Second-trimester Sonography Research Articles

Antenatal down syndrome screening in the united states in 2001: A survey of maternal-fetal medicine specialists

Objective: Our objectives were to determine patterns of antenatal Down syndrome screening and risk adjustment by maternal-fetal medicine specialists in the United States in 2001. Study Design: A survey to investigate Down syndrome screening practice patterns was mailed to the 1638 members of the Society of Maternal-Fetal Medicine in the United States. Practice demographics, screening patterns, and the numeric risks quoted in counseling were analyzed. Results: Five hundred forty-three specialists (33.2%) responded; 530 of these specialists (97.6%) performed antenatal Down syndrome screening; all of them offered second-trimester screening, and 247 of them (45.5%) offered first-trimester screening. With the use of second-trimester ultrasonography, risk was increased by 69.4% of respondents and decreased by 33.1%. Amniocentesis was the most frequently used diagnostic test (83.2%), with loss rates quoted at 1:100 to 1:1000. Conclusion: Maternal-fetal medicine specialists show a wide in variation practices used for Down syndrome screening, modification of risk, and quoted procedure-related loss rates. This information calls for a consensus regarding risks that are quoted in Down syndrome counseling. (Am J Obstet Gynecol 2002;187:1230-4.)

A normal second-trimester ultrasound does not exclude intracranial structural pathology.

To report the prenatal diagnosis and management of 34 fetuses with various intracranial structural pathologies diagnosed following a normal second-trimester ultrasound examination. We retrospectively reviewed the images of 203 abnormal central nervous system ultrasound examinations performed between 13 and 37 weeks of gestation at our prenatal diagnosis unit. In 34 (16.7%) of them at least one previous second-trimester ultrasound examination had been performed and considered normal. These 34 fetuses represent the study group. The following intracranial pathologies were diagnosed: dysgenesis of the corpus callosum, ventriculomegaly, cerebral cysts or hemorrhage, migrational disorders, vermian dysgenesis, arachnoid cysts, macrocephaly, enlarged subarachnoid space, brain calcifications and microcephaly. A normal second-trimester ultrasound scan does not rule out significant intracranial anomalies. Parents and physicians should be informed about the limitations of second-trimester sonography as far as brain diagnosis is concerned. A repeat third-trimester scan may enable more accurate diagnosis and counseling.

Prenatal Detection by Real-Time Quantitative PCR and Characterization of a New CFTR Deletion, 3600+15kbdel5.3kb (or CFTRdele19)

Cystic fibrosis (CF; MIM No. 219700), the most common autosomal recessive disease in Caucasians (1), is caused by mutations in the gene encoding CF transmembrane conductance regulator (CFTR; MIM No. 602421) (2). The disease may be revealed by fetal bowel hyperechogenicity during routine ultrasonography in the second trimester of pregnancy, even when there is no family history of CF. However, fetal bowel hyperechogenicity is not specific for CF: when found at this stage of pregnancy, it corresponds to CF in 2–20% of cases (1)(3)(4)(5). Diagnostic investigations are based on screening for CF-causing mutations, fetal karyotyping, and screening for infections. Normal intestinal enzyme activities in amniotic fluid before 18 weeks of gestation reasonably rules out CF (6). However, most women are referred after this time, and it is necessary to screen for CF mutations in the parents and, if possible, fetus. To date, almost 900 mutations have been described throughout the CFTR gene, but very few deletions have been identified (7). Indeed, large deletions are not routinely screened for, given their rarity and the lack of suitable diagnostic tools. Conventional PCR-based methods usually detect deletions only when they are present in the homozygous state. As a result, the frequency of CFTR deletions is underestimated. Two relatively frequent large deletions have recently been described: 3120+1kbdel8.6kb was found in 13% of CF chromosomes in Israeli-Arab patients (8), and CFTRdele2,3 accounts for 1–6.4% of CF chromosomes in Slavic populations (9). A couple was referred to our laboratory for fetal hyperechogenic bowel diagnosed during a routine ultrasound scan at 20 weeks of gestation. The couple, who were first cousins of Turkish extraction, had no family history of CF. Diagnostic investigations were requested after genetic counseling, with the couple’s informed consent. The fetal karyotype (amniotic cells) was normal, as …

