Vasa previa in singleton pregnancies: diagnosis and clinical management based on an international expert consensus.

BACKGROUND: There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies. OBJECTIVE: This study aimed to systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions and a Delphi technique. STUDY DESIGN: A 4-round focus group discussion and a 3-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected on the basis of their publication record on vasa previa. First, we convened a focus group discussion panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A 3-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa, which the experts were asked to rate on a 5-point Likert scale (from "strongly disagree"=1 to "strongly agree"=5). Consensus was defined as a median score of 5. Following responses to each round, any statements that had median scores of ≤3 were deemed to have had no consensus and were excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and nonconsensus statements were then aggregated. RESULTS: A total of 68 international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on 5 continents and have contributed to >80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, and 91% for the first, second, and third rounds, respectively, and 71% completed all 3 rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including the following: (1) although there is no agreement on the distance between the fetal vessels and the cervical internal os to define vasa previa, the definition should not be limited to a 2-cm distance; (2) all pregnancies should be screened for vasa previa with routine examination for placental cord insertion and a color Doppler sweep of the region over the cervix at the second-trimester anatomy scan; (3) when a low-lying placenta or placenta previa is found in the second trimester, a transvaginal ultrasound with Doppler should be performed at approximately 32 weeks to rule out vasa previa; (4) outpatient management of asymptomatic patients without risk factors for preterm birth is reasonable; (5) asymptomatic patients with vasa previa should be delivered by scheduled cesarean delivery between 35 and 37 weeks of gestation; and (6) there was no agreement on routine hospitalization, avoidance of intercourse, or use of 3-dimensional ultrasound for diagnosis of vasa previa. CONCLUSION: Through focus group discussion and a Delphi process, an international expert panel reached consensus on the definition, screening, clinical management, and timing of delivery in vasa previa, which could inform the development of new clinical guidelines.

Incidence and causes of perinatal death in prenatally diagnosed vasa previa: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to estimate the perinatal mortality associated with prenatally diagnosed vasa previa and to determine what proportion of those perinatal deaths are directly attributable to vasa previa. DATA SOURCES: The following databases have been searched from January 1, 1987, to January 1, 2023: PubMed, Scopus, Web of Science, and Embase. STUDY ELIGIBILITY CRITERIA: Our study included all studies (cohort studies and case series or reports) that had patients in which a prenatal diagnosis of vasa previa was made. Case series or reports were excluded from the meta-analysis. All cases in which prenatal diagnosis was not made were excluded from the study. METHODS: The programming language software R (version 4.2.2) was used to conduct the meta-analysis. The data were logit transformed and pooled using the fixed effects model. The between-study heterogeneity was reported by I2. The publication bias was evaluated using a funnel plot and the Peters regression test. The Newcastle-Ottawa scale was used to assess the risk of bias. RESULTS: Overall, 113 studies with a cumulative sample size of 1297 pregnant individuals were included. This study included 25 cohort studies with 1167 pregnancies and 88 case series or reports with 130 pregnancies. Moreover, 13 perinatal deaths occurred among these pregnancies, consisting of 2 stillbirths and 11 neonatal deaths. Among the cohort studies, the overall perinatal mortality was 0.94% (95% confidence interval, 0.52-1.70; I2=0.0%). The pooled perinatal mortality attributed to vasa previa was 0.51% (95% confidence interval, 0.23-1.14; I2=0.0%). Stillbirth and neonatal death were reported in 0.20% (95% confidence interval, 0.05-0.80; I2=0.0%) and 0.77% (95% confidence interval, 0.40-1.48; I2=0.0%) of pregnancies, respectively. CONCLUSION: Perinatal death is uncommon after a prenatal diagnosis of vasa previa. Approximately half of the cases of perinatal mortality are not directly attributable to vasa previa. This information will help in guiding physicians in counseling and will provide reassurance to pregnant individuals with a prenatal diagnosis of vasa previa.

Circulating Cell-Free DNA to Determine the Fetal RHD Status in All Three Trimesters of Pregnancy.

