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.

Chronic intervillositis of unknown etiology (CIUE): relation between placental lesions and perinatal outcome.

OBJECTIVES: To evaluate perinatal outcome of pregnancies complicated by chronic intervillositis of unknown etiology (CIUE) and to study the relation between extent of such placental histological lesions and clinical expression. STUDY DESIGN: Descriptive and retrospective study including all cases of CIUE diagnosed between 2000 and 2006 in the university hospital of Toulouse (France). Perinatal outcome was evaluated according to the extent of placental lesions assessed by semi-quantitative graduation. RESULTS: Twenty pregnancies complicated by CIUE were included (14 patients). Three pregnancies were prematurely interrupted spontaneously during the first trimester. Perinatal outcome of the remaining 17 pregnancies beyond 22 WG was: 4 intrauterine fetal deaths, 3 terminations of pregnancy for early and severe intrauterine growth restriction (IUGR), and 10 live births (58.8%). All fetal deaths, 82.3% of pregnancies beyond 22 WG and 70% of live births were growth restricted. Severe intervillositis with massive fibrinoid deposition was associated with a severe perinatal prognosis whereas focal forms had a best evolution. The rate of recurrence was 100% in the reported cases. CONCLUSION: CIUE have a poor perinatal outcome and a high rate of recurrence. There is a relation between clinical expression and histological lesions.

Fetal ovarian cysts management and ovarian prognosis: a report of 82 cases.

BACKGROUND/PURPOSE: Fetal ovarian cysts are frequently complicated by intracystic hemorrhage without associated clinical signs, which is often secondary to ovarian torsion leading to loss of the ovary. The aim of this study was to evaluate ovarian outcome and the place of prenatal management and surgery in the first few days of life in order to save the ovary. METHODS: Between January 1987 and June 2006, 82 fetal ovarian cysts in 79 patients were managed and clinically and ultrasonographically followed up for several months (median, 11 months; range, 6 months to 10 years) in all of the cases where the ovary was not removed. The ultrasonographic results regarding the ovarian parenchyma were broken down into 3 categories: follicular ovary, homogeneous ovary, and undetected ovary. RESULTS: Twenty-seven cysts remained simple throughout their evolution, and 55 were complicated by intracystic hemorrhage usually several weeks before birth. Overall, after disappearance of the cyst, a follicular ovary was detected in only 39% of the cases (32/82) and more often when the cyst was simple than when it presented an intracystic hemorrhage (85% vs 16.4%, chi(2), P < .0001). CONCLUSIONS: A review of our series confirms the poor ovarian outcome linked to ultrasonographic signs of intracystic hemorrhage. Preventive action by puncture of "simple" cysts is still being studied. The presence of a bilateral cyst can, if pulmonary maturity has been reached, be an argument for inducement of premature birth with a view to performing conservative surgery. After birth, surgery in the first few days of life is only justified if the signs of intracystic hemorrhage appeared in the period very close to birth.

Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys.

Prenatal discovery of fetal bilateral hyperechogenic kidneys is very stressful for pregnant women and their family, and accurate diagnosis of the cause of the moderate forms of this pathology is very difficult. Hepatocyte nuclear factor-1beta that is encoded by the TCF2 gene is involved in the embryonic development of the kidneys. Sixty-two pregnancies with fetal bilateral hyperechogenic kidneys including 25 fetuses with inaccurate diagnosis were studied. TCF2 gene anomalies were detected in 18 (29%) of these 62 patients, and 15 of these 18 patients presented a complete heterozygous deletion of the TCF2 gene. Family screening revealed de novo TCF2 anomalies in more than half of the patients. TCF2 anomalies were associated with normal amniotic fluid volume and normal-sized kidneys between -2 and +2 SD in all patients except for two sisters. Antenatal cysts were detected in 11 of 18 patients, unilaterally in eight of 11. After birth, cysts appeared during the first year (17 of 18), and in patients with antenatal cysts, the number increased and developed bilaterally with decreased renal growth. In these 18 patients, the GFR decreased with longer follow-up and was lower in patients with solitary functioning dysplastic kidney. Heterozygous deletion of the TCF2 gene is an important cause of fetal hyperechogenic kidneys in this study and showed to be linked with early disease expression. The renal phenotype and the postnatal evolution were extremely variable and need a prospective long-term follow-up. Extrarenal manifestations are frequent in TCF2-linked pathologies. Therefore, prenatal counseling and follow-up should be multidisciplinary.

Prenatal diagnosis and outcome of congenital splenic cyst: report of two cases.

Congenital splenic cyst (CSC) is a rare condition, and only a few cases with prenatal diagnosis and no associated malformation have been reported. Spontaneous regression is possible in case of mild CSC (under 40 mm), but enlargement or secondary complications may lead to surgical treatment. We report, herein, two cases of isolated mild CSC with complete spontaneous postnatal regression.