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Background: Posterior urethral valves (PUVs) account for 17% of pediatric renal failure. The management of pregnancies involving fetuses with PUV is hampered by the fact that current clinical parameters obtained from fetal ultrasound and/or fetal urine biochemistry are insufficient to predict postnatal renal function. We previously have developed a fetal urine peptide signature (12PUV) that predicted with high precision postnatal renal failure at 2 years of age in fetuses with PUV. Here, we evaluated the accuracy of this signature to predict postnatal renal outcome in fetuses with PUV in an independent single-center study., Methods: Thirty-three women carrying fetuses with suspected PUV were included. Twenty-five fetuses received vesicoamniotic shunts during pregnancy. PUV was confirmed postnatally in 23 patients. Of those 23 fetuses, 2 were lost in follow-up. Four and 3 patients died in the pre- and perinatal periods, respectively. Follow-up renal function at 6 months of age was obtained for the remaining 14 patients. The primary outcome was early renal failure, defined by an eGFR < 60 mL/min/1.73 m 2 before 6 months of age or pre- or perinatal death., Results: The peptide signature predicted postnatal renal outcome in postnatally confirmed PUV fetuses with an AUC of 0.94 (95%CI 0.74-1.0) and an accuracy of 90% (95%CI 78-100). The signature predicted postnatal renal outcome for the suspected PUV cases with an AUC of 0.89 (95%CI 0.72-0.97) and an accuracy of 84% (95%CI 71-97)., Conclusions: This single-center study confirms the predictive power of the previously identified 12PUV fetal urinary peptide signature.

The aim of this study is to evaluate the significance of renal pelvis aspiration (RPA) in the management of antenatal hydronephrosis (AHN). This study enrolled 15 AHN cases (one twin pregnancy) that necessitated RPA for AHN. Chromosomal abnormalities, gene disorders, and additional life-threatening congenital abnormalities were eliminated prior to intrauterine interventions. Urine analysis were performed for the evaluation of renal function. Normal renal function was observed in six neonates/infants (40%) (group 1), whereas impaired renal function and various type of urinary system anomalies were observed in 9 neonates/infants (60%) (group 2) during the short-term and longitudinal follow-up periods. There were statistically significant differences in the oligohydroamniosis rate, mean fetal urine sodium value, mean fetal urine β2-microglobulin, mean gestational week at birth, and mean birthweight values between the groups (P = 0.007, P < 0.001, P = 0.035, P < 0.001, and P = 0.001, respectively). Renal pelvis aspiration and urine analysis were substantial for the management of AHN in necessary cases. β2-microglobulin and sodium are clinically useful markers to detect the presence of severe renal damage due to obstructive uropathy and thus, important adjuvants in the proper selection of fetuses for further antenatal interventions., (© 2019 Japanese Teratology Society.)

Objectives: Cardiac remodeling due to renal dysfunction may have an impact on myocardial function (MF) of fetuses with lower urinary tract obstruction (LUTO). The aim was to identify possible differences in MF in LUTO fetuses compared with healthy controls and to look for interactions between urine biochemistry and MF indices., Methods: This is a cohort study consisting of 31 LUTO fetuses and 45 healthy controls. Subgroups were generated according to intrauterine therapy (group 1: LUTO after therapy, group 2: LUTO without therapy at the time of examination, and group 3: controls). MF indices were measured using pulsed wave tissue Doppler imaging and M-mode. Furthermore, results of fetal urine biochemistry were gathered retrospectively., Results: Among other findings, right ventricular (RV) e'/a' ratio was lower in group 1 compared with group 3 (p = .050). According to gestational age (GA) level-dependent analysis, RV isovolumetric relaxation time was significantly longer in group 2 compared with group 1 and group 3 at GA level 1 (19 wk of gestation). A significant positive correlation between RV e'/a' ratio and β-2-microglobulin as well as α-1-microglobulin and potassium could be observed., Conclusion: We observed differences in MF and an association between ventricular filling pattern and renal protein secretion in LUTO fetuses. This can be interpreted as a sign of intrauterine cardiac remodeling., (© 2019 John Wiley & Sons, Ltd.)

Objective: Because the literature on the predictive value of fetal urinalysis is controversial in fetuses with lower urinary tract obstruction, we determined the best model of fetal urine biochemical markers correlated with long-term postnatal renal function based on glomerular filtration rate (GFR)., Method: This retrospective study concerned 89 fetuses with lower urinary tract obstruction and their renal function after 10 years of age. We correlated fetal urine biochemical markers (total protein, β2-microglobulin, sodium, chloride, glucose, calcium, and phosphorus) with GFR at 10 to 30 years of age in 89 patients with posterior urethral valves. We defined five stages of chronic kidney disease (CKD)., Results: Of the 89 patients, 18 (20%) are 20 years old or over. Postnatal renal function was good in 67.4% (GFR > 60 mL/min/1.73 m 2 ) and poor in 17% (GFR < 30 mL/min/1.73 m 2 ). All fetal urine markers differed between CKD stage 1 + 2 and CKD stage 4 + 5 (P < 0.001). β2-microblobulin showed an 87% sensitivity for a 72% specificity. A combination of β2-microglobulin and chloride gave the best results (93% sensitivity and 71% specificity) versus amniotic fluid volume (80% sensitivity and 73% specificity)., Conclusion: Fetal urine biochemistry predicts long-term (10-30 years) postnatal renal function., (© 2018 John Wiley & Sons, Ltd.)

