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.

Perinatal mortality and morbidity, timing and route of delivery in monoamniotic twin pregnancies: a retrospective cohort study.

PURPOSE: Monoamniotic twin pregnancies are at high risk of perinatal complications and fetal loss. The objective of this study is to describe the management and outcomes of monoamniotic twin pregnancies in a French university obstetrics department. METHODS: Retrospective review of all consecutive monoamniotic twin pregnancies managed between 1992 and 2018 in a level-3 university hospital maternity unit. Antenatal variables, gestational age and other neonatal characteristics at delivery, mode of delivery, and its reason were recorded, together with outcomes, including a composite adverse neonatal outcome. RESULTS: Overall, 46 monoamniotic twin pregnancies (92 fetuses) were identified during the study period. Among them, 27 fetal losses and 2 early neonatal deaths were reported. Congenital abnormalities accounted for 33.3% of the 27 fetal losses, and unexpected fetal deaths for 29.6%. Among the 37 women who gave birth to 65 live infants at 23 or more weeks of gestation, 17 had cesarean and 19 vaginal deliveries. Overall and composite adverse neonatal outcomes did not differ significantly for the 33 children born vaginally and the 31 by cesarean deliveries. The prospective risk of intrauterine death in all 92 fetuses reached its nadir of 1.8% at 336/7 weeks. CONCLUSION: This series confirms the still high risk of fetal and neonatal death of these twins and shows that congenital abnormalities but also unexpected fetal deaths account for the majority of pre- and postnatal mortality. Our data suggest that vaginal delivery of monoamniotic twins is safe and that delivery for uncomplicated monoamniotic twins should be considered around 33 weeks of gestation, but not later than 35 weeks.

Loss-of-Function Variants in MYLK Cause Recessive Megacystis Microcolon Intestinal Hypoperistalsis Syndrome.

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital disorder characterized by loss of smooth muscle contraction in the bladder and intestine. To date, three genes are known to be involved in MMIHS pathogenesis: ACTG2, MYH11, and LMOD1. However, for approximately 10% of affected individuals, the genetic cause of the disease is unknown, suggesting that other loci are most likely involved. Here, we report on three MMIHS-affected subjects from two consanguineous families with no variants in the known MMIHS-associated genes. By performing homozygosity mapping and whole-exome sequencing, we found homozygous variants in myosin light chain kinase (MYLK) in both families. We identified a 7 bp duplication (c.3838_3844dupGAAAGCG [p.Glu1282_Glyfs∗51]) in one family and a putative splice-site variant (c.3985+5C>A) in the other. Expression studies and splicing assays indicated that both variants affect normal MYLK expression. Because MYLK encodes an important kinase required for myosin activation and subsequent interaction with actin filaments, it is likely that in its absence, contraction of smooth muscle cells is impaired. The existence of a conditional-Mylk-knockout mouse model with severe gut dysmotility and abnormal function of the bladder supports the involvement of this gene in MMIHS pathogenesis. In aggregate, our findings implicate MYLK as a gene involved in the recessive form of MMIHS, confirming that this disease of the visceral organs is heterogeneous with a myopathic origin.

Prenatal diagnosis of megacystis microcolon intestinal hypoperistalsis syndrome by biochemical analysis of fetal urine.

OBJECTIVES: The objective of the study is to determine a model of fetal urine biochemical markers to differentiate megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) from other megacystis. METHOD: This is a retrospective study of biochemical analysis of fetal urine in patients who presented prenatally with megacystis. We studied ß2-microglobulin, sodium, calcium, and phosphorus. Twenty-six patients subsequently diagnosed with MMIHS were compared with 2 control groups: one of end-stage renal failure (64 fetuses) and the second of "good" postnatal renal function (control group, 64 fetuses). RESULTS: Mean fetal urine ß2-microglobulin was significantly higher (P < .001) in end-stage renal failure (15.7 mg/L) than in MMIHS (2.2 mg/L) and the control group (3.2 mg/L). Fetal urine profiles differed significantly (P < .001) between MMIHS and the control group: median sodium 46.5 and 51 mmol/L, median calcium 1.12 and 0.73 mmol/L, and median phosphorus 0.03 and 0.15 mmol/L respectively. Fetal urinary ionic index [ratio: calcium / (phosphorus × sodium)] gave an area under the ROC curve of 0.86, at 54% sensitivity and 97% specificity, with correct classification in 84% of cases. We defined a nomogram to obtain a probability for MMIHS. CONCLUSION: Fetal urinalysis can be helpful in prenatal differentiation of MMIHS from posterior urethral valves with good postnatal renal function.