OBJECTIVE: To estimate the accuracy of a new assay to determine the fetal RHD status using circulating cell-free DNA. METHODS: This was a prospective, observational study. Maternal blood samples were collected in each trimester of pregnancy in 520 nonalloimmunized RhD-negative patients. Plasma samples were analyzed for circulating cell-free DNA using the SensiGENE RHD test, which used primers for exons 4 and 7 as previously described and incorporated a new primer design for exon 5 of the RHD gene. Neonatal serology for RhD typing using cord blood at birth was undertaken and results were stored in a separate clinical database. After unblinding the data, results of the DNA analysis were compared with the neonatal serology. RESULTS: Inconclusive results secondary to the presence of the RHD pseudogene or an RHD variant were noted in 5.6%, 5.7%, and 6.1% of the first-, second-, and third-trimester samples, respectively. The incidence of false-positive rates for RhD (an RhD-negative fetus with an RHD-positive result) was 1.54% (95% confidence interval [CI] 0.42-5.44%), 1.53% (CI 0.42-5.40%), and 0.82% (CI 0.04-4.50%), respectively. There was only one false-negative diagnosis (an RhD-positive fetus with an RHD-negative result), which occurred in the first trimester (0.32%; 95% CI 0.08-1.78%). Genotyping for mismatches across repeated samples revealed that this error was related to mislabeling of samples from two patients collected on the same day at one of the collection sites. Overall test results were in agreement across all three trimesters (P>.99). CONCLUSION: Circulating cell-free DNA can accurately predict the fetal RhD status in all three trimesters of pregnancy.

Clinical significance of amniotic fluid sludge in twin pregnancies with a short cervical length.

OBJECTIVE: The objective of the study was to determine the clinical significance of amniotic fluid (AF) sludge in twin pregnancies with a short cervix. STUDY DESIGN: We evaluated twin pregnancies with a short cervical length that had an ultrasound between 16 and 26 weeks (n = 78). Pregnancy outcomes in those with sludge (n = 27) and those without (n = 51) were compared. Outcome variables included gestational age at delivery, premature rupture of the membranes, chorioamnionitis, funisitis, composite neonatal morbidity, and perinatal death. For statistical analysis, the first-born (A) and second-born (B) twins were studied separately. RESULTS: The prevalence of AF sludge was 34.6% (27 of 78). Pregnancies with sludge delivered earlier (27.2 ± 5.6 weeks vs 31.0 ± 4.05 weeks, P < .01) and had a higher rate of extreme prematurity (<26 weeks: 52.2% [12 of 23] vs 15.6% [5 of 32]; P < .01). Both twins had higher rates of histological chorioamnionitis (twin A, 50.0% [13 of 26] vs 12.8% [6 of 47]; P < .01; twin B, 42.3% [11 of 26] vs 13.3% [6 of 45]; P < .01) and neonatal death (twin A, 33.3% [9 of 27] vs 3.9% [2 of 51]; P < .01; twin B, 33.3% [9 of 27] vs 6.0% [3 of 50]; P = .01). Higher rates of funisitis (23.1% [6 of 26] vs 4.3% [2 of 47]; P = .02) and composite neonatal morbidity were observed for twin A only (66.7% [14 of 21] vs 37.5% [18 of 48]; P = .04). CONCLUSION: The presence of AF sludge in twin pregnancies with a short cervix is a risk factor for extreme prematurity, histological chorioamnionitis, and perinatal death. Twin A had higher rates of funisitis and neonatal morbidity in the presence of AF sludge.

Vasa previa: clinical presentations, outcomes, and implications for management.

OBJECTIVE: To review experience with diagnosis, clinical associations, and outcomes of vasa previa in a single institution. METHODS: This was a retrospective review of all identified vasa previa cases from January 1 1990, to June 30, 2010. RESULTS: Sixty cases of vasa previa were identified (53 singletons, seven twins); 56 cases were diagnosed before delivery. An abnormal cord insertion or abnormal placental location was present in 55 cases. Missed diagnoses were attributed to technical and observer factors. Preterm bleeding was encountered in 25 (42%) case group participants. Seven case group participants required an emergent delivery, with significant neonatal morbidity and mortality. Twin pregnancies had a significantly earlier median age at delivery of 32 weeks of gestation compared with 35 weeks of gestations in singletons (P=.01). The seven twin pregnancies had a 28.6% emergent preterm delivery rate, whereas singletons had a 4.1% rate (P=.07). In 14 case group participants, the membranous fetal vessel was located in the lower uterus and not directly over the cervix. The vessel location was not related to the risk of emergent delivery. CONCLUSION: Transvaginal ultrasound scans of at-risk patients can identify most cases of vasa previa. Preterm bleeding does not usually require immediate delivery. The rate of emergent preterm delivery was low in singleton pregnancies. Twins were delivered, on average, 3 weeks earlier than singletons. LEVEL OF EVIDENCE: III.

Fetal heart: a 4-chamber view is not enough.

