United States' experience in nuchal translucency measurement: variation according to provider characteristics in over five million ultrasound examinations.

OBJECTIVE: The Nuchal Translucency Quality Review (NTQR) program has provided standardized education, credentialing and epidemiological monitoring of nuchal translucency (NT) measurements since 2005. Our aim was to review the effect on NT measurement of provider characteristics since the program's inception. METHODS: We evaluated the distribution of NT measurements performed between January 2005 and December 2019, for each of the three primary performance indicators of NT measurement (NT median multiples of the median (MoM), SD of log10 NT MoM and slope of NT with respect to crown-rump length (CRL)) for all providers within the NTQR program with more than 30 paired NT/CRL results. Provider characteristics explored as potential sources of variability included: number of NT ultrasound examinations performed annually (annual scan volume of the provider), duration of participation in the NTQR program, initial credentialing by an alternative pathway, provider type (physician vs sonographer) and number of NT-credentialed providers within the practice (size of practice). Each of these provider characteristics was evaluated for its effect on NT median MoM and geometric mean of the NT median MoM weighted for the number of ultrasound scans, and multiple regression was performed across all variables to control for potential confounders. RESULTS: Of 5 216 663 NT measurements from 9340 providers at 3319 sites, the majority (75%) of providers had an NT median MoM within the acceptable range of 0.9-1.1 and 85.5% had NT median MoM not statistically significantly outside this range. Provider characteristics associated with measurement within the expected range of performance included higher volume of NT scans performed annually, practice at a site with larger numbers of other NT-credentialed providers, longer duration of participation in the NTQR program and alternative initial credentialing pathway. CONCLUSIONS: Annual scan volume, duration of participation in the NTQR program, alternative initial credentialing pathway and number of other NT-credentialed providers within the practice are all associated with outcome metrics indicating quality of performance. It is critical that providers participate in ongoing quality assessment of NT measurement to maintain consistency and precision. Ongoing assessment programs with continuous feedback and education are necessary to maintain quality care. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Accuracy of automated three-dimensional ultrasound imaging technique for fetal head biometry.

OBJECTIVES: To evaluate the accuracy of an automated three-dimensional (3D) ultrasound technique for fetal intracranial measurements compared with manual acquisition. METHODS: This was a prospective observational study of patients presenting for routine anatomical survey between 18 + 0 and 22 + 6 weeks' gestation. After providing informed consent, each patient underwent two consecutive ultrasound examinations of the fetal head, one by a sonographer and one by a physician. Each operator obtained manual measurements of the biparietal diameter (BPD), head circumference (HC), transcerebellar diameter (TCD), cisterna magna (CM) and posterior horn of the lateral ventricle (Vp), followed by automated measurements of these structures using an artificial intelligence-based tool, SonoCNS® Fetal Brain. Both operators repeated the automated approach until all five measurements were obtained in a single sweep, up to a maximum of three attempts. The accuracy of automated measurements was compared with that of manual measurements using intraclass correlation coefficients (ICC) by operator type, accounting for patient and ultrasound characteristics. RESULTS: One hundred and forty-three women were enrolled in the study. Median body mass index was 24.0 kg/m2 (interquartile range (IQR), 22.5-26.8 kg/m2 ) and median subcutaneous thickness was 1.6 cm (IQR, 1.3-2.0 cm). Fifteen (10%) patients had at least one prior Cesarean delivery, 17 (12%) had other abdominal surgery and 78 (55%) had an anterior placenta. Successful acquisition of the automated measurements was achieved on the first, second and third attempts in 70%, 22% and 3% of patients, respectively, by sonographers and in 76%, 16% and 3% of cases, respectively, by physicians. The automated algorithm was not able to identify and measure all five structures correctly in six (4%) and seven (5%) patients scanned by the sonographers and physicians, respectively. The ICCs reflected good reliability (0.80-0.88) of the automated compared with the manual approach for BPD and HC and poor to moderate reliability (0.23-0.50) for TCD, CM and Vp. Fetal lie, head position, placental location, maternal subcutaneous thickness and prior Cesarean section were not associated with the success or accuracy of the automated technique. CONCLUSIONS: Automated 3D ultrasound imaging of the fetal head using SonoCNS reliably identified and measured BPD and HC but was less consistent in accurately identifying and measuring TCD, CM and Vp. While these results are encouraging, further optimization of the automated technology is necessary prior to incorporation of the technique into routine sonographic protocols. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Clinical experience of laboratory follow-up with noninvasive prenatal testing using cell-free DNA and positive microdeletion results in 349 cases.

