(New) antenatal ultrasound signs of fetal junctional epidermolysis bullosa: A case report and systematic review of literature.

Epidermolysis bullosa is a rare hereditary autosomal disease that is included in the heterogeneous group of genodermatosis. It is characterized by skin and mucous membranes fragility and denudation, and it can be associated with pyloric atresia. Prognosis is often poor, and death can occur in neonatal period due to severe sepsis. We present a case of fetal junctional epidermolysis bullosa in a consanguineous couple, highly suggested by previous obstetric history and several antenatal ultrasound signs, such as polyhydramnios, gastric enlargment, the "snowflake sign", abnormal external ears, signs of skin desquamation, lower limbs anomalies and chorioamniotic membrane separation. We describe a marked perioral hipoecogenicity as a novel sign of skin-mucous denudation, which could be helpful for future diagnosis. A review of literature, focused specifically on the antenatal sonography role, is also reported. Prenatal ultrasound-based diagnosis of epidermolysis bullosa is difficult, especially in apparently low risk contexts, but may be possible.

Accuracy of prenatal ultrasound in the diagnosis of corpus callosum anomalies.

Objectives: The main objective of this study was to evaluate the accuracy of prenatal ultrasound to diagnose corpus callosum alterations, compared to prenatal magnetic resonance imaging (MRI), postnatal image techniques (ultrasound and/or MRI), and post-mortem examination in terminated pregnancies.Methods: Retrospective review of 86 cases of prenatal ultrasound diagnosis of corpus callosum anomalies between January 2007 and December 2015 at a third level Maternal Fetal Medicine center. The study reviewed the findings of prenatal ultrasound and MRI, post-mortem examination in cases of termination of pregnancy (TOP) or stillbirths and postnatal ultrasound, and MRI in neonates. The anomalies of corpus callosum (CC) were classified as complete agenesis of the corpus callosum (ACC), partial ACC, or dysgenesis of CC.Results: Fifty-eight (67.4%) cases resulted in TOP, 26 (30.2%) cases opted to continue with the pregnancy and two (2.3%) cases were lost to follow up. Among the 26 cases that continued with the pregnancy, 24 (92.3%) were live births and two (7.7%) were stillborn. All cases in which a third trimester MRI was performed (n = 46) confirmed the prenatal ultrasound diagnosis of CC anomaly. In seven (15.2%) of them, the MRI found additional intracranial findings and in three cases (6.5%) the type of CC anomaly (complete, partial, or dysgenesis) was reclassified (Kappa index: 0.86, 95% CI: 0.71-1.00). CC anomalies were confirmed in 46 (95.8%) of the 48 cases in which a post-mortem examination was available, the type of anomaly being reclassified in three cases (6.3%) (Kappa index: 0.88, 95% CI: 0.75-1.00). Among the 10 cases in which a postnatal ultrasound was performed, the CC anomaly was confirmed in all and the type of anomaly was reclassified in 1 (10%) of them (Kappa index: 0.75, 95% CI: 0.32-1.00).Conclusion: Corpus callosum agenesis can be detected on the routine mid-trimester ultrasound scan. Prenatal ultrasound and MRI can accurately classify the type of CC abnormality. Moreover, third trimester MRI can detect additional intracranial anomalies in 15% of cases.

Prenatal diagnosis of fetal skeletal dysplasias in a tertiary Hospital in Spain.

