Antenatal biochemical expression of cystinuria and relation to fetal hyperechogenic colon.
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Amino Acids↗
Biomedical subjects
Françoise Muller
Publications and source records attributed to Françoise Muller.
Prenatal diagnosis of inherited epidermolysis bullosa in a patient with no family history: a case report and literature review.
OBJECTIVE: The junctional form of epidermolysis bullosa (EB) is a recessively inherited mechanobullous disease in which minimal trauma results in blister formation at the dermal-epidermal junction. A rare form associated with pyloric atresia (JEB-PA) is a severe clinical subtype leading to rapid demise after birth, thus justifying prenatal diagnosis. The case characterized by abnormal ultrasound findings at 35 weeks of gestation (gastric dilatation associated with polyhydramnios) of a patient with no family history is reported. METHOD: Postabortion skin biopsies were analyzed by immunofluorescence that revealed marked reduction of integrin alpha6beta4 in accordance with the diagnosis of JEB-PA. RESULTS: Amniotic fluid contained excess total protein (4 MoM), abnormally high AFP (20.4 MoM) related to skin lesions and abnormally elevated digestive enzyme suggestive of fetal vomiting of bile. The electrophoretic pattern of cholinesterases was unusual (additional slow band). Maternal serum AFP was 3.14 MoM and free beta-hCG 13.1 MoM. Because of these concomitant findings, JEB-PA was suspected. CONCLUSION: The case under study was atypical because of late clinical manifestations of the disease: polyhydramnios, gastric enlargement. As maternal serum AFP at 15 weeks may be normal, it was suggested that discovery of polyhydramnios during the second or the third trimester should prompt biochemical analysis of amniotic fluid, such as AFP and GGTP assay in all cases.
Adult↗
Fetal serum beta2-microglobulin as a marker for fetal infectious diseases.
OBJECTIVES: To evaluate whether fetal serum beta2-microglobulin could be used as a marker of fetal cytomegalovirus (CMV) or toxoplasmosis infection. METHODS: beta2-microglobulin was retrospectively assayed in fetal serum collected from 64 patients with maternal infectious seroconversion (toxoplasmosis in 49 cases, CMV in 15). Using a beta2-microglobulin cutoff of 5 mg/L, infection and control groups were compared. RESULTS: Fetal serum beta2-microglobulin was >5 mg/L (5.2-13.5 mg/L) in 12 of the 13 cases with proved fetal toxoplasmosis infection, indicating 90% sensitivity. In the 39 pregnancies with maternal seroconversion but no laboratory signs of fetal infection, fetal serum beta2-microglobulin was <5 mg/L, indicating 100% specificity. Fetal serum was >5 mg/L (6.3-32 mg/L) in 14 of the 15 cases with proved fetal CMV infection, indicating 93.3% sensitivity. Specificity cannot be evaluated because maternal serum is not routinely screened for CMV during pregnancy. CONCLUSIONS: Fetal serum beta2-microglobulin is a reliable marker of fetal CMV or toxoplasmosis infection, which can be used in ambiguous situations. Because this increase is not specific, fetal serum beta2-microglobulin would potentially be raised in other fetal infections.
Biomarkers↗
Neural tube defects cannot be diagnosed prenatally by electrophoresis of amniotic fluid transferrin isoforms.
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Amniotic Fluid↗
Prenatal diagnosis of megacystis-microcolon-intestinal hypoperistalsis syndrome: contribution of amniotic fluid digestive enzyme assay and fetal urinalysis.
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.
Adolescent↗
Fetal anal incontinence evaluated by amniotic fluid digestive enzyme assay in myelomeningocele spina bifida.
The goals of this study were to determine whether anal sphincter dysfunction in spina bifida develops during fetal life or after birth and whether it reflects the severity of spina bifida and therefore can be used as a criterion to select the cases that could benefit from in uterosurgery. Total protein and digestive enzyme activities [gamma-glutamyl transpeptidase (GGTP), aminopeptidase M (AMP), and alkaline phosphatase isoenzymes including the intestinal form (iALP)] were assayed retrospectively in amniotic fluid from 80 myelomeningocele spina bifida cases without unrelated associated malformation (gestational age 14-33 wk). A normal enzyme activity profile was observed in 46 of the 80 cases. Two abnormal profiles were observed: 1) bilious vomiting, characterized by abnormally high GGTP and AMP activities but normal iALP, and 2) digestive enzyme leakage, characterized by abnormally high activities of GGTP, AMP, and iALP, typical of anal incontinence. No relation was observed between these enzyme activity profiles and the different secondary signs of spina bifida or the level of the damage. In conclusion, anal sphincter dysfunction in spina bifida revealed by amniotic fluid digestive enzyme activities occurred before 24 wk in fetal life in 28.7% of cases. This criterion may be indicative of the severity of spina bifida and therefore perhaps could be used to select cases that are suited to in utero surgery. It could also be used to establish the potential benefit of this surgery in fecal incontinence.