Routine second-trimester ultrasonography in the United States: A cost-benefit analysis

Objective:The objective of this study was to perform a cost-benefit analysis of routine second-trimester screening ultrasonography in the United States as compared with performing ultrasonography only in the presence of indications. Study Design:It was assumed that 1 million pregnant women are available annually who otherwise would not have an indication for an ultrasonographic examination. Cost savings from early detection and therapeutic abortion were considered only for fetal conditions for which lifetime cost estimates are available, including spina bifida, major cardiac disease, cleft lip or palate, renal agenesis or dysgenesis, urinary obstruction, lower or upper limb reduction, omphalocele, gastroschisis, and diaphragmatic hernia. Two separate cost-benefit analyses were considered with the range of fetal anomaly detection rates before 24 weeks' gestation as reported by tertiary and non-tertiary centers in the Routine Antenatal Diagnostic Imaging with Ultrasound (RADIUS) trial. Potential cost savings from averting treatment for preterm labor and postdate gestations were also considered. Results:The ratio of savings to cost was between 1.35 and 1.70 (savings of $1.35–$1.70 per $1 spent) if the ultrasonographic examinations were performed in tertiary care centers. The ratio of savings to cost was between 0.40 and 0.74 (loss of $0.26–$0.60 per $1 spent) if the examinations were performed in nontertiary centers. If the screening ultrasonography was performed in tertiary centers, the expected annual net benefits were estimated at $97 to 189 million. If ultrasonographic screening was performed in nontertiary centers, the expected annual net losses were estimated at $69 to 161 million. Conclusions:Routine second-trimester ultrasonographic screening appears to be associated with net benefits only if the ultrasonography is performed in tertiary care centers.

Ultrasound screening for fetal chromosome anomalies.

Ultrasound evidence for aneuploidy may be found in almost every organ of the fetus and can be used to modify the risk of aneuploidy. The diagnosis of these minor anomalies on second-trimester ultrasonography will increase the risk of an abnormal karyotype whereas the absence of these findings may reduce this danger. The most specific and most ominous isolated markers for fetal aneuploidy are nuchal findings (edema or cysts), indicating the need to obtain a fetal karyotype in all cases irrespective of maternal age or results of biochemical serum screening. Hyperechoic fetal bowel is apparently also a strong indicator of fetal aneuploidy. Other isolated sonographic markers may increase the risk of an abnormal karyotype three- to ninefold. Most sonographic markers for aneuploidy specify an increased risk for Down syndrome, but choroid plexus cysts are apparently more specific for trisomy 18. Along with other screening methods, ultrasound screening for fetal aneuploidy should be used routinely to identify additional pregnancies at need for evaluation of fetal karyotype.

Indication-specific accuracy of second-trimester genetic ultrasonography for the detection of trisomy 21

Objective: The object of this study was to determine whether there are any clinically significant indication-specific variations in the accuracy of second-trimester genetic ultrasonography and to provide a risk adjustment for fetal trisomy 21 according to the results of genetic ultrasonography. Study Design: From November 1, 1992, to September 30, 1998, a second-trimester genetic sonogram was offered to all pregnant women who were at an increased risk for fetal trisomy 21 (≥1:274) because of either advanced maternal age (≥35 years) or abnormal serum biochemical profile or both of these. Outcome information included the results of genetic amniocentesis if performed and the results of pediatric assessment and follow-up after birth. In determining diagnostic accuracy of the genetic sonogram the presence of ≥1 abnormal ultrasonographic marker was considered an abnormal test result. Results: A total of 1835 fetuses with known outcomes underwent genetic ultrasonography between 15 and 24 weeks’ gestation; of these 1792 had normal results, 34 had trisomy 21, and 9 had other chromosomal abnormalities. The likelihood of fetal trisomy 21 was reduced by 80% after a normal result of genetic ultrasonography. The overall sensitivity, specificity, and positive and negative predictive values of genetic ultrasonography for the detection of trisomy 21 were 82%, 91%, 15%, and 99.6%, respectively. There were no significant indication-specific variations in the accuracy of second-trimester ultrasonography. The sensitivity for the detection of fetal trisomy 21 ranged from 80% among women with advanced maternal age to 100% among women with both an abnormal biochemical profile and advanced maternal age. Conclusions: The likelihood of fetal trisomy 21 risk was reduced 80% after a normal result of genetic ultrasonography. In addition there were no significant indication-specific variations in the detection rate of genetic ultrasonography. (Am J Obstet Gynecol 1999;181:1045-8.)