OBJECTIVE: Screening via noninvasive prenatal testing (NIPT) involving the analysis of cell-free DNA (cfDNA) from plasma has become readily available to screen for chromosomal and DNA aberrations through maternal blood. This report reviews a laboratory's experience with follow-up of positive NIPT screens for microdeletions. METHODS: Patients that were screened positive by NIPT for a microdeletion involving 1p, 4p, 5p, 15q, or 22q who underwent diagnostic studies by either chorionic villus sampling or amniocentesis were evaluated. RESULTS: The overall positive predictive value for 349 patients was 9.2%. When a microdeletion was confirmed, 39.3% of the cases had additional abnormal microarray findings. Unrelated abnormal microarray findings were detected in 11.8% of the patients in whom the screen positive microdeletion was not confirmed. Stretches of homozygosity in the microdeletion were frequently associated with a false positive cfDNA microdeletion result. CONCLUSIONS: Overall, this report reveals that while cfDNA analysis will screen for microdeletions, the positive predictive value is low; in our series it is 9.2%. Therefore, the patient should be counseled accordingly. Confirmatory diagnostic microarray studies are imperative because of the high percentage of false positives and the frequent additional abnormalities not delineated by cfDNA analysis.

Aneuploidy screening by non-invasive prenatal testing in twin pregnancy.

OBJECTIVES: To describe our experience with non-invasive prenatal testing (NIPT) in twin pregnancy. METHODS: Two sets of maternal blood samples from twin pregnancies were analyzed at our laboratory using NIPT: 115 stored samples from pregnancies with known outcome (Clinical Study A) and 487 prospectively collected samples for which outcomes were requested from providers (Clinical Study B). NIPT was used to screen for the presence of fetal aneuploidy on chromosomes 13, 18, 21, X and Y in all cases, and results were compared with outcomes when known. RESULTS: In Clinical Study A, all 115 samples were classified correctly by NIPT: three cases of trisomy 21 (one fetus affected), one of monochorionic trisomy 18 (both fetuses affected) and 111 euploid. In Clinical Study B, a NIPT result was reported for 479 (98.4%) of the 487 samples. Aneuploidy was detected or suspected in nine (1.9%) cases: seven cases of trisomy 21 detected, one case of trisomy 21 suspected and one case with trisomy 21 detected and trisomy 18 suspected. Information on aneuploidy outcome was available for 171 (35.7%) cases in Clinical Study B. Of the nine cases with aneuploidy detected or suspected, six were confirmed to be a true positive in at least one twin based on karyotype or birth outcome and two were suspected to be concordant based on ultrasound findings; the one known discordant result was for the aneuploidy suspected case. No false negatives were reported. CONCLUSION: NIPT performed well in the detection of trisomy 21 in twin pregnancy, with a combined false-positive frequency for trisomies 13, 18 and 21 of 0% for Clinical Study A and 0.2% for Clinical Study B. © 2016 Illumina. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Nuchal Translucency Quality Review (NTQR) program: first one and half million results.

OBJECTIVE: To evaluate the performance of first-trimester nuchal translucency (NT) measurement by providers (physician-sonologists and sonographers) within the Nuchal Translucency Quality Review (NTQR) program. METHODS: After training and credentialing providers, the NTQR monitored performance of NT measurement by the extent to which an individual's median multiple of the normal median (MoM) for crown-rump length (CRL) was within the range 0.9-1.1 MoM of a published normal median curve. The SD of log10 MoM and regression slope of NT on CRL were also evaluated. We report the distribution between providers of these performance indicators and evaluate potential sources of variation. RESULTS: Among the first 1.5 million scans in the NTQR program, performed between 2005 and 2011, there were 1 485 944 with CRL in the range 41-84 mm, from 4710 providers at 2150 ultrasound units. Among the 3463 providers with at least 30 scans in total, the median of the providers' median NT-MoMs was 0.913. Only 1901 (55%) had a median NT-MoM within the expected range; there were 89 above 1.1 MoM, 1046 at 0.8-0.9 MoM, 344 at 0.7-0.8 MoM and 83 below 0.7 MoM. There was a small increase in the median NT-MoM according to providers' length of time in the NTQR program and number of scans entered annually. On average, physician-sonologists had a higher median NT-MoM than did sonographers, as did those already credentialed before joining the program. The median provider SD was 0.093 and the median slope was 13.5%. SD correlated negatively with the median NT-MoM (r = -0.34) and positively with the slope (r = 0.22). CONCLUSION: Even with extensive training, credentialing and monitoring, there remains considerable variability between NT providers. There was a general tendency towards under-measurement of NT compared with expected values, although more experienced providers had performance closer to that expected.