OBJECTIVE: To assess the diagnostic accuracy of prenatal ultrasound for detecting fetal skeletal dysplasias and to describe its role in orienting genetic studies. STUDY DESIGN: Observational study of pregnant women surveyed in our hospital, between 2011 and 2018, with fetal long bones below the 3rd centile (shortened long bones), either as an isolated finding or associated to other skeletal anomalies. We used a systematic protocol for the ultrasound evaluation and selection of those fetuses suspected of having a skeletal dysplasia. We report the demographics of these patients along with the sonographic follow-up of their fetuses, the genetic results and the outcome of the pregnancies and the newborn in the entire group and also compare data between the two sub-groups (isolated shortened long bones vs shortened long bones associated to other anomalies). RESULTS: A total of 81 pregnancies with a suspected fetal skeletal dysplasia were included, with a complete follow-up available in 75 cases, 22 with isolated shortened long bones and 53 cases that presented shortened long bones with other skeletal anomalies. In the shortened long bones sub-group, a total of five (23 %) were born healthy neonates, 10 (45 %) were small for gestational age or intrauterine growth restricted (one of them of genetic origin) and seven (32 %) had a skeletal dysplasia (6 of them with genetic diagnosis). Whilst among the 53 cases that presented with shortened long bones + other skeletal anomalies, three (6%) were healthy neonates, five (9%) were small for gestational age/intrauterine growth restricted (two of genetic origin) and 45 (85 %) had a skeletal dysplasia (19 genetically confirmed and 26 with a clinical diagnosis). These differences in frequencies between the two sub-groups were determined to be statistically significant (χ2: p = 0.02). CONCLUSION: Around one third of fetuses with isolated shortened long bones will have a skeletal dysplasia. If abnormal skeletal ultrasound findings are associated with shortened long bones, the risk for skeletal dysplasia is significantly increased (85 %). Prenatal systematic approach in a multidisciplinary unit is useful in the orientation of genetic studies.

Clinical application of a contingent screening strategy for trisomies with cell-free DNA: a pilot study.

BACKGROUND: Different strategies have been designed for clinical implementation of cell-free DNA (cfDNA) testing. We aimed to evaluate the performance of a contingent strategy based on conventional screening and offering cfDNA to the intermediate-risk group, for the screening for trisomies 21, 18 and 13. Secondary objectives were to assess the uptake of cfDNA in women with intermediate-risk, to evaluate the performance of cfDNA testing, and the preferences of pregnant women with intermediate risk. METHODS: Prospective observational pilot study between February 2016 and March 2017. Singleton pregnancies with a known outcome were included in the study. At the conventional screening (first trimester combined test or second trimester quadruple test) women were classified in high (risk ≥1:250) or low risk (< 1:250). For the study, a contingent strategy was applied: following the conventional screening women were classified into three groups: high risk (risk ≥1:10 or nuchal translucency ≥3 mm), intermediate-risk (risk 1:11 to 1:1500) and low risk (< 1:1500), and a cfDNA test was offered to those at the intermediate risk. RESULTS: For the analysis, 2639 women were included, 2422 (91.8%) had a first trimester combined test and 217 (8.2%) a second trimester quadruple test. There were 5 cases of trisomy 21, 4 of trisomy 18 and none of trisomy 13. For the contingent strategy, the detection rate and false positive rates were 88.9% (8/9) and 1.3% (35/2630), respectively. For the conventional strategy, the detection rate and false positive rates were 66.7% (6/9) and 5.3% (140/2630), respectively. The cfDNA test had a detection rate for trisomy 21 of 100% (3 out of 3), and a false positive rate of 0.2% (1/466). In a survey, 81.8% (374/457) of women in the intermediate-risk group would choose cfDNA testing as the second line test, mainly due to the lack of risk for the fetus. CONCLUSION: A contingent screening strategy for trisomies 21, 18 and 13, based on conventional screening, and offering a cfDNA test to women with a risk between 1:11 to 1:1500, reduced the false positive rate and increased the detection rate for these trisomies. Moreover, this strategy is well accepted by women.

Fetal intracranial hemorrhage. Prenatal diagnosis and postnatal outcomes.

OBJECTIVE: To present our experience with 14 cases of fetal intracranial hemorrhage (ICH). METHODS: Cases of fetal ICH detected in our institution between 2005 and 2016 by ultrasonography. Maternal characteristics, ultrasound and MRI findings, and postnatal outcome were noted. RESULTS: Twelve cases (86.7%) were identified during a third trimester routine scan at a median gestational age of 30.6 weeks. The ICH was classified as Grade 2 in two cases, Grade 3 in three cases, and Grade 4 in nine cases. Nine cases were bilateral and five were unilateral (four left/one right). The 11 MRI available confirmed grade and location and, in six cases (54.5%), added new findings. There were six terminations of pregnancy, one intrauterine fetal death and seven babies born alive. These were followed up for 28 months (range 3-96). Some grade of neurologic impairment was observed in five children (71.4%, one Grade 3/four Grade 4), mainly mild to moderate motor sequelae. CONCLUSION: Diagnosis of fetal ICH is amenable to antenatal US. Most of the cases identified are of high grade and usually detected during the third trimester. MRI is a valuable complementary tool in evaluating ICH. Conversely to that previously reported, postnatal survival is high but it entails the risk of adverse neurologic outcome in most neonates.