Most of biomarker panels, extracted from single omics traits, still need improvement since they display a gray zone where prediction is uncertain. Here we verified whether a combination of omics traits, fetal urinary metabolites and peptides analyzed in the same sample, improved prediction of postnatal renal function in fetuses with posterior urethral valves (PUV) compared to individual omics traits. Using CE-MS, we explored the urinary metabolome of 13 PUV fetuses with end stage renal disease (ESRD) and 12 PUV fetuses without postnatal ESRD at 2 years postnatally. This allowed the selection of 24 differentially abundant metabolite features which were modelled into predictive classifiers, alone or in combination with 12 peptides previously identified as predictive of ESRD. Validation in 35 new fetuses showed that the combination of peptides and metabolites significantly outperformed the 24 metabolite features with increased AUC (0.987 vs 0.905), net reclassification improvement (36%) and better sensitivity accuracy (86% vs 60%). In addition, the two trait combination tended to improve, but without reaching statistical significance, the already high performances of the 12 peptide biomarkers (AUC 0.967, accuracy 80%). In conclusion, this study demonstrates the potential of cumulating different omics traits in biomarker research where single omics traits fall short., Significance: Although increasingly proposed in disease-diagnosis and -prognosis because of their improved efficacy over single markers, panels of body fluid biomarkers based on single omics analysis still fail to display perfect accuracy, probably due to biological variability. Here, we hypothesized that combination of different omics traits allowed to better capture this biological variability. As proof of concept, we studied the added value of fetal urine metabolites and peptides using CE-MS, starting from the same urine sample, to predict postnatal renal outcome in fetuses with posterior urethral valves. We observed that the prognostic power of combined metabolite and peptide markers was clearly higher than that of metabolites alone and slightly, but non-significantly, improved compared to the peptides alone. To our knowledge, this report is the first to demonstrate that combining multiomics traits extracted from (fetal) urine samples displays clear promise for kidney disease stratification., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Although POR deficiency (PORD) is assumed to be accompanied by excessive placental androgen accumulation and enhanced adrenal and testicular androgen production via the backdoor pathway as well as compromised testicular androgen production via the frontdoor pathway, there is no direct evidence for the flux of excessive placental androgens into the fetal circulation and for the production of dihydrotestosterone (DHT) via the backdoor pathway. We examined longitudinal serum and urine steroid metabolite profiles in a 46,XY infant with PORD who was prenatally identified because of the progressive fetal masculinization and maternal virilization from the mid-gestation and the presence of fetal radio-humeral synostosis and was confirmed to have compound heterozygous mutations of POR (p.Q201X and p.R457H). The results showed (1) markedly and inappropriately elevated serum androstenedione and testosterone (T) values at birth, (2) a markedly increased serum DHT value with a normal DHT/T ratio at birth, (3) transient elevation of serum T and DHT values accompanied by a normal DHT/T ratio and concomitant elevations of intermediate steroid metabolites on both the frontdoor and backdoor pathways at 30 days of age, and (4) persistent PORD-compatible urine steroid profiles. Although the data obtained from a single infantile patient are too premature to be generalized, they imply: (1) the transfer of excessive placental androgens into the fetal as well as the maternal circulations from the mid-gestation, (2) lack of a clinically discernible amount of DHT production via the adrenal backdoor pathway around birth, and (3) the activation of both the frontdoor and backdoor pathways in the testis around the mini-puberty, with no production of a clinically discernible amount of DHT via the testicular backdoor pathway., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The authors present an overview of lower urinary tract obstruction (LUTO) in the fetus with a particular focus on the insult to the developing renal system. Diagnostic criteria along with the challenges in estimating long-term prognosis are reviewed. A proposed prenatal LUTO disease severity classification to guide management decisions with fetal intervention to maintain or salvage in utero and neonatal pulmonary and renal function is also discussed. Stage I LUTO (mild form) is characterized by normal amniotic fluid index after 18 weeks, normal kidney echogenicity, no renal cortical cysts, no evidence of renal dysplasia, and favorable urinary biochemistries when sampled between 18 and 30 weeks; prenatal surveillance is recommended. Stage II LUTO is characterized by oligohydramnios/anhydramnios, hyperechogenic kidneys but absent renal cortical cysts or apparent signs of renal dysplasia and favorable fetal urinary biochemistry; fetal vesicoamniotic shunting (VAS) or fetal cystoscopy is indicated to prevent pulmonary hypoplasia and renal failure. Stage III LUTO is oligohydramnios/anhydramnios, hyperechogenic kidneys with cortical cysts and renal dysplasia and unfavorable fetal urinary biochemistry after serial evaluation; fetal vesicoamniotic shunt may prevent severe pulmonary hypoplasia but not renal failure. Stage IV is characterized by intrauterine fetal renal failure, defined by anhydramnios and ultrasound (US) findings suggestive of severe renal dysplasia, and is associated with death in 24 h of life or end-stage renal disease (ESRD) within the first week of life; fetal vesicoamniotic shunt and fetal cystoscopy are not indicated.

Objective: To evaluate maternal urinary CA19-9 as a potential marker to diagnose severe antenatal hydronephrosis (ANH) during pregnancy and to compare the values with those in normal pregnancies as controls., Patients and Methods: A total of 20 women in their third pregnancy trimester were enrolled. An anteroposterior pelvic diameter (APD) of ≥15 was considered as severe ANH. Case group consisted of 10 women with a diagnosis of severe ANH. Ten women with similar age, gestational age, fetal sex, normal ultrasonography, and no history of any congenital anomalies were chosen as controls. Urine samples were collected and maternal urinary CA19-9 was measured. The levels in case and control groups were compared using Mann-Whitney U test., Results: Each group consisted of nine mothers with male fetuses and one with female fetus. The APD in the ANH group ranged from 17 to 40 mm. Five of 10 children in the ANH group also had contralateral APD of ≥4 mm (bilateral ANH). The mean age and gestational age of pregnant women in the two groups were comparable. The mean maternal CA19-9 was significantly higher in the ANH group compared with the controls (mean: 134.5 U/mL vs 22.2 U/mL, P < .001)., Conclusion: To our best knowledge, this is the first time that maternal urinary CA19-9 has been used as a marker for ANH. Based on these pilot data, CA19-9 levels are significantly higher in the urine of pregnant women carrying fetuses with severe ANH, and it may have the potential to serve as a noninvasive and useful biomarker to diagnose ANH., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To evaluate the association between ultrasonographic renal parameters and urine biochemistry in fetuses with lower urinary tract obstruction (LUTO)., Methods: Data were collected prospectively from 31 consecutive fetuses with LUTO that underwent vesicocentesis for fetal urinary biochemistry between April 2013 and September 2015. The following renal ultrasound markers were assessed immediately before the vesicocentesis: renal echogenicity, presence of cortical cysts, presence of findings suggestive of 'renal dysplasia' (hyperechogenic cystic kidneys with no cortical-medullary differentiation) and severe oligohydramnios (amniotic fluid < 5th percentile). The association of these parameters to the fetal urinary concentration of sodium, chloride, calcium, osmolality and beta2-microglobulin was investigated by logistic regression analysis., Results: There was no relationship between any of the ultrasonographic fetal renal characteristics and fetal urinary biochemistry., Conclusions: In LUTO, the ultrasound appearance of the fetal kidneys and urinary biochemistry are not correlated. It may be better to take both ultrasound and biochemistry into account when evaluating fetuses with fetal LUTO. © 2016 John Wiley & Sons, Ltd., (© 2016 John Wiley & Sons, Ltd.)

Objectives: To assess the value of fetal urine biochemistry before 23 weeks of gestation in cases of lower urinary tract obstruction (LUTO) to refine prognosis and to select potential candidates for in-utero intervention., Methods: This was a retrospective study including 72 cases of LUTO with fetal urine sampled before 23 weeks and assayed for total protein, β-2-microglobulin, sodium, chloride, calcium, phosphorus, glucose and gamma-glutamyl transpeptidase (GGTP). Two groups were defined according to renal outcome: 1) bilateral renal dysplasia on histological examination or renal failure at birth; 2) normal postnatal renal function or histologically normal appearance of the kidneys. Correlations between fetal urinary biochemical markers and postnatal renal function were studied., Results: LUTO was isolated in 56/72 (77.8%) cases and was associated with other malformations in 16/72 (22.2%) cases. High GGTP levels (236 IU/L vs 5 IU/L; P < 0.0001) were observed in fetal urine in the five cases of urodigestive fistula. A significant difference between outcome groups was observed for β-2-microglobulin (P = 0.0017), sodium (P = 0.0008), chloride (P = 0.0028) and calcium (P = 0.0092) but not for protein, glucose or phosphorus. Sensitivity and specificity in defining a poor renal prognosis were 80.6% and 89% for β-2-microglobulin, 61.3% and 100% for sodium and 64.5% and 100% for calcium, respectively., Conclusions: Fetal urinalysis before 23 weeks of gestation allowed distinction between three groups: 1) fetuses with normal urine biochemistry for which fetal therapy should be discussed; 2) fetuses with abnormal urine biochemistry for which prognosis for renal outcome is poor and for which the benefit of fetal therapy is likely to be compromised; 3) fetuses with urodigestive fistula., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

