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.

Incidence of gastro-intestinal anomalies and surgical outcome of fetuses diagnosed with echogenic bowel and bowel dilatation.

BACKGROUND: We aimed to evaluate the incidence of gastro-intestinal (GI) anomalies and surgical outcome in fetuses diagnosed with either echogenic bowel (EB) or EB plus bowel dilatation (BD) but no associated chromosomal, DNA and/or additional structural defects. METHODS: A 10-year (2008-2018) retrospective review was performed on all fetuses diagnosed with EB and EB+BD (RES-18-0000-072Q). Results are reported as number of cases (%) and mean ±SD. Fisher's exact test, Mann-Whitney U test and logistic regression were used to identify differences between groups and predisposing factors for gastro-intestinal anomalies. RESULTS: We identified 41 fetuses with EB and 14 fetuses with EB+BD. Post-natal surgical intervention was required in no patient of the EB group and in 7/14 (50%) of the EB+BD group, p<0.001. The risk of having a GI anomaly was higher in the EB+BD group (RR 42.0 [2.5-691.6]; p=0.009). Advanced maternal age (p=0.04), ascites (p=0.006) and polyhydramnios (p=0.007) were associated with a higher incidence of GI pathology. CONCLUSIONS: In fetuses with no associated chromosomal, DNA and/or additional structural defects, the finding of EB+BD is associated with 50% incidence of GI anomalies at birth. Advanced maternal age, ascites and polyhydramnios are also associated with higher incidence of GI pathology at birth.

Hyperechogenic Bowel: Etiologies, Management, and Outcome according to Gestational Age at Diagnosis in 279 Consecutive Cases in a Single Center.

Introduction The aim of the study was to investigate perinatal outcome of fetuses with hyperechogenic bowel (HB) in relation to gestational age at diagnosis. Materials and Methods This is a retrospective observational study of fetal HB cases from 2002 to 2012. Patients were divided into three groups according to trimester at diagnosis. For each group, data from fetal ultrasound examination, fetal medicine investigations, intrapartum cares, and neonatal outcome were obtained. Results A diagnosis of HB was made in 279 fetuses among them 17 (6%) during the first trimester, 186 (67%) during the second trimester, and 75 (27%) during the third trimester. A significant prevalence of maternal comorbidities was noticed in group 1 (12%: p = 0.02). A chromosomal defect was identified in 13% of the fetuses without difference among the three groups. HB was associated with prenatal infection in 11.5% (n = 32) of the cases, with an equal distribution between groups 2 and 3. Intrauterine growth retardation was noticed in 23% (n = 64) of the cases with a slightly high prevalence in groups 1 (35%). HB was the only ultrasonographic intestinal soft marker in 80% (n = 223) of the fetuses, two-third of them were detected during the first and the second trimesters (p = 0.001). However, HB was associated with bowel dilation in 33% of the cases diagnosed during the third trimester (p = 001). Ultrasonographic extraintestinal anomalies were identified in 30% of the fetuses with a higher prevalence in group 1 (59%). HB resolved spontaneously in 55 (19.7%) cases-without difference among the three groups. In group 1 we recorded a significant prevalence of intrauterine demise (23.5%, p = 0.004). Two hundred twenty-seven (81.3%) pregnancies resulted in live-born neonates; among them gastrointestinal anomalies were noticed in 12.5% with a significant prevalence in group 3 (36%) compared with 6 and 5.4% in groups 1 and 2, respectively (p = 0.001). Extraintestinal anomalies were confirmed in 27% of the cases, whereas postnatal mortality rate was of 7% without differences between the three groups. Conclusion Detection of HB during the first trimester is associated with an increased risk for maternal comorbidities, intrauterine growth retardation, and adverse pregnancy outcome. Moreover, if HB is detected during the second trimester, it is associated with a favorable prognosis. Otherwise, HB detected during the third trimester is associated with a significant risk of gastrointestinal anomaly.

[Detailed in utero ultrasound description of 34 cases of congenital cytomegalovirus infection]. / Étude descriptive de signes échographiques anténataux de 34 cas d'infections congénitales à cytomégalovirus.