Follow-up of fetuses with congenital diaphragmatic hernia: The quantitative lung index.

OBJECTIVE: To assess the longitudinal behavior of Quantitative Lung Index (QLI) for the follow-up of fetuses with congenital diaphragmatic hernia. STUDY DESIGN: Retrospective study of fetuses with isolated left congenital diaphragmatic hernia. The fetuses were assessed by ultrasound at different gestational ages and QLI was retrospectively calculated by means of previous lung-to-head ratio measurements. We used a random effects model (mixed model with repeated measurements) to compare the performance of the QLI in operated and non-operated fetuses throughout pregnancy. RESULTS: Fifty-eight cases of isolated left diaphragmatic hernia with complete follow-up were assessed in Hospital Universitari Vall d'Hebron in Barcelona (2003-2015). Thirty-eight of them were managed expectantly (non-TO) and the other 20 underwent tracheal occlusion (TO). All fetuses undergoing tracheal occlusion had lung-to-head ratio (LHR) <1, observed-to-expected LHR (o/eLHR) ≤45%, QLI <0.6 and liver up inside the thorax. The survival rate was 87% for the non-TO group and 60% for the TO group (p = 0.02). The QLI remained constant throughout pregnancy in both groups. The QLI in the TO group had lower values than the non-TO group (p < 0.03). CONCLUSION: The quantitative lung index was constant during pregnancy. This index was lower in fetuses undergoing tracheal occlusion but no significant changes were seen in its performance during pregnancy.

Brainstem-vermis and brainstem-tentorium angles: 3D ultrasound study of the intra- and inter-observer agreement.

OBJECTIVE: The brainstem-vermis angle (BVA) and the brainstem-tentorium angle (BTA) have been proposed to quantify vermian and tentorial alterations associated to fetal posterior fossa malformations. Our objective is to evaluate the intra- and inter-observer agreement for the measurement of these angles during the prenatal ultrasound scan. METHODS: Fifteen 3 D sets from fetuses with posterior fossa pathology were processed by multiplanar navigation. Four experts in prenatal ultrasound measured the BVA and the BTA on a mid-sagittal view of the fetal brain, following the criteria described by Volpe. Observer 1 did also repeated measurements following both the criteria by Volpe and Ghi. The intraclass correlation coefficient (ICC) was used to test consistency and absolute agreement for intra- and inter-observer measurements. The concordance is poor when ICC <0.40 and excellent when ICC >0.75. RESULTS: Consistency ICC for measurements between the 4 observers was 0.74 (95% CI: 0.54-0.89) for the BVA and 0.55 (95% CI: 0.29-0.78) for the BTA. Absolute agreement ICC was 0.67 (BVA) and 0.45 (BTA). The intra-observer study showed a significantly greater angle with the criteria by Ghi (mean 52.1°, 95% CI: 49.5-54.8) than with the criteria by Volpe (mean 37.4°, 95% CI: 33.1-41.6). CONCLUSIONS: A more precise methodology for the measurement of these angles should be described.

The quantitative lung index and the prediction of survival in fetuses with congenital diaphragmatic hernia.