Prenatal Genetic Testing

In Brief Objective To document the content and accuracy of discussions about prenatal genetic testing between obstetric providers and pregnant women. Methods The first prenatal visits of 169 pregnant women with 21 obstetricians and 19 certified nurse-midwives were audiotaped and analyzed for whether a discussion of family history or genetic testing took place and if so, its length, content, and accuracy. Results Family history was discussed in 60% of visits, maternal serum marker screening in 60%, second-trimester ultrasonography for fetal anomalies in 34%, and for women at least 35 years old, amniocentesis or chorionic villus sampling (CVS) in 98%. The length of discussions of genetic testing averaged 2.5 minutes for women younger than 35 years of age and 6.9 minutes for older women. Topics discussed most often were the practical details of testing, the purpose of testing, and the fact that testing is voluntary. Discussions seldom were comprehensive. Obstetricians were more likely to make a recommendation about testing than were nurse-midwives and were less likely to indicate that testing is voluntary. Most women were satisfied with the amount of information, and the majority of women of advanced maternal age had made a decision about amniocentesis or CVS by the end of the visit. Conclusion The information about genetic testing provided in the first prenatal visit is inadequate for ensuring informed autonomous decision-making. Guidelines addressing the content of these discussions should be developed with input from obstetricians, nurse-midwives, genetic counselors, and pregnant women. Discussions about prenatal genetic testing between obstetric providers and pregnant women are limited, and guidelines for content are needed to ensure informed decision-making.

Prenatal Genetic Testing: Content of Discussions Between Obstetric Providers and Pregnant Women

Objective: To document the content and accuracy of discussions about prenatal genetic testing between obstetric providers and pregnant women. Methods: The first prenatal visits of 169 pregnant women with 21 obstetricians and 19 certified nurse-midwives were audiotaped and analyzed for whether a discussion of family history or genetic testing took place and if so, its length, content, and accuracy. Results: Family history was discussed in 60% of visits, maternal serum marker screening in 60%, second-trimester ultrasonography for fetal anomalies in 34%, and for women at least 35 years old, amniocentesis or chorionic villus sampling (CVS) in 98%. The length of discussions of genetic testing averaged 2.5 minutes for women younger than 35 years of age and 6.9 minutes for older women. Topics discussed most often were the practical details of testing, the purpose of testing, and the fact that testing is voluntary. Discussions seldom were comprehensive. Obstetricians were more likely to make a recommendation about testing than were nurse-midwives and were less likely to indicate that testing is voluntary. Most women were satisfied with the amount of information, and the majority of women of advanced maternal age had made a decision about amniocentesis or CVS by the end of the visit. Conclusion: The information about genetic testing provided in the first prenatal visit is inadequate for ensuring informed autonomous decision-making. Guidelines addressing the content of these discussions should be developed with input from obstetricians, nurse-midwives, genetic counselors, and pregnant women.

