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.

A serologic strategy for detecting neonates at risk for congenital cytomegalovirus infection.

OBJECTIVES: To evaluate the feasibility of a serologic screening program in pregnant women to detect neonates at risk for a congenital cytomegalovirus infection. STUDY DESIGN: Unselected mother-infant pairs (n = 7140) were studied. In the mother, serologic screening consisted of the testing for cytomegalovirus antibodies at the first prenatal visit and at birth. In the neonate, cytomegalovirus urine culture was performed to diagnose congenital infection. RESULTS: Serologic screening showed evidence of past infection in 3850 women (53.9%); 192 (2.7%) women had both immunoglobulin (Ig)G and IgM antibodies when first tested during pregnancy. Seroconversion was detected in 44 seronegative women (1.4%). Forty-four congenital infections were diagnosed (0.62%): 8 in women with past infections, 22 in women who seroconverted, and 14 in women who initially had positive IgM antibodies. CONCLUSIONS: Screening at the first prenatal visit and at birth defines two major risk groups for congenital cytomegalovirus infection: women with seroconversion during pregnancy and women with IgM antibodies in their first prenatal serum sample (0.6% and 2.7%, respectively, of the pregnant population). In these selected babies (3.3% of the study group), cytomegalovirus urine culture should be performed. This type of screening allows the detection of 82% of all congenital cytomegalovirus infections.