The majority of children born with congenital heart disease have no identifiable risk factors and, therefore, prenatal diagnosis relies on routine ultrasonographic screening. First proposed in 1985, the 4-chamber view is a component of the basic fetal cardiac examination. However, many life-threatening conditions (eg, transposition of the great arteries) can present with a normal 4-chamber view and may only be detected by systematic evaluation of the outflow tracts. Although this is a technically challenging skill, its mastery is a worthwhile goal of ultrasonography training, as it likely to improve the lives of at least some of the children affected by the most severe forms of congenital heart disease.

Paradoxical motion: a useful tool in the prenatal diagnosis of congenital diaphragmatic hernias and eventrations.

OBJECTIVE: The purpose of this series was to determine whether paradoxical motion of the diaphragm reliably identifies congenital diaphragmatic hernias (CDHs). METHODS: Sonographic evaluation of diaphragmatic motion was attempted in all fetuses undergoing a targeted examination for findings suggestive of a possible CDH. During any respiratory motion or hiccupping, the posterior chest and abdomen were visualized in a coronal plane at the level of the descending aorta to evaluate ascent and descent of the hemidiaphragms. Normal motion was defined as descent of both during inspiration. Paradoxical motion was defined as descent of one hemidiaphragm and ascent of the opposite one during inspiration. If no breathing motion was observed during the examination, the results were termed "poor visualization." If there was poor visualization, the diaphragm was reevaluated at any return visits. In the second part of this study, diaphragmatic motion in 120 fetuses of at least 15 weeks' gestational age without abnormalities was evaluated. The diagnosis of a CDH needed to be confirmed by pathologic examination or surgery. RESULTS: No fetus without abnormalities showed paradoxical breathing. There were 15 fetuses who had a confirmed CDH and showed breathing during an examination. Fourteen of 15 had paradoxical motion; the fetus who did not had a very small defect containing a single loop of bowel. Thirteen fetuses had CDHs, and 2 had eventrations. CONCLUSIONS: Paradoxical motion is specific for CDHs and eventrations and can be seen as early as 17 weeks' gestation.

Insights into angiogenic imbalances during pregnancy.

BACKGROUND: An excess of either angiogenic or antiangiogenic factors may participate in the pathophysiology of life-threatening pregnancy complications. CASES: We describe two patients with severe early onset preeclampsia associated with partial mole or sacrococcygeal teratoma who had an excess of circulating concentrations of the antiangiogenic factors soluble vascular endothelial growth factor receptor-1 and soluble endoglin. In contrast, a patient with severe ovarian hyperstimulation syndrome at 5 weeks of gestation had an excess of circulating free vascular endothelial growth factor, a key angiogenic factor. CONCLUSION: Angiogenic imbalances may participate in the pathophysiology of early onset preeclampsia associated with partial mole or sacrococcygeal teratoma as well as in the pathophysiology of severe ovarian hyperstimulation syndrome during pregnancy.

Fetal mediastinal lymphangiomas.

OBJECTIVE: The purpose of this series was to evaluate the prenatal sonographic findings and postnatal outcomes in 2 fetuses with mediastinal lymphangiomas. METHODS: The fetal images were compared with postnatal imaging and surgical findings. RESULTS: The 2 fetuses had anechoic mediastinal masses at 25 and 22 weeks, which proved to be lymphangiomas. One, located in the anterior mediastinum, also enveloped the superior vena cava, brachial plexus, phrenic nerve, larynx, and lower parts of the neck vessels and extended into the subcutaneous tissues of the anterior chest wall through an intercostal space. In the second patient, the lymphangioma appeared to be a unilocular cyst, which involved the deep tissues of the neck as well as the posterior and lateral mediastinum. Both required 2 interventions after birth. CONCLUSIONS: Fetal mediastinal lymphangiomas appeared anechoic and sent extensions into the neck in the first case, around the superior vena cava, through the intercostal spaces to the skin, and around the brachial plexus in the second case, and deviated the trachea in both cases. In 1 case, there was also ectasia of the superior vena cava. This ability to entwine around vital structures can make it difficult to determine the extent of involvement on antenatal sonography and to remove lymphangiomas completely, and recurrence is common.

Isolated choroid plexus separation on second-trimester sonography: natural history and postnatal importance.

