Sequential fetal serum ß2-microglobulin to predict postnatal renal function in bilateral or low urinary tract obstruction.

OBJECTIVE: Fetal serum ß2-microglobulin has been shown to predict postnatal renal outcome in cases of fetal obstructive uropathy. We assessed the value of serial measurements of fetal serum ß2-microglobulin in the prediction of postnatal renal outcome. METHODS: We retrospectively studied renal outcome in 42 fetuses with bilateral or low urinary tract obstruction that had fetal blood sampling on at least two occasions to assay serum levels of ß2-microglobulin. Amniotic fluid volume at the time of each sampling was recorded. We classified renal outcome as either favorable (when postnatal renal function was normal) or adverse (when postnatal chronic renal failure occurred or when renal dysplasia at autopsy was noted). A ß2-microglobulin cut-off of 5 mg/L and amniotic fluid index of 5 cm were used to predict postnatal renal outcome. RESULTS: Renal outcome was adverse in 28 cases and favorable in 14. In 12 (28.6%) cases, fetal serum ß2-microglobulin concentration differed between the first and last measurement. Prediction of postnatal renal outcome was correct in 11 of these cases based on the last ß2-microglobulin measurement. The sensitivity of ß2-microglobulin in predicting renal outcome was significantly higher (P = 0.005) when using the last rather than the first measurement (96.4% vs 64.3%), with similar specificity for both measurements (85.7% vs 78.6%, non-significant). The sensitivity of amniotic fluid volume was also significantly higher (P = 0.005) when using the last rather than the first measurement (75.0% vs 35.7%), with similar specificity for both measurements (64.3% vs 71.4%, non-significant). CONCLUSION: Sequential measurement of serum ß2-microglobulin, performed for adverse ultrasound findings, such as renal parenchymal abnormality or decreasing amniotic fluid volume, predicts postnatal renal outcome more accurately than does a single assay. This may be due to possible worsening of renal injury with increasing duration of urinary tract obstruction. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Non-invasive prenatal testing for trisomy 21 based on analysis of cell-free fetal DNA circulating in the maternal plasma.

OBJECTIVE: By-the-book implementation of non-invasive prenatal test and clinical validation for trisomy 21. STUDY DESIGN: Publicly funded prospective study of 225 cases. Women at risk for trisomy 21 > 1/250 based on combined ultrasound and serum markers during first or second trimester were eligible following an informed consent. The technique was established from the available literature and performed on 10 mL of venous blood collected prior to chorionic villus sampling or amniocentesis. Investigators were blinded to the fetal karyotype. Results were expressed in Z-scores of the percentage of each chromosome. RESULTS: Among 976 eligible cases, 225 were processed: 8 were used for pretesting phase and 23 to build a reference set. One hundred thirty six euploid cases and 47 with trisomy 21 were then run randomly. Eleven cases yielded no result (4.8%). Z-scores were above 3 (7.58+/-2.41) for chromosome 21 in all 47 trisomies and in none of the euploid cases (0.11+/-1.0). Z-scores were within normal range for the other chromosomes in both groups. Using a cut-off of 3, sensitivity and specificity were of 100% 95% CI [94.1, 100] and 100% 95% CI [98, 100], respectively. CONCLUSION: Non-invasive prenatal test for trisomy 21 is a robust strategy that can be translated from seminal publications. Publicly funded studies should refine its indications and cost-effectiveness in prenatal screening and diagnosis. © 2015 John Wiley & Sons, Ltd.

Fetal urine biochemistry at 13-23 weeks of gestation in lower urinary tract obstruction: criteria for in-utero treatment.

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, ß-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 ß-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 ß-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.

Fetal airway management on placental support: limitations and ethical considerations in seven cases.

The aim of this study was to evaluate the paediatric and maternal outcome after ex utero intrapartum treatment (EXIT). A retrospective review was carried out of the medical charts (gestational age, circumstances of diagnosis, multidisciplinary prenatal decision, date of surgery, paediatric and maternal outcome) of all the fetuses eligible for/delivered via the EXIT procedure in our paediatrics and obstetrics tertiary care and teaching centre, between October 2004 and May 2011. Seven fetuses with cervical teratoma, epignathus tumour or congenital high airway obstruction syndrome (CHAOS) were included in our study. Two pregnancies were terminated and five fetuses were delivered alive. The airway was secured in all five cases (two endotracheal intubations and three tracheostomies). No maternal complications were observed. On average, babies were delivered at 32 gestational weeks, and spent 31 days in the intensive care unit. All but one baby were ventilated for 18 days. Long-term paediatric outcome was favourable. It is concluded that airway management by the EXIT procedure has become an efficient technique. A multidisciplinary prenatal assessment is essential in order to select appropriate cases.