INTRODUCTION: The lung-to-head ratio (LHR) is routinely used to select the best candidates for prenatal surgery and to follow-up the fetuses with congenital diaphragmatic hernia (CDH). Since this index is gestation-dependent, the quantitative lung index (QLI) was proposed as an alternative parameter that stays constant throughout pregnancy. Our objective was to study the performance of QLI to predict survival in fetuses with CDH. MATERIALS AND METHODS: Observational retrospective study of fetuses with isolated CDH, referred to our center. LHR was originally used for the prenatal surgery evaluation. We calculated the QLI and compared the performance of both indexes (QLI and LHR) to predict survival. RESULTS: From January-2009 to February-2015 we followed 31 fetuses with isolated CDH. The mean QLI was 0.66 (95% CI: 0.57-0.75) for survivors and 0.41 (95% CI: 0.25-0.58) for non-survivors (p<0.01) and the mean LHR was 1.38 (95% CI: 1.17-1.60) for survivors and 0.91 (95% CI: 0.57-1.25) for non-survivors (p<0.02). All operated fetuses (n=12) had a LHR <1 and a QLI <0.5 and none of them survived when the QLI was <0.32. When separately considering the prenatal surgery status, the mean values of the QLI (but not those of the LHR) were still significantly different between survivors and non-survivors. The comparative ROC curves showed a better performance of the QLI with respect to the LHR for the prediction of survival, especially in the group of operated fetuses, although differences were not statistically significant. COMMENT: The QLI seems to be a better predictor for survival than the LHR, especially for the group of fetuses undergoing prenatal surgery.

Single center experience in selective feticide in high-order multiple pregnancy: clinical and ethical issues.

OBJECTIVE: This paper describes the 20-year experience with selective feticide (SF) of high-order multiple quadruplet and higher pregnancies in a single center. METHODS: The paper describes protocols, procedures, management, outcomes, and ethical issues. RESULTS: SF was performed in 49 pregnancies with 244 fetuses, with median gestational age of 12+2 weeks. The initial number was nine (one case), eight (one case), seven (three cases), six (11 cases), five (eight cases), and four (27 cases). Nuchal translucency was utilized prior to the procedure starting in 1996. The technique was transabdominal ultrasound-guided and intrathoracic injection of potassium chloride. One pregnancy (with seven fetuses) was reduced to three, 42 to two, and four (starting with four fetuses) to singletons. There were ten pregnancy losses (20.4%). A decreasing trend in losses was evident over the 20-year time period: 7/23 (30.4%) from 1994 to 2004 down to 3/26 (11.5%) for 2004-2014. No chromosomal abnormalities were present in any of the survivors. The ethical issues focus on the justification of SF in high-order multifetal pregnancies. CONCLUSION: In this series, pregnancy loss decreased with operator experience. Excellent outcomes can be achieved with the ethically justified use of feticide in high-order multiple pregnancies.

Influence of gravidity and foetal gender on the value of screening variables in the first trimester of pregnancy.

OBJECTIVES: Combined screening for chromosome abnormalities in the first trimester of pregnancy is based on maternal age, nuchal translucency (NT) and biochemical markers (PAPP-A and free ß-hCG). We sought to assess the value of the variables used in the combined screening strategy taking into account maternal gravidity and foetal gender. STUDY DESIGN: Between July 1999 and December 2009, a total of 21,193 singleton pregnancies were screened for aneuploidy in the first trimester, in the Hospital Clínico San Carlos (Madrid, Spain). In the original database foetal gender data were available in 4370 euploid cases, and there were 2343 women with at least two consecutive pregnancies. We conducted a retrospective assessment of ultrasound and biochemical markers taking into account foetal gender and maternal gravidity, and evaluated the effect on the performance of screening, in terms of detection rates and false positive rates. Information on pregnancy outcome was obtained from the hospital's intranet medical records or by contacting the patient by telephone postpartum. Karyotype was ascertained by amniocentesis or chorionic villus sampling, and euploid status was assumed in newborns with normal phenotype. Student's t-tests (paired or unpaired as appropriate) were applied to the data, and the Bland-Altmann method was applied in evaluating individual differences in markers between successive gestations. RESULTS: PAPP-A decreased significantly between the first and the second pregnancy (p<0.01). PAPP-A and free ß-hCG values were significantly higher (p=0.04 and p<0.01 respectively) and NT was lower (p=0.02) in pregnancies with a female foetus. CONCLUSIONS: Correlations between the biochemical variables in relation to gravidity and foetal gender can introduce a bias in the calculated risk of chromosome abnormalities. Differences in NT measurements with respect to foetal gender do not seem to be of clinical importance. NT is independent of gravidity so routine use of NT compensates for the influence of these maternal-foetal variables on the values of biochemical parameters. Hence, the bias in overall combined screening is small.