OBJECTIVE: This study was undertaken to investigate the natural history and clinical importance of choroid plexus separation (a > or = 3 mm distance between the choroid plexus and medial wall of the lateral ventricle) as an isolated finding in the second trimester. METHODS: This was a 5-year retrospective review of an ultrasound database, looking for singleton fetuses with a menstrual age of 16 to 26 weeks and a finding of isolated choroid plexus separation. RESULTS: There were 78 cases available for study. The finding of choroid plexus separation was usually transient. Resolution was noted in 37% of the cases that were rescanned within 2 weeks and 71% of the cases that were rescanned more than 2 weeks after the initial diagnosis. Two abnormal karyotypes (trisomy 21 and 47,XXY) and 3 cases with abnormal development not associated with an abnormal karyotype were noted on neonatal follow-up. Cases with abnormal development were quite varied in their presentation. CONCLUSIONS: The finding of isolated choroid plexus separation is usually temporary, resolving in most cases within 4 weeks of the initial diagnosis. Most infants with this finding have no abnormalities. The clinical implication of the lone case of trisomy 21 was limited by a major preexisting risk in this patient. The 3 cases of abnormal development had varying presentations; the causal nature of this association is not yet clear. No trends were noted between the changing choroid plexus appearance with time and abnormal neonatal outcome, but the number of abnormal cases was quite limited.

Clinical implications of the prenatal sonographic finding of fetal myocardial echogenic foci.

OBJECTIVE: The purpose of this study was to investigate the clinical implications of fetal echogenic foci limited to the myocardium of the ventricular wall (EMF) or intraventricular septum detected during prenatal sonography. METHODS: A retrospective review of fetuses found to have EMF during prenatal sonography from April 1990 through December 2003 was undertaken. Videotapes and reports were reviewed to determine the indication for sonography, gestational age, location, sonographic characteristics of the masses, and additional fetal findings. Sources of outcome data included neonatal and pediatric records and echocardiographic reports. RESULTS: Five fetuses were identified. Indications for sonographic evaluation included fetal growth (n = 4) and follow-up twin-twin transfusion syndrome (n = 1). Mean gestational age +/- SD at diagnosis was 23.7 +/- 8.0 weeks (range, 17.1-36.4 weeks). The EMF identified were within the right ventricular myocardium (n = 2), intraventricular septum (n = 1), left ventricular myocardium (n = 1), and myocardium of the cardiac apex (n = 1). All foci appeared sonographically "bright as bone." The foci ranged in size from 0.1 x 0.1 to 1.2 x 0.9 cm. Neonatal echocardiographic findings were reported as normal for each of the cases. Follow-up examinations available for up to 2.5 years of age showed normal cardiac function. CONCLUSIONS: The prenatal identification of EMF is unlikely to lead to notable short-term pathologic conditions because the fetuses in this investigation had unremarkable neonatal and pediatric echocardiograms and normal cardiac function.

Sonographic detection of placenta accreta in the second and third trimesters of pregnancy.

OBJECTIVE: The purpose of this study was to determine whether ultrasonography can detect placenta accreta reliably in at-risk patients. STUDY DESIGN: All patients with a previous cesarean delivery and an anterior placenta or placenta previa were evaluated prospectively at each visit for sonographic signs of placenta accreta (interruption of the posterior bladder wall-uterine interface, absence of the retroplacental clear zone, and placental lacunae). RESULTS: This evaluation involved 2002 patients over a 12-year period. Of the 14 patients with a confirmed diagnosis of placenta accreta who had ultrasound examinations between 15 and 20 weeks of gestation, the diagnosis was suspected strongly in 86% of the patients (12/14 patients). There were 18 false-positive cases (54.5%; 18/33 patients), most of which were due to a lack of visualization of the echolucent area between the placenta and the myometrium (obliteration of the 'clear space') during the third trimester. The presence of multiple linear irregular vascular spaces within the placenta (placental lacunae) was the diagnostic sign with the highest positive predictive value for placenta accreta. CONCLUSION: Placenta accreta can be detected as early as 15 to 20 weeks of gestation in most at-risk patients by visualization of irregular vascular spaces within the placenta (placental lacunae). Obliteration of the retroplacental 'clear space' is not a reliable diagnostic sign for placenta accreta.

Second-trimester sonography and trisomy 18.