In a context of foetal obstructive uropathies, biochemical markers can be helpful to assess the renal function, but most studies to date have focused on their correlation with ultrasound findings and neonatal outcome. Our aim was to evaluate foetal β2-microglobulin as an index of histological injury to the kidney. β2-microglobulin was measured in serum and/or urine from 27 foetuses with bilateral obstructive uropathy, and compared to the findings of kidney examination following the termination of pregnancy. In serum, increased β2-microglobulin levels correlated to a decreased number of glomeruli, a reduction in the blastema and the presence of primitive ducts reflecting renal hypoplasia and dysplasia. However, elevated β2-microglobulin levels in the urine correlated only to a decreased number of glomeruli., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine whether there is an association between the fetal ultrasound finding of hyperechoic colon and the gestational age at which it presents and cystinuria., Methods: A prospective national survey was performed in France including all observations of isolated fetal hyperechoic colon detected at routine second- and third-trimester ultrasound over a 2-year period. Collected images were reviewed by experts. Colon was defined as being hyperechoic when its echogenicity was at least equal to that of the iliac bone. It was diagnosed when large tubular echogenic portions of the colon, without a focal mass and without posterior acoustic shadows, were observed at the periphery of the abdomen. Urinary amino acid analysis was performed after birth in the cases identified to test for cystinuria., Results: Nineteen fetuses with ultrasound findings of hyperechoic colon were included, and the mothers of 16 of these agreed to participate in the study. In eight of nine cases of hyperechoic colon observed before 36 weeks' gestation cystinuria was confirmed at birth. In the seven remaining cases, observed after 36 weeks, none was found to have cystinuria and all had normal images at previous routine ultrasound scans at 22 and 33 weeks. When present, no difference in the sonographic appearance of hyperechoic colon was noted between the two groups. In the cystinuria-affected cases, the length of the hyperechoic mass appeared to increase with gestational age., Conclusions: In our experience, the presence of a hyperechoic colon at routine ultrasound scan before 36 weeks' gestation should prompt screening for cystinuria at birth, while later observation (> 36 weeks) of this finding does not appear to be related to any disease., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

This work describes an exploratory NMR metabonomic study of second trimester maternal urine and plasma, in an attempt to characterize the metabolic changes underlying prenatal disorders and identify possible early biomarkers. Fetal malformations have the strongest metabolic impact in both biofluids, suggesting effects due to hypoxia (leading to hypoxanthine increased excretion) and a need for enhanced gluconeogenesis, with higher ketone bodies (acetone and 3-hydroxybutyric acid) production and TCA cycle demand (suggested by glucogenic amino acids and cis-aconitate overproduction). Choline and nucleotide metabolisms also seem affected and a distinct plasma lipids profile is observed for mothers with fetuses affected by central nervous system malformations. Urine from women who subsequently develop gestational diabetes mellitus exhibits higher 3-hydroxyisovalerate and 2-hydroxyisobutyrate levels, probably due to altered biotin status and amino acid and/or gut metabolisms (the latter possibly related to higher BMI values). Other urinary changes suggest choline and nucleotide metabolic alterations, whereas lower plasma betaine and TMAO levels are found. Chromosomal disorders and pre-preterm delivery groups show urinary changes in choline and, in the latter case, in 2-hydroxyisobutyrate. These results show that NMR metabonomics of maternal biofluids enables the noninvasive detection of metabolic changes associated to prenatal disorders, thus unveiling potential disorder biomarkers.

The introduction of prenatal ultrasonography as a screening method entails an increasing number of infants diagnosed with prenatal hydronephrosis. Ureteropelvic junction obstruction accounts for 35% of prenatal hydronephrotic cases. Urinary tract obstruction that occurs during early kidney development affects renal morphogenesis, maturation and growth, and in the most severe cases this will ultimately cause renal insufficiency. A major challenge in the clinical management of these patients is to preserve renal function by selection of the 15%-20% who require early surgical intervention, leaving those for whom watchful waiting may be appropriate because of spontaneous resolution/stabilization without significant loss of renal function. Today, this requires medical surveillance, including repetitive invasive diuretic renograms relying on arbitrary threshold values, and therefore there is a need for non-arbitrary, non-invasive urinary biomarkers that may be used as predictors for renal structural changes and/or decreasing renal function, and thereby provide the surgeon with more clear indications for surgical intervention. In this review, we summarize the currently well-known facts about urinary biomarkers in ureteropelvic junction obstruction concerning renal function, and we also suggest potential novel urinary biomarkers., (Copyright © 2010 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Aim: Chronic lung disease (CLD) is a major component in the morbidity of premature infants suffering from fetal inflammatory response (FIRS). The aim of the present study was to compare the value of measuring neonatal urinary beta(2)-microglobulin (beta(2)-MG) levels with fetal blood interleukin (IL)-6 levels in premature infants at risk of developing CLD., Methods: Premature infants (gestational age <30 weeks) without CLD (n = 19) and with CLD (n = 10) were enrolled. We measured IL-6 levels in umbilical cord blood and beta(2)-MG levels in urine obtained within 48 h after birth., Results: IL-6 and beta(2)-MG levels were significantly higher in infants who developed CLD than in those who did not (median IL-6, 54.7 vs 7.6 pg/mL; P < 0.005; beta(2)-MG 17.7 vs 9.3 x 10(4) microg/gCr; P < 0.05). The sensitivity and negative predictive value of beta(2)-MG at the cut-off value at 10.0 x 10(4) microg/gCr (0.90 and 0.92) were comparable to IL-6 at 16 pg/mL (0.90 and 0.94)., Conclusion: We suggest that measuring urinary beta(2)-MG in premature infants soon after birth can monitor FIRS and may provide information on the risk of subsequent CLD development that is as clinically important as information derived from umbilical cord blood IL-6.

Beside prevention routine antenatal care involves screening examinations for early diagnosis and therapy of pregnancy associated complications. Antenatal care guidelines recommend physical and especially vaginal examination, ultrasonographic evaluation, laboratory examinations, but also urine analysis. The commonly used urine analysis by dipstick can provide information on urinary tract infections, glucosuria and proteinuria. While the estimation of glucosuria has been found to be of no use for the detection of gestational diabetes and therefore is not recommended as a screening method for this disorder, urine analysis by dipstick or culture for bacteriuria or urinary tract infection followed by an antibiotic treatment is able to reduce maternal and neonatal complications. The most important role for urine analysis is the detection of proteinuria by routine dipstick examination and the quantification of proteinuria by 24 hour urin sampling in women with hypertensive disorders in pregnancy, especially in preeclampsia.

