The role of renal biomarkers to predict the need of surgery in congenital urinary tract obstruction in infants.

INTRODUCTION: The diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. The use of new renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and the prevention or minimization of definitive renal damage. OBJECTIVE: The aim of the study was to investigate a selection of promising biomarkers of renal injury with the intention of evaluating and comparing their profile with clinically based decisions for surgical intervention of infants with congenital obstructive uropathies. STUDY DESIGN: The first-year profile of renal biomarkers, serum creatinine (sCr), serum and urine cystatin C (CyC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-ß1), retinol-binding protein (RBP), and microalbuminuria (µALB), was analyzed in a cohort of 37 infants with congenital UTO, divided into three subgroups, 14 cases with grade III unilateral hydro(uretero)nephrosis, 13 cases with grade III bilateral hydro(uretero)nephrosis, and 10 cases with low urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. Serum and urine samples were stored at -70 °C and thereafter analyzed by quantitative enzymatic immunoassay. RESULTS: Compared with the control group (Figure), all renal biomarker values were significantly increased in patients (P ≤ 0.02). In the unilateral hydronephrosis and LUTO group, RBP (P ≤ 0.043), NGAL (P ≤ 0.043), KIM-1 (P ≤ 0.03), and TGF-ß1 (P ≤ 0.034) values dropped significantly after surgery. Neutrophil gelatinase-associated lipocalin alone and in combination with urine and serum CyC demonstrated the best performance in determining the need for surgery (area under the curve, 0.801 and 0.881, respectively). Biomarker profile analysis was suggestive of surgical intervention in 55.4% (7/13) of non-operated cases, and most of the biomarker values were above the cutoff levels within at least 3 months before the clinically based surgical decision in 58% (14/24) of all operated patients. DISCUSSION: To the best of the authors' knowledge, this is the first study to present the clinical use of selected group of serum and urinary biomarkers in the setting of UTO to distinguish between patients who would benefit from surgery intervention. The most promising results were obtained using NGAL, RBP, TGF-ß1, and KIM-1, especially in the unilateral hydro(uretero)nephrosis and LUTO subgroups when compared with the control group. CONCLUSIONS: Urine biomarkers, alone and in combination, demonstrated high potential as a non-invasive diagnostic tool for identifying infants who may benefit from earlier surgical intervention.

Sonographic markers of exencephaly below 10 weeks' gestation.

We report two cases of exencephaly diagnosed by transvaginal ultrasonography at 8 weeks 4 days and at 9 weeks 3 days of gestation. Both cases presented an irregular cephalic pole, and, in the case seen at 8 weeks 4 days, brain vesicles were also absent, whereas in the case seen at 9 weeks 3 days, the midline echo was indistinguishable with disorganized choroid plexuses. In both cases, anencephaly was evident at 11 and 12 weeks' gestation and the postmortem confirmed the diagnosis.

Fetal nasal bone length: reference range and clinical application in ultrasound screening for trisomy 21.

OBJECTIVES: Fetuses with trisomy 21 typically present with subtle facial abnormalities, including a hypoplastic nasal bone. The aim of this study was to provide a reference range for the length of the fetal nasal bone and to test its value in second-trimester ultrasound screening for trisomy 21. DESIGN: A reference range of fetal nasal bone length was established from cross-sectional data on 1923 consecutive singleton pregnancies scanned at 16-24 weeks' gestation in women older than 35 years. Screening for trisomy 21 was prospectively studied using the measurement of fetal nasal bone lengths smaller than the 5(th) percentile as a cut-off value. RESULTS: Follow-up was possible in 1631 cases (84.8%). Trisomy 21 was found in 22 cases (1.35%). Nasal bone length measurement increased as a function of gestational age (P < 0.05) showing a linear relationship. Screening for trisomy 21 using the 5(th) percentile as a cut-off value resulted in a sensitivity of 59.1% for a 5.1% false-positive rate. The likelihood ratio was 11.6. CONCLUSION: Screening for trisomy 21 using fetal nasal bone length measurements showed a sensitivity comparable to that of maternal biochemistry for a given false-positive rate of 5%. Association of nasal bone lengths with other sonographic markers, taking into account the background risk for maternal and gestational age, may further improve sensitivity and reduce false positives, allowing avoidance of unnecessary invasive diagnostic procedures.

Prenatal diagnosis and follow up of congenital splenic cyst: a case report.