Alkaline Phosphatase↗
Paradoxic activation of the renin-angiotensin system in twin-twin transfusion syndrome: an explanation for cardiovascular disturbances in the recipient.
Despite advances in treatment, twin-to-twin transfusion syndrome (TTTS) still carries a high risk for perinatal mortality and morbidity. Simple blood transfer from the donor to the recipient twin cannot explain all of the features of this disease, in particular the recipient's hypertensive cardiomyopathy. We report a case in which TTTS resulted in preterm delivery with early neonatal death of both twins, allowing assessment of the renin angiotensin system (RAS) status of each fetus, both by cord blood renin and aldosterone assay and by renal immunohistochemistry. The donor had severe oliguria/oligohydramnios, whereas the recipient, in addition to severe polyuria/polyhydramnios, had cardiomyopathy, atrioventricular regurgitation, and ascites. Although immunohistochemistry demonstrated that renal secretion of renin was up-regulated in the donor and down-regulated in the recipient, cord blood levels of renin and aldosterone were similar, with high renin levels in both twins. This observation supports the hypothesis that despite renal RAS down-regulation, the recipient is exposed to RAS effectors elaborated in the donor and transferred via placental shunts. This may contribute to cardiomyopathy and hypertension in the recipient, which cannot be accounted for by hypervolemia alone. We thus hypothesized that in TTTS, the recipient's hypertensive cardiomyopathy could be due to a mechanism similar to the classical model of hypertension referred to as "2 kidneys-1 clip." Thus the hypovolemic donor twin, comparable to the clipped kidney, produces vasoactive hormones that compromise the recipient, comparable to the normal kidney, causing hypertension and cardiomyopathy.
Adult↗
Fetal toxic effects of angiotensin II receptor antagonists: case report and follow-up after birth.
OBJECTIVE: To report a child born with renal impairment following severe anhydramnios due to maternal exposure to an angiotensin II receptor type 1 (AT1) antagonist, valsartan, and hydrochlorothiazide during the first 28 weeks of pregnancy. CASE SUMMARY: A hypertensive woman treated with valsartan 80 mg/day, hydrochlorothiazide 12.5 mg/day, prazosin 10 mg/day, lysine acetylsalicylate 100 mg/day, and levothyroxine 250 microg/day became pregnant. At 28 weeks' gestational age, severe anhydramnios associated with high beta2-microglobulin levels in the fetal blood cord was observed. Upon discontinuation of valsartan, fetal renal prognosis improved. In this case, using the Naranjo probability scale, the renal insufficiency of the child was probably related to valsartan. At the age of 2.5 years, the child presented with only mild chronic renal insufficiency. Growth parameters were within the normal range, and there was no evidence of developmental delay. DISCUSSION: Exposure to AT1 antagonists during the second part of pregnancy can lead to abnormalities similar to those observed after exposure to angiotensin-converting enzyme inhibitors, that is, reduced fetal kidney perfusion that may result in oligoamnios and neonatal renal insufficiency. Fourteen previous reports of maternal exposure to AT1 antagonists during this period have been published. In 6 cases, fetal or neonatal death occurred; in 2 cases, pregnancy was terminated because of complete anhydramnios or fetal abnormalities; in 1 case, renal insufficiency persisted at 8 months of age; in 2 cases, kidney function was fairly normal at birth; and in 4 cases, including the one described here, neonatal renal failure improved in the first year of life. CONCLUSIONS: AT1 antagonists should be avoided throughout pregnancy. If these agents are prescribed accidentally to a pregnant woman, monitoring of amniotic fluid volume and beta2-microglobulin fetal blood levels after discontinuation of the AT1 antagonist can provide critical data for advising parents on pregnancy and fetal outcome.
Amniotic Fluid↗
Fetal serum ss2-microglobulin and cystatin C in the prediction of post-natal renal function in bilateral hypoplasia and hyperechogenic enlarged kidneys.