Intracranial translucency at 11-13 weeks of gestation: prospective evaluation and reproducibility of measurements.

OBJECTIVE: This paper aimed to determine the feasibility of identification and measurement reproducibility of intracranial translucency (IT) in our population. METHODS: This is a prospective study in which five accredited operators attempted to identify and measure the IT during first-trimester sonographic screening for aneuploidy in 990 fetuses. The presence or absence of spina bifida was determined at the time of the second-trimester scan or after birth. Measurement reproducibility was assessed through intraclass correlation coefficient (ICC) on a subgroup of 150 fetuses. RESULTS: Identification and measurement of the IT were possible in 961 (97%) cases. The mean IT anteroposterior diameter was 1.8 mm (SD ± 0.37; range 0.8-3.1), and the size increased linearly with advancing gestation (IT = 0.74 + 0.02 × crown-rump length; r(2) = 0.15, p < 0.0001). The only fetus with spina bifida in this series presented with absent IT. Intra-observer and inter-observer ICCs were 0.79 and 0.75, respectively (95% confidence intervals 0.72-0.84 and 0.67-0.81, respectively; both p < 0.001). CONCLUSIONS: The IT increases linearly with increasing crown-rump length and seems to be of value in the first-trimester detection of spina bifida. It is easy to identify and measure and shows excellent intra-observer and inter-observer reproducibility measurements.

First trimester screening for aneuploidies in successive pregnancies: correlations between markers.

OBJECTIVES: Screening for chromosomal abnormalities in the first trimester of pregnancy is based on maternal age, nuchal translucency (NT), and biochemical markers (pregnancy-associated plasma protein-A and free beta human chorionic gonadotrophin). We have assessed the influence of screenings and outcomes in previous pregnancies on screenings in subsequent pregnancies. METHODS: Retrospective study of the correlation between the variables of first trimester combined screening for chromosome abnormalities in patients with subsequent pregnancies. Excluded were gestations with fetal aneuploidies. RESULTS: Between July 1999 and December 2009, there were 2291 women with more than 1 euploid pregnancy screened in the first trimester in our hospital. There was a moderate correlation for pregnancy-associated plasma protein-A (ρ = 0.530, p <0.001) and free beta human chorionic gonadotrophin (ρ = 0.439, p <0.001) between the first and second pregnancy. The trend continued in successive pregnancies. NT showed no correlations of clinical importance. With an overall false positive (FP) rate of 2.1% for the combined screening, the probability of having a recurrent FP in the second pregnancy was 4.3% (not significant). CONCLUSION: There are significant correlations between biochemical markers but not NT in successive pregnancies, leading to increased risk of recurrence of FP results. However, such increase is not statistically significant if the overall FP rate is very low.

¿Cuál es tu diagnóstico? Caso iconográfico número 12 / What is your diagnosis? Illustrated case number 12

No disponible

Antenatally diagnosed renal duplex anomalies: sonographic features and long-term postnatal outcome.

OBJECTIVES: The purpose of this study was to assess the diagnostic accuracy and infant outcomes of antenatally detected renal duplex anomalies. METHODS: An observational longitudinal study of cases of renal duplex anomalies diagnosed on prenatal sonography was conducted. Information on the prenatal sonographic findings, antenatal course, and perinatal outcome was obtained by reviewing the sonography reports and delivery records. Postnatal follow-up, including neonatal and infant evaluations, was obtained from hospital records. RESULTS: During a 7-year period, a total of 24 cases of renal duplex anomalies were identified prenatally. Three cases were excluded from subsequent analysis because of termination of pregnancy after the diagnosis of a severe brain abnormality, loss to follow-up, and an inability to confirm the prenatal diagnosis on neonatal renal sonography. Among the 21 confirmed cases, the presence of two separate renal pelvises was the most common prenatal sonographic feature (n = 15 [71%]), followed by dilatation of a single moiety with a dilated ipsilateral ureter or ureterocele (n = 6 [29%]). In 43% of cases, the renal duplex anomalies had no adverse associations, but in 48%, they were complicated by a urinary tract infection, and 48% of the infants required a surgical procedure during early childhood. CONCLUSIONS: Renal duplex anomalies can be accurately diagnosed by prenatal sonography even when there is minimal dilatation of the renal pelvis. Antenatal diagnosis allows planning of postnatal care, which may prevent urinary tract infections and renal function impairment. The natural history of antenatally diagnosed duplex anomalies seems to be overall benign, with urinary tract infections and the need for surgery being the most common complications in affected infants.