Fetal anomaly detection by second-trimester ultrasonography in a tertiary center

Objective: Our purpose was to determine the relative accuracy of indicated versus screening second-trimester ultrasonography for detection of fetal anomalies and to assess the cost effectiveness of anomaly screening. Study Design: The study population consisted of 2031 pregnant women with singleton gestations who prospectively underwent ultrasonographic scanning between 15 and 22 weeks and received complete obstetric care at the Medical University of South Carolina between July 1, 1993, and June 30, 1996. Patients were divided into two groups: (1) indicated and (2) screening. The cost of screening ultrasonography was compared with the cost of newborn care for selected anomalous fetuses. Results: Forty-seven fetuses (2.3%) were diagnosed by ultrasonography as having a major anomaly: 8.6% in the indicated group and 0.68% in the screening group ( p = 0.001). The sensitivity for detecting the anomalous fetus was 75.0% overall: 89.7% in the indicated group and 47.6% in the screening group ( p = 0.001). Of the 47 patients diagnosed with fetal anomalies, 11 (23.4%) chose pregnancy termination; of the 35 (74.5%) live-born anomalous infants, 29 (82.9%) were discharged alive. Projected newborn cost savings offset the cost of routine midtrimester screening. Conclusions: Detection of anomalous fetuses was significantly better in the indicated compared with the screening group. Nevertheless, routine ultrasonographic screening appeared cost-effective in our population. (Am J Obstet Gynecol 1998;178:742-9.)

LANGER MESOMELIC DWARFISM: ULTRASONOGRAPHIC DIAGNOSIS OF TWO CASES IN EARLY MID‐TRIMESTER

This is a report on two cases of mesomelic dysplasia Langer type. This is a rare kind of dwarfism which combines severe dwarfism with predominant shortening of the forearms and lower legs and other morphological abnormalities. The diagnosis can be made by ultrasonography in the early second trimester of the pregnancy.

LANGER MESOMELIC DWARFISM: ULTRASONOGRAPHIC DIAGNOSIS OF TWO CASES IN EARLY MID-TRIMESTER

This is a report on two cases of mesomelic dysplasia Langer type. This is a rare kind of dwarfism which combines severe dwarfism with predominant shortening of the forearms and lower legs and other morphological abnormalities. The diagnosis can be made by ultrasonography in the early second trimester of the pregnancy.

Adjusting the Risk for Trisomy 21 on the Basis of Second-Trimester Ultrasonography

Adjusting the Risk for Trisomy 21 on the Basis of Second-Trimester Ultrasonography

Adjusting the risk for trisomy 21 on the basis of second-trimester ultrasonography

OBJECTIVE: Our purpose was to establish the sensitivity and specificity of various ultrasonographic markers of trisomy 21 in the second trimester of pregnancy on the basis of literature review and to generate tables that would allow adjusting the risk for trisomy 21, and therefore the need for genetic amniocentesis, depending on the presence or absence of these markers. STUDY DESIGN: A computer search was performed of the English literature, including the years 1983 through 1993, of studies that used second-trimester ultrasonography to detect fetuses with trisomy 21. After statistical analysis of the reported studies was performed, the average sensitivity and specificity of the following ultrasonographic markers were determined: structural malformations, short femur, short humerus, combination of short femur and short humerus, pyelectasis, nuchal fold thickening, echogenic bowel, and short ear length. After the average sensitivity and specificity of these ultrasonographic markers were established, apropriate tables were generated by Bayes' theorem to adjust the risk for trisomy 21 in the second trimester depending on the presence or absence of these markers. Statistical analyses were performed with the statistical package Excel on a personal computer. RESULTS: The average detection rate (sensitivity) of structural fetal malformations was 28%, short femur 31%, short humerus 33%, short femur and humerus 32%, nuchal fold thickening 32%, echogenic bowel 7%, and short ear length 71%. The nuchal fold thickening had the highest specificity (99.5%). Isolated pyelectasis was not associated with an increased risk for trisomy 21. However the risk was increased when pyelectasis was associated with other markers. In the presence of normal ultrasonographic results, the negative prediction can be combined with maternal age-related or biochemical prediction of trisomy 21 to help in the informed consent processin counseling women about the benefits and harms of genetic amniocentesis. Genetic amniocentesis should be considered in women of any age when second-trimester ultrasonography reveals the presence of one or more of the following: fetal structural malformations, short femur (determined by biparietal diameter-to-femur length ratio), combination of short femur and humerus, abnormal (≥ 6 mm) nuchal fold thickening, echogenic bowel, or short ear length. CONCLUSION: In experienced hands second-trimester ultrasonography may be used to adjust the priori risk of both high and low-risk women for trisomy 21 and therefore the need for genetic amniocentesis.

