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

Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease.

Although a rare disease, bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage kidney disease in children. Ultrasound-based prenatal prediction of postnatal kidney survival in CAKUT pregnancies is far from accurate. To improve prediction, we conducted a prospective multicenter peptidome analysis of amniotic fluid spanning 140 evaluable fetuses with CAKUT. We identified a signature of 98 endogenous amniotic fluid peptides, mainly composed of fragments from extracellular matrix proteins and from the actin binding protein thymosin-ß4. The peptide signature predicted postnatal kidney outcome with an area under the curve of 0.96 in the holdout validation set of patients with CAKUT with definite endpoint data. Additionally, this peptide signature was validated in a geographically independent sub-cohort of 12 patients (area under the curve 1.00) and displayed high specificity in non-CAKUT pregnancies (82 and 94% in 22 healthy fetuses and in 47 fetuses with congenital cytomegalovirus infection respectively). Change in amniotic fluid thymosin-ß4 abundance was confirmed with ELISA. Knockout of thymosin-ß4 in zebrafish altered proximal and distal tubule pronephros growth suggesting a possible role of thymosin ß4 in fetal kidney development. Thus, recognition of the 98-peptide signature in amniotic fluid during diagnostic workup of prenatally detected fetuses with CAKUT can provide a long-sought evidence base for accurate management of the CAKUT disorder that is currently unavailable.

Ultrasound features of fetal toxoplasmosis: A contemporary multicenter survey in 88 fetuses.

OBJECTIVE: To describe the lesions detected by prenatal ultrasound examination in congenital toxoplasmosis (CT). METHODS: We retrospectively analyzed all cases of fetal infection with Toxoplasma gondii with ultrasound anomalies described by fetal medicine experts in 2009 to 2019 in 30 French centers. RESULTS: Eighty-eight cases of CT were included. Forty-five (51.1%) had one or more cerebral signs only, 35 (39.8%) had cerebral plus extracerebral signs and 8 (9.1%) had extracerebral signs only. The main cerebral signs were intracranial hyperechogenic nodular foci (n = 60) of which 20 were isolated, ventriculomegalies (n = 44) which generally increased during follow-up, and periventricular abscesses (n = 12). The main extracerebral signs were hepatomegaly and/or splenomegaly (n = 14), small for gestational age (n = 14), ascites (n = 14, including 2 with hydrops), and hyperechogenic bowel (n = 11). Maternal infection occurred mostly in the first or second trimester (81 cases), periconceptionally in one and in the third trimester in six cases. The first ultrasound signs were detected after a median of 7 weeks (range: 1.4; 24.0) following maternal toxoplasmosis seroconversion. CONCLUSION: While no sign was specific of CT, there were typical associations of cerebral signs with or without extracerebral signs. Detailed ultrasound examination could improve prognostic evaluation, as well as diagnosis of CT in settings lacking serological screening.

Is laterality of congenital diaphragmatic hernia a reliable prognostic factor? French national cohort study.

OBJECTIVES: The objective of this study was to assess whether the laterality of congenital diaphragmatic hernia (CDH) was a prognostic factor for neonatal survival. METHODS: This was a cohort study using the French national database of the Reference Center for Diaphragmatic Hernias. The principal endpoint was survival after hospitalization in intensive care. We made a comparative study between right CDH and left CDH by univariate and multivariate analysis. Terminations and stillbirths were excluded from analyses of neonatal outcomes. RESULTS: A total of 506 CDH were included with 67 (13%) right CDH and 439 left CDH (87%). Rate of survival was 49% for right CDH and 74% for left CDH (P < .01). Multivariate analysis showed two factors significantly associated with mortality: thoracic herniation of liver (OR 2.27; IC 95% [1.07-4.76]; P = .03) and lung-to-head-ratio over under expected (OR 2.99; IC 95% [1.41-6.36]; P < .01). Side of CDH was not significantly associated with mortality (OR 1.87; IC 95% [0.61-5.51], P = .26). CONCLUSION: Rate of right CDH mortality is more important than left CDH. Nevertheless after adjusting for lung-to-head-ratio and thoracic herniation of liver, right CDH does not have a higher risk of mortality than left CDH.

Prenatal hyperechogenic kidneys in three cases of infantile hypercalcemia associated with SLC34A1 mutations.

BACKGROUND: Prenatal diagnosis of hyperechogenic kidneys is associated with a wide range of etiologies and prognoses. The recent advances in fetal ultrasound associated with the development of next-generation sequencing for molecular analysis have enlarged the spectrum of etiologies, making antenatal diagnosis a very challenging discipline. Of the various known causes of hyperechogenic fetal kidneys, calcium and phosphate metabolism disorders represent a rare cause. An accurate diagnosis is crucial for providing appropriate genetic counseling and medical follow-up after birth. METHODS: We report on three cases of fetal hyperechogenic kidneys corresponding to postnatal diagnosis of nephrocalcinosis. In all cases, antenatal ultrasound showed hyperechogenic kidneys of normal to large size from 22 gestational weeks, with a normal amount of amniotic fluid. Postnatal ultrasound follow-up showed nephrocalcinosis associated with hypercalcemia, hypercalciuria, elevated 1,25(OH)2-vitamin D, and suppressed parathyroid hormone levels. RESULTS: Molecular genetic analysis by next-generation sequencing performed after birth in the three newborns revealed biallelic pathogenic variants in the SLC34A1 gene, encoding the sodium/phosphate cotransporter type 2 (Npt2a), confirming the diagnosis of infantile hypercalcemia. CONCLUSIONS: Nephrocalcinosis due to infantile hypercalcemia can be a cause of fetal hyperechogenic kidneys, which suggests early antenatal anomaly of calcium and phosphate metabolism. This entity should be considered in differential diagnosis. Postnatal follow-up of infants with hyperechogenic kidneys should include evaluation of calcium and phosphate metabolism.