Background: Until the publication of the Serum Urine and Ultrasound Screening Study (SURUSS) report, it was difficult to compare the different antenatal screening tests for Down's Syndrome because of variations in study designs. We here present the main results from SURUSS, updated to take account of recent information on nuchal translucency in Down's Syndrome pregnancies, and discuss their implications., Methods: SURUSS was a prospective study of 47,053 singleton pregnancies (including 101 pregnancies with Down's Syndrome) conducted in 25 maternity units. Nuchal translucency measurements were taken. Serum and urine samples collected between 9 and 13 weeks, and again between 14 and 20 weeks of pregnancy were stored. Samples from each affected pregnancy and five matched controls were tested for currently used or suggested biochemical Down's Syndrome screening markers. Pregnancies were followed up to determine the presence or absence of Down's Syndrome. For an 85% Down's Syndrome detection rate, the false-positive rate for the Integrated test (nuchal translucency and pregnancy associated plasma protein-A [PAPP-A] at 11 completed weeks of pregnancy, and alpha-fetoprotein, unconjugated oestriol [uE3], free beta or total human chorionic gonadotrophin (hCG) and inhibin-A in the early second trimester) was 0.9%, the Serum integrated test (without nuchal translucency) 2.7%, the Combined test (nuchal translucency with free beta-hCG and PAPP-A at 11 weeks) 4.3%, the Quadruple test (alpha-fetoprotein, uE3, free beta or total hCG and inhibin-A) 6.2%, and nuchal translucency at 11 weeks, 15.2%. All tests included maternal age. Using the Integrated test at an 85% detection rate, there would be six diagnostic procedure-related unaffected fetal losses following amniocentesis per 100,000 women screened compared with 35 using the Combined test or 45 with the Quadruple test., Conclusions: The Integrated test offers the most effective and safe method of screening for women who attend in the first trimester. The next best test is the Serum integrated test. The Quadruple test is the best test for women who first attend in the second trimester. There is no justification for retaining the Double (alpha-fetoprotein and hCG) or Triple (alpha-fetoprotein, uE3, and hCG) tests, or nuchal translucency alone (with or without maternal age) in antenatal screening for Down's Syndrome.

Amniotic fluid (AF) is a complex substance essential to fetal well-being. This article reviews recent discoveries and the current understanding of the origin and circulation of AF and its nutritive, protective, and diagnostic functions. Future directions for AF research are also discussed.

Objectives: Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a usually lethal disease during the first year of life. There is no specific ultrasound prenatal diagnosis and no identified genetic locus. The value of amniotic fluid digestive enzyme assay and fetal urine biochemistry in the prediction of MMIHS was analysed., Methods: Retrospective study of 14 MMIHS cases. Amniotic fluid digestive enzymes and fetal urine biochemistry were compared in MMIHS and megabladder (63 and 264 cases respectively)., Results: Abnormal amniotic fluid digestive enzyme profile (vomiting of bile or digestive secretion leakage) was observed in 8/10 MMIHS cases. These profiles were observed in 7/63 controls; 80% sensitivity (95%CI = 55%-100%); 89% specificity (95%CI = 81%-96%). Fetal urinalysis was normal in 12/12 MMIHS cases except high calcium (>0.6 mmol/l). This profile was observed in 33/264 megabladder control cases; 100% sensitivity; 98.7% specificity (95%CI = 83.5%-91.5%)., Conclusion: For the first time, we propose a prenatal diagnosis of MMIHS based on amniotic fluid digestive enzyme assay and on fetal urinalysis., (Copyright 2005 John Wiley & Sons, Ltd.)

Objective: We reviewed the prenatal and postnatal management of fetal lower urinary tract obstruction (LUTO) in a large geographically defined population., Methods: The records of 113 cases of LUTO seen over a 14-year period were examined. The predictive accuracy of prenatal findings for chronic renal failure (CRF) and a comparison of prenatal-suspected and non-suspected cases were made., Results: The incidence of LUTO was 2.2 in 10 000 births. During the study period, prenatal detection improved from 33 to 62%. Sensitivity of prenatal ultrasound detection of renal dysplasia and fetal urinary sodium, calcium, and beta2-microglobulin for CRF or renal dysplasia on autopsy were 59, 33, 66, and 63% respectively. Compared to undetected cases, those detected prenatally had higher mortality and a higher rate of CRF at 24 months (17% vs 57%, p < 0.01)., Conclusion: Our observations confirm the poor prognosis associated with fetal LUTO. The value of serial fetal urine biochemistry, other prenatal predictors of postnatal renal function, and the benefits of vesicoamniotic shunting require larger series and longer follow-up., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

The aim of this study is to implement the use of biochemical parameters in the analysis of fetal urine to assist with decision making for surgical intervention for fetal obstructive uropathy. Three patients were selected over a 6 month period following ultrasound diagnosis of megabladder and oligohydramnios. Amniocentesis and cystocentesis were performed for karyotyping and biochemical urinary electrolyte evaluation, respectively. Fetal urine biochemistry assisted in decision making with regard to patient and fetal well being. In each of the cases the parameter cutoffs were diagnostic of fetal condition. While the long term benefits of fetal intervention for obstructive uropathy are still debated, we feel that the use of urine biochemical criterIa provide the best current method to select the subjects to be submitted to vesicoamniotic shunt centres.

Background: C-reactive protein has been measured in amniotic fluid in the second and third trimesters of gestation, and its elevated concentration has been found to be associated with adverse pregnancy outcome. It remains unexplained whether amniotic fluid C-reactive protein is of fetal origin., Case: We report the measurement of C-reactive protein in fetal urine obtained by transabdominal vescicocentesis in a fetus at 15 weeks' gestation affected by obstructive uropathy. Using an enzyme-linked immunosorbent assay, C-reactive protein was detected at a concentration of 234 ng/mL., Conclusion: The fetal kidneys excrete C-reactive protein as early as 15 weeks' gestation.

Objective: To present the outcome of a consecutive series of 19 fetuses referred to our center for megacystis in the first half of the pregnancy., Study Design: Retrospective analysis., Methods: 19 cases of early fetal megacystis were reviewed. Inclusion criteria were the visualization of an enlarged bladder with a maximum longitudinal diameter >10 mm and a gestational age of no more than 19 weeks., Results: The median gestational age at diagnosis was 16 weeks (range 12-19 weeks). The median maximum longitudinal diameter of the fetal bladder at the time of diagnosis was 21 mm (range 11-35 mm). The fetal megacystis was associated with another extra renal anomaly in six cases (30%). There was no fetus with abnormal karyotype. Termination of pregnancy was performed in 11 cases because of the severity of the renal disease. One spontaneous intrauterine death occurred. A vesicoamniotic shunt was inserted in three cases, two of which died in utero. The surviving fetus that was shunted died in the neonatal period from acute renal failure. In the remaining four fetuses, resolution of the megacystis occurred spontaneously (n = 2) or following serial single-needle aspiration (n = 2). One of these had renal insufficiency requiring kidney transplantation., Conclusion: The outcome of fetuses with early obstructive uropathy is poor, with or without in utero therapy. Pathophysiology, clinical presentation and outcome of fetuses with early uropathy may differ from those previously described in the latter part of pregnancy., (Copyright 2003 John Wiley & Sons, Ltd.)

There are a number of potential biochemical markers that may have some role in predicting renal function postnatally. These include urinary sodium, calcium and beta2-microglobulin. The latter may also be measured in fetal serum. However, the accuracy of these parameters at a point in time is far from perfect as urinary tract obstruction is a progressive disease which may be best defined by repeated observations throughout pregnancy., (Copyright 2001 John Wiley & Sons, Ltd.)

