Hourly fetal urine production rate in isolated oligohydramnios at term

Objective The aim of this study was to evaluate the hourly fetal urine production rate (HFUPR) via three-dimensional ultrasonography in women with isolated oligohydramnios and compare with normal pregnant women at term. Materials and methods This was a prospective observational cohort study of 112 women from 34 to 40 6/7 weeks’ gestation. They were classified into three groups according to the amniotic fluid index (AFI) and ultrasonographic estimated fetal weight (EFW) as isolated oligohydramnios (defined as AFI below 5% and appropriate EFW corresponding to gestational age) (n = 34) and IUGR (defined as EFW below 5% corresponding to gestational age irrespective amniotic fluid) (n = 17), and normal pregnancy (n = 61). HFUPR was measured using three-dimensional virtual organ computer-aided analysis. Adverse perinatal outcomes in all participants were examined. Results There was no significant difference in HFUPR between patients with isolated oligohydramnios and women with normal pregnancies (median, 40.0 mL/h [interquartile range [IQR] 31.0–66.5] vs. 48.6 [31.5–81.2], p = 0.224). HFUPR was significantly decreased in the IUGR group (13.8 mL/h [IQR 10.1–24.8]), compared to the normal pregnancy group (p<0.001) and the isolated oligohydramnios group (p<0.001). HFUPR was significantly decreased in neonates with adverse perinatal outcomes compared to the control (24.7 mL/h [IQR 13.4–47.4] vs. 43.6 [29.8–79.0], p = 0.016). Conclusion HFUPR was not decreased in patients with isolated oligohydramnios but was decreased in patients with IUGR when compared to normal controls at term.

Comparison of the amniotic fluid and fetal urine peptidome for biomarker discovery in renal developmental disease

Production of amniotic fluid (AF) is view as predominately driven by excretion of fetal urine (FU). However, the origin of AF peptides, often considered as potential biomarkers of developmental diseases, has never been investigated. Here, we evaluated the FU origin of AF peptides and if the AF peptide content can be used as a surrogate of FU. The abundance of endogenous peptides was analyzed by capillary electrophoresis coupled to mass spectrometry in 216 AF and 64 FU samples. A total of 2668 and 3257 peptides was found in AF and FU respectively. The AF peptidome largely overlapped with the FU peptidome, ranging from 54% in the second pregnancy trimester to 65% in the third trimester. Examination of a subset of 16 paired AF and FU samples revealed that 67 peptides displayed a significant positively correlated abundance in AF and FU, strongly suggesting that their presence in AF was directly associated to FU excretion. As proof-of-concept we showed that measuring the AF abundance of these 67 peptides of FU origin allowed prediction of postnatal renal survival in fetuses with posterior urethral valves. These results demonstrate that the AF peptidome can be considered as a good surrogate of the FU peptidome.

The ANTENATAL multicentre study to predict postnatal renal outcome in fetuses with posterior urethral valves: objectives and design

Background Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature. Methods Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in &gt;30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1–β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature. Results In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment. Conclusions Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV.