Society for Maternal-Fetal Medicine Consult Series #57: Evaluation and management of isolated soft ultrasound markers for aneuploidy in the second trimester: (Replaces Consults #10, Single umbilical artery, October 2010; #16, Isolated echogenic bowel diagnosed on second-trimester ultrasound, August 2011; #17, Evaluation and management of isolated renal pelviectasis on second-trimester ultrasound, December 2011; #25, Isolated fetal choroid plexus cysts, April 2013; #27, Isolated echogenic intracardiac focus, August 2013).

Soft markers were originally introduced to prenatal ultrasonography to improve the detection of trisomy 21 over that achievable with age-based and serum screening strategies. As prenatal genetic screening strategies have greatly evolved in the last 2 decades, the relative importance of soft markers has shifted. The purpose of this document is to discuss the recommended evaluation and management of isolated soft markers in the context of current maternal serum screening and cell-free DNA screening options. In this document, "isolated" is used to describe a soft marker that has been identified in the absence of any fetal structural anomaly, growth restriction, or additional soft marker following a detailed obstetrical ultrasound examination. In this document, "serum screening methods" refers to all maternal screening strategies, including first-trimester screen, integrated screen, sequential screen, contingent screen, or quad screen. The Society for Maternal-Fetal Medicine recommends the following approach to the evaluation and management of isolated soft markers: (1) we do not recommend diagnostic testing for aneuploidy solely for the evaluation of an isolated soft marker following a negative serum or cell-free DNA screening result (GRADE 1B); (2) for pregnant people with no previous aneuploidy screening and isolated echogenic intracardiac focus, echogenic bowel, urinary tract dilation, or shortened humerus, femur, or both, we recommend counseling to estimate the probability of trisomy 21 and a discussion of options for noninvasive aneuploidy screening with cell-free DNA or quad screen if cell-free DNA is unavailable or cost-prohibitive (GRADE 1B); (3) for pregnant people with no previous aneuploidy screening and isolated thickened nuchal fold or isolated absent or hypoplastic nasal bone, we recommend counseling to estimate the probability of trisomy 21 and a discussion of options for noninvasive aneuploidy screening through cell-free DNA or quad screen if cell-free DNA is unavailable or cost-prohibitive or diagnostic testing via amniocentesis, depending on clinical circumstances and patient preference (GRADE 1B); (4) for pregnant people with no previous aneuploidy screening and isolated choroid plexus cysts, we recommend counseling to estimate the probability of trisomy 18 and a discussion of options for noninvasive aneuploidy screening with cell-free DNA or quad screen if cell-free DNA is unavailable or cost-prohibitive (GRADE 1C); (5) for pregnant people with negative serum or cell-free DNA screening results and an isolated echogenic intracardiac focus, we recommend no further evaluation as this finding is a normal variant of no clinical importance with no indication for fetal echocardiography, follow-up ultrasound imaging, or postnatal evaluation (GRADE 1B); (6) for pregnant people with negative serum or cell-free DNA screening results and isolated fetal echogenic bowel, urinary tract dilation, or shortened humerus, femur, or both, we recommend no further aneuploidy evaluation (GRADE 1B); (7) for pregnant people with negative serum screening results and isolated thickened nuchal fold or absent or hypoplastic nasal bone, we recommend counseling to estimate the probability of trisomy 21 and discussion of options for no further aneuploidy evaluation, noninvasive aneuploidy screening through cell-free DNA, or diagnostic testing via amniocentesis, depending on clinical circumstances and patient preference (GRADE 1B); (8) for pregnant people with negative cell-free DNA screening results and isolated thickened nuchal fold or absent or hypoplastic nasal bone, we recommend no further aneuploidy evaluation (GRADE 1B); (9) for pregnant people with negative serum or cell-free DNA screening results and isolated choroid plexus cysts, we recommend no further aneuploidy evaluation, as this finding is a normal variant of no clinical importance with no indication for follow-up ultrasound imaging or postnatal evaluation (GRADE 1C); (10) for fetuses with isolated echogenic bowel, we recommend an evaluation for cystic fibrosis and fetal cytomegalovirus infection and a third-trimester ultrasound examination for reassessment and evaluation of growth (GRADE 1C); (11) for fetuses with an isolated single umbilical artery, we recommend no additional evaluation for aneuploidy, regardless of whether results of previous aneuploidy screening were low risk or testing was declined. We recommend a third-trimester ultrasound examination to evaluate growth and consideration of weekly antenatal fetal surveillance beginning at 36 0/7 weeks of gestation (GRADE 1C); (12) for fetuses with isolated urinary tract dilation A1, we recommend an ultrasound examination at ≥32 weeks of gestation to determine if postnatal pediatric urology or nephrology follow-up is needed. For fetuses with urinary tract dilation A2-3, we recommend an individualized follow-up ultrasound assessment with planned postnatal follow-up (GRADE 1C); (13) for fetuses with isolated shortened humerus, femur, or both, we recommend a third-trimester ultrasound examination for reassessment and evaluation of growth (GRADE 1C).