Lower urinary tract obstruction has a significant impact on neonatal and child health. Pulmonary hyperplasia and renal impairment could be direct or indirect consequences of this condition leading to significant morbidity and mortality. Evaluation of fetuses with suspected lower urinary tract obstruction is performed not only to confirm the diagnosis but also to assess renal prognosis. Ultrasound examination and urinary analysis aid in the evaluation of these fetuses. The decision to perform fetal intervention in these cases is a difficult one. Vesico-amniotic fetal shunting, open fetal surgery and more recently endoscopic fetal surgery for this condition are available as possible modalities of fetal intervention. Case selection for fetal intervention is extremely important in order to both avoid unnecessary intervention in those unlikely to survive, and also to avoid procedure related complications in fetuses likely to do well without intervention. Vesico-amniotic shunting has the advantage of bypassing the obstruction, however it is often associated with complications. Open fetal surgery is not usually recommended because of the complications and high fetal loss rate. Endoscopic surgery to visualise and treat the cause of lower urinary tract obstruction has been tried. Fetal endoscopic surgery is in its infancy and endoscopic procedures are limited to a few groups. This current review addresses evaluation, case selection and therapeutic options for lower urinary tract obstruction in utero. It also discusses the limited data against which the efficacy of the various options can be assessed. The current state of fetal intervention is detailed in the present review., (Copyright 2001 John Wiley & Sons, Ltd.)

This report summarizes the National Institute of Child Health and Development sponsored conference on amniotic fluid (AF) biology, held 28-29 September 1999, in Detroit, Michigan. National and international investigators with expertise in AF biology addressed the regulation of AF volume and composition as well as the clinical aspects of interpreting fetal health and well-being from AF indices. A major purpose of the meeting was to consider future directions and opportunities for basic and clinical research which focus on understanding the physiology and pathophysiology and providing therapeutic interventions for abnormalities of AF volume. To achieve this, the workshop participants addressed the current state of knowledge, recent scientific advances and priorities for major questions for which answers must be sought. The fact that it is not known whether AF volume is regulated or what volume-regulatory mechanisms might be involved is a major problem that needs addressing. In the later half of gestation, potential AF volume-regulatory pathways include the two major inflows into the amniotic compartment, i.e. fetal urine and lung liquid, and the two major outflows, i.e. fetal swallowing and intramembranous absorption. If AF volume is regulated, then this must occur through regulation of intramembranous flow, because the other three flows are regulated by the fetus to meet fetal needs. Regulation of AF composition is similarly unknown. In clinical practice, a variety of ultrasonographic indices of AF volume are used, but the relationships of these indices to AF volume have not been determined, nor have their dependency on fetal size, shape or position within the uterus. Further, although aberrations in AF volume both above and below normal are associated with increased fetal and neonatal morbidity and mortality, the predictive utility of the various AF indices remains low and there is little consensus on which is best utilized under conditions of oligohydramnios, normal AF volumes, or polyhydramnios. Further, various clinical AF therapies remain largely experimental and their optimization and utilization need exploration. This report is a condensation of the views presented by the conference participants.

Unlabelled: Obstructive uropathies are a frequent cause of child renal failure. The prenatal diagnosis of such abnomalities should lead to appropriate management., Objective: To evaluate the interest of ultrasonographic prenatal diagnosis of urinary tract malformations., Patients and Methods: Retrospective study of 10 cases of urinary tract malformations diagnosed in utero. The mean age of the patients was 34.9 years and the mean gestational age at the prenatal diagnosis was 28.2 weeks of amenorrhea. The abnormalities diagnosed were: 2 cases of ureteropelvic junction obstruction, 3 cases of posterior urethral valves and 5 cases of mild hydronephrosis. The fetal karyotype, realised in 8 cases, was normal. In one case the urinary abnormalities was part of a multiple malformation syndrome and led to the termination of the pregnancy. 7 cases had a post-natal follow-up: 5 had a surgical management and two new borns had transient pyelectasies. The prediction of postnatal renal function is made by ultrasonographic appearance of the kidney and the amniotic fluid. Although the analysis of fetal urine for the assessment of renal function leads to conflicting results, it seems that sodium and beta-2 microglobulin urinary rates provide useful informations.

Objective: Severe fetal anemia is associated with polyhydramnios in both human and ovine fetuses. This study examined the relationship between varying degrees of anemia and amniotic fluid volume in fetal sheep., Study Design: Eleven long-term catheterized ovine fetuses at 126 +/- 1 days' gestation (mean +/- SE) were subjected to hemorrhage of 20 to 80 mL daily for 9 consecutive days to produce varying degrees of fetal anemia. Five additional animals served as time control animals. Statistical analysis was by least squares regression and 3-factor analysis of variance., Results: Amniotic fluid volume was 793 +/- 147 mL and did not change with time in the control fetuses. In the fetuses that were subjected to hemorrhage the amniotic fluid volume changed little through the hematocrit range of 40% to 25%. As fetal hematocrit fell below approximately 25%, amniotic fluid volume began to increase. With greater degrees of anemia the amniotic fluid volume increased as an exponential function of hematocrit and approached 2000 mL excess fluid as hematocrit dropped to <15%. According to bivariate regression the increase in amniotic fluid volume was related to fetal hematocrit, PaO(2), and urinary flow rate as well as to plasma and amniotic fluid lactate concentrations. According to multivariate regression only fetal PO(2) and urinary flow rate were significantly related to the increase in amniotic fluid volume., Conclusions: Although mild anemia was not associated with increased amniotic fluid volume, moderate to severe fetal anemia was associated with an exponential rise in amniotic fluid volume. This rise may have been mediated by a hypoxemia-induced diuresis, by a diuresis related to a lactate-induced osmotic accumulation of fetal fluid, or by both mechanisms.

The aim of this study was to investigate the second trimester concentrations of maternal urine human chorionic gonadotrophin beta-core fragment (HCGbetacf) in Asian pregnanci2es with fetal chromosomal abnormalities. HCGbetacf concentrations were analysed from 34 urine samples in chromosomally abnormal pregnancies, including 28 cases of Down's syndrome, one case of trisomy 18, and five cases of other chromosomal abnormalities (one mosaic deletion and four translocations), and in a cohort of 268 normal pregnancies receiving second trimester amniocentesis. Results were normalized to urine creatinine (Cr) concentration and converted to the multiple of the median (MOM) concentration for the appropriate gestation. The median HCGbetacf MOM concentrations of Down's syndrome pregnancies (12.89) was significantly higher than that of normal pregnancies (1. 06) (P < 0.00001). Wide variations of HCGbetacf concentrations were observed in other chromosomally abnormal pregnancies. There were 18 of 28 (64%) Down's syndrome cases but one of five (20%) other chromosomally abnormal cases with HCGbetacf concentrations above the 95th centile of the control values (8.22 MOM cut-off). These findings suggest that HCGbetacf could be a potential marker in urine screening for fetal Down's syndrome in Asians.