Safety of ultrasonography in pregnancy: WHO systematic review of the literature and meta-analysis.

OBJECTIVE: In the context of the planned International Society of Ultrasound in Obstetrics and Gynecology-World Health Organization multicenter study for the development of fetal growth standards for international application, we conducted a systematic review and meta-analysis to evaluate the safety of human exposure to ultrasonography in pregnancy. METHODS: A systematic search of electronic databases, reference lists and unpublished literature was conducted for trials and observational studies that assessed short- and long-term effects of exposure to ultrasonography, involving women and their fetuses exposed to ultrasonography, using B-mode or Doppler sonography during any period of pregnancy, for any number of times. The outcome measures were: (1) adverse maternal outcome; (2) adverse perinatal outcome; (3) abnormal childhood growth and neurological development; (4) non-right handedness; (5) childhood malignancy; and (6) intellectual performance and mental disease. RESULTS: The electronic search identified 6716 citations, and 19 were identified from secondary sources. A total of 61 publications reporting data from 41 different studies were included: 16 controlled trials, 13 cohort and 12 case-control studies. Ultrasonography in pregnancy was not associated with adverse maternal or perinatal outcome, impaired physical or neurological development, increased risk for malignancy in childhood, subnormal intellectual performance or mental diseases. According to the available clinical trials, there was a weak association between exposure to ultrasonography and non-right handedness in boys (odds ratio 1.26; 95% CI, 1.03-1.54). CONCLUSION: According to the available evidence, exposure to diagnostic ultrasonography during pregnancy appears to be safe.

Ovulation induction in clomiphene-resistant anovulatory women: differential follicular response to purified urinary follicle-stimulating hormone (FSH) versus purified urinary FSH and luteinizing hormone.

We studied 15 anovulatory women undergoing ovulation induction with purified human urinary FSH or purified human urinary FSH and LH [human menopausal gonadotropins (hMG)]. All patients had either sporadic or no vaginal bleeding after progesterone therapy and failed to ovulate after receiving clomiphene (250 mg for 5 days) plus hCG. Other causes of infertility were ruled out. Sixteen cycles of FSH and 12 cycles of hMG were administered according to a standard protocol. Estradiol, progesterone, androstenedione, testosterone, LH, and FSH concentrations were quantitated by RIA. Follicular diameter was determined using ultrasound. There was no significant difference in the amount of FSH or hMG used per patient, in the duration of therapy before hCG administration, or in the length of the luteal phase in any patient. There was a difference in the number of follicles greater than 1000 mm3 per cycle in those patients receiving FSH compared to the number in those receiving hMG [2.8 +/- 1.3 (+/- SEM) vs. 4.4 +/- 1.5 follicles; P = 0.026). The maximum follicular phase serum estradiol (18.3 vs. 34.8 ng/ml) and maximum luteal phase progesterone concentrations (1289 vs. 2808 pg/ml; P = 0.026) were also different between the FSH and hMG groups. Linear regression analysis revealed a significant correlation between the peripheral serum estradiol levels and the total follicular volume of follicles in the hMG-treated group which was not apparent in the FSH-treated group. These findings suggest that exogenous LH may not be required to induce folliculogenesis in anovulatory patients.

Congenital gastric teratoma in Wiedemann-Beckwith syndrome.