[Epignathus teratoma: diagnostic and neonatal management; a case report]. / Tératome épignathe: diagnostic et prise en charge néonatale; à propos d'un cas.

Epignathus teratoma is a rare tumor whose prognosis essentially depends on its resectability and on neonatal care. When it is undiagnosed prenatally, mortality is close to 100 % at birth, because of obstruction of the upper airways. We present a case of epignathus teratoma detected during obstetrical ultrasound screening. Diagnosis enabled planning for a safe delivery in a suitable multidisciplinary unit and use of the EXIT procedure.

Binder phenotype: clinical and etiological heterogeneity of the so-called Binder maxillonasal dysplasia in prenatally diagnosed cases, and review of the literature.

OBJECTIVE: Prenatal Binder profile is a well known clinical phenotype, defined by a flat profile without nasal eminence, contrasting with nasal bones of normal length. Binder profile results of a hypoplasia of the nasal pyramid (sometimes referred to as maxillonasal dysplasia). We report 8 fetuses prenatally diagnosed as Binder phenotype, and discuss their postnatal diagnoses. METHODS: Ultrasonographic detailed measurements in 2D and 3D were done on the 8 fetuses with Binder profile, and were compared with postnatal phenotype. RESULTS: All fetuses have an association of verticalized nasal bones, abnormal convexity of the maxilla, and some degree of chondrodysplasia punctata. The final diagnoses included fetal warfarin syndrome (one patient), infantile sialic acid storage (one patient), probable Keutel syndrome (one patient), and five unclassifiable types of chondrodysplasia punctata. CONCLUSION: This series demonstrates the heterogeneity of prenatally diagnosed Binder phenotype, and the presence of chondrodysplasia punctata in all cases. An anomaly of vitamin K metabolism, possibly due to environmental factors, is suspected in these mild chondrodysplasia punctata. We recommend considering early prophylactic vitamin K supplementation in every suspected acquired vitamin K deficiency including incoercible vomiting of the pregnancy.

Prenatal imaging findings in rapidly involuting congenital hemangioma of the skull.

We report two cases of rapidly involuting congenital hemangioma (RICH) of the skull diagnosed in the third trimester of gestation, and also present a brief review of the literature. In both of our cases ultrasound examination showed a soft tissue vascular mass of the skull with a specific sonographic finding: a thin hyperechogenic line over the lesion and continuous with the calvaria, suggesting a subperiosteal origin and possibly accounting for a mass effect on the underlying skull. This was slight in one case and marked in the other (and associated with involvement of the calvaria). On prenatal T2-weighted magnetic resonance imaging, the signal of each of the lesions was less marked than the hypersignal encountered in the postnatal period. Postnatal clinical and radiological follow-up over the first few months after delivery confirmed the diagnosis of RICH in each case by demonstrating a significant decrease in the size of the tumor and regression of the vascular component, with complete involution of the lesion within a year.

Comparison between magnetic resonance imaging and fetopathology in the evaluation of fetal posterior fossa non-cystic abnormalities.

OBJECTIVES: To compare magnetic resonance imaging (MRI) and fetopathological findings in the evaluation of non-cystic fetal posterior fossa anomalies and to describe associated abnormalities. METHODS: This was a prospective study from 2000 to 2005 of fetuses identified on ultrasound as having sonographic suspicion of posterior fossa malformation. All underwent a thorough MRI examination of the fetal brain, after which we classified each fetus as presenting one of the following pathologies: vermian hypoplasia or agenesis, cerebellar and/or brain stem hypoplasia, destructive or dysplastic lesions. All of the pregnancies were then terminated, after which the whole fetus underwent fetopathological examination. We compared the findings from MRI and fetopathological examinations and recorded the associated cerebral and extracerebral abnormalities. RESULTS: Twenty-five fetuses were included. MRI was performed at a mean gestational age of 31 weeks, and fetopathological examination at 33 weeks. In 12 cases we observed vermian hypoplasia, six had partial vermian agenesis, 11 had cerebellar hemisphere hypoplasia, seven had brain stem hypoplasia, four had destructive lesions and six had dysplastic lesions. The two techniques were similar in their performance with respect to the detection of vermian agenesis, brain stem hypoplasia and destructive lesions. There were four false-positive results of MRI for vermian hypoplasia and a poor agreement regarding cerebellar hemisphere hypoplasia. No dysplastic lesions were diagnosed by MRI. None of the posterior fossa malformations was isolated and many cerebral and extracerebral abnormalities were found. CONCLUSION: A systematic analysis of the posterior fossa in fetal MRI makes it possible to diagnose accurately most posterior fossa malformations. These malformations never occurred in isolation in our study.