Variable results have been reported using urine beta-core fragment as a marker for fetal Down syndrome. Initial studies by Cuckle et al. (1994) and Canick et al. (1995) indicated that beta-core fragment was an outstanding marker, detecting >80 per cent of Down syndrome cases. Since these reports, widely varying results have been published, indicating between 20 per cent and 66 per cent detection of cases at 5 per cent false-positive rate. The wide variation in the reported data has led to a loss of enthusiasm for this marker as a useful test for Down syndrome screening. Here we report the results of a three-year prospective study in which urine samples were collected daily from women undergoing fetal karyotype analysis for advanced maternal age. Samples were tested within one week of collection and then frozen. We also investigated the likely causes of the variability observed in beta-core fragment data. We collected 1157 urine samples over 955 days. Beta-core fragment levels were measured. A regression line was calculated for the weekly medians of the 1134 control samples and multiples of the control median (MoM) were determined. The median MoM for the controls was 1.0 and the logarithmic standard deviation (log SD) was 0.41. The median MoM for the 23 Down syndrome cases was 5.44 and the log SD was 0.45. Over the study period, 65 per cent of Down syndrome cases exceeded the 95th centile of the control group. The median MoM of control samples and the proportion of Down syndrome cases detected by the test was relatively constant during the study period. The unaffected cases were divided into three equal divisions, corresponding to approximately the first, second and third year of sample collection. No trend was found in the median control MoM values in three sample collection periods (r2=0.04). A similar number of cases exceeded the 95th centile of control samples in the three sample collection periods, 63 per cent, 66 per cent and 66 per cent. Consistent results were indicated during the three years of sample testing. Levels of total oestriol were determined in urine samples and MoM statistics derived. The median oestriol level in Down syndrome cases was 0.59 MoM. Only 12 per cent of cases had MoM levels below the fifth centile. Gaussian models were prepared combining biochemical data and maternal age distribution. While beta-core fragment by itself detected 65 per cent of Down syndrome cases, beta-core fragment modelled with maternal age detected 66 per cent, and modelled with age and total oestriol levels detected 82 per cent of cases at 5 per cent false-positive rate. At the completion of the study, we thawed and reassayed 20 random urine samples (10 control and 10 Down syndrome) collected at different times during the study period. While the control samples (74-1700 ng/ml) had slightly increased values when reassayed (mean value 137 per cent of original prospective value), the Down syndrome samples (360-20,500 ng/ml) all had decreased values when reassayed (mean=53 per cent, t-test, controls versus cases, p = 0.0003). The Down syndrome samples were decreased to between 93 per cent and 12 per cent of the original value. A relationship was identified between the magnitude of the original beta-core fragment value and the change in immunoreactivity when reassayed (r2=0.998). The higher the initial beta-core fragment value the greater the loss of immunoreactivity. We considered the possibility that the beta-core fragment molecules aggregate upon storage in the freezer. We repeated the assay of the 20 samples after treatment with a high salt buffer. Down syndrome samples recovered half of the lost beta-core fragment immunoreactivity (mean increase in beta-core fragment levels 56 per cent, t-test, controls versus cases, p=0.004). We infer that aggregation of beta-core fragment upon storage interferes with beta-core fragment measurements. This may be the cause of the poor beta-core fragment screening performance reported using sto

Our understanding of the causes, mechanisms, and prenatal management of fetal obstructive uropathy has increased significantly. Improved methods of prenatal evaluation have allowed the better selection of fetuses for invasive therapy, and studies indicate better survival and renal outcomes in carefully selected cases. New biological markers in fetal urine may provide a better understanding of the pathological processes of renal damage, additional prognostic markers, and lead to non-surgical approaches to preventing renal damage.

Hyperglycosylated hCG is a form of hCG with more complex oligosaccharide side chains. A specific immunoassay was developed to measure hyperglycosylated hCG. Levels were measured in urine samples from 1157 women between 11 to 22 weeks of gestation, undergoing genetic analysis because of advanced maternal age. Values were normalized to urine creatinine concentration and plotted against gestational age, median values were determined and multiples of the control median (MoM) calculated. The median MoM and log standard deviation (log SD) of the 1134 control samples was 1.0 and 0.47, and of the 23 Down syndrome cases was 7.8 and 0.48, respectively. This indicated a 7.8-fold increase in hyperglycosylated hCG levels in Down syndrome cases. In the accompanying article, a stability problem was found with beta-core fragment measurements in frozen urine samples. In anticipation of similar problems, nine urine samples were tested for hyperglycosylated hCG fresh and after storage in the freezer. No clear difference was found in hyperglycosylated hCG values. In addition, no trend was found in hyperglycosylated hCG MoM values or in Down syndrome detection rates in urine samples stored for one, two or three years in the freezer. Samples were split into five equal groups according to creatinine concentration. A trend was observed, hyperglycosylated hCG MoM values decreasing with advancing creatinine concentration (1.77, 1.08, 1.01, 0.73 and 0.60 at 0.25, 0.50, 0.79, 1.11 and 1.73 mg/ml, respectively). An error was noted. This was corrected with a regression equation. After correction, the median MoM and log SD of the control samples was 1.0 and 0.44, and of Down syndrome samples was 7.3 and 0.42, respectively. Correction of this error, while reducing the elevation of Down syndrome cases, tightened the spread of samples. Samples were ranked and centiles determined. 18 of 23 Down syndrome cases (78 per cent) exceeded the 95th centile of the control population. ROC analysis indicated 79 per cent detection at 5 per cent false-positive rate. Urine samples were collected during two periods of gestation, an early period (11th to 14th completed week) and the period when chemical screening is normally performed (15th to 21st week). ROC analysis indicated 80 per cent and 78 per cent detection rates, respectively, at 5 per cent false-positive rate, in the two gestational periods. Hyperglycosylated hCG values were modelled with beta-core fragment values, total oestriol values and maternal age. ROC analysis indicated 97 per cent detection rate at 5 per cent false-positive rate. This detection rate and this level of Down syndrome and control patient discrimination surpasses that of any other serum, urine or ultrasound screening protocol. Hyperglycosylated hCG should be considered as a new screening test for aneuploid pregnancies, with the potential of detecting almost all cases of Down syndrome. Evaluation is needed by other centres in order to bring hyperglycosylated hCG into clinical practice.

Magnetic resonance urographic (MRU) techniques possess image quality and diagnostic capability that are improving with increasingly sophisticated imaging sequences and shorter scanning times. We describe the application of a fast breath-hold MR sequence (HASTE) in the assessment of ureteric obstruction in pregnancy. In the patient presented, HASTE MRU was successful in depicting ureteral anatomy and demonstrated dilation of both ureters below the level of the pelvic brim. This observation suggested distal ureteral obstruction rather than simple hydronephrosis of pregnancy. As a result, bilateral nephrostomies were performed and neonatal prematurity was avoided. Interestingly, in this patient, HASTE MR imaging also showed evidence of concurrent fetal hydronephrosis.

Objective: Previously we reported 3,3'-diiodothyronine sulfate-like material (compound W) in maternal serum, and studies suggest that compound W is derived from thyroid hormones of fetal origin. In this study we characterized gestational changes of urinary compound W concentrations to correlate with changes in serum concentrations., Study Design: Urinary samples were collected from 94 women at various gestational ages ranging from 3 to 40 weeks. Urinary compound W was first identified biochemically. The concentrations of compound W (adjusted for creatinine levels) were assessed by a 3,3'-diiodothyronine sulfate radioimmunoassay in ethanol extracts of urine samples., Results: Compound W increased to 88 +/- 1.4 pmol (of 3,3'-diiodothyronine sulfate equivalent)/mmol creatinine in urinary samples obtained from 26 women in the first trimester of pregnancy compared with 40 +/- 6.9 pmol/mmol creatinine in 10 nonpregnant women. Excretion of compound W increased further during the second and third trimesters: 171 +/- 17 (n = 18) and 434 +/- 26 (n = 50) respectively. In contrast, urinary 3,3',5-triiodothyronine sulfate concentrations measured by radioimmunoassay were similar during pregnancy to values in nonpregnant women., Conclusions: Urinary compound W concentrations increase with the progression of normal pregnancy and correlate with the increase in serum levels. Random spot urine compound W concentrations, adjusted for creatinine levels, may be used in place of serum levels in conditions in which obtaining serum samples may be technically difficult, especially during population screening.