Wiedemann-Beckwith syndrome (WBS) may be associated with abdominal tumors, including Wilms tumor, adrenocortical carcinoma, hepatoblastoma, gonadoblastoma, rhabdomyosarcoma, and neuroblastoma. We report on a newborn infant with WBS and a congenital teratoma of the stomach. This is the sole report of any teratoma being associated with WBS and also the first report of a tumor present at birth and visible prenatally in WBS. At birth this infant boy had the diagnostic findings of WBS with macroglossia, ear lobule creases and pits, nevus flammeus, and omphalocele, and an abdominal mass. Abnormalities were detected prenatally when ultrasound examination showed placental overgrowth, polyhydramnios, omphalocele, and posterior abdominal calcifications. Resection of the mass and partial gastrectomy were performed at age 10 days; histologic study showed an immature grade-II teratoma containing a mixture of mature and immature tissues from all germ layers. Results of cytogenetic studies of blood and teratoma were normal (46,XY). This congenital gastric teratoma in a newborn boy with classical WBS may represent either a tumor or an included twin. We discuss its implications for the association of WBS with neoplasia and monozygotic (MZ) twinning, review various neoplasias associated with WBS, and consider pathogenetic mechanisms.

Monocyte monolayer assay: an efficient noninvasive technique for predicting the severity of hemolytic disease of the newborn.

The authors performed monocyte monolayer assays (MMAs) with the use of normal donor monocytes, and homologous reagent red blood cells, sensitized in vitro, with antibodies in maternal sera. The sera were from 16 pregnant women with Rh antibodies, drawn at the time of amniotic fluid analysis. They compared the predictive value (PV) of the MMAs and the delta OD 450 of amniotic fluid in forecasting the need for transfusing the infant. The PV of the delta OD 450 result in Liley zone mid II-III was 100%, but in zones 0 to low II it was only 60% (13 samples from ten women were in these zones but four babies required transfusion). In contrast, the PV of a positive (greater than 20% reactivity) MMA was 91% (one false positive result) and the PV of a negative MMA was 100%. Thus, the MMA was more efficient than amniotic fluid analysis at predicting hemolytic disease of the newborn severe enough to require transfusion. The noninvasive MMA could be used as a screening test, reducing the number of amniocenteses or ultrasound evaluations performed on Rh-sensitized women.

Maternal hypoxemia and fetal breathing movements.

Fetal breathing movements (FBM) were observed daily using a real-time B-mode ultrasound method in a patient with sickle cell anemia in crisis. Observations were made on 2 occasions in the presence of maternal hypoxemia (PO2 less than or equal to 40 mmHg), and FBM were noted to be absent. Conversely, when maternal PO2 was 60 mmHg or greater, FBM were present 23--80% of the time. The FBM were reduced or absent within 90 minutes of maternal Demerol injection. These observations suggest that the human fetal response to hypoxemia may be similar to that observed under expermental conditions in the animal fetus.

Incidental adnexal neoplasms at cesarean section.

A 10-year retrospective review was conducted of incidental adnexal neoplasms found at the time of cesarean section. During the 10-year period between July 1, 1976 and June 30, 1986, 17,902 cesarean sections were performed at Women's Hospital of the Los Angeles County/University of Southern California Medical Center. Adnexal neoplasms were identified with an incidence of one neoplasm per 197 cesarean sections. When a neoplasm is discovered during surgery, conservative surgery is recommended.

Fetal movements in human pregnancies in the third trimester.

Fetal movements (FM) were measured using a real-time B-scan method in 50 women in the third trimester. One hundred ninety-five observations were made. The number of FM per 20-minute observation period was similar in normal, diabetic, and hypertensive pregnancies and in patients with placenta previa, but was significantly lower in patients with Rh isoimmunization and an affected fetus. The number of FM did not vary with gestational age, mode of delivery, or birth weight and was significantly increased in patients either with a reactive nonstress test (NST) or in the presence of fetal breathing movements (FBM). Fetal movements were absent before delivery in 4 patients: In 3, the fetus died in utero and in the other a positive contraction stress test (CST) was observed. Conversely, in 2 other fetuses who died in utero, FM were observed during the last examination before death. In both, the cause of fetal death was related to an acute change. No relationship between FM and neonatal death was observed. These data suggest FM monitoring may be helpful in evaluating antepartum fetal condition.