Differential Diagnosis of the Nonvisualized Fetal Urinary Bladder by Transvaginal Sonography in the Early Second Trimester

To describe the pathologic situations associated with the persistently nonvisualized fetal urinary bladder in the early second trimester. We analyzed retrospectively 13,458 ultrasound examinations performed between 12-16 weeks' gestation in search of fetal malformations. Seventy percent of the patients were at low risk and 30% comprised a high-risk group for the detection of fetal anomalies. Seven cases of persistent nonvisualization of the fetal urinary bladder were detected by transvaginal sonography among 13,458 fetuses. In one case bladder exstrophy, and in another bilateral multicystic dysplastic kidneys were diagnosed by postabortal examination. Five cases were associated with bilateral renal agenesis. When one fails persistently to demonstrate the fetal urinary bladder during an examination lasting 30 minutes or longer, urinary tract pathology should be highly suspected. Failure to visualize the bladder may be associated with bladder exstrophy, bilateral renal agenesis, or late onset of bilateral multicystic dysplastic kidneys.

Differential Diagnosis of the Nonvisualized Fetal Urinary Bladder by Transvaginal Sonography in the Early Second Trimester

Objective: To describe the pathologic situations associated with the persistently nonvisualized fetal urinary bladder in the early second trimester. Methods: We analyzed retrospectively 13,458 ultrasound examinations performed between 12-16 weeks' gestation in search of fetal malformations. Seventy percent of the patients were at low risk and 30% comprised a high-risk group for the detection of fetal anomalies. Results: Seven cases of persistent nonvisualization of the fetal urinary bladder were detected by transvaginal sonography among 13,458 fetuses. In one case bladder exstrophy, and in another bilateral multicystic dysplastic kidneys were diagnosed by postabortal examination. Five cases were associated with bilateral renal agenesis. Conclusion: When one fails persistently to demonstrate the fetal urinary bladder during an examination lasting 30 minutes or longer, urinary tract pathology should be highly suspected. Failure to visualize the bladder may be associated with bladder exstrophy, bilateral renal agenesis, or late onset of bilateral multicystic dysplastic kidneys.(Obstet Gynecol 1993;82:490-3)

The early diagnosis of neural tube defects.

The sonographic diagnosis of fetal neural tube defects (NTDs) has been enhanced by the recognition of associated brain and skull anomalies. Previous reports have found these anomalies to be accurate in predicting spina bifida after 16 weeks' gestation, and an inverse correlation was suggested between the presence of these sonographic markers and gestational age. Therefore, we assumed that early second-trimester sonography would be at least as accurate as that performed after 16 weeks' gestation. To examine this hypothesis, we looked for the presence of these cranial sonographic markers suggestive of open NTDs in 8011 low-risk cases, using transvaginal sonography (TVS), between the 12th and 17th week of gestation (menstrual age). Fetal NTDs were identified in ten cases (1.25/1000). The NTDs were cervico-cranial in three, lumbo-sacral in six, and thoracal in one of the ten cases. None of the seven cases examined was dyskaryotic. Cerebellar dysmorphism, 'banana' sign, cerebellar absence, and hypoplasia were detected in all the low NTDs, usually before the detection of the spinal lesion. All the sonographically diagnosed malformations were confirmed by post-abortal examination except in one case, where the patient decided to continue the pregnancy and refused follow-up. We therefore conclude that transvaginal sonographic examination of the fetal skull before the 17th week of gestation is an accurate method for the detection of low NTDs.

Abnormal second-trimester ultrasounds: an indication for karyotype.