Urine biochemistry to predict long-term outcomes in fetuses with posterior urethral valves.

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, ß2-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 m2 ) and poor in 17% (GFR < 30 mL/min/1.73 m2 ). All fetal urine markers differed between CKD stage 1 + 2 and CKD stage 4 + 5 (P < 0.001). ß2-microblobulin showed an 87% sensitivity for a 72% specificity. A combination of ß2-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.

Socioeconomic Deprivation and Utilization of Anesthetic Care During Pregnancy and Delivery: A Secondary Analysis of a French Prospective, Multicenter, Cohort Study.

BACKGROUND: Socioeconomic deprivation is associated with reduced use of antenatal resources and poor maternal outcomes with pregnancy. Research examining the association between socioeconomic deprivation and use of obstetric anesthesia care in a country providing universal health coverage is scarce. We hypothesized that in a country providing universal health coverage, France, socioeconomic deprivation is not associated with reduced use of anesthetic care during pregnancy and delivery. This study aimed to examine the association between socioeconomic deprivation and (1) completion of a mandatory preanesthetic evaluation during pregnancy and (2) use of neuraxial analgesia during labor. METHODS: Data were from a cohort of 10,419 women who delivered between 2010 and 2011 in 4 public teaching hospitals in Paris. We used a deprivation index that included 4 criteria: social isolation, poor housing condition, no work-related household income, and state-funded health care insurance. Socioeconomic deprivation was defined as a deprivation index greater than 1. Preanesthetic evaluation was considered completed if performed more than 48 hours before delivery. The association between socioeconomic deprivation and completion of the preanesthetic evaluation and use of neuraxial labor analgesia was assessed by multivariable logistic regression adjusting for education level, country of birth, and maternal and pregnancy characteristics. RESULTS: Preanesthetic evaluation was completed for 8142 of the 8624 women (94.4%) analyzed and neuraxial labor analgesia was used by 6258 of the 6834 women analyzed (91.6%). After adjustment, socioeconomic deprivation was associated with reduced probability of completed preanesthetic evaluation (adjusted odds ratio 0.88 [95% confidence interval, 0.79-0.98]; P = .027) but not use of neuraxial labor analgesia (adjusted odds ratio 0.97 [95% confidence interval, 0.87-1.07]; P = .540). CONCLUSIONS: In a country providing universal health care coverage, women who were socioeconomically deprived showed reduced completion of preanesthetic evaluation during pregnancy but not reduced use of neuraxial labor analgesia. Interventions should be targeted to socioeconomically deprived women to increase the completion of the preanesthetic evaluation.

Association between maternal social deprivation and prenatal care utilization: the PreCARE cohort study.

BACKGROUND: Maternal social deprivation is associated with an increased risk of adverse maternal and perinatal outcomes. Inadequate prenatal care utilization (PCU) is likely to be an important intermediate factor. The health care system in France provides essential health services to all pregnant women irrespective of their socioeconomic status. Our aim was to assess the association between maternal social deprivation and PCU. METHODS: The analysis was performed in the database of the multicenter prospective PreCARE cohort study. The population source consisted in all parturient women registered for delivery in 4 university hospital maternity units, Paris, France, from October 2010 to November 2011 (N = 10,419). This analysis selected women with singleton pregnancies that ended after 22 weeks of gestation (N = 9770). The associations between maternal deprivation (four variables first considered separately and then combined as a social deprivation index: social isolation, poor or insecure housing conditions, no work-related household income, and absence of standard health insurance) and inadequate PCU were tested through multivariate logistic regressions also adjusted for immigration characteristics and education level. RESULTS: Attendance at prenatal care was poor for 23.3% of the study population. Crude relative risks and confidence intervals for inadequate PCU were 1.6 [1.5-1.8], 2.3 [2.1-2.6], and 3.1 [2.8-3.4], for women with a deprivation index of 1, 2, and 3, respectively, compared to women with deprivation index of 0. Each of the four deprivation variables was significantly associated with an increased risk of inadequate PCU. Because of the interaction observed between inadequate PCU and mother's country of birth, we stratified for the latter before the multivariate analysis. After adjustment for the potential confounders, this social gradient remained for women born in France and North Africa. The prevalence of inadequate PCU among women born in sub-Saharan Africa was 34.7%; the social gradient in this group was attenuated and no longer significant. Other factors independently associated with inadequate PCU were maternal age, recent immigration, and unplanned or unwanted pregnancy. CONCLUSION: Social deprivation is independently associated with an increased risk of inadequate PCU. Recognition of risk factors is an important step in identifying barriers to PCU and developing measures to overcome them.