Rh sensitization after genetic amniocentesis.

A retrospective evaluation was undertaken of 78 Rh-negative women who underwent genetic amniocentesis without Rh-immune globulin prophylaxis. Of the 56 patients at risk for sensitization, 3 (5.4%) became sensitized during the pregnancy in which amniocentesis was performed. This number is not statistically different from the 2.1% incidence of spontaneous Rh immunization during pregnancy. However, a trend toward increasing sensitization after second-trimester amniocentesis was noted. As the fetoplacental blood volume at 16 weeks' gestation is approximately 12 to 13 ml, a 150-micrograms dose of Rh-immune globulin is recommended for the Rh-negative patient who is undergoing genetic amniocentesis.

Maternal tobacco use and substance abuse: reported prevalence rates and associations with the delivery of small for gestational age neonates.

OBJECTIVE: To determine the changes in reported prevalence rates of tobacco use and substance abuse in a population of pregnant women, as well as to evaluate the associations between such use and sociodemographic characteristics and the delivery of small for gestational age (SGA) neonates. METHODS: We studied 7741 women who delivered at Cedars-Sinai Medical Center from 1986-1990. Antenatal and delivery information was entered prospectively into the computerized perinatal data base. Subjects were classified according to tobacco use and substance abuse status. We defined SGA as a birth weight less than the tenth percentile for gestational age at delivery. Univariate and multivariate analyses were used to determine the associations between SGA and tobacco use, substance abuse, and sociodemographic characteristics. RESULTS: We found that the reported prevalence rates of tobacco use and substance abuse declined between 1986-1990 (10 versus 6% and 7 versus 2%, respectively; P < .001). Tobacco use and substance abuse were reported as being highest in black women (11 and 6%) and lowest in Asian and Hispanic women (4 and 3%), a significant difference (P < .001). Tobacco use and race-ethnicity were found to have the strongest independent associations with SGA. The incidence of SGA was highest in black women identified as tobacco users and substance abusers. CONCLUSIONS: The reported rates of tobacco use and substance abuse varied by year, race-ethnicity, and insurance status. There were significant associations between maternal tobacco use, substance abuse, and race-ethnicity and the incidence of SGA neonates.

Molecular genetic prenatal determination of twin zygosity.

A method of human identity determination using synthetic oligonucleotide probes was applied to prenatal determinations of twin zygosity. Deoxyribonucleic acid "fingerprints" were obtained from chorionic villi or amniocytes. In all cases, the technique predicted twin zygosity with very small tissue samples. The accuracy and simplicity of the method far exceed those of any other currently used technique. This technique should be applicable in those situations in which prenatal determination of relationship is needed.

The ultrasound triad of fetal hydramnios, abnormal hand posturing, and any other anomaly predicts autosomal trisomy.

Our definition of hydramnios is an amniotic fluid index of 24 cm or greater. We evaluated by ultrasound examination 49 consecutive patients who met this definition of hydramnios. Of these, 22 (44.9%) had anomalies visible by ultrasound. The combination of hydramnios, abnormal hand posturing, and any other anomaly created a constellation of sonographic findings enabling us to predict six specific autosomal trisomies (27.27%): three trisomy 18, two trisomy 21, and one trisomy 13. The 27 fetuses with "idiopathic hydramnios" (no identifiable anomaly or abnormal hand posturing) had normal karyotypes. We recommend that any patient with confirmed hydramnios have a detailed ultrasound examination by an experienced sonographer, with special attention paid to the heart, face, and hands. If no abnormality is seen and the hands are normally postured, expectant management may be appropriate. If the late second- or third-trimester fetus displays abnormal hand posturing with any other abnormality, rapid karyotyping by funipuncture or placental biopsy should be recommended to facilitate appropriate management.

Urinary tract injury during cesarean section.

Lower urinary tract injury at the time of cesarean section is an uncommon complication. During a 5-year period, the incidence of bladder and ureter injuries at the Los Angeles County/University of Southern California Medical Center was .31 and .09%, respectively. When bladder injury occurs, it usually is due to surgical difficulty encountered while developing the bladder flap over the lower uterine segment. The difficulty is caused usually by scar tissue from previous surgery. Ureteral injury is a rare complication of cesarean section. It is attributable most often to ureteral transection or ligation associated with uterine incision extensions in the lower uterine segment or the vagina, and to attempts to achieve hemostasis. The data presented in this report indicate that cystotomy, when adequately repaired, is not associated with any complications. Furthermore, diagnostic cystotomy with intravenous injection of indigo carmine is a rapid, safe method of evaluating ureteral patency.

