Biomedical subjects
Publications and source records attributed to M Dommergues.
On the basis of prenatal identification of a cleft lip by embryoscopy, a case of van der Woude syndrome was diagnosed at 11 menstrual weeks, allowing for early termination of pregnancy. The potential of embryoscopy to detect minor malformations in early pregnancy is discussed from both the technical and the ethical point of view.
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.
OBJECTIVE: Fetal hyperchogenic bowel is associated with a variety of conditions, the incidence of which has yet to be studied. STUDY DESIGN: The outcomes of 182 cases of fetal hyperechogenic bowel were reviewed. Screening for maternal toxoplasmosis, fetal karyotyping, and amniotic fluid digestive enzyme assays were performed in all cases. Eight mutations associated with cystic fibrosis were analyzed in 116 cases. RESULTS: Of 135 newborns, 121 were normal, but nine underwent surgery for gastrointestinal obstruction, three had cytomegalovirus or parvovirus infection, one had a triple X chromosome, and one died from sudden infant death syndrome. In utero fetal death was observed in 24 cases. Elective termination of pregnancy was performed in 23 cases for associated anomalies. CONCLUSIONS: Hyperechogenic fetal bowel was associated with increased risk for adverse outcome. Prenatal management should include ultrasonographic surveillance, fetal karyotyping, amniotic digestive enzyme assays, and screening for cystic fibrosis and infectious disease.
OBJECTIVE: Our purpose was to evaluate the safety of vaginal delivery of triplets. STUDY DESIGN: A retrospective case-control study on 69 consecutive triplet pregnancies delivered in the same institution between 1981 and 1992. Vaginal delivery was attempted in 23 otherwise uncomplicated triplet pregnancies, which form the study group. They were compared with 23 controls undergoing routine cesarean section and matched for gestational age at birth. Maternal hospital stay, neonatal mortality, hospitalization in the neonatal intensive care unit, and 5-minute Apgar scores were compared by means of paired t tests. RESULTS: In the vaginal delivery group there was one neonatal death related to prematurity (32 weeks) after intrapartum cesarean section for failure to progress. However, neonatal mortality was not significantly increased in comparison with controls (1 of 69 vs 0). In the study group Apgar scores were significantly higher (9.5 vs 8.4) and hospitalization in the neonatal care intensive unit was significantly shorter (6 vs 18 days) than in the cesarean section group (p < or = 0.002). CONCLUSION: In carefully selected cases vaginal delivery of triplets may be safe.
Multifetal pregnancy reduction has had a major impact upon perinatal morbidity and mortality following iatrogenic multiple pregnancies. There are still residual risks, however, that are higher for higher order multiples than for pregnancies that started out at lower numbers. There are many, but not complete, parallels between reductions for number per se, and selective termination because of diagnosed abnormalities.
Linkage analyses in generalized recessive dystrophic epidermolysis bullosa (RDEB) have implicated the type VII collagen gene (COL7A1), which encodes the major component of anchoring fibrils, and recent identification of COL7A1 mutations has provided direct evidence for COL7A1 defects underlying RDEB. In this study, COL7A1 gene analysis was used to successfully perform first-trimester prenatal diagnosis in six families at risk for recurrence of the disease. In four families, three affected with the most severe variant of RDEB (the Hallopeau-Siemens form, HS-RDEB) and one with generalized nonmutilating RDEB, prenatal diagnosis was established by linkage analysis using polymerase chain reaction-based detection of PvuII and AluI intragenic restriction fragment length polymorphism. In two other HS-RDEB families, prenatal diagnosis was carried out by direct detection of mutations in COL7A1, using denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplified genomic fragments. Analysis of fetal DNA from chorionic villus biopsy or from amniotic fluid cells showed that the fetus had inherited at least one normal COL7A1 allele in all cases. Therefore, the fetus was predicted to be unaffected in the six pregnancies, and this has been confirmed in the newborn infants. Genotype analysis with COL7A1 polymorphic markers, or direct COL7A1 mutation detection in families at risk for the disease, represent early and rapid diagnostic alternatives to second-trimester evaluation of fetal skin samples, and thus offer a major advance in prenatal diagnosis of this life-threatening form of epidermolysis bullosa.
We consecutively managed 25 cases of fetal chylothorax with hydrops (pleuroamniotic shunting in 20/25 cases). Three of the 16 liveborn infants died before day 5 from malformations (n = 1) or complications of antenatal origin (n = 2). Eleven of the 13 survivors were treated in our unit. Four infants whose chylothorax had resolved before birth following antenatal shunting were delivered at term, and had no respiratory disease. Seven infants, whose chylothorax persisted, were delivered prematurely and required intensive respiratory care (with mechanical ventilation for a median duration of 34 days). The 11 infants were maintained on total parenteral nutrition for a median duration of 31 days. They were discharged home after complete clinical recovery at a median age of 64 days. Antenatal pleuroamniotic shunting may improve the prognosis of congenital chylothorax with hydrops. Chylothorax persisting at birth resolves progressively with medical management.
The object of this study was to explore the role of folate in the pathophysiology of neural tube defects (NTD). Maternal and fetal serum and red blood cell folate were assayed in 14 cases of NTDs and compared with 14 controls with other malformations and matched for gestational age (range 18-36 weeks). In mothers of NTD fetuses, serum folate (5.2 ng/ml), red blood cell folate (294 ng/ml) and the folate methylation rate (65%) were significantly lower than in controls (6.6 and 399 ng/ml, respectively, and 77%). However, the fetal folate status was similar in cases and controls. In the NTD group, folate metabolism was altered in the mothers but not in the fetuses. Therefore, a normal folate placental transfer can be assumed in this group. In addition, it could be speculated that decreased maternal folate methylation might be involved in the pathogenesis of NTDs.
