Fetal intestinal loop dilatation: Follow-up and outcome of a series of 133 consecutive cases (the DILDIG study).

OBJECTIVES: To define the prognostic markers of fetal dilated bowel loops. METHODS: National non-interventional study of 133 consecutive prenatal observations of dilated loops including ultrasound examinations, complementary laboratory tests, magnetic resonance imaging (MRI), outcomes, and postnatal diagnosis. RESULTS: One hundred twenty seven cases were classified according to outcome: Group 1, very severe (n = 43), Group 2, children needing specific care (n = 39), and Group 3, healthy children (n = 45). Prenatal ultrasound scan suggested duodenal obstruction in 30 cases, small bowel obstruction in 81, colonic obstruction in 11, and diffuse dilatation in 5. Diameter of dilated loops did not significantly differ between the groups. A poor prognosis was significantly associated with duodenal obstruction, genetic anomalies (53% vs. 21.8%), including aneuploidies or CFTR gene mutations and abnormal amniotic fluid biochemistry (86.4% vs. 38.7%). A good prognosis was associated with regression of dilatation and normal MRI. CONCLUSION: In this study, postnatal outcomes for fetuses with intestinal dilatation were best predicted by assessing the level of obstruction with prenatal ultrasound and MRI, determining the presence of associated malformations, amniotic fluid biochemical and genetic testing, and monitoring for regression of bowel dilatation. These results should help inform future guidelines on the prenatal and neonatal management of congenital intestinal obstruction.

Should prenatal chromosomal microarray analysis be offered for isolated fetal growth restriction? A French multicenter study.

BACKGROUND: Compared with standard karyotype, chromosomal microarray analysis improves the detection of genetic anomalies and is thus recommended in many prenatal indications. However, evidence is still lacking on the clinical utility of chromosomal microarray analysis in cases of isolated fetal growth restriction. OBJECTIVE: This study aimed to estimate the proportion of copy number variants detected by chromosomal microarray analysis and the incremental yield of chromosomal microarray analysis compared with karyotype in the detection of genetic abnormalities in fetuses with isolated fetal growth restriction. STUDY DESIGN: This retrospective study included all singleton fetuses diagnosed with fetal growth restriction and no structural ultrasound anomalies and referred to 13 French fetal medicine centers over 1 year in 2016. Fetal growth restriction was defined as an estimated fetal weight of

Prenatal Ultrasound Suspicion of Cystic Fibrosis in a Multiethnic Population: Is Extensive CFTR Genotyping Needed?

In families without a Cystic Fibrosis (CF) history, fetal ultrasound bowel abnormalities can unexpectedly reveal the disease. Isolated or in association, the signs can be fetal bowel hyperechogenicity, intestinal loop dilatation and non-visualization of fetal gallbladder. In these cases, search for CF transmembrane conductance regulator (CFTR) gene mutations is part of the recommended diagnostic practices, with a search for frequent mutations according to ethnicity, and, in case of the triad of signs, with an exhaustive study of the gene. However, the molecular diagnosis remains a challenge in populations without well-known frequent pathogenic variants. We present a multiethnic cohort of 108 pregnancies with fetal bowel abnormalities in which the parents benefited from an exhaustive study of the CFTR gene. We describe the new homozygous p.Cys1410* mutation in a fetus of African origin. We did not observe the most frequent p.Phe508del mutation in our cohort but evidenced variants undetected by our frequent mutations kit. Thanks to the progress of sequencing techniques and despite the difficulties of interpretation occasionally encountered, we discuss the need to carry out a comprehensive CFTR study in all patients in case of fetal bowel abnormalities.

Antenatal Management of Bronchopulmonary Sequestration by Intrafetal Vascular Laser Ablation under Ultrasound Control: Narrative Review of the Literature and Report of Three Cases.

OBJECTIVE: The objective of this study is to assess the effectiveness and safety of intrafetal vascular laser ablation (VLA) for fetuses with bronchopulmonary sequestration (BPS) with hydrops. METHODS: First, we present 3 cases of fetuses with BPS and hydrops treated by VLA. Second, we aimed to conduct a narrative review to identify all reported cases of fetuses with BPS treated by intrafetal VLA. RESULTS: The review of the literature identified 41 fetuses treated by VLA for BPS with hydrops. The median gestational age of the VLA was 27+0 weeks' gestation [25+0-31+0] with an associated procedure at the same time in 43% of the cases (pleuroamniotic shunt, thoracentesis, and amniodrainage). A second procedure was required in 25% of cases for residual flow in the feeding vessel. No stillbirth or neonatal death was reported. The complications reported were a fetal thoracic hematoma complicated by fetal anemia and 4 preterm deliveries with a rate of 9%. CONCLUSION: VLA of the feeding vessel can be an effective treatment but is not without complications. In cases demonstrating cardiac output failure, intrafetal VLA should be considered as a treatment for BPS.

Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies.

Atypical fetal chromosomal anomalies are more frequent than previously recognized and can affect fetal development. We propose a screening strategy for a genome-wide non-invasive prenatal test (NIPT) to detect these atypical chromosomal anomalies (ACAs). Two sample cohorts were tested. Assay performances were determined using Cohort A, which consisted of 192 biobanked plasma samples-42 with ACAs, and 150 without. The rate of additional invasive diagnostic procedures was determined using Cohort B, which consisted of 3097 pregnant women referred for routine NIPT. Of the 192 samples in Cohort A, there were four initial test failures and six discordant calls; overall sensitivity was 88.1% (37/42; CI 75.00-94.81) and specificity was 99.3% (145/146; CI 96.22-99.88). In Cohort B, there were 90 first-pass failures (2.9%). The rate of positive results indicating an anomaly was 1.2% (36/3007) and 0.57% (17/3007) when limited to significant unbalanced chromosomal anomalies and trisomies 8, 9, 12, 14, 15, 16, and 22. These results show that genome-wide NIPT can screen for ACAs with an acceptable sensitivity and a small increase in invasive testing, particularly for women with increased risk following maternal serum screening and by limiting screening to structural anomalies and the most clinically meaningful trisomies.

Managing the Unusual Causes of Fetal Anemia.

BACKGROUND: Rare causes of fetal anemia requiring intrauterine transfusion (IUT) are challenging for fetal medicine specialists. OBJECTIVES: The aim of this study was to describe the perinatal patterns and prognosis in a consecutive series of fetuses transfused for fetal anemia of rare or unknown etiology, and to propose a protocol of investigation for fetal anemia of undetermined cause and for the management of subsequent pregnancies. METHOD: We conducted a retrospective descriptive study on fetuses transfused for severe anemia of rare or unknown etiology managed in our national referral center (Centre National de Référence d'Hémobiologie Périnatale) and born between 2010 and 2017. RESULTS: During the study period, 584 IUT were performed in 253 fetuses. Among those IUT, 23 (3.9%) were performed for a rare or unknown cause of anemia in 13 fetuses (5.1% of transfused fetuses). The median gestational age at diagnosis was 26 weeks of gestation (WG; range 21-33). Hemoglobin levels ranged from 1.6 to 9.1 g/dL (0.18-0.83 multiples of median) before the first IUT. The fetuses received between 1 and 6 IUT (39% received at least 2 IUT). The definitive etiologies for central anemia were: congenital syphilis, neonatal poikilocytosis, type II congenital dyserythropoietic anemia (CDA), and neonatal hemochromatosis. There was 1 case with suspected type I CDA and 1 with suspected Diamond-Blackfan anemia. There was 1 case of peripheral anemia, secondary to cerebral hemorrhages of different ages, related to a variant of the COL4A1 gene. In 6 fetuses corresponding to 4 mothers, no precise diagnosis was found despite a complete workup. In our series, there were 8 live births, 4 terminations of pregnancy, and 1 intrauterine fetal death. CONCLUSIONS: Fetal anemia of rare or unknown diagnosis represents 5% of all transfused fetuses in our cohort. Fetal and neonatal anemias can be recurrent in further pregnancies, with variable expressivity.

In utero ultrasound diagnosis of corpus callosum agenesis leading to the identification of orofaciodigital type 1 syndrome in female fetuses.

BACKGROUND: OFD1 syndrome is a rare ciliopathy inherited on a dominant X-linked mode, typically lethal in males in the first or second trimester of pregnancy. It is characterized by oral cavity and digital anomalies possibly associated with cerebral and renal signs. Its prevalence is between 1/250,000 and 1/50,000 births. It is due to heterozygous mutations of OFD1 and mutations are often de novo (75%). Familial forms show highly variable phenotypic expression. OFD1 encodes a protein involved in centriole growth, distal appendix formation, and ciliogenesis. CASES: We report the investigation of three female fetuses in which corpus callosum agenesis was detected by ultrasound during the second trimester of pregnancy. In all three fetuses, fetopathological examination allowed the diagnosis of OFD1 syndrome, which was confirmed by molecular analysis. CONCLUSIONS: To our knowledge, these are the first case reports of antenatal diagnosis of OFD1 syndrome in the absence of familial history, revealed following detection of agenesis of the corpus callosum. They highlight the impact of fetal examination following termination of pregnancy for brain malformations. They also highlight the contribution of ciliary genes to corpus callosum development.

Accuracy of Middle Cerebral Artery Doppler Assessment between 34 and 37 Weeks in Fetuses with Red Cell Alloimmunization.