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.

Analysis of the clinical outcomes of fetal bowel dilatation combined with other abnormal ultrasonographic features.

OBJECTIVES: To explore the significance of fetal bowel dilatation combined with other abnormal ultrasound features in the diagnosis of gastrointestinal malformation. METHODS: A retrospective study of fetuses with bowel dilatation was performed, from August 2012 to October 2015. All the cases were identified from the ultrasound database and all observations of the relationship of prenatal abnormal abdominal ultrasound features and intestinal malformation were performed through the infancy stage. RESULTS: We found 52 fetuses with prenatal suspicion of bowel dilatation. Of these, 20 cases were surgically confirmed to have intestinal malformation, 13 cases had no abnormal bowel loops after birth, 8 cases had abnormal intestinal features while no surgical intervention was performed after birth, 10 cases were lost to follow-up and 1 fetus died in utero at 34 weeks of gestation. Forty cases with full data were divided into three groups, including Group A (Small bowel dilatation combined with other features vs. Isolated small bowel dilatation), Group B (Colonic bowel dilatation combined with other features vs. Isolated colonic bowel dilatation) and Group C (Bowel dilatation combined with other features vs. Isolated bowel dilatation). The intestinal malformation occurrence rates were 73.33% vs. 31.25% in Group A, 50% vs. 25% in Group B, and 70% vs. 30% in Group C. These results suggest that malformation occurs at a lesser frequency in simple bowel dilatation versus bowel dilatation in combination with other abnormal ultrasound features (p = .026), similarly in simple small bowel dilatation versus small bowel dilatation in combination with other abnormal ultrasound features (p = .032). CONCLUSIONS: Prenatal bowel dilatation in combination with other abnormal ultrasound features, especially small bowel dilatation in combination with other abnormal ultrasound features, detected in the second and third trimesters, tended to indicate intestinal malformation, which contributes to enhance the accuracy of prenatal diagnosis of intestinal malformation.

Isolated fetal echogenic bowel in a retrospective cohort: The role of infection screening.

OBJECTIVE: Fetal echogenic bowel (FEB) is an ultrasonographic marker of fetal infection. We aimed to determine the utility of infection screening when FEB is isolated. STUDY DESIGN: Retrospective observational study of isolated FEB cases between 2006-2014. Infection screening included toxoplasmosis, rubella, syphilis, cytomegalovirus (CMV), herpes simplex virus and parvovirus B19. Fetal karyotyping, screening for cystic fibrosis (CF) and follow-up scans were also offered, according to international standards. Incidence of infection and 95% confidence interval (CI) were calculated. RESULTS: 148 patients with 154 fetuses were included. 4.7% of mothers developed acute infection: four patients developed CMV infection (2.7%, 95% CI 1.1-6.9%), in two fetuses infection was confirmed with amniocentesis and pregnancies were terminated; Parvovirus B19 infection was detected in 2 patients (1.4%, 95% CI 0.4-5.0) and confirmed in one fetus, which developed anemia; there was one toxoplasmosis maternal infection (0.7%, 95% CI 0.1-3.8%) treated with spyramicin, whose fetus was not infected. Percentage of chromosomal/genetic abnormalities was 3.2%, CF 1.3%, intra-amniotic bleeding 1.3%, FGR 34% and other ultrasonographic abnormalities at follow-up scans 18%. CONCLUSIONS: The association between isolated FEB and fetal infection is uncommon (1.9% in our population). CMV maternal infection screening is supported by our findings, whereas screening for other infections needs to be further investigated.

Incidence and Carrier Frequency of CFTR Gene Mutations in Pregnancies With Echogenic Bowel in Nova Scotia and Prince Edward Island.