OBJECTIVES: To evaluate fetal serum ss2-microglobulin and cystatin C in the prediction of post-natal renal function in bilateral hypoplasia and hyperechogenic enlarged kidneys. Predicting post-natal renal function is crucial to the prenatal evaluation of fetal nephropathies. Prenatal ultrasound can identify terminal renal failure, but is not sensitive enough to identify infants whose post-natal renal function will be impaired. Fetal serum ss2-microglobulin and cystatin C are potential predictors of post-natal renal function. METHODS: Fifty-four prenatally diagnosed cases of bilateral nephropathy were retrospectively reviewed. Final diagnosis was established using histological or post-natal findings: renal hypoplasia (n = 7), cystic dysplasia (n = 9), autosomal dominant polycystic kidney disease (ADPKD; n = 8) or autosomal recessive polycystic kidney disease (ARPKD; n = 22) and transient sonographic abnormalities (n = 8). Fetal serum ss2-microglobulin and cystatin C were assayed respectively in 54 and 38 cases. The prognostic value of these markers was assessed in terms of the post-natal outcome. RESULTS: In bilateral kidney hypoplasia and cystic dysplasia, ss2-microglobulin and cystatin C were significantly (p < 0.0001 and p < 0.02 respectively) higher than in the normal control group. In hyperechogenic fetal kidneys (ARPKD, ADPKD and transient sonographic abnormalities), these markers were not different from controls. However, whereas normal values cannot exclude renal failure, abnormal values predict post-natal renal failure. CONCLUSIONS: In bilateral renal hypoplasia and dysplasia, fetal serum ss2-microglobulin and cystatin C are good markers for post-natal renal function. However, in bilateral renal hyperechogenic enlargement, abnormal values are associated with poor post-natal renal function, but normal values cannot preclude renal failure.
Cystatins↗
Nonimmune fetal ascites: a series of 79 cases.
OBJECTIVE: The purpose of this study was to analyze the precision of ultrasonography in defining the cause and prognosis in fetal ascites. STUDY DESIGN: We conducted a retrospective study of 79 cases of fetal ascites. RESULTS: The mortality rate was 57% overall and ranged from 100% (7/7 cases) for metabolic storage disease to 0% (0/3 cases) in chylous ascites. Ascites before 24 weeks of gestation or combined with fetal hydrops indicates poor prognosis (respectively, 78.6% vs 45% mortality rate after 24 weeks; P<.01; and 77% vs 50.8% without hydrops; P<.02). Ascites was organic in 45 cases, infectious in 13 cases, idiopathic in 12 cases, and genetic in 9 cases. The cause was defined ultrasonographically in 28 of the 45 organic ascites and in 8 of the 25 isolated ascites. Urinary cause was the most frequent and the most successfully specified cause (14/15 cases). CONCLUSION: Routine ultrasonography detects fetal ascites, but the cause is extremely variable and difficult to specify. When associated with fetal hydrops, the prognosis is poor.
Adolescent↗
Medically assisted reproduction and second-trimester maternal serum marker screening for Down syndrome.
OBJECTIVES: To evaluate the effect of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) on total hCG, free ss-hCG, AFP and unconjugated estriol (uE3) used as markers for second-trimester Down syndrome maternal serum screening. METHODS: Second-trimester maternal sera from 1515 singleton pregnancies (970 by IVF, 545 by ICSI) were compared with control sera (21 014 cases). Free ss-hCG, total hCG, AFP and uE3 were compared between the control group and the medically assisted reproduction groups. The percentages of at-risk patients (>/=1/250) were also compared. RESULTS: No differences in values of the maternal serum markers were observed between the medically assisted and control groups. When maternal age was taken into account, the screen-positive rate for Down syndrome screening did not differ between the two groups. CONCLUSION: Patients undergoing assisted reproduction techniques can be counseled for maternal serum Down syndrome screening with the same efficacy as patients with naturally conceived pregnancies.
Adult↗
Prenatal biochemical screening for neural tube defects.
INTRODUCTION: Neural tube defects (NTDs) can be considered as a folate deficiency disorder. The prevalence of NTDs ranges from about 0.5 to 6 in 1,000 births. DISCUSSION: Two steps can be distinguished in biochemical screening for NTDs: 1. Screening in the general population, which is based on two complementary methods, maternal serum AFP screening and ultrasound screening; 2. Screening in a high-risk group, which requires fetal scanning by an expert sonographer. CONCLUSION: Amniocentesis for acetylcholinesterase electrophoresis is indicated when sonographic scans are difficult to interpret.