BACKGROUND: The Doppler measurement of middle cerebral artery peak systolic velocity (MCA-PSV) is considered the gold standard for the noninvasive detection of moderate to severe anemia. However, the accuracy of this test has not been evaluated so far, specifically beyond 34 weeks. OBJECTIVES: To assess the accuracy of MCA-PSV to detect moderate to severe fetal anemia and to identify risk factors associated with false-positive and false-negative MCA-PSV values after 34 weeks. STUDY DESIGN: We studied a retrospective cohort of 150 pregnant women with severe alloimmunization who delivered between 2010 and 2014 and correlated MCA-PSV and fetal or neonatal hemoglobin levels. RESULTS: Sensitivity to predict severe anemia was 69%, with a false-negative rate of 3.6%. When MCA Doppler assessment was normal, the identification of serosal effusions increased the detection rate of severe fetal anemia to 94%, with a false-negative rate of 0.8%. False-positive MCA-PSV measurements were more frequent in fetuses with 1 previous intrauterine transfusion (p = 0.0002), but were not associated with MCA resistance index, intrauterine growth restriction and fetal heart rate. CONCLUSIONS: Between 34 and 37 weeks, sensitivity of MCA-PSV Doppler assessment alone is 69% and increases to 94% when also considering signs of hydrops. False-positive MCA-PSV measurements are more frequent in case of former fetal transfusion.

Clinical presentation and outcome of 20 fetuses with parvovirus B19 infection complicated by severe anemia and/or fetal hydrops.

AIM: The aim of this study was to assess the prognosis of parvovirus B19 infection with severely anemic and/or hydropic fetuses according to initial ultrasound and biological criteria. MATERIAL AND METHODS: Retrospective study of 20 cases of congenital parvovirus B19-proven infection (positive PCR) complicated by fetal anemia and/or hydrops was examined. Anemia was suspected on an elevated peak systolic velocity of the middle cerebral artery and was confirmed by fetal blood sampling. RESULTS: Survival rate was 70% (14/20) overall and 76% (13/17) for fetuses with one or more transfusions. When fetal effusion regressed after the transfusion, all 11 fetuses survived, and neonatal condition was favorable for all. Among the 14 live-born children, there was one neonatal death and one admission to the neonatal care unit with no major complications. CONCLUSION: Despite active management by transfusion in fetuses with parvovirus B19 infection, mortality remained substantial during the acute phase of anemia and fetal hydrops. Regression of effusion appears to be an important variable for prognosis. Non-anemic forms exist with isolated refractory ascites or pleural effusion. Maternal mirror syndrome appears to reflect the intensity and persistence of the fetal anemia.

Fetal anemia as a signal of congenital syphilis.

An upsurge in syphilis has been observed almost everywhere over the past decade. The mother's clinical presentation is often uninformative. The diagnosis of maternal syphilis infection is most often based on serologic tests that allow early Extencilline treatment. Syphilis ultrasound findings are non-specific, and delay before treatment can be decisive for prognosis. Fetal anemia is a physiological consequence of severe infection. We confirmed that syphilis can be suggested non-invasively by MCA-PSV measurements in a context of ascitis or atypical hydrops in the absence of usual causes. It is therefore important to perform maternal TPHA/VDRL serology if fetal anemia is suspected. In association with Extencilline treatment, intra uterine transfusion can limit consequences of infection. Reduced fetal movements and non-reactive fetal heart rate may prefigure acute perinatal complications or stillbirth.

Management of very early fetal anemia resulting from red-cell alloimmunization before 20 weeks of gestation.

OBJECTIVE: To evaluate the results of management of very early fetal anemia (before 20 weeks of gestation) in cases of red-cell alloimmunization. METHODS: Retrospective study of the outcome of all in utero transfusions performed before 20 weeks of gestation and all pregnancies requiring an in utero transfusion before 20 weeks in our reference center from January 1990 through August 2011 in cases with severe alloimmunization. RESULTS: Twenty-five in utero transfusions were performed in 18 pregnancies in 16 patients during the study period. A vascular access was performed successfully in 22 of the 24 cases in which it was attempted. An intraperitoneal transfusion was necessary in two cases. Two in utero deaths attributable to the intravascular procedure occurred during attempts before 18 weeks of gestation and another, not associated with a transfusion, at 29 weeks. The overall survival rate was 83.3% (compared with 88.0% when the first in utero transfusion took place before 22 weeks). The risk of fetal loss for each transfusion was 8.0% before 20 weeks and 6.3% before 22 weeks. An intraperitoneal transfusion at 17 2/7 weeks allowed one fetus to survive until the first intravascular in utero transfusion could take place at 18 2/7 weeks. CONCLUSION: Fetal anemia before 20 weeks remains at high risk of lethal complications compared with later gestational ages. Technical difficulties in a vascular access are mainly encountered before 18 weeks of gestation. At an earlier gestational age, intraperitoneal transfusion may gain the days necessary to perform an intravascular transfusion more safely. LEVEL OF EVIDENCE: III.