OBJECTIVE: Fetal echogenic bowel (echogenic bowel) is associated with cystic fibrosis (CF), with a reported incidence ranging from 1% to 13%. Prenatal testing for CF in the setting of echogenic bowel can be done by screening parental or fetal samples for pathogenic CFTR variants. If only one pathogenic variant is identified, sequencing of the CFTR gene can be undertaken, to identify a second pathogenic variant not covered in the standard screening panel. Full gene sequencing, however, also introduces the potential to identify variants of uncertain significance (VUSs) that can create counselling challenges and cause parental anxiety. To provide accurate counselling for families in the study population, the incidence of CF associated with echogenic bowel and the carrier frequency of CFTR variants were investigated. METHODS: All pregnancies for which CF testing was undertaken for the indication of echogenic bowel (from Nova Scotia and Prince Edward Island) were identified (January 2007-July 2017). The CFTR screening and sequencing results were reviewed, and fetal outcomes related to CF were assessed. RESULTS: A total of 463 pregnancies with echogenic bowel were tested. Four were confirmed to be affected with CF, giving an incidence of 0.9% in this cohort. The carrier frequency of CF among all parents in the cohort was 5.0% (1 in 20); however, when excluding parents of affected fetuses, the carrier frequency for the population was estimated at 4.1% (1 in 25). CFTR gene sequencing identified an additional VUS in two samples. CONCLUSION: The incidence of CF in pregnancies with echogenic bowel in Nova Scotia and Prince Edward Island is 0.9%, with an estimated population carrier frequency of 4.1%. These results provide the basis for improved counselling to assess the risk of CF in the pregnancy, after parental carrier screening, using Bayesian probability. Counselling regarding VUSs should be undertaken before gene sequencing.

Microarray analysis in pregnancies with isolated echogenic bowel.

INTRODUCTION: Fetal echogenic bowel is a frequent sonographic finding, demonstrated in about 1% of pregnancies. The advised evaluation of fetal echogenic bowel includes maternal serology, genetic testing for cystic fibrosis, detailed sonographic anatomic survey, and invasive prenatal testing for fetal chromosomal aberrations. The objective of our study was to evaluate the risk for clinically significant chromosomal microarray analysis (CMA) findings in pregnancies with isolated echogenic bowel. METHODS: Data from all CMA analyses performed due to isolated echogenic bowel reported to the Israeli Ministry of Health between January 2013 and September 2016 were retrospectively obtained. Risk estimation was performed comparing the rate of abnormal microarray findings to the control population, based on a systematic review of 9272 pregnancies and a large local cohort of 5541 fetuses with normal ultrasound, undergoing CMA testing due to maternal request. RESULTS: Of 103 CMA analyses performed due to isolated echogenic bowel, two (1.94%) pathogenic findings were detected (47,XYY and 16p11.2 duplication). This risk was not significantly elevated compared to the control groups. In addition, three variants of unknown significance were demonstrated. CONCLUSIONS: To our best knowledge, our study is the first report describing the rate of clinically significant copy number variants in pregnancies with isolated echogenic bowel. According to our results, it seems that pregnancies with isolated echogenic bowel do not have an increased risk for abnormal CMA compared to fetuses with no evidence of sonographic anomalies. Our findings suggest that the consideration to perform CMA analysis in such pregnancies should not differ from any pregnancy with normal ultrasound.

Antenatal prognostic factor of fetal echogenic bowel.