Amniotic Fluid↗
Second-trimester Down syndrome maternal serum screening in twin pregnancies: impact of chorionicity.
OBJECTIVE: To evaluate the diagnostic value of second-trimester maternal serum screening for Down syndrome in twin pregnancies. METHOD: On the basis of a prospective study of second-trimester maternal serum screening, we studied the distribution of alpha-fetoprotein (AFP) and free ss hCG in 3043 twin pregnancies with known outcome. There were 1561 dichorionic and 244 monochorionic pregnancies. The placental type was not available in 1238 cases. We compared 5 screening policies with the same risk, 1/250, cut-off: maternal age, maternal age corrected for the risk of having at least one affected twin in dichorionic pregnancies, maternal serum marker screening using observed AFP and free ss-hCG values divided by a factor of 2, by using the median values actually observed in the global twin population, or by the median values specific to mono- or dichorionic twins. RESULTS: When expressed in singleton-derived MoMs, the median was 2.10 for AFP and 2.11 for free ss-hCG. The median AFP did not differ between monochorionic and dichorionic pregnancies. The distribution of free ss-hCG was significantly shifted towards greater values in monochorionic (2.16 MoM) compared to dichorionic (2.07) pregnancies (p < 0.0001). Screened-positive and detection rates were, respectively, 6.6% and 27.3% using maternal age alone, 24.6% and 54.5% using maternal age corrected for the risk of having at least one affected twin in dichorionic pregnancies, 7.75% and 54.5% using observed AFP and free beta-hCG values divided by a factor of 2, 8.05% and 54.5% using the median values actually observed in the global twin population, and 7.75% and 54.5% using the median values specific to mono- or dichorionic twins. CONCLUSION: Trisomy 21 second-trimester maternal serum screening is feasible in twins, and is better than a policy based on maternal age alone.
Adolescent↗
Very low alpha-fetoprotein in Down syndrome maternal serum screening.
OBJECTIVE: To establish the frequency of very low maternal serum AFP and to differentiate congenital AFP deficiency from those diseases known to be associated with low AFP. METHODS: AFP values below 2 microg/L and borderline values up to 3 microg/L were retrospectively analysed in 839 773 singleton pregnancies included in a programme for routine screening of trisomy 21 maternal serum markers. RESULTS: Serum AFP was undetectable (< or =2 microg/L) in 8 cases, giving a frequency of 1/105 000. The calculated risk of Down syndrome was > or =1/250 in 5 cases. Fetal karyotype was normal. Seven of these pregnancies went to term (39-41 weeks) uneventfully, and birth weight was normal (3050-4110 g). In the 8th case, fetal death occurred at 35 weeks due to severe maternal diabetes. AFP levels between 2.1 and 3.0 microg/L were noted in 7 other cases. The calculated risk of Down syndrome was > or =1/250 in 5 cases, and fetal karyotype was normal. Pregnancies went to term in 4 cases (33-41 weeks), and birth weight was normal (3000-3380 g). In 3 cases, low hCG (<0.6 MoM) was associated with low AFP, and fetal death occurred at 15 to 16 weeks. CONCLUSION: Once technical errors have been excluded (repeat assay in a second run, calcium assayed to exclude the interference of EDTA for fluorimetric methods, dilution to exclude interfering antibodies, running on an alternative analyser, checking a second sample), very low second-trimester maternal serum AFP should prompt ultrasound examination in order to check fetal viability. Congenital AFP deficiency, an extremely rare disorder (1/100 000), should be suspected. It has no consequences for fetal and infant development, and parents should be reassured.
Adult↗
First-trimester screening for Down syndrome in France combining fetal nuchal translucency measurement and biochemical markers.