Massive fetomaternal hemorrhage secondary to intrauterine intravascular transfusion.

BACKGROUND: Small-volume fetomaternal hemorrhage is frequently observed after intrauterine transfusion. The Kleihauer-Betke test, the reference method for identifying fetomaternal hemorrhage, cannot be used after intrauterine transfusion, because the adult red blood cells used for transfusion cannot be distinguished from maternal red blood cells. CASE: Massive fetomaternal hemorrhage secondary to intrauterine transfusion led to fetal hemorrhagic stroke. We used a method based on blood group identification in the maternal blood to confirm and to quantify fetomaternal hemorrhage. CONCLUSION: Fetal stroke may result from severe hypovolemia and low cerebral blood flow caused by fetomaternal hemorrhage, rather than from fetal anemia itself.

Surgical approach to and reproductive outcome after surgical correction of a T-shaped uterus.

BACKGROUND: The aim of this study was to describe the surgical approach to, and evaluate the reproductive outcome of, a T-shaped uterus. METHODS: The study included 97 women who were eligible for hysteroscopic surgery, by either monopolar or bipolar electrosurgical instruments. All had diagnostic hysteroscopy 2 months afterwards to assess the success of the procedure and determine whether any synechiae were present. RESULTS: Forty-eight women (49.5%) became pregnant after metroplasty. The overall live birth rate per pregnancy before surgery was 0%; for these patients, it increased to 73%, and their miscarriage rate fell from 78 to 27% (P < 0.05). For all 57 pregnancies in 48 women, the ectopic pregnancy rate was 9% (n = 5), the miscarriage rate 28% (n = 16), the preterm delivery rate 14% (n = 8), the term delivery rate 49% (n = 28) and the live birth rate was 63% (n = 36). CONCLUSIONS: Hysteroscopic metroplasty improves the live birth rate for women with a T-shaped uterus and a history of primary infertility, recurrent abortion or preterm delivery, although it is not a treatment of infertility.

Prenatal evaluation of the middle ear and diagnosis of middle ear hypoplasia using MRI.

BACKGROUND: Analysis of the middle ear with fetal MRI has not been previously reported. OBJECTIVE: To show the contribution of fetal MRI to middle ear imaging. MATERIALS AND METHODS: The tympanic cavity was evaluated in 108 fetal cerebral MRI examinations (facial and/or cerebral malformation excluded) and in two cases, one of Treacher Collins syndrome (case 1) and the other of oculo-auriculo-vertebral (OUV) spectrum (case 2) with middle ear hypoplasia identified by MRI at 27 and 36 weeks' gestation, respectively. RESULTS: In all 108 fetuses (mean gestational age 32.5 weeks), the tympanic cavity and T2 hypointensity related to the ossicles were well visualised on both sides. Case 1 had micro/retrognathia and bilateral external ear deformity and case 2 had retrognathism with a left low-set and deformed ear. MRI made it possible to recognize the marked hypoplasia of the tympanic cavity, which was bilateral in case 1 and unilateral in case 2. Both syndromes are characterized by craniofacial abnormalities including middle ear hypoplasia, which cannot be diagnosed with US. CONCLUSION: The middle ear cavity can be visualized with fetal MRI. We emphasize the use of this imaging modality in the diagnosis of middle ear hypoplasia.

Prenatal diagnosis of anoxic cerebral lesions caused by profound fetal anemia secondary to maternal red blood cell alloimmunization.

BACKGROUND: The long-term neurological prognosis of severe fetal anemia is usually considered favorable, especially when fetal hydrops regresses after successful in utero transfusion. CASES: We report two cases of prenatally diagnosed fetal cerebral anoxic lesions associated with severe fetal anemia despite appropriate and successful treatment by in utero transfusion. The two pregnancies were terminated. CONCLUSION: Profound fetal anemia may cause anoxic lesions of the fetal brain that may be diagnosed prenatally. If new onset ventriculomegaly is observed on ultrasonography after in utero transfusion for severe fetal anemia, anoxic lesions could be suspected.

[Gynecological cancers and pregnancy: the point of view of the oncology gynecologist]. / Cancers gynécologiques et grossesse: le point de vue du gynécologue oncologue.

Cervical cancer and nonepithelial ovarian cancer are the most frequent gynecological tumors diagnosed during the pregnancy. The management of patients with a malignant tumor discovered during her pregnancy depends on the type of the tumor, the tumor stage and the term of the pregnancy. In most of cases, a conservative management of the pregnancy could be offered without affect the optimal approach for the treatment of the tumor nor the survival of the patient. But such management needs to be determined in a multidisciplinary staff with oncologists, neonatologists, obstetricians but also the point of view of the patient.