Recent articles by Cuckle et al., Canick et al., and Isozaki et al. have evaluated urine beta-core fragment as a screening test for Down syndrome in second-trimester pregnancies. They found over four-fold elevation of beta-core fragment levels in Down syndrome pregnancies, and between 62 and 88 per cent detection of this trisomy at a 5 per cent false-positive rate. Urine beta-core fragment may be a superior screening test for Down syndrome pregnancies. In the present study, urinary total oestriol has been evaluated as a marker to use in combination with beta-core fragment in screening for Down syndrome pregnancies. The two markers were evaluated separately in relation to the urine creatinine concentration. To amplify screening performance, we evaluated the ratio of beta-core fragment to total oestriol levels (creatinine-independent). beta-core fragment and total oestriol levels were determined (normalized to creatinine, ng/mg creatinine) in urine samples from 480 unaffected and 12 Down syndrome pregnancies, collected consecutively at a single prenatal diagnosis centre. The median beta-core fragment level in Down syndrome cases was 4.5 MOM. Fifty-eight per cent of Down syndrome cases had beta-core fragment levels exceeding the 95th centile of unaffected pregnancies. The median total oestriol level in Down syndrome cases was 0.33 MOM. Forty-two per cent of Down syndrome cases had total oestriol levels exceeding the 95th centile of unaffected pregnancies. We investigated the ratio of the two determinants (beta-core fragment, ng/ml divided by total oestriol, ng/ml) in our sample set. The median beta-core fragment:total oestriol ratio in Down syndrome cases was 13 MOM. Seventy-five per cent of Down syndrome cases had a ratio exceeding the 95th and the 99.5th centile of unaffected pregnancies. Total oestriol complements beta-core fragment in urine screening for Down syndrome pregnancies. A test measuring the ratio of the two urine determinants may be a significant improvement over current serum methods for detecting Down syndrome.

Human chorionic gonadotropin (hCG) free beta-subunit levels were determined in 709 control and 13 Down syndrome urine samples from the second trimester of pregnancy. Results were normalized to urine creatinine concentration and converted to multiples of the unaffected pregnancy medium (MOM). The concentration of free beta-subunit in Down syndrome cases was 3.9 MOM. Seven of 13 Down syndrome pregnancies (54 per cent) had free beta-subunit levels at or above the 95th centile of unaffected pregnancies. Urine free beta-subunit may potentially be useful as a screening test for Down syndrome.

Maternal urinary gonadotrophin peptide (UGP) was recently found to be elevated in second-trimester Down syndrome pregnancies. There is controversy about its screening efficacy. Data in the Asian population are scanty. We measured the UGP levels in 29 Down syndrome pregnancies and 297 controls and expressed them as a ratio of the urine creatinine concentration. Median UGP MOM was elevated to 3.44 (95 per cent confidence interval 1.99-5.13) in cases, compared with controls. UGP values were widely scattered in cases and controls with extensive overlap such that only 35 per cent of Down syndrome cases were expected to be detected at a 5 per cent false-positive rate. The data of the present study and previous reports show that there is a wide variability of gestation-specific UGP median values. UGP alone does not appear to be an effective screening marker for fetal Down syndrome.

Levels of beta-core fragment and total oestriol in second-trimester maternal urine samples were measured in 32 Down syndrome pregnancies and 206 control pregnancies. Beta-core fragment and total oestriol values were corrected for the urinary creatinine level and expressed as multiples of the control medians (MOM). In addition, the ratio of the beta-core fragment level to the total oestriol level, without creatinine correction, was calculated, and expressed as MOM values. The median beta-core fragment, total oestriol, and ratio levels in Down syndrome cases were 5.42, 0.64, and 9.32 MOM, respectively. In the Down syndrome pregnancies, 66 per cent of the beta-core fragment levels were above the 95th centile of control levels, while 22 per cent of the total oestriol levels were below the fifth centile of control levels. In combination with maternal age, measurement of beta-core fragment and total oestriol levels in Down syndrome pregnancy resulted in an 80 per cent detection rate at a 5 per cent false-positive rate. Use of the ratio resulted in a univariate detection rate of 72 per cent. In combination with maternal age, the ratio resulted in a detection rate of 81 per cent at a 5 per cent false-positive rate. Based on this unmatched study, the measurement of a ratio of beta-core fragment to total oestriol levels, without the need for creatinine correction, may be useful in screening for fetal Down syndrome in second-trimester urine.

Objective: Our goal was to assess fetal kidney function in fetuses with megavesica diagnosed during the first half of pregnancy before treatment., Study Design: In a prospective interventional study 9 fetuses with megavesica diagnosed during the first half of pregnancy underwent vesicocentesis. Fetal urine biochemical markers (urine electrolytes, osmolarity, and beta 2-microglobulins) were determined after diagnostic vesicocentesis of the fetal megavesica., Results: Surprisingly, in four fetuses who underwent sampling at 13 to 18 postmenstrual weeks, vesicocentesis proved both diagnostic and therapeutic. Pregnancy proceeded with normal amniotic fluid volume, a normal-sized urinary bladder with normal dynamics, and normal postnatal renal function. A fifth fetus had trisomy 18. In three of the remaining four fetuses in whom sampling was performed at 16 to 20 postmenstrual weeks, biochemical markers indicated a poor prognosis. In the remaining fetus marginal results of biochemical studies prompted intrauterine treatment, but death from respiratory problems ensued after premature delivery at 31 weeks., Conclusions: Fetal megavesica in the first half of pregnancy is an indication for an immediate diagnostic vesicocentesis. This is the first report emphasizing early diagnosis of fetal megavesica with subsequent fetal vesicocentesis and demonstrating that this minimally invasive procedure can be life-saving if performed in early pregnancy.

Objective: Our purpose was to determine the effects of prolonged hypoxemia on fetal renal function and amniotic fluid volume and composition., Study Design: Twelve pregnant ewes underwent surgery at 115 +/- 2 days after mating (term approximately 147 days) for the implantation of fetal vascular, bladder, and amniotic sac catheters. At 125 +/- 1 days seven fetuses were studied during 6 days of hypoxemia and five control fetuses were studied over six days of normoxemia. Index values of fetal renal function and amniotic fluid volume were measured., Results: During hypoxemia fetal SaO2 and PaO2 were reduced from 60.9% +/- 1.6% and 21.9 +/- 0.6 mm Hg to 29.6% +/- 3.8% and 14.9 +/- 0.8 mm Hg, respectively. Fetal hypoxemia was associated with a transient acidemia (arterial pH 7.29 +/- 0.02) at 4 hours. There were no sustained alterations in fetal urine production (9.5 +/- 0.8 ml/hr/kg) or glomerular filtration rate (1.3 +/- 0.1 ml/min/kg) during hypoxemia. In control fetuses the amniotic fluid volume increased over 7 days, from 717 +/- 169 ml to 1031 +/- 147 ml, whereas in the hypoxemic fetuses it did not change (741 +/- 68 ml) over the same period., Conclusion: During prolonged fetal hypoxemia in the absence of acidemia, fetal urine production is maintained, whereas the normal gestational increase in amniotic fluid volume is prevented, raising the possibility that intramembranous reabsorption of amniotic fluid is increased by hypoxemia.