Prenatal diagnosis of some metabolic diseases using early amniotic fluid samples: report of a 15 years, experience.

BACKGROUND: In the present study, we report the results of 132 prenatal diagnoses performed on chorionic villi and cell-free amniotic fluid obtained simultaneously at 12-13 weeks of gestation. In addition, we report the result of 59 prenatal diagnoses performed at 12-13th week using amniotic fluid only. METHODS AND RESULTS: A total of one fetal loss (1/191) was observed when a sample of amniotic fluid was obtained at around 12-13 weeks, whereas three losses (3/82) were observed after midtrimester amniocentesis. We attribute this finding to the fact that only a very small volume of amniotic fluid was sampled using a very small needle. CONCLUSION: From these data it appears that when a couple is facing a high risk of recurrence of some metabolic diseases, the study of chorionic villus and amniotic fluid sampled simultaneously offers a safe and reliable method of early prenatal diagnosis.

Fetal aqueductal glioneuronal hamartoma: a clinicopathological and physiopathological study of three cases.

UNLABELLED: Fetal hydrocephalus due to aqueductal stenosis is classified into two main groups: congenital (X-linked, atresia, septa and forking) and acquired (post-infectious or post-hemorrhagic, gliosis and tumors). MATERIAL AND METHODS: We report three fetal cases presenting with severe hydrocephalus, two of which being apparently sporadic, and the third possibly inherited. On macroscopic examination, no associated malformations were identified, either craniofacial dysmorphy, or visceral abnormalities. Neuropathological study revealed massive hydrocephalus caused by narrowing of the Aqueduct of Sylvius. Histological examination evidenced a nodular, well-demarcated mass producing into the aqueductal lumen, and containing numerous immature proliferating glioneuronal cells. Immunohistochemical analyses did not suggest a developmental abnormality of the subcommissural organ but rather a hamartomatous malformative process. RESULTS: Hamartoma of the posterior fossa has been rarely reported. Post-natal cases have been described in the cerebello-pontine angle or in the quadrigeminal plate, and have always been diagnosed as pilocytic or low-grade astrocytomas. In our cases, the lesions could be related to so-called pencil glioma, sometimes associated with type 1 neurofibromatosis and, to our knowledge, have never been described prior to birth. The occurrence during fetal life and the progressive maturation of the nodules are more likely in favor of a hamartomatous process. CONCLUSION: Even though they could sporadically occur, an accurate genetic counseling should be required in order to ensure that there is no familial history of Recklinghausen disease, and to provide a more precise evaluation of recurrence risk.

Isolated pericardial effusion in the human fetus: a report of three cases.

OBJECTIVE: Our objective was to determine the possible underlying etiologies and outcome in isolated fetal pericardial effusion. METHODS: Doppler fetal echocardiography allowed the diagnosis of pericardial effusion in three patients and revealed the etiology in two. RESULTS: We present the findings in three cases of isolated pericardial effusion. In the first, the pericardial effusion was a manifestation of trisomy 21 associated with a myeloproliferative disorder. In the second, the pericardial fluid collection was the first sign of an autosomal recessive disease, idiopathic infantile arterial calcification. The third case was remarkable because of the spontaneous resolution of a large pericardial fluid collection. CONCLUSION: Isolated fetal pericardial effusion covers a wide spectrum of etiologies from severe genetic and chromosomal diseases to transient forms.

Maternal smoking during pregnancy and nicotine and cotinine concentrations in maternal and neonatal hair.

OBJECTIVE: Conflicting data have been reported in the association between maternal smoking and adverse effects during pregnancy and in neonates. Some studies, conducted on a limited number of patients have evaluated maternal consumption and fetal exposure by measuring nicotine and cotinine in the hair. Our aims were to evaluate the relationship among maternal cigarette consumption, fetal smoking exposure and outcome of pregnancy in a population of pregnant women who smoked. DESIGN: Mothers smoking during pregnancy were included at their first prenatal visit and followed prospectively. Maternal data (demographic variables, obstetrical history and cigarette consumption), neonatal data and birth indicators (number of weeks of gestation, type of delivery, weight) were collected. Hair samples from the mothers and the babies were collected at birth. SETTING: The present study was conducted in the Department of Obstetrics of the University Hospital Robert Debré in Paris. POPULATION: A total of 254 women smokers were included in the study and 182 mother/neonate pairs were analyzed after exclusion of 50 babies whose hair samples were inadequate and 22 for various other reasons. METHODS: Nicotine and cotinine concentrations in the maternal and neonatal hair were measured at birth by radio-immunoassay. MAIN OUTCOME MEASURES: Cigarette consumption was based on self reporting and quantified each trimester. It was expressed more precisely during the third trimester by the mean number per cigarette per day. Nicotine and cotinine concentrations in the maternal and neonatal hair at birth were also analysed. RESULTS: Nicotine and cotinine concentrations in maternal hair were associated with cigarette consumption during the third trimester of pregnancy (P < 0.003 and P < 0.01, respectively). In neonates, only cotinine concentrations were associated to maternal cigarette consumption (P < 0.0001). This association remained significant in a multivariate analysis, which included maternal cotinine hair concentrations and the ethnic group. CONCLUSIONS: Our results have shown a strong relationship between maternal cigarette consumption and fetal exposure to smoking measured by cotinine concentrations in neonatal hair. Further studies are required to look for associations between fetal exposure and adverse pregnancy outcome.

Esophageal ligature in experimental gastroschisis.

BACKGROUND/PURPOSE: Recently, the authors have shown that in human fetuses suffering from gastroschisis, there is an amniotic fluid inflammatory response and that amniotic fluid exchange designed to disrupt the inflammatory loop seems to have a favorable impact on outcome. The authors, therefore, designed in the fetal sheep a model of gastroschisis in which amnioinfusion significantly improved the deleterious process. They hypothesized that regurgitation and presence of digestive enzyme in the amniotic fluid triggers and maintains the process of inflammation. METHODS: To test this hypothesis, the authors used their model of gastroschisis in the fetal lamb combined with esophageal ligation and compared it with gastroschisis with or without amnioinfusion. RESULTS: Of 34 fetuses operated on at midgestation (days 70 through 80), 11 died in utero or were stillborn, 8 had gastroschisis and amnioinfusion, 8 had gastroschisis and no amnioinfusion, and 7 had gastroschisis and esophageal ligation. There were 9 control fetuses. Fetuses were killed at day 145 by cesarean section. Extraabdominal bowels with fibrous peel were processed for histologic examination. Thickness of bowel muscularis (micrometers) was 82.7 +/- 19 for controls, 159 +/- 56 for the nonamnioinfused fetuses, 126 +/- 21 for the amnioinfused fetuses (P =.001), and 240 +/- 225.8 for fetuses with esophageal ligature combined with gastroschisis. The same results were obtained for thickness of serous fibrosis and plasma cell infiltration. Assay of amniotic fluid ferritin, lipase, and protein showed that only amnioinfusion lowered ferritin and protein to levels similar to those of controls, thus, illustrating its preventive effect on inflammation and that esophageal ligature did not prevent digestive enzyme presence in the amniotic fluid. CONCLUSION: In this model of gastroschisis in the fetal sheep, ligature of the esophagus, which was supposed to protect the extruded bowel by preventing oral regurgitation of digestive enzymes and by creating a relative hydramnios, did not improve the inflammatory and deleterious process, which is best prevented by amnioinfusion.

[Severe post-partum hemorrhage: descriptive study at the Robert-Debré Hospital maternity ward]. / Hémorragie grave du post-partum. Etude descriptive à la maternitè de l'hôpital Robert-Debré.