BACKGROUND: In France, there is a strictly regulated National Screening Programme for Down syndrome, based on second-trimester maternal serum markers. A prospective study of nuchal translucency together with retrospective evaluation of maternal serum markers was carried out to inform decisions on whether to move the programme to the first trimester. METHODS: Between January 1998 and June 2001, all women who presented for their prenatal care at 12 participating maternity units were, regardless of age, invited to provide a blood sample and to attend for an NT scan at 11 to 13 weeks. The results were used to derive Gaussian distribution parameters. Detection and false-positive rates were computed in two ways: statistical modelling and directly. The cut-off risk was 1 in 250 at term. RESULTS: A total of 5694 women with singleton pregnancies were screened including 26 with Down syndrome and 24 with other aneuploidies. The model-predicted detection and false-positive rates for combined ultrasound and serum screening were 81 and 4.5% compared to 64 and 6.0% for ultrasound alone. The directly observed rates were 73 and 4.7%, compared to 62 and 5.0% respectively. CONCLUSION: In France, first-trimester screening with nuchal translucency and maternal serum markers is likely to achieve a high screening efficiency. This has important implications for the national screening policy.
Adult↗
Hyperechogenic fetal bowel and Down syndrome. Results of a French collaborative study based on 680 prospective cases.
Hyperechogenic fetal bowel is prenatally detected by ultrasound during the second trimester of pregnancy in 0.1% to 1.8% of foetuses. It has been described as a normal variant and has often been associated with severe diseases, notably Down syndrome. The aim of the present study was to determine the risk of trisomy 21 in a prospective study of 680 fetuses with hyperechogenic foetal bowel. Karyotyping was performed on amniotic cells in 632 cases, and outcome was known in 655 cases. A 2.5% risk of Down syndrome and a 1% risk of other severe chromosomal anomalies were observed. Hyperechogenicity was isolated in 11/17 Down syndrome cases, and associated with other ultrasound anomalies in all seven cases of severe chromosomal anomalies. In conclusion, fetal bowel hyperechogenicity indicates a risk of chromosomal anomalies ten-fold higher than that expected on the basis of maternal age, therefore justifying invasive procedures.
Chromosome Aberrations↗
Detection and false-positive rates of maternal serum markers for Down syndrome screening according to maternal age in women over 35 years of age. A study of the agreement of eight dedicated software packages.
Maternal serum markers for trisomy 21 screening (MSS) can be assayed in women > or =35 years in an attempt to reduce the need for invasive procedures and thereby avoid their side effects. Our objective was to compare, in women > or =35, eight different software packages dedicated to second trimester MSS, thus providing reliable data for patient counselling. A simulation study was carried out on 189 sera from women with Down syndrome fetuses and 11 962 sera from mothers of unaffected babies. The first step was to estimate the joint distribution of alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG). The second step was to calculate trisomy 21 detection and false-positive rates for each software according to maternal age (35-45 years), using the usual 1:250 risk threshold. Agreement between software packages was measured using 2 x 2 kappa coefficients. Detection rates and false-positive rates increased with maternal age. Depending on the software, 57-71% detection rates were achieved at 35 years with 12-18% false-positive rates. At 45 years, 61-100% detection rates were achieved with 66-95% false-positive rates. Up to 39 years, all softwares were concordant (kappa coefficients >0.75). In the range 35-45 years, false-positive and detection rates increased substantially with maternal age and differences between software packages are observed.
Adult↗
Second trimester two-step trisomy 18 screening using maternal serum markers.
Trisomy 21 maternal serum marker screening has led to screening for other anomalies, including trisomy 18. Trisomy 18 is generally prenatally diagnosed because of major morphological defects. However, in up to 30% of cases ultrasound signs are unclear, and in most cases diagnosis is performed late in pregnancy. Of the different maternal serum markers, PAPP-A is now considered as the best for trisomy 18 screening. However, pregnancy-associated plasma protein A (PAPP-A) is of value in first trimester screening for trisomy 21, but not in the second trimester. We therefore propose a two-step screening strategy. Based on 45 trisomy 18 cases, we confirm the values of alpha-fetoprotein (AFP) (median 0.61 MoM), free beta-human chorionic gonadotrophin (beta-hCG) (median 0.24 MoM) and of PAPP-A (median 0.08 MoM). In the first step, a 0.5 MoM cut-off for AFP or for free beta-hCG resulted in detection of 37/45 trisomy 18 cases (82%) with a 10% false-positive rate. The second step consisted of the measurement of PAPP-A for all these false-positive cases. Using a PAPP-A cut-off of 0.5 MoM, all the 37 trisomy 18 cases were detected, but now with a 0.1-0.2% false-positive rate. Amniocentesis was only offered to these few patients. This two-step second trimester screening will be of value for patients who have not been included in first trimester screening based on nuchal translucency (NT) measurement combined with the first trimester markers, PAPP-A and free beta-hCG.
Adult↗