Purpose: Establish a clinically relevant threshold for urinary beta 2-microglobulin (beta 2m) to predict the presence of several renal damage in fetuses with obstructive uropathies., Methods: Retrospective review was conducted of urinary beta 2m levels, clinical outcomes, and pathological findings in 36 fetuses evaluated for presumed obstructive uropathy. Patients were divided into those free of renal injury (group 1, n = 13) and those with clinical or pathological evidence of severe irreversible renal injury (group 2, n = 23)., Results: Including all patients, a threshold beta 2m value of > 6 was able to predict the presence of severe renal damage with a 83% sensitivity and 71% specificity. beta 2m levels tended to decrease with increasing gestational age among those patients without renal injury (group 1), while beta 2m levels increased among those with severe renal damage (group 2). There was no difference in mean beta 2m levels in those < 20 weeks (p = 0.065) while there was a high degree of difference in those > 20 weeks of gestation (p < 0.001). In those > 20 weeks, a threshold of > 10 predicted the presence of severe renal damage with 100% sensitivity and specificity., Conclusions: Urinary beta 2m, especially in the fetus > 20 weeks, may be a clinically useful marker to detect the presence of severe renal damage due to obstructive uropathy and thus be an important adjuvant in the proper selection of fetuses for antenatal intervention.

Evaluation of fetal renal function by analysis of fetal urine sampled in utero may improve perinatal care after a prenatal diagnosis of bilateral obstructive uropathy. We provide reference intervals for 10 fetal urinary compounds and examine their variation with gestational age. Forty-one fetuses with bilateral obstructive uropathy (urine sampled between 20 and 38 weeks of gestational age) had normal, healthy values for serum creatinine (< or = 50 mumol/L) at ages 1-2 years. These cases were thus assumed to represent a reasonable approximation to healthy values. Sodium and beta 2-microglobulin concentrations significantly decreased with gestational age; calcium, ammonia, and creatinine significantly increased; glucose, phosphorus, chloride, urea, and total protein concentrations did not vary. Our results provide reference values for prenatal evaluation of fetal renal function and suggest that glomerular filtration of macromolecules and tubular reabsorption of glucose and phosphorus are mature by 20 weeks of gestation, whereas tubular reabsorption of sodium and beta 2-microglobulin increases progressively during the second half of gestation.

Ten fetuses with hydronephrosis underwent one to seven urine sampling procedures at 23 to 36 weeks' gestation to evaluate renal function. Postnatally, the infants' renal function was assessed by a combination of serum creatinine measurement, ultrasonography and renal scintigraphy. Six infants had pyelo-ureteric junction obstruction, two had megabladder with megaureter, and two had vesico-ureteric reflux. All infants had normal serum creatinine levels at the time of postnatal follow-up, but five of the seven with unilateral involvement had moderate or severe renal damage. Abnormal urinary electrolyte concentrations were found antenatally in only two of them. For the three infants with bilateral hydronephrosis, postnatal evaluation showed moderately or severely damaged kidneys despite prenatal evidence of normal biochemical indexes. Fetal urine electrolyte measurement may be accurate in the diagnosis of renal dysplasia, but its sensitivity is poor in predicting moderate renal dysfunction.

We evaluated 8 second-trimester fetuses who had undergone termination because of obstructive uropathies and correlated the renal histopathology with fetal urine biochemical prognostic parameters. Prenatal evaluation included serial vesicocentesis, karyotyping, and sonography. According to the urinary biochemical parameters, 3 fetuses were classified to be in the good prognostic category, 2 in the borderline prognostic category, and 3 in the poor prognostic category. The kidneys were evaluated both grossly and microscopically for hydronephrosis, pelvicaliceal dilatation, cystic changes and fibrosis. Fetuses in the poor prognostic category had severely damaged renal architecture, microcysts, macrocysts, and extensive fibrosis. Fetuses in the good prognostic category had minimal histopathologic changes with preservation of the architecture. Fetuses in the borderline category showed a moderate degree of renal damage but with focally preserved architecture. We conclude (1) that there is a direct correlation between elevation in urinary electrolytes and proteins and extent of underlying renal histopathological damage and (2) that appropriate detailed prenatal evaluation of the renal function can identify fetuses who could potentially benefit from in utero therapy.

Fetal urinary concentrations of insulin-like growth factor I (UIGF-I) and binding protein 3 (UIGFBP-3) were determined in patients with prenatal diagnosis of bilateral obstructive uropathy. Patients were retrospectively assigned to three groups, on the basis of outcome: group 1, termination of pregnancies (n = 11) with sonographic evidence of severe oligohydramnios or renal dysplasia, confirmed at histological examination; group 2, patients (n = 10) with postnatal plasma creatinine > 50 mumol/l at the age of 1 year (1 yr-pCreat); and group 3, patients (n = 16) with 1 yr-pCreat < or = mumol/l. The results show a significant increase in UIGF-I and UIGFBP-3 in groups 1 (18,159 +/- 9083 pg/ml; 2657 +/- 669 ng/ml) and 2 (1574 +/- 847 pg/ml; 176 +/- 50 ng/ml) in comparison with group 3 (35 +/- 6 pg/ml; 21 +/- 2 ng/ml). UIGF-I and UIGFBP-3 were significantly correlated with postnatal plasma creatinine, and were both sensitive (90 per cent; 80 per cent) and specific (88 per cent; 88 per cent) for prediction of elevated 1 yr-pCreat (> 50 mumol/l). Fetal urinary IGF-I and IGFBP-3 are increased in severe fetal bilateral obstructive uropathy, possibly reflecting tubular dysfunction or/and increased synthesis consequent upon fetal kidney injury. Their predictive value for postnatal renal function needs further assessment.

It is generally recognized that the sonographic findings of infantile polycystic kidney disease (IPKD) are bilaterally enlarged kidneys, oligohydramnios, an absent fetal bladder, and the typical kidney texture. Since there is a broad spectrum of renal compromise with IPKD, in utero diagnosis is thought to be limited to the severe forms. This paper reports a mild case of IPKD, where the in utero diagnosis was established by measuring fetal urine production and amniotic fluid volume serially during pregnancy, and by ultrasonographic examination of fetal kidneys.

Human chorionic gonadotrophin (hCG) is the most discriminatory maternal serum marker of Down's syndrome. We have carried out a study to establish whether urinary beta-core-hCG, a major metabolic product of hCG, might be an even better marker. Urine samples were available from seven singleton pregnancies with Down's syndrome, and one each of Edwards' syndrome, triploidy, and twins discordant for Down's syndrome. beta-Core-hCG levels were corrected for creatinine and expressed as multiples of the normal gestation-specific median (MOM) level derived from 67 singleton controls. There was a highly statistically significant elevation in level among the singleton Down's syndrome cases (P < 0.0005; Wilcoxon rank sum test). All had levels exceeding 2 MOM with a median of 6.11 MOM (95 per cent confidence interval 3.7-10.0). The levels were extremely low in Edwards' syndrome (0.08 MOM) and triploidy (0.02 MOM), but the twin pregnancy discordant for Down's syndrome did not have a raised beta-core-hCG level (0.64 MOM). The findings are sufficiently encouraging to investigate the possibility of urinalysis as a routine modality in the prenatal screening for Down's syndrome and other common serious aneuploidies.