Prenatal diagnosis of Bartter syndrome: amniotic fluid aldosterone.

OBJECTIVE: Bartter syndrome is a severe inherited tubulopathy characterized by postnatal salt wasting, severe polyuria, dehydration, failure to thrive and secondary hyperaldosteronism. Prenatally, the disease is usually discovered following the onset of severe polyhydramnios in the second trimester. We studied amniotic fluid aldosterone concentration in Bartter syndrome and in controls. METHODS: Amniotic fluid aldosterone was assayed by radioimmunoassay. We undertook a retrospective case-control study based on 36 cases of prenatally suspected and postnatally confirmed Bartter syndrome (22 with identified mutations): and 72 gestational age matched controls presenting with polyhydramnios and 72 without polyhydramnios. Amniotic fluid aldosterone was compared between the three groups. RESULTS: The median amniotic fluid aldosterone concentration in the Bartter syndrome group (90 pg/mL) was not different from that in the controls with polyhydramnios (90 pg/mL, P = 0.33) or without polyhydramnios (87 pg/mL, P = 0.41). CONCLUSION: Amniotic fluid aldosterone assay cannot be used for prenatal diagnosis of Bartter syndrome. © 2015 John Wiley & Sons, Ltd.

Posterior urethral valves and vesicoureteral reflux: can prenatal ultrasonography distinguish between these two conditions in male fetuses?

OBJECTIVE: The objective of the study was to evaluate prenatal sonographic signs that distinguish male fetuses with posterior urethral valves (PUV) from those with vesicoureteral reflux (VUR). METHODS: Prenatal data were retrospectively retrieved from all consecutive women delivering between 2003 and 2012 of a male newborn with a postnatal diagnosis of PUV or VUR. Prenatal parameters included fetal bladder characteristics, identification of a dilated posterior urethra, and change in shape and size in the fetal renal pelvis or ureter. RESULTS: One hundred thirty-six women gave birth to a male newborn with a postnatal diagnosis of PUV (n = 49) or VUR (n = 87). The presence of posterior urethral dilatation [21 (42.9%) fetuses versus 0 (0%), p = 0.000], a thickened fetal bladder wall [37 (75.5%) vs 4 (4.6%), p = 0.000], and anhydramnios [14 (28.6%) vs 0, p = 0.000] were strongly associated with the postnatal diagnosis of PUV. Change in shape and size in the fetal renal pelvis or ureter was observed in 15 (17.2%) of 87 children with VUR versus 1 (2.0%) out of 49 with PUV (p = 0.010). CONCLUSIONS: Prenatal ultrasound may differentiate with reasonable accuracy male fetuses with a postnatal diagnosis of PUV from those with VUR. © 2016 John Wiley & Sons, Ltd.

Amniotic fluid biochemistry in isolated polyhydramnios: a series of 464 cases.

OBJECTIVE: To report amniotic fluid biochemistry in a large series of 464 cases of isolated polyhydramnios in order to analyze both the outcome and the benefit of amniotic fluid biochemistry. METHODS: This retrospective cohort (2008-2012) included polyhydramnios cases for which amniotic fluid samples were sent to our laboratory for biochemical analysis (total protein, alpha-fetoprotein and gamma-glutamyl transpeptidase) so as to investigate the etiology. A Bartter index and an esophageal atresia index were defined. Final diagnoses were compared between groups to determine the association between these indices and the frequency and type of adverse outcomes. RESULTS: Among 464 cases of polyhydramnios considered isolated at ultrasound examination, severe fetal diseases were diagnosed in 136 (29.3%): 46 (9.9%) chromosomal anomalies, 28 (6%) Bartter syndrome, 23 (4.95%) other genetic syndromes, 22 (4.75%) swallowing disorders and 17 (3.7%) uro-nephrological disorders. Amniotic fluid biochemistry identified esophageal atresia with 66.6% (10/15) sensitivity and 100% specificity and Bartter syndrome with 85.7% (24/28) sensitivity and 84.2% specificity. CONCLUSION: Isolated polyhydramnios is associated with a high risk of severe fetal diseases. Molecular cytogenetics and amniotic fluid biochemistry are helpful tools.

Prevalence and outcome of teenage hospital births at the Buea Health District, South West Region, Cameroon.

BACKGROUND: Teenage pregnancy is a high-risk condition that requires skilled antenatal care for good outcome. World estimates in 2008 report about 16 million births to adolescent mothers, most of them occurring in low and middle-income countries. In Cameroon, about 12% of all births are to adolescent mothers. This study determines the prevalence of hospital teenage deliveries in the Buea Health District and compares the delivery outcomes and demographic characteristics between pregnant teenage mothers (14-19) and adult mothers (20-29 years). We also identify factors associated with adverse pregnancy outcomes. METHODS: We undertook a retrospective study of case files of patients who gave birth in the Buea Regional Hospital during the period 2009-2012, to determine the prevalence of hospital-delivered teenage pregnancies in the BHR. We also undertook a, cross-sectional study to compare the outcomes of 148 singleton adolescent births with 360 adult births in three health facilities in the Buea Health District during the period March 1 to August 31, 2013. RESULTS: The prevalence of teenage births was 13.3%. The adverse fetal outcomes imputable to adolescent births were low birth weight (<2,500 g) (OR, 2.79; 95% CI, 1.28-6.09), preterm babies (<37 weeks) (OR: 1.85; 95% CI, 1.01-3.41), low 5 min Apgar score < 7 (OR: 1.66; 95% CI, 0.91-3.0). Adverse maternal outcomes associated with teenage pregnancies were mainly perineal tear (OR, 1.6; 95% CI, 0.95-2.7). Teenage births were not discovered in any significant way to cause preeclampsia/eclampsia, episiotomy, premature rupture of membranes and caesarean section. Maternal factors like age and gravidity were discovered to lead to adverse fetal outcomes in adolescents, while maternal factors like age, unemployment, marital status and gravidity were, for their part, directly responsible for adverse maternal outcomes in adolescents. CONCLUSION: Teenage pregnancies are quite prevalent in the Buea Health District, and hospital delivery common. Adolescent pregnancies are more likely to lead to adverse fetal and maternal outcomes than adult pregnancies.

Apparent diffusion coefficient measurements of the fetal brain during the third trimester of pregnancy: how reliable are they in clinical practice?

OBJECTIVE: The objective of this study was to determine the reproducibility, the inter-hemispheric difference and the reference apparent diffusion coefficient (ADC) values of the fetal brain according to gestational age. METHOD: One hundred and one normal fetal brain (29.4-38.4 weeks) were analysed with diffusion-weighted MR imaging. ADC was measured in frontal white matter (FWM), occipital white matter (OWM), centrum semi-ovale (CSO), basal ganglia (BG), cerebellar hemisphere (CBM) and pons. ADC ratios (fronto-occipital, fronto-cerebellar and occipito-cerebellar) were calculated. Inter-observer reproducibility was assessed on 27 studies, using intra-class correlation coefficient and Bland-Altman plot. Inter-hemispheric difference was evaluated with Bland-Altman plot. Gestation-specific reference intervals were estimated for each brain region. RESULTS: Inter-observer bias was near zero. Limits of agreement (LOA) were clinically acceptable (-0.17; 0.20 to -0.38; 0.31 × 10(-3) mm(2) /s) for all brain regions except for CSO and pons. Inter-hemispheric bias was near zero. Smallest LOA were for FWM (±0.09 mm(2) /s) and BG (±0.019 mm(2) /s). ADC values decreased, whereas ADC ratio increased with gestational age, reflecting normal maturation. Fronto-occipital, fronto-cerebellar and occipito-cerebellar ratios were consistently above 0.8, 1 and 1, respectively. CONCLUSION: The fetal brain regions with the highest reproducibility and smallest inter-hemispheric differences are the frontal, occipital, cerebellar white matter and BG. ADC ratio could be useful to assess differential temporo-spatial maturation.

Diet or medically treated gestational diabetes: is there any difference for obstetrical and neonatal complications? A French cohort study.

OBJECTIVE: The aim of the present study was to determine specific obstetrical and neonatal complications associated with diet-treated gestational diabetes (DTGD) and medically treated gestational diabetes (MTGD). METHODS: This is a prospective cohort study of women followed in the Robert Debré Hospital (France, Paris) and who have given birth between 1 January, 2004, and 19 November, 2010. Clinical, biological, maternal and neonatal data were reported in the maternity database. Associations between obstetrical and neonatal complications and gestational diabetes were evaluated by estimating odd ratios (ORs) and their 95% CIs, using a logistic regression model. RESULTS: 16,244 pregnancies were included in the study. 1515 (9.3%) women had gestational diabetes: 1108 (7.3%) had DTGD, 243 (1.7%) had MTGD. After full adjustment, MTGD was associated with an increased risk of nonscheduled cesarean (ORnonscheduled=2.3; 95% CI: 1.6-3.3; P<0.001) while DTGD was not (ORnonscheduled=1.0; 95% CI: 0.8-1.3; P<0.96). Clinical macrosomia was positively associated with DTGD (OR=2; 95% CI: 1.7-2.4; P<0.0001) or MTGD (OR=2.9; 95% CI: 2.1-3.9; P<0.0001). CONCLUSION: This study confirms that macrosomia is the main complication of DTGD. By contrast, DTGD was not associated with neonatal hypoglycemia and cesarean, while these complications were associated with MTGD.

Specific biochemical amniotic fluid pattern of fetal isolated esophageal atresia.

BACKGROUND: Perinatal care of esophageal atresia (EA) may be improved by prenatal diagnosis. Ultrasound findings (polyhydramnios and/or nonvisualization of fetal stomach) lead to a detection rate of ~50%. An amniotic fluid (AF) biochemical pattern characterized by high total protein, γ-glutamyl transpeptidase (GGTP), and normal l-leucine-aminopeptidase (AMP) leads to a 100% detection rate. The aim of this study was to explain this specific pattern. METHODS: On the basis of enzyme activities assay, the following four objectives were sought: (i) comparing AF markers between EA and other digestive tract atresias, (ii) determining local GGTP synthesis in the esophagus (immunohistobiochemistry), (iii) determining the presence of a specific AF-AMP activity inhibitor, and (iv) comparing AF-AMP and AF-GGTP half-lives. RESULTS: The AF-EA pattern was similar to that observed in upper duodenal atresia (above the Oddi sphincter). No local synthesis of GGTP was observed in the esophagus. No AF-AMP activity inhibitor was found. AF-GGTP had a longer half-life than AF-AMP. CONCLUSION: Due to the swallowing anomaly observed in EA, GGTP and AMP values physiologically observed at 18 wk will decrease on the basis of the half-lives of markers, with a flat slope for GGTP and a sharp slope for AMP, therefore explaining the differences observed in the AF-EA pattern.

Is fetal cerebral MRI worthwhile in antenatally diagnosed isolated cleft lip with or without palate?

OBJECTIVE: This study aims to evaluate the use of fetal brain magnetic resonance imaging (MRI) following an antenatal sonographic diagnosis of isolated cleft lip with or without cleft palate (CL/P). METHOD: This was a retrospective study of 92 fetuses antenatally diagnosed with isolated CL/P on screening ultrasound. All patients underwent expert diagnostic antenatal ultrasound, fetal brain MRI, and karyotype analysis. RESULTS: Five cases were excluded from the study as associated abnormalities were detected on expert ultrasound: corpus callosum agenesis (n = 1), retrognathism (n = 3), and ectrodactyly (n = 1). Fetal MRI diagnosed unsuspected midline cerebral abnormalities in four out of the 87 remaining cases (4.6%): vermis agenesis (n = 1), isolated arhinencephaly (n = 2), and suspicion of pituitary abnormality (n = 1). All karyotype analyses were normal. CONCLUSION: In CL/P, the incidence of associated cerebral abnormalities overlooked on ultrasound is 4.6%. Careful evaluation of midline structures by expert ultrasound in CL/P is necessary and may be sufficient. MRI can be useful if the US examination is limited or in case of family history. However, the choice to proceed to fetal MRI may vary from institution to institution.

Outcome following prenatal diagnosis of severe bilateral renal hypoplasia.

OBJECTIVE: The aim of this research was to evaluate the outcome and prognostic value of fetal serum ß2-microglobulin in case of prenatal diagnosis of severe bilateral renal hypoplasia. METHODS: Cases of hypoplastic kidneys were detected on ultrasound and referred to our laboratory for determination of fetal blood ß2-microglobulin, over a 12-year period. Prenatal prognostic assessment was based upon amniotic fluid volume and fetal serum ß2-microglobulin (cut-off: 5 mg/L). Outcome measures were postnatal renal function or renal pathological features when termination of pregnancy (TOP) and genetic studies were performed. RESULTS: A total of 34 cases were identified; 13 (38%) were liveborn and 21 (62%) underwent TOP. Renal hypoplasia was confirmed postnatally in all cases. Oligohydramnios/anhydramnios was observed in 30/34 (88%) cases. Associated genetic or anatomical anomalies were found in 8/34 (24%) cases. Renal function of liveborn infants was normal in 4/13 cases. Renal lesions were observed in all TOPs (21/21 cases). Overall, 30/34 (88.2%) cases had a poor outcome. ß2-microglobulin accurately predicts poor renal outcome in 27/31 (87.1%) cases. ß2-microglobulin was not interpretable in three cases due to amniotic fluid contamination. The prognostic value of ß2-microglobulin was similar to that of amniotic fluid volume assessment. CONCLUSION: Hypoplastic kidneys complicated by oligohydramnios/anhydramnios are associated with poor outcome. Fetal serum ß2-microglobulin and oligohydramnios both predicted poor outcome.

Outcome and etiologies of fetal megacystis according to the gestational age at diagnosis.

OBJECTIVE: To investigate the gestational age-specific outcomes and the different etiologies of megacystis diagnosed at screening ultrasound. METHODS: A retrospective single-center study was conducted between 1989 and 2009. We identified all consecutive cases of megacystis prenatally diagnosed during routine ultrasound screening. Outcome, final diagnosis, and renal function were recorded. RESULTS: Eighty-four patients were included. An isolated lower urinary tract obstruction was observed in 38/84 (45.2%), ureterovesical reflux in 9/84 (10.7%), an associated congenital abnormality in 32/84 (38.1%) and a normal bladder in 5/84 (6%). Increased gestational age at diagnosis was correlated with an increased rate of live born children (P < 0.01). No cases of megacystis diagnosed in the first trimester were born alive. When diagnosis of posterior urethral valves (PUV) was made in the third trimester, the ultimate survival rate was 11/13 (84.6%) compared with 3/12 (25%) for a diagnosis made in the second trimester (P = 0.02). CONCLUSION: Lower urinary tract obstruction is the main etiology of megacystis. Megacystis can also be part of more complex malformations. Outcome of megacystis detected in the first trimester is poor. PUV detected in the third trimester had a better overall survival rate than PUV detected in the second trimester.

Biochemical analysis of cystic fluid in the diagnosis of fetal intra-abdominal masses.