OBJECTIVES: To describe precisely prenatal ultrasound features in congenital cytomegalovirus (CMV) infection. MATERIAL AND METHODS: We retrospectively evaluated the ultrasound descriptions of cases of congenital CMV infection between 2004 and 2013. RESULTS: In 74 congenital CMV infections, related ultrasound abnormalities were reported in 34 cases (45.9%). Abnormalities reported were either cerebral (11 cases), either extracerebral (6 cases), or associated (17 cases). A total of 22/34 cases presented extracerebral features of 11 different sorts of abnormalities, mainly intra-uterine growth retardation (11 cases) and hyperechogenic bowel (10 cases) and 26/34 cases presented cerebral features of 14 different sorts, mainly brain calcifications (12 cases) and occipital horn cavity (12 cases). MRI was performed in 25 cases and have found additional abnormalities in 8 cases. These abnormalities are not specific to CMV infection. However, a frequent finding attracted our attention: the anechogenic cavity located on the extremity of the occipital horn. CONCLUSION: A potentially specific sign, inexistent in other fetal pathologies, is an anechogenic cavity located on the extremity of the occipital and/or temporal horn, a germinal region which contains numerous proliferating and differentiating germinal cells. A better understanding of these signs could increase the sensitivity of ultrasound, and clarify the pathophysiology of congenital CMV infection.

Meconium ileus in a Lebanese family secondary to mutations in the GUCY2C gene.

Meconium ileus is most often associated with mutations in the CFTR gene; however recently, mutations in GUCY2C in the Bedouin population have also been shown to result in this phenotype. This gene codes for an intestinal transmembrane receptor that generates cyclic GMP, which activates cystic fibrosis transmembrane receptor. We report a third family that supports the association of variants in the GUCY2C gene with meconium ileus (MI). A Lebanese kindred was studied and individuals affected with MI had either homozygous or compound heterozygous variants in GUCY2C. The earliest manifestation of the affected individuals was the presence of second trimester fetal echogenic bowel, thus resulting in the expansion of the differential diagnosis of this ultrasound finding.

Fetal echogenic bowel in association with Zellweger syndrome.

Increased echogenicity of fetal bowel in the second trimester obstetrical ultrasound has been described in association with several pathologic conditions, such as growth restriction, aneuploidy, cystic fibrosis, congenital infections, and gastrointestinal malformations. Zellweger syndrome (ZS) is the prototype of peroxisomal disorders characterized by craniofacial dysmorphism and severe neurologic abnormalities. We report two cases with fetal echogenic bowel (FEB) but no associated anomalies and normal fetal growth. After birth, clinical and laboratory findings led to diagnosis of ZS. Association of FEB with neurometabolic disorders is limited to a few case reports in the medical literature. To the best of our knowledge, this is the first report of ZS associated with FEB.

Fetal hyperechogenic bowel may indicate congenital cytomegalovirus disease responsive to immunoglobulin therapy.

OBJECTIVE: To determine whether fetal hyperechogenic bowel is associated with a poor outcome with or without immunoglobulin therapy. METHODS: Sixteen pregnant women whose 17 fetuses had hyperechogenic bowel were followed by a protocol of offering additional serologic testing, amniocentesis, hyperimmunoglobulin (HIG), serial ultrasounds, and evaluation of their children. RESULTS: Of 17 fetuses with hyperechogenic bowel, 13 showed hyperechogenic bowel as a single or first ultrasound sign compared to four who showed it concomitantly or after other ultrasound abnormalities appeared (P = 0.02). Of the 17 fetuses with hyperechogenic bowel, nine were treated with HIG. Eight of the nine were normal at birth and during a follow-up of 3-8 years. One treated fetus is deaf at 4 years of age. A significantly different result (P < 0.0004) occurred among seven untreated fetuses who were each severely affected at 2-7 years of age, and the remaining one died soon after preterm birth. Among seven of nine fetuses (77.8%) of treated mothers the fetal hyperechogenic bowel resolved after HIG administration. There were no significant differences between treated and untreated fetuses for gestational age at maternal infection, gestational age at birth, and birth weight. CONCLUSION: Hyperechogenic bowel may be a marker of congenital cytomegalovirus (CMV) disease, which may be prevented by HIG.