OBJECTIVE: The aim of this study was to identify antenatal prognostic factors of neonatal outcomes in cases of fetal echogenic bowel (FEB). STUDY DESIGN: A retrospective study in three tertiary referral centers including fetal echogenic bowel over a 10-year period (from January 2003 to December 2013). The echogenicity of the fetal bowel was graded from 1 to 3, according to Slotnick's definition. Associated echographic findings such as bowel dilations, gallbladder abnormalities, calcifications, extra-abdominal abnormalities, intrauterine growth restriction (IUGR) and a decrease in amniotic fluid volume, if present were also recorded. This was followed by the FEB's sonographic evolution. The sonographic evolution was considered favorable if it was stable or decreasing and unfavorable if the echogenicity of the bowel increased or if additional sonographic findings appeared. Neonates had a pediatric examination in the delivery room and upon discharge from the maternity hospital. An outcome was considered good in the case of on-term delivery of a newborn with normal clinical examination and meconium elimination. RESULTS: Complete pregnancy outcome data were available for 409 pregnancies. 338 newborns had uneventful outcomes (82.6%). Antenatal exploration diagnosed 4 cases of aneuploidy (1 case of trisomy 13, 1 case of trisomy 18 and 2 cases of triploidies), 16 cases of congenital infections, 9 cases of cystic fibrosis and 11 cases of bowel abnormalities. After a multivariate analysis, we discovered the sonographic grade of the echogenic bowel was not a prognostic factor of neonatal outcome. The isolated fetal echogenic bowel had a 6.6-fold increase chance of uneventful outcomes (adjusted odd ratio (aOR) 6.6, 95% CI 3-14.4). Notably, favorable sonographic evolution (aOR 8.1, 95% CI 4.1-16) and late gestational age at the time of the diagnosis (aOR 1.17, 95% CI 1.07-1.27) are independent, good prognostic factors of good neonatal outcomes. None of the 180 fetuses with isolated fetal echogenic bowel and favorable sonographic evolution had adverse outcomes. Among these, 4 cases (0.98%) of aneuploïdy, 17 cases (4.2%) of congenital infections and 9 cases (2.2%) of cystic fibroses were also diagnosed. No cases of Down syndrome (DS) were reported. CONCLUSION: Our study shows that the grade should not be considered a prognostic factor of neonatal outcomes. Our data suggests the need to reevaluate the concept of systematic amniocentesis. Sonographic evolution of fetal bowel is an independent, strong prognostic factor for good neonatal outcomes. It also better defines the FEB prognostic.

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.

Predicting Perinatal Outcome from Prenatal Ultrasound Characteristics in Pregnancies Complicated by Gastroschisis.

INTRODUCTION: The objective of the study was to establish the predictive value of prenatal ultrasound markers for complex gastroschisis (GS) in the first 10 days of life. MATERIAL AND METHODS: In this retrospective cohort study over 11 years (2000-2011) of 117 GS cases, the following prenatal ultrasound signs were analyzed at the last second- and third-trimester ultrasounds: intrauterine growth restriction, intra-abdominal bowel dilatation (IABD) adjusted for gestational age, extra-abdominal bowel dilatation (EABD) ≥25 mm, stomach dilatation, stomach herniation, perturbed mesenteric circulation, absence of bowel lumen and echogenic dilated bowel loops (EDBL). RESULTS: Among 114 live births, 16 newborns had complex GS (14.0%). Death was seen in 16 cases (13.7%): 3 intrauterine fetal deaths, 9 complex GS and 4 simple GS. Second-trimester markers had limited predictive value. Third-trimester IABD, EABD, EDBL, absence of intestinal lumen and perturbed mesenteric circulation were statistically associated with complex GS and death. IABD was able to predict complex GS with a sensitivity of 50%, a specificity of 91%, a positive predictive value of 47% and a negative predictive value of 92%. DISCUSSION: Third-trimester IABD adjusted for gestational age appears to be the prenatal ultrasound marker most strongly associated with adverse outcome in GS.

[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.

Controversial ultrasound findings in mid trimester pregnancy. Evidence based approach.

Mid trimester fetal anatomy scan is a fundamental part of routine antenatal care. Some U/S soft markers or controversial U/S signs are seen during the scan and create some confusion regarding their relation to fetal chromosomal abnormalities. Example of these signs: echogenic focus in the heart, echogenic bowel, renal pyelectasis, ventriculomegaly, polydactely, club foot, choroid plexus cyst, single umbilical artery. We are presenting an evidence based approach from the literature for management of these controversial U/S signs.

Retrospective analysis of prenatal ultrasound of children with Hirschsprung disease.

OBJECTIVE: Hirschsprung disease (HD) is a rare gastrointestinal disorder. Our aim was to study the prenatal ultrasound findings of children who were diagnosed with HD after birth. METHODS: The study population included children who suffered from HD between 1990 and 2008. Data of anomaly scan findings in prenatal ultrasound, demographic and post-natal physical abnormalities and treatment were retrieved from medical files and interviews with the parents. RESULTS: Twenty-two patients confirmed histopathological diagnosis of HD at age of 1 day to 15 months. Nineteen fetuses had anomaly scan during pregnancy, which revealed minor sonographic abnormalities in three fetuses; two of them had hyperechogenic bowel. One fetus with hyperechogenic bowel had polyhydramnion, and another had a family history of three brothers with HD. A third fetus had dilated pelvic kidney. None of them had sonographic evidence of bowel dilatation. After birth, six patients (31%) were found to have other structural anomalies: ventriculoseptal defect, atriseptal defect, atrio-ventricular septal defect, and pyloric stenosis. CONCLUSIONS: Abnormal sonographic findings of fetal bowel are absent in the vast majority of fetuses who are diagnosed with HD after birth. In women with a family history of HD, a third trimester anomaly scan may be warranted.