First-trimester assessment of the nasal bones using the retronasal triangle view: a 3-dimensional sonographic study.

OBJECTIVE: The purpose of this study was to evaluate a new sonographic technique for identifying the nasal bones using the retronasal triangle view, ie, the coronal plane at which the palate and frontal processes of the maxilla are simultaneously visualized. METHODS: Three-dimensional (3D) volumes were acquired from women undergoing first-trimester sonographic screening for aneuploidy by 2 accredited operators. Those data sets in which the fetal face was clearly identified were selected for offline analysis by 2 other observers who were unaware of the sonographic or clinical findings. The nasal bones were classified as both present, only 1 present (right or left), or absent according to the presence or absence of 2 small paired echogenic linear structures at the upper tip of the retronasal triangle as determined by 3D navigation in the coronal plane and compared to those findings obtained by 3D navigation in the sagittal plane. Additional 3D data sets involving a subset of 4 first-trimester fetuses with trisomy 21 and absent nasal bones were also analyzed retrospectively and included randomly in the study group. RESULTS: A total of 110 3D data sets were analyzed, of which 86% were obtained transabdominally and 14% transvaginally. The quality of nasal bone identification was classified subjectively by the observers as good in 67% of cases, fair in 29%, and poor in 4%. The nasal bones were classified as at least 1 present in 106 of the cases (96%) and absent in 4 (4%), with complete agreement between observers in both the sagittal and coronal planes (κ = 1). Discrimination between the right and left nasal bones was possible in 89% and 93% for observer A and in 96% and 96% for observer B by assessing the sagittal and coronal views, respectively (right nasal bone: κ = 0.90 [95% confidence interval (CI), 0.79-1]; left nasal bone: κ = 0.85 [95% CI, 0.60-0.99]). The nasal bones were not identified at the level of the retronasal triangle view in any of the fetuses with trisomy 21 and absent nasal bones. CONCLUSIONS: This study shows that the nasal bones can be confidently identified as paired echogenic structures located at the upper tip of the retronasal triangle. This coronal view of the fetal face offers the possibility of screening for the presence or absence of the nasal bones in the first trimester, especially when the standard midsagittal views of the fetal face are suboptimal because of fetal or maternal factors. Because both nasal bones can be evaluated simultaneously in the coronal plane, the retronasal triangle view may be advantageous over the conventional midsagittal view assessment, in which only 1 of the 2 nasal bones is evaluated.

Selective pelvic arterial embolization in the management of obstetric hemorrhage.

OBJECTIVE: Retrospective evaluation of pelvic arterial embolization for the treatment of severe post-partum hemorrhage. METHODS: Data were collected, from our departmental clinical records, on all patients with life-threatening post-partum hemorrhage managed with arterial embolization between January 2001 and December 2003. RESULTS: During the period analyzed, there were 29,119 deliveries in our institution. Of these, 27 patients underwent pelvic arterial embolization to control severe hemorrhaging despite conservative management. Of the 27 patients, 22 (81.5%) had a vaginal delivery and 5 had a caesarean section. The major indication for embolization was uterine atony (15 women). Disseminated intravascular coagulation developed in 20 cases (74.1%). There were eight cases (29.6%) who underwent hysterectomy, seven of them pre-embolization. The most frequent vessel embolized was the uterine artery (13 cases; 38.3%). One patient (3.7%) presented complications related to the procedure. The success rate was 96.3%. CONCLUSION: Pelvic arterial embolization is a good therapeutic choice for severe post-partum hemorrhage refractory to conservative treatment measures.