Endovenous Celon radiofrequency-induced thermal therapy of great saphenous vein: A retrospective study with a 3-year follow-up.

OBJECTIVE: Our main objective was to evaluate the short- and long-term efficacy of Celon radiofrequency-induced thermal therapy for endovenous treatment of incompetent great saphenous vein. The secondary objectives were to report on possible short-term side effects and complications. METHODS: This was a retrospective study of 112 consecutive patients included between 2013 and June 2015. These patients were treated (146 great saphenous vein, C2-C6) either at the hemodynamic room using local anesthesia or at the operating theater under general anesthesia with or without phlebectomy. All patients received radiofrequency-induced thermal therapy at 18 W power, 1 s/cm pullback rate and 5-7 pullbacks per segment of 10 cm (i.e. maximum 10 pullbacks). A clinical follow-up via ultrasound monitoring was done at 1 week, 1 month, 6 months, 1 year, 2 years and 3 years. RESULTS: The 3-year survival occlusion rate was 96.71% and 98% for overall and radiofrequency-induced thermal therapy patients, respectively. No major side effects were observed. A case of endovenous heat-induced thrombosis was reported. Slight neurological disorders were reported (0.88%). CONCLUSION: Our unit's endovenous Celon radiofrequency-induced thermal therapy of incompetent great saphenous vein was efficient, well tolerated, without major side effects. Moreover, in order to reduce possible neurological disorders, we advise multiple pullbacks at 1 s/cm and using tumescence anesthesia.

What prenatal ultrasound features are predictable of complex or vanishing gastroschisis? A retrospective study.

OBJECTIVE: To evaluate prenatal ultrasound parameters as prognostic factors for complex and vanishing gastroschisis. METHODS: Retrospective multicentre study of 200 gastroschisis over 13 years (2000-2013). Collection of prenatal ultrasound evaluation on maternal and fetal growth parameters, intra- and extra-abdominal bowel and stomach dilation, abdominal wall defect diameter and changes in bowel appearance. Correlation of these factors with the presence of mechanical intestinal complications at birth, named 'complex gastroschisis'. RESULTS: Fifty-two patients (26%) had complex gastroschisis (CG), including ten vanishing gastroschisis. The presence of intra-abdominal bowel dilation at the second (T2) or third (T3) trimester ultrasound was predictive for CG, with odds ratios at 6.69 (95%CI 2.41-18.55) and 4.72 (95%CI 2.16-10.28), respectively, with a cut-off value at the last examination of >19 mm. A small abdominal wall defect diameter was also predictive for CG, with cut-off values of <9.2 mm at T2 and <12.5 mm at T3. Vanishing gastroschisis recorded earlier intra-abdominal bowel dilation diagnosis, associated with a small wall defect and no extra-abdominal dilation. CONCLUSION: Intra-abdominal bowel dilation and a small abdominal wall defect diameter accurately predict CG and could be a first sign of vanishing gastroschisis when they occur early. © 2016 John Wiley & Sons, Ltd.

Nonvisualization of fetal gallbladder increases the risk of cystic fibrosis.

OBJECTIVE: The aim of our study is to evaluate the prevalence of cystic fibrosis (CF) in fetuses referred for genetic testing because of ultrasonographic sign (nonvisualized fetal gallbladder--NVFGB). METHOD: We reviewed the results of CFTR gene analysis over the period 2002 to 2009 in all consecutive cases referred because of NVFGB in Western France. We correlated these data with the presence of a more classical ultrasonographic finding (fetal echogenic bowel - FEB). RESULTS: Cystic fibrosis was diagnosed in 5 of the 37 fetuses with NVFGB (13.5%, 95% confidence interval (CI): [2.5%; 24.5%]) and in only 9 of the 229 other cases referred because of FEB (3.9%, 95% CI: [3.2%; 14.7%]). In our series, all CF-affected fetuses with NVFGB also had FEB. The risk of CF was 11.6-fold higher in fetuses with both indications (NVFGB + FEB) than in fetuses with isolated FEB (45.5% vs 3.9%, RR = 11.6, 95% CI: [4.7%; 28.8%], p = 0.0001). We also estimated that the residual risk of CF was less than 1 in 68 (1.5%) when a single mutation was identified in the fetus by our molecular protocol. CONCLUSION: Ultrasonographic evidence of NVFGB is an additional risk factor for CF in cases with FEB.