effects were controlled and there were matched sham exposures. The synergistic effects of theophylline with ultrasonography also were investigated. Small increases in sister chromatid exchange levels were observed after ultrasonic exposure, but increases were so small as to be unlikely to have clinical relevance. Theophylline was found to have no effect and ultrasonography had no effect on cell viability.

Doppler umbilical velocimetry in women with polydrug abuse including cocaine.

Doppler umbilical artery velocimetry was performed in 40 chemically dependent women. The mean S/D ratio was 2.7 with 15/66 values greater than or equal to 3.0. No cases of absent or reverse end-diastolic flow were noted. The mean S/D ratio in women with positive toxicologies for cocaine use was not statistically elevated compared to women with negative screens (2.8 versus 2.7, P = 0.51). In this study an S/D ratio greater than or equal to 3.0 had a sensitivity of 40% for identifying intrauterine growth retardation with a positive predictive value of 20%.

Infants of diabetic mothers with accelerated fetal growth by ultrasonography: are they all alike?

We studied longitudinal ultrasonographic growth patterns (abdominal circumference, biparietal diameter) initiated early in gestation in 52 pregnancies complicated by pregestational diabetes mellitus and 19 controls. Three predominant patterns of growth were ascertained including a heretofore unrecognized pattern characterized by accelerated abdominal circumference growth (greater than 90th percentile) before 24 weeks' gestational age. Maternal and neonatal anthropometric and metabolic parameters were contrasted for the three patterns. The findings suggest that in some cases of diabetic macrosomia that can be recognized before 24 weeks' gestation, augmented growth may be influenced by factors other than fetal hyperinsulinism.

Estimation of birth weight by use of ultrasonographic formulas targeted to large-, appropriate-, and small-for-gestational-age fetuses.

This report sought to determine whether estimates of fetal weight are enhanced by using ultrasonographic formulas targeted to the large-, appropriate-, and small-for-gestational-age fetus in both preterm and term pregnancies. Ultrasonographic fetal measurements from 575 singleton pregnancies were obtained within 7 days of delivery. The first 194 fetuses were classified into three groups on the basis of the growth percentile rank of the abdominal circumference (greater than or equal to 90%, greater than 5% and less than 90%, and less than or equal to 5%). Regression analyses were performed to generate three formulas for estimating fetal weight on the basis of the following: Gestational age (weeks) + Head circumference (cm) + 2 x Abdominal circumference (cm) + Femur length (cm). This mathematic model allowed formulation of accurate and concise tables relating the sum of these measurements to estimated birth weight. The accuracy of these formulas was then prospectively compared, first, with the formula published by Hadlock et al. (in 32 large-, 279 appropriate-, and 70 small-for-gestational-age fetuses) and second, with the formula of Weiner et al. (in 82 preterm fetuses). The difference between actual and estimated birth weights generated by the three study formulas had no systemic error (t test, p greater than 0.05). Cumulatively, there was a statistically significant reduction of random error in the birth weight estimates by use of the three study formulas versus the best single formulas of Hadlock et al. (2 SD reduced from 21.6% to 19.8% and absolute 2 SD reduced from 15.6% to 12.2%). Additionally, the three study formulas resulted in a statistically significant reduction in the absolute 2 SD error compared with the best formula by Weiner et al. in fetuses less than or equal to 34 weeks' gestation (2 SD reduced from 19.1% to 13.6%).

Differing fetal growth patterns in pregnancies complicated by preterm labor.