OBJECTIVE: The aim of the study was to evaluate a biochemical analysis of fluid sampled in utero from fetal abdominal cystic masses. METHODS: A retrospective study of 42 intra-abdominal cystic masses [ovarian cysts (n = 22), cloaca (n = 8), urodigestive fistulae (n = 4), and urogenital sinuses (n = 8)] was carried out. The control group (n = 30) consisted of fetal urine. Seven biochemical markers were assayed: sodium, estradiol, ß(2) -microglobulin, total proteins and digestive enzymes, gamma-glutamyl transpeptidase, aminopeptidase M, and intestinal alkaline phosphatase isoenzyme. Outcome of pregnancies and final diagnosis of intra-abdominal mass were known in all cases. RESULTS: Biochemical patterns allowed to demonstrate (1) an ovarian origin based on elevated level of estradiol and of total proteins (100% specificity, 100% sensitivity); (2) urodigestive fistula based on the presence of high levels of digestive enzymes (cloaca in female fetuses or recto-urethral fistula in male fetuses); and (3) a renal origin (urinary pattern with low total proteins and absence of digestive enzymes); however, a biochemical pattern could not differentiate between fetal urogenital sinus and megacystis. CONCLUSION: Etiological diagnosis of a fetal cystic abdominal mass could impact both prenatal and postnatal management providing adapted prenatal counseling by a pediatric surgeon in surgically correctable congenital anomalies.

Outcome of prenatally detected bilateral higher urinary tract obstruction or megacystis: sex-related study on a series of 709 cases.

OBJECTIVE: To compare the sex specific outcome of fetuses with prenatally detected urinary tract dilatation, with the exclusion of pyelectasia. METHOD: Included in the study were 709 cases of major dilatation of the fetal urinary tract, diagnosed at routine ultrasound scan. For each sex group, cases were divided into two subgroups depending on the level of dilatation. Final diagnosis was based on postnatal evaluation or on fetal autopsy. Postnatal renal function was evaluated using serum creatinine at two years of age. RESULTS: Bilateral higher urinary tract dilatation was prenatally observed in 148 (20.8%) and lower urinary tract obstruction or bladder dilatation in 561 (79.1%) of the 709 cases (121 female and 588 male fetuses) (P <0.001). Bladder dilatation was less frequent in female fetuses (62%) than in males (82.6%) (P <0.001). At final diagnosis, associated malformations were observed in 53.7% of female fetuses versus 11% in males (P <0.001). The survival rate was 42.7%. Postnatal renal function, evaluated in 289/303 live infants, was impaired in 29.7% of cases and depended on the level of obstruction, but not on the sex. CONCLUSION: Prenatally detected urinary tract dilatation has a poor prognosis both in male and female fetuses. Associated malformations are observed more frequently in female than in male fetuses.

Inner ear lesions in congenital cytomegalovirus infection of human fetuses.

Congenital cytomegalovirus (CMV) infection is the leading cause of non-hereditary congenital sensorineural hearing loss (SNHL). The natural course and the pathophysiology of inner ear lesions during human fetal CMV infection have not yet been reported. Inner ear lesions were investigated in six CMV-infected fetuses aged 19-35 postconceptional weeks and correlated with central nervous system (CNS) lesions. All the fetuses had high viral loads in the amniotic fluid and severe visceral and CNS lesions visible by ultrasound. Diffuse lesions consisting of both cytomegalic cells containing inclusion bodies and inflammation were found within all studied structures including the inner ear, brain, other organs, and placenta, suggesting hematogenous dissemination. Cochlear infection was consistently present and predominated in the stria vascularis (5/6), whereas the supporting cells in the organ of Corti were less often involved (2/6). Vestibular infection, found in 4/6 cases, was florid; the non-sensory epithelia, including the dark cells, were extensively infected. The endolymphatic sac was infected in 1 of 3 cases. The severity of inner ear infection was correlated with the CNS lesions, confirming the neurotropism of CMV. This study documenting infection of the structures involved in endolymph secretion and potassium homeostasis in fetuses with high amniotic fluid viral loads suggests that potassium dysregulation in the endolymphatic compartment of the inner ear may lead to secondary degeneration of the sensory structures. In addition, the occurrence of SNHL depends on the intensity and duration of the viral infection and inflammation.