[Hyperechogenic fetal bowel: Which fetal and neonatal outcome? A French study of 149 cases]. / Hyperéchogénicité intestinale fœtale : quel bilan proposer et quel pronostic ? À propos d'une série continue de 149 patientes.

OBJECTIVES: In case of hyperechogenic fetal bowel (HFB), invasive procedures such as amniocentesis are often proposed to detect an underlying cause. Our goal is to study etiologies and prognosis of HFB according to antenatal sonographic findings in order to evaluate the relevance of antenatal assessment. MATERIALS AND METHODS: It is a retrospective monocentric study lead from 2008 to 2012, including all patients with a suspicion of HFB on routine sonography. We analysed the antenatal and neonatal results, distinguishing four situations: isolated HFB, HFB+other digestive anomalies, HFB+vascular pathology, HFB+other associated anomalies. RESULTS: For 149 patients, HBF was confirmed. Sixty-nine were isolated HFB, 24 associated with other digestive anomalies, 16 with vascular pathology and 40 with other anomalies. Pregnancy outcomes were different with 92.8, 41.7, 0 and 45.0% of healthy newborns. In the case of isolated HBF, we noted 2.9% cystic fibrosis and 2.9% congenital infection. CONCLUSION: Isolated HBF seems to have a better prognosis than associated forms. However, prenatal investigations to eliminate cystic fibrosis or congenital infection should be offered and may be initially non-invasive, if a larger series confirmed the absence of dyschromosomy in this population.

The Welsh study of mothers and babies: protocol for a population-based cohort study to investigate the clinical significance of defined ultrasound findings of uncertain significance.

BACKGROUND: Improvement in ultrasound imaging has led to the identification of subtle non-structural markers during the 18 - 20 week fetal anomaly scan, such as echogenic bowel, mild cerebral ventriculomegaly, renal pelvicalyceal dilatation, and nuchal thickening. These markers are estimated to occur in between 0.6% and 4.3% of pregnancies. Their clinical significance, for pregnancy outcomes or childhood morbidity, is largely unknown. The aim of this study is to estimate the prevalence of seven markers in the general obstetric population and establish a cohort of children for longer terms follow-up to assess the clinical significance of these markers. METHODS/DESIGN: All women receiving antenatal care within six of seven Welsh Health Boards who had an 18 to 20 week ultrasound scan in Welsh NHS Trusts between July 2008 and March 2011 were eligible for inclusion. Data were collected on seven markers (echogenic bowel, cerebral ventriculomegaly, renal pelvicalyceal dilatation, nuchal thickening, cardiac echogenic foci, choroid plexus cysts, and short femur) at the time of 18 - 20 week fetal anomaly scan. Ultrasound records were linked to routinely collected data on pregnancy outcomes (work completed during 2012 and 2013). Images were stored and reviewed by an expert panel.The prevalence of each marker (reported and validated) will be estimated. A projected sample size of 23,000 will allow the prevalence of each marker to be estimated with the following precision: a marker with 0.50% prevalence to within 0.10%; a marker with 1.00% prevalence to within 0.13%; and a marker with 4.50% prevalence to within 0.27%. The relative risk of major congenital abnormalities, stillbirths, pre-term birth and small for gestational age, given the presence of a validated marker, will be reported. DISCUSSION: This is a large, prospective study designed to estimate the prevalence of markers in a population-based cohort of pregnant women and to investigate associations with adverse pregnancy outcomes. The study will also establish a cohort of children that can be followed-up to explore associations between specific markers and longer-term health and social outcomes.

[Neonatal outcome of fetal hyperechogenic bowel]. / Devenir néonatal des fœtus présentant un intestin hyperéchogène.