Previous studies have demonstrated diminished ultrasonic fetal growth parameters in women delivering preterm. In this study, we tested the following hypothesis: In pregnancies complicated by spontaneous preterm labor, 1) unsuccessful tocolysis is likely to be associated with diminished fetal growth, and 2) successful tocolysis is likely to occur when fetal growth is normal. Ultrasound examinations were performed in 78 pregnancies complicated by preterm labor before 35 weeks' gestation. Tocolysis was attempted unless contraindicated or unless cervical dilatation was advanced (4 cm or greater). Pregnancies delivering before 36 weeks' gestation were compared with those delivering after this gestational age. Among the 48 pregnancies delivered before 36 weeks' gestation, a significantly greater proportion had ultrasonic growth parameters lower than normal values at corresponding gestational ages. In contrast, those pregnancies that had successful tocolysis and delivered near term demonstrated a normal distribution of ultrasound growth parameters. In pregnancies complicated by preterm labor, ultrasonic documentation of diminished fetal growth may identify the subgroup at increased risk for preterm delivery.

Ultrasonic growth parameters in fetuses of mothers with primary addiction to cocaine.

Sixty-seven women with primary addiction to cocaine were evaluated during their pregnancies by multiple ultrasound studies. Ultrasonic parameters included biparietal diameter, femur length, abdominal circumference, and head circumference. These values were compared with ultrasonic growth parameters in nonaddicted fetuses. Head and abdominal circumference data were used to evaluate the fetuses according to growth pattern. With this system of scoring, subtleties of asymmetric versus symmetric intrauterine growth retardation become apparent. In addition, birth weights of addicted infants were compared with birth weights of nonaddicted infants. The results suggest that, although statistically significant differences in birth weights cannot be demonstrated, abnormal growth of the addicted fetuses does occur. Addicted fetuses show a greater proportion of biparietal diameter and abdominal circumference values below the 50th and 25th percentiles than nonaddicted fetuses, and addicted fetuses more frequently exhibit intrauterine growth retardation patterns. These data suggest that it is fruitful to study these infants with near-normal size but with abnormal intrauterine growth patterns.

Ultrasonic imaging of normal fetal response to external vibratory acoustic stimulation.

Fetal facial reactions and response decrement patterns to external noise stimulation were studied to characterize normal fetal neurobehavior in the third trimester. Response decrement, or habituation, is thought to reflect higher central nervous system function. Two hundred women with uncomplicated pregnancies, who were subsequently delivered of healthy infants at term, were studied between 26 and 41 weeks' gestation. After ultrasound views of the fetal face were obtained, a vibratory acoustic stimulus was applied repetitively to the maternal abdomen near the fetal head. Response decrement was defined as cessation of all components of the facial reaction, except eye blinking, over two sequential stimuli. Three response patterns were scored: (1) no startle, (2) startle without response decrement, and (3) response decrement by 12 stimuli. Whereas only 53% of fetuses between 26 and 27 weeks displayed startle reaction, all fetuses displayed startle responses by 28 weeks. As gestational age advances, an increasing number of fetuses exhibit response decrement, from no decrement at 26 to 27 weeks to 100% decrement at 40 to 41 weeks. A maturation of neurobehavioral response patterns takes place in normal third-trimester pregnancies. Response decrement testing may be a useful tool for in utero neurologic evaluation.

Ultrasonic prediction of birth weight in preterm fetuses: which formula is best?

Data from previous studies have suggested that birth weight prediction was enhanced by using formulas specifically derived from preterm fetuses. However, no prospective comparison of different formulas was performed. We obtained ultrasonic data on 61 pregnancies at risk for preterm delivery with a gestational age of 29.0 +/- 3.0 weeks (mean +/- SD). In all women birth weight was predicted within 7 days of delivery. Of the 61 pregnancies, 49 (80%), 41 (67%), 30 (49%), and 17 (28%) weighed less than 1750, 1500, 1250, and 1000 gm, respectively; 14 published formulas were compared for accuracy in predicting birth weight in these four categories. The formulas with the smallest absolute mean percent errors incorporated head and abdominal circumferences and femur length. The formula of Weiner et al., derived from low birth weight infants, produced the smallest absolute mean percent error and SD, 10.9% +/- 7.9%; this error was further reduced to 7.7% +/- 6.5% in infants weighing less than 750 gm. These findings suggest that birth weight in the preterm fetus is best predicted by a formula targeted to such a population.