There are limited data on the risks of aneuploidy for normal-appearing fetuses with amniotic fluid volume (AFV) abnormalities. The purpose of this study was to determine the relative risks of aneuploidy associated with second-trimester abnormal AFVs and fetal structural anomalies in a cohort of 2,823 singleton, viable fetuses. Compared to gravidas younger than 35 with normal ultrasounds, normal fetuses had an increased incidence of aneuploidy with polyhydramnios, increased AFV, i.e. subjectively increased but normal by maximum vertical pocket (MVP) and/or amniotic fluid index (AFI), oligohydramnios, and decreased AFV, i.e. subjectively decreased but normal by MVP and/or AFI. These included: increased AFV [odds ratio = 12.9, 95% confidence interval (CI) = 4.1-39.4], polyhydramnios (odds ratio = 4.6, CI = 0.6-36.8), and decreased AFV (odds ratio = 3.8, CI = 1.1-13.1). There were no aneuploidies among the 28 normal fetuses with oligohydramnios. Anomalous fetuses had a markedly increased incidence of aneuploidy (odds ratio = 13.4, CI = 7.2-24.9). We conclude that fetal structural anomalies as well as isolated AFV abnormalities were associated with an increased risk for aneuploidy.

Transperineal sonography in second trimester to term pregnancy and early labor.

We studied the diagnostic potential of transperineal sonography in 184 pregnant women from midtrimester to term pregnancies and at early labor. In 65 patients in false labor, we established cervical effacement and dilatation. We confirmed the clinical diagnosis of premature rupture of the membranes (PROM) in 27 cases and assessed the placental relationship with the internal cervical os in 20 patients. In 61 women in early labor we measured cervical dilatation, and in 11 patients we looked for details of fetal anatomy. Adequate diagnostic information was obtained in 180 cases (97%). Our results and data from the literature suggest that transperineal sonography is the imaging technique of choice in the situations we studied.

Ultrasonographic screening for the Down syndrome fetus

The usefulness of ultrasonography in detecting fetuses with Down syndrome in the second trimester has been the subject of considerable debate during the past 3 years. Conflicting reports have led to increasing confusion about the subject in the medical community and among the public. A review of the existing literature indicates that structural malformations that are chiefly cardiac are present in half of Down syndrome fetuses but are not consistently found during routine second-trimester ultrasonography. Although excess posterior nuchal skin-fold thickness is frequently present in infants with Down syndrome, it is also not consistently identified during second-trimester ultrasonographic examinations. Studies evaluating the efficacy of screening programs that are based on femur length shortening associated with Down syndrome have revealed markedly discrepant intercenter results. Although variations in methods may account for some of the observed variability, the magnitude of femoral shortening in Down syndrome suggests that this measurement may be only marginally useful. In summary, antenatal ultrasonography will allow for the detection of only those fetuses with Down syndrome who have multiple characteristic phenotypic features or anomalies. Moreover, current second-trimester ultrasonography does not appear to be either sensitive enough specific enough to be used as a unique Down syndrome screening modality; however, it may be a useful adjunct to maternal age and serum biochemical markers in the assignment of risk for Down syndrome.

The fetal spine.

Ultrasonography has made it possible to evaluate the fetal spine in utero. Vertebral ossifications are demonstrable by ultrasonography in the early second trimester. Most spinal defects are apparent by 20-22 weeks menstrual age. Early detection of spinal anomalies allows for parental counseling and appropriate obstetrical management. Real-time equipment allows the fetal spine to be examined in parasagittal, transverse and coronal planes. The transverse plane provides the best view of the three ossification centers that form each fetal vertebra. Evaluation of the neural arch ossifications in the transverse view is crucial in detecting spina bifida defects. Ultrasonography of the fetal spine complements the use of alpha-fetoprotein levels in screening for neural tube defects. Examination of the fetal spine is also important in detecting vertebral ossification defects, particularly in cases of short-limbed dwarfs and infants of diabetic mothers.