Urinary bladder distention: effect on labor and uterine activity.

To study quantitatively the effect of urinary bladder distention on labor and uterine activity, 68 patients requiring catheterization were studied. All patients were in the active phase of labor and had transcervical intrauterine pressure monitoring. Patients were studied in the same lateral position for 30 minutes before and after a catheterization interval, during which time uterine activity units were quantitated on line and changes were noted in cervical dilation and station and contraction frequency and tonus. Results were analyzed for the entire study group, for individual patients, and by urine volumes (10 to 550 ml) obtained at catheterization. Total uterine activity units increased in 43 patients and decreased in 25 after catheterization, but when compared with expected increases calculated from the slopes of the precatheterization interval in individual patients, there were 36 increases and 32 decreases. Individual slopes of uterine activity increased in 36 and decreased in 31 cases. There were no differences when the data were analyzed by urine volume, parity, or bith weight except possibly at large volumes. Changes in rates of cervical dilation and descent of the presenting part conform to the expected normal labor pattern. Within the limits of this study, emptying the urinary bladder has no effect on the course of labor or uterine activity based on the dynamic model of labor.

Quantifiable polyhydramnios: diagnosis and management.

Little has been written regarding the ultrasonographic quantification of polyhydramnios or its subsequent management. Therefore, we designed this study to define polyhydramnios using the amniotic fluid index of greater than 2 SDs above the mean for late second- to third-trimester pregnancies, or 24 cm or greater. One hundred twelve nondiabetic women referred to Women's Hospital, Los Angeles County/University of Southern California Medical Center with the descriptive diagnosis of polyhydramnios made by experienced ultrasonographers were included in the study. There was poor correlation between these descriptions and fetal outcome. Twenty-six were qualitatively described as having severe, 29 as moderate, and 57 as mild polyhydramnios. Forty-nine of the 112 patients met our definition of significant polyhydramnios by having an amniotic fluid index of 24 cm or more. This particular definition allowed the inclusion of all fetuses with serious structural defects and/or death. Seven patients had an amniotic fluid index less than 24 cm, but with the traditional quantitative definition of one pocket of 8 cm or more; none of these patients had poor fetal outcome. These data appear to suggest that the use of descriptive definitions of polyhydramnios or a single fluid pocket of 8 cm or greater should be discarded in favor of using an amniotic fluid index of 24 cm or more. Once the diagnosis of polyhydramnios is made, the patient should have a detailed sonographic evaluation, be offered cytogenetic studies, and have antepartum surveillance.

Fetal umbilical blood flow velocity waveforms using Doppler ultrasonography in patients with late decelerations.

The purpose of this study was to assess placental vascular resistance as measured by peak systolic to end-diastolic ratios (S/D) of the umbilical artery waveforms in patients with late decelerations. Fifty patients with persistent late decelerations and 50 gestational age-matched controls with reactive tracings underwent umbilical velocimetry with measurement of S/D ratios. The mean (+/- SD) S/D ratio in the late-deceleration group (4.32 +/- 1.1) was significantly higher than that of the control group (2.32 +/- 0.21) (P less than .01). Patients with late decelerations had a significantly higher incidence of adverse pregnancy outcome, as judged by the incidence of small for gestational age infants, meconium, cesarean section for fetal distress, low Apgar scores, and neonatal intensive care unit admissions, compared with the control group. However, there was no difference in the incidence of adverse pregnancy outcome in the late-deceleration group with normal S/D ratios compared with controls. The sensitivity, specificity, and positive and negative predictive values of S/D ratios in the late-deceleration group for predicting adverse pregnancy outcome were 85.7, 100, 100, and 89.6%, respectively. These data suggest that umbilical velocimetry might be able to discriminate late decelerations that constitute a false-positive test. Incorporation of umbilical velocimetry into antepartum and intrapartum fetal surveillance schemes may therefore be helpful.