OBJECTIVE: To analyze the prevalence, cause, treatment, and risk factors of severe post-partum hemorrhage (transfusion, surgery, radiology) observed at the maternity ward of the Robert-Debré Hospital, Paris. Method. This retrospective cohort was collected from a database including 19182 deliveries from 1992 to 1998. The entire medical file was reviewed in cases of severe hemorrhage. RESULTS: The prevalence of severe post-partum hemorrhage was 23 per 10,000 deliveries (44 patients). Transfusion was performed in 44/44 and hysterectomy in 3/44. Three patients were transferred to the intensive care unit. There were no deaths. At multivariate analysis, risk factors for severe post-partum hemorrhage were: abnormal placental insertion (OR=7.2; 95CI: 2.18-18.3), cesarean (OR=5.8; 95CI: 2.9-11.6), multiple pregnancy (OR=3.2; 95CI: 1.3-7.8), prematurity (OR=3, 95CI: 1.5-6.2), hypertension (OR=2.9; 95CI: 1.3-6.3). Twenty-six percent of the patients had no risk factors. CONCLUSION: The prevalence of severe pot-partum hemorrhage is low in our experience. The methodology used for this retrospective cohort does not enable an explanation. Intensive obstetrical care is necessary in case of abnormal placenta insertion. In 10 out of 44 cases, severe post-partum hemorrhage occurred in a context of insufficient monitoring, late or erroneous diagnosis, or incorrect treatment.

[Pregnancy outcome and infant follow-up after diagnosis of nuchal anomalies at the 1st or 2nd trimester ultrasound examination]. / Etude de l'issue des grossesses et du devenir des enfants nés après un diagnostic de pathologie de la nuque à l'échographie du 1er ou 2e trimestre.

OBJECTIVES: The aim of this study was to determine pregnancy outcome and investigate infant follow-up after diagnosis of nuchal anomalies at the first or second trimester ultrasound examination in order to identify prognosis factors and improve prenatal counseling. PATIENTS AND METHODS: Between January 1994 and June 2000, double skin fold 3mm or cystic hygroma at the first trimester ultrasound, or thicken nuchal anomaly at second trimester ultrasound explorations were diagnosed at the Robert Debré maternity ward. RESULTS: One hundred fifty-nine pregnancies were terminated and 131 infants were delivered and followed with four pediatric examinations during the first two years of life. Among the 131 newborns, 104 (79%) progressed normally, 16 had a major malformation (heart, kidney, skeletal; 9 (6.8%) with a unique anomaly and 7 (5.3%) with malformation syndromes), and 14 (10.6%) presented nonspecific retardation of psychomotor development either alone (7 cases) or associated with an identified genetic syndrome (7 cases). DISCUSSION: Neonates who presented a nuchal anomaly during pregnancy are a high-risk population, particularly for retardation of psychomotor development which is not always diagnosed during the neonatal period. Careful postnatal follow-up is required to identify developmental disorders undiagnosed at birth. CONCLUSION: This series is the largest reported in the literature in terms of number of infants and also for postnatal pediatric follow-up and homogeneous pedratrician follow-up.

Correlation of alkaline phosphatase (ALP) determination and analysis of the tissue non-specific ALP gene in prenatal diagnosis of severe hypophosphatasia.

Prenatal diagnosis of severe hypophosphatasia by mutation analysis of the tissue non-specific alkaline phosphatase (TNSALP) gene is reliable and mostly informative. However, alkaline phosphatase (ALP) assay of CVS may be a useful complementary and independent method, especially when a mutation is unidentified and DNA from the index case is unavailable, rendering impossible the use of DNA polymorphisms as genetic markers of the disease. We report here mutation analysis of the TNSALP gene and ALP assay in nine cases of prenatal diagnosis of severe hypophosphatasia. The results showed a good correlation between ALP assay and DNA analysis in all but one case, which suggested that in at least some cases low values of ALP may correspond to affected fetuses as well as to heterozygotes.

[Prenatal MRI of corpus callosum agenesis. Study of 20 cases with neuropathological correlations]. / IRM anténatale des agénésies calleuses. Etude de 20 cas avec corrélations neuropathologiques.

Twenty prenatal MR studies of corpus callosum agenesis were retrospectively studied and compared with neuropathologic examinations (18) or postnatal imaging (2). Corpus callosum agenesis were either complete (14) or partial (6). Positive diagnosis was made in 19 cases/20. The diagnosis of "isolated" or "associated" corpus callosum agenesis was assessed in 11 cases/15. MR depicted 15 of the 33 associated neurologic abnormalities. Prenatal MR is a valuable complementary technique for the diagnosis of corpus callosum agenesis when sonography is doubtful. MR could improve prognosis evaluation, since it enables depiction of associated abnormalities, notably gyral abnormalities, posterior fossa malformations, and intra-cranial cysts. MR images prove to be useful before neuropathologic examinations.