OBJECTIVE: Echogenic bowel (EB) represents 1 % of pregnancy and is a risk factor of fetal pathology (infection, cystic fibrosis, aneuploidy). The aim of our study was to determine the fetuses' outcomes with isolated EB. PATIENTS AND METHODS: This is a retrospective study of all patients who presented singleton gestations with a fetal isolated echogenic bowel between 2004 and 2011 in two prenatal diagnosis centers. Search of aneuploidy, infection and cystic fibrosis was systematically proposed as well as an ultrasound monitoring. RESULTS: On 109 fetus addressed for isolate echogenic bowel five had other signs associated and 74 had a real isolated echogenic bowel (without dilatation, calcification, intrauterine growth restriction). In 30 cases, the EB was not found. Eighty-five percent of the patients had in the first trimester a screening for trisomy 21. None fetus with isolated EB had trisomy, infection or cystic fibrosis. One fetus died in utero and one newborn died of a metabolic disease without digestive repercussions. DISCUSSION AND CONCLUSION: The risk of trisomy 21 and the risk to have a serious disease appear low for the fetus with EB. It does not seem necessary to propose a systematic amniocentesis in case of isolated echogenic bowel.

Outcome of infants presenting with echogenic bowel in the second trimester of pregnancy.

OBJECTIVE: Fetal echogenic bowel (FEB) is a soft marker found on second trimester sonography. Our main aim was to determine the outcome of infants who presented with FEB and secondarily to identify additional sonographic findings that might have clinical relevance for the prognosis. DESIGN: We reviewed all pregnancies in which the diagnosis FEB was made in our Fetal Medicine Unit during 2009-2010 (N=121). We divided all cases into five groups according to additional sonographic findings. Group 1 consisted of cases of isolated FEB, group 2 of FEB associated with dilated bowels, group 3 of FEB with one or two other soft markers, group 4 of FEB with major congenital anomalies or three or more other soft markers, and group 5 consisted of FEB with isolated intrauterine growth restriction (IUGR). RESULTS: Of 121 cases, five were lost to follow-up. Of the remaining 116 cases, 48 (41.4%) were assigned to group 1, 15 (12.9%) to group 2, 15 (12.9%) to group 3, 27 (23.2%) to group 4, and 11 (9.5%) to group 5. The outcome for group 1 was uneventful. In group 2 and 3, two anomalies, anorectal malformation and cystic fibrosis, were detected postnatally (6.7%). In group 4, mortality and morbidity were high (78% resp. 22%). Group 5 also had high mortality (82%) and major morbidity (18%). CONCLUSIONS: If FEB occurs in isolation, it is a benign condition carrying a favourable prognosis. If multiple additional anomalies or early IUGR are observed, the prognosis tends to be less favourable to extremely poor.

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.

Perinatal outcomes following the ultrasound diagnosis of echogenic bowel: an Australian perspective.

INTRODUCTION: The aim of this study was to describe the association between fetal echogenic bowel (FEB) diagnosed during the second trimester and adverse perinatal outcomes in an Australian antenatal population. METHODS: A retrospective analysis of ultrasound scans was performed between March 1, 2004 and March 1, 2009 at The Royal Women's Hospital, Melbourne, Vic., Australia. Cases reported as having FEB on second trimester ultrasound were included. Medical records of each case were reviewed and information concerning additional investigations and perinatal outcomes were extracted. RESULTS: A total of 66 cases were identified in our database. Three patients (5%) were excluded from further analysis as they were lost to follow-up, leaving 63 (95%) cases in this series. Thirty-two fetuses (52%) underwent karyotyping via amniocentesis, 5 (16%) of which were found to have chromosomal defects. Maternal serology for cytomegalovirus (CMV) was performed in 49 (78%) cases. Investigations indicated a total of 5 women who had CMV infection during their pregnancy. Thirty-three pregnancies (53%) were tested for cystic fibrosis (CF) and 1 baby was confirmed to have CF postnatally. Among the 50 liveborn infants, 3 cases of fetal growth restriction were apparent. Overall, 42 of the 50 liveborn infants (84%) and 67% of the entire cohort of 63 patients with a midtrimester diagnosis of FEB had a normal short-term neonatal outcome. CONCLUSION: This study reiterates the increased prevalence of aneuploidy, CMV, CF and fetal growth restriction in pregnancies complicated by the midtrimester sonographic finding of FEB. However, reassuringly, 67% of cases with ultrasound-detected echogenic bowel in the second trimester had a normal short-term neonatal outcome in this multiethnic Australian population.