We report a case of congenital splenic cyst that was identified by prenatal sonography at 25 gestational weeks. Serial scans demonstrated an increase in size during the prenatal period but after birth the cyst progressively decreased in size until its complete regression at 6 months of age.

Prenatal sonographic diagnosis of adrenal neuroblastoma.

Neuroblastoma is the most frequent extracranial solid tumor in childhood, but it is seldom diagnosed prenatally. We report a case of adrenal neuroblastoma identified at 39 weeks' menstrual age and successfully treated by postnatal surgery and chemotherapy. Sonography revealed a hyperechoic mass in the right upper quadrant of the fetal abdomen associated with hydramnios and hydronephrosis. Two days after delivery, the tumor was resected. No metastasis was identified. The infant received 6 cycles of chemotherapy, and at 2 years of age she was well, with no signs of recurrence.

Prognostic factors associated with congenital cystic adenomatoid malformation of the lung.

This study presents 18 cases of prenatally diagnosed congenital cystic adenomatoid malformation (CCAM) to identify potential factors that could predict prognosis. Comparisons of prenatal parameters were made between fetuses that survived and those that died perinatally. It was found that microcystic lesion, bilateral lung involvement and hydrops were each highly correlated with poor prognosis, while neither polyhydramnios nor mediastinal shift was significantly associated with had outcome. Fetal interventions were indicated only in two of the surviving cases: a thoracocentesis and a cysto-amniotic shunt. A therapeutic amniocentesis was performed in one case of polyhydramnios. The diagnosis of CCAM was histologically confirmed in all cases by necropsy or by postnatal lobectomy.

Fetal renal biopsies in obstructive uropathy: feasibility and clinical correlations--preliminary results.

Final assessment on the outcome of fetal obstructive uropathy is a challenging matter. Ultrasonography, fetal urine electrolytes, and beta 2 microglobulin are postulated as being useful in many cases. For cases in which renal function remains unclear, ultrasound-guided fetal kidney biopsy may be used in order to detect histologic features distinctive of renal dysplasia. We present preliminary results aimed at studying the feasibility and possible risks. Biopsies were initially performed in 11 severely malformed fetuses, three of them with associated renal abnormalities. The success rate in obtaining renal material was 63.6 per cent with no maternal complications. In the next phase of this study, ten biopsies and urine collections were performed in fetuses with bilateral obstructive uropathy. The success rate was 50 per cent with no complications. Normal fetal renal histology was seen in 80 per cent of cases. In one case, although electrolytes were normal, a histologic diagnosis of renal dysplasia was made, showing a good correlation with outcome. In conclusion, fetal kidney biopsies for obstructive uropathy are feasible and further studies are needed to show their clinical relevance and risks.

Maternal-fetal folate status and neural tube defects: a case control study.

The object of this study was to explore the role of folate in the pathophysiology of neural tube defects (NTD). Maternal and fetal serum and red blood cell folate were assayed in 14 cases of NTDs and compared with 14 controls with other malformations and matched for gestational age (range 18-36 weeks). In mothers of NTD fetuses, serum folate (5.2 ng/ml), red blood cell folate (294 ng/ml) and the folate methylation rate (65%) were significantly lower than in controls (6.6 and 399 ng/ml, respectively, and 77%). However, the fetal folate status was similar in cases and controls. In the NTD group, folate metabolism was altered in the mothers but not in the fetuses. Therefore, a normal folate placental transfer can be assumed in this group. In addition, it could be speculated that decreased maternal folate methylation might be involved in the pathogenesis of NTDs.

Meckel-Gruber syndrome: prenatal diagnosis at 10 menstrual weeks using embryoscopy.

A case of Meckel-Gruber syndrome was diagnosed by embryoscopy at 10 menstrual weeks, allowing for early termination of pregnancy. Post-mortem examination confirmed the presence of polydactyly and bilateral cystic lesions of the mesonephros and metanephros. Both the forming nephrons and the collecting ducts were involved in the formation of renal cysts.

Serum hCG assay: a method for detection of contamination of fetal blood samples.

Serum human chorionic gonadotrophin (hCG) can be assayed in specimens obtained by percutaneous fetal blood sampling to check for the absence of maternal blood or amniotic fluid contamination. In order to assess the accuracy of this approach, we measured serum hCG in 44 pure fetal blood samples obtained by intracardiac puncture. The mean fetal serum hCG concentration was 52 IU/l, and the ratio of maternal to fetal serum hCG concentration never exceeded 1.1 per cent, which represents the smallest contamination rate detectable by this method.