OBJECTIVE: This report presents the findings seen on initial second-trimester sonography in a large group of fetuses with trisomy 18. The object of this study was to describe the types and frequencies of abnormal sonographic findings seen and to further evaluate those cases in which no abnormal findings were noted. METHODS: A retrospective chart review of the prenatal sonograms in cases of trisomy 18 was conducted. RESULTS: Forty-nine fetuses with trisomy 18 were examined by second-trimester sonography. Multiple fetal anomalies were seen in most cases. The most frequent structural findings involved the brain (82%), heart (55%), and upper extremities (53%). Growth abnormalities occurred in 39% of these fetuses. Choroid plexus cysts were the most common individual findings. Larger cysts increased the likelihood of trisomy 18, although no fetuses with trisomy 18 had isolated choroid plexus cysts. Seven fetuses (14%) had no anomalies seen on their initial scans. In each of these scans, the fetal anatomy was incompletely visualized because of technical constraints. Six had subsequent scans approximately 2 weeks later, which showed abnormal sonographic findings. CONCLUSIONS: Most fetuses with trisomy 18 were identified by structural anomalies, typically seen in the brain, heart, and upper extremities. Larger choroid plexus cysts were associated with this aneuploidy. Technical factors, which limit fetal visualization, were noted in all cases in which no sonographic abnormalities were detected during the initial sonographic examinations. Detection of abnormal cases will rely on a completed evaluation of a routine fetal anatomic survey.

Second-trimester sonography and trisomy 18: the significance of isolated choroid plexus cysts after an examination that includes the fetal hands.

OBJECTIVE: To estimate the risk of trisomy 18 with the finding of isolated choroid plexus cysts after a standard sonographic examination that is extended to include the fetal hands. METHODS: Aretrospective chart review was performed on all fetuses with choroid plexus cysts on second-trimester sonographic examinations. When choroid plexus cysts were identified, our standard protocol for fetal evaluation was expanded to include the hands. If no other findings were noted on completion of this examination, the choroid plexus cysts were classified as "isolated." These results were correlated with the presence or absence of trisomy 18 to determine the impact of this approach for the detection of fetuses with this aneuploidy. RESULTS: From March 1990 to the end of 2001, 49,435 fetuses that were subsequently delivered at our hospital were scanned between 16 and 25 menstrual weeks. At least 1 choroid plexus cyst was detected in 1209 fetuses (2.3%), of which 1060 were isolated. No fetuses with isolated choroid plexus cysts had trisomy 18. However, 3 fetuses with trisomy 18 had choroid plexus cysts and abnormal hands as their only abnormal findings. CONCLUSIONS: Fetuses with an apparently isolated finding of choroid plexus cysts can be further evaluated by extending the standard examination to include the hands. If no other findings are identified, the risk of trisomy 18 appears to be low.

Clinical outcome of fetuses with sonographic diagnosis of isolated micrognathia.

OBJECTIVE: To describe the clinical outcome of fetuses with the prenatal sonographic diagnosis of isolated micrognathia. METHODS: A retrospective review of fetuses and infants with the prenatal diagnosis of isolated micrognathia for April 1990 to August 2001 was undertaken. Isolated micrognathia was considered if no other anatomic, growth, or amniotic fluid abnormalities were detected by a detailed ultrasound examination. Sources of outcome data included maternal and neonatal medical records, prenatal genetics records, and karyotype results. RESULTS: Fifty-eight fetuses with the diagnosis of micrognathia were identified. Fifteen fetuses (26%) had isolated micrognathia by prenatal sonogram. After neonatal examination, 14 of 15 were found to have at least one additional abnormality. Eleven had a cleft of the soft and/or hard palate. Seven (54%) of 13 live-born neonates had mild to severe airway obstruction that required intervention. Four (31%) of 13 experienced feeding difficulties of varying duration. Follow-up data were available for 1 to 10 years. Eight (62%) of 13 children are reported to be doing well. Five (38%) of 13 children are reported to have mild to severe developmental delay. CONCLUSION: If micrognathia is the only sonographic finding identified, physicians and families should be prepared for possible respiratory difficulty at delivery, the presence of a cleft palate, and/or developmental delay.

The early sonographic appearance of placenta accreta.

OBJECTIVE: To determine whether any sonographic findings in the first trimester predict placenta accreta. METHODS: Patients who had a diagnosis of placenta accreta, increta, or percreta by clinical course or pathologic examination of the uterus and who had had a sonographic examination at 10 weeks or earlier were included in this study. RESULTS: Seven patients met the study criteria. In 6 of these, who had had at least 1 previous cesarean delivery, the gestational sac was located in the lower uterine segment at the time of the early scan. Two of these pregnancies failed shortly after the early scan, and the patients underwent dilation and curettage, at which time severe bleeding necessitated a hysterectomy. The other 4 continued to term but had sonographic findings typical of placenta accreta during subsequent scans. In the seventh patient (who had had no previous cesarean deliveries), the gestational sac was located in the uterine fundus. CONCLUSIONS: In a patient with a previous cesarean delivery, a sac lying in the lower uterine segment on a scan at 10 weeks or earlier suggests the possibility of placenta accreta.