BACKGROUND: Tenascin is a mesenchymal extracellular matrix glycoprotein transiently expressed during development, mainly at the site of epithelial-mesenchymal interactions. It is thought to play a key role in morphogenesis. Little is known about the distribution of tenascin in normal human fetal kidney, and, so far, no data have been reported concerning the distribution of the protein in fetal cystic kidneys. EXPERIMENTAL DESIGN: Using specific mAb and the immunofluorescence technique, we analyzed the distribution of tenascin in normal human embryonic (n = 3), fetal (n = 15), and mature kidneys (n = 4) and in fetuses affected with autosomal recessive polycystic disease (n = 3), autosomal dominant polycystic disease (n = 3), and cystic dysplasia (n = 3). We compared the distribution of this protein with that of fibronectin and types I, III, V, and VI collagens. RESULTS: In normal developing kidneys, tenascin is present in the uninduced blastema and in the mesenchyme around differentiating nephrons. It is homogeneously distributed in the inner cortex and in the medulla. During maturation, tenascin expression persists in the medulla but progressively decreases in the cortex. Tenascin is present in the mesangial area from the S-shaped body stage. Both types of polycystic diseases are characterized by a marked and diffuse increase in cortical and medullary expression of tenascin as well as types III, V, and VI collagen. In cystic dysplasia, two types of changes were observed: (a) increased tenascin and interstitial collagen expression in the subcapsular strips of condensed mesenchyme; and (b) heterogeneous medullary tenascin distribution with positive labeling of the condensed mesenchyme surrounding cysts and primitive ducts and negative labeling of the loose interstitial mesenchyme, contrasting with the diffuse accumulation of types III, V, and VI collagen. CONCLUSIONS: In the human fetal kidney, tenascin is expressed by blastema cells and disappears when converted to epithelium. In polycystic diseases, an early increase in tenascin and interstitial collagen expression suggests that renal mesenchyme per se may contribute to the progressive alteration of the kidney. In cystic dysplasia, phenotypic changes in metanephric blastema indicate inappropriate commitment of blastema cells into interstitial cells, leading to the definitive arrest of nephrogenesis; the heterogeneity in tenascin medullary expression underlines the heterogeneity in the mesenchymal cell population.
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A case of Meckel-Gruber syndrome was diagnosed by embryoscopy at 10 menstrual weeks, allowing for early termination of pregnancy. Post-mortem examination confirmed the presence of polydactyly and bilateral cystic lesions of the mesonephros and metanephros. Both the forming nephrons and the collecting ducts were involved in the formation of renal cysts.
The diagnostic value of amniotic fluid gamma-glutamyl-transpeptidase (GGTP) and intestinal alkaline phosphatase (iALP) was evaluated in 55 patients who underwent amniocentesis for karyotyping because fetal gastric or small bowel dilatation had been detected by ultrasound. Gastrointestinal malformation was confirmed in 46 cases and there was no gastrointestinal anomaly in nine cases. Prenatal ultrasound was suggestive of gastroduodenal dilatation in 34 cases (group I) and small bowel dilatation in 21 cases (group II). In group I, amniotic fluid GGTP above the 99th percentile was 71 per cent sensitive and 100 per cent specific for a true anatomical defect of the digestive tract (mainly duodenal atresia). In group II, high levels of GGTP and/or iALP were 69 per cent sensitive and 83 per cent specific for a fetal digestive tract anomaly. In other words, when digestive tract dilatations were diagnosed by prenatal sonography, abnormal amniotic fluid enzyme activities were strongly suggestive of such an anomaly, the possibility of which was not precluded by normal amniotic fluid iALP and GGTP activities. But amniotic fluid digestive enzyme activities do not help in defining the prognosis.
In a mother with clinical evidence of chicken-pox at 12.5 weeks, fetal herpes varicella zoster infection was revealed by transient fetal ascites with liver calcifications at 27 weeks routine ultrasound. At 27 and 35 weeks fetal blood sampling and amniocentesis failed to demonstrate fetal viral infection. However, the diagnosis was confirmed postnatally based on thoracic herpes zoster at 8 months in an otherwise healthy infant. Polymerase chain reaction (PCR) on stored amniotic cells performed retrospectively was positive for varicella zoster virus (HVZV). This observation suggests that (1) in contrast to PCR, conventional fetal biology lacks sensitivity for prenatal diagnosis of HVZV infection, (2) the association of fetal sonographic abnormalities and positive amniotic PCR can be associated with a favorable pediatric outcome. Therefore, prenatal diagnosis of HVZV infection should be considered with the greatest caution.
OBJECTIVE: Our goal was to develop the most comprehensive database possible to counsel patients about selective termination for fetal abnormalities, because no one center has sufficient data to assess much more than crude loss rates. STUDY DESIGN: A total of 183 completed cases of selective termination from 9 centers in 4 countries were combined (169 twins, 11 triplets, 3 quadruplets). Variables included indications, methods, (potassium chloride, exsanguination, air embolus), gestational age at procedure, pregnancies lost (< or = 24 weeks), gestational age at delivery, and neonatal outcome. RESULTS: Indications for selective termination were 96 chromosomal, 76 structural, and 11 mendelian. Selective termination was technically successful in 100% of cases. In 23 of 183 (12.6%) miscarriage occurred before 24 weeks; 2 of 37 (5.4%) occurred when the procedure done at < or = 16 weeks and 21 of 146 (14.4%) when it was done thereafter. Air embolization had a higher loss rate: 10 of 24 (41.7%) compared with 13 of 156 (8.3%) by potassium chloride (chi 2 = 117, p < 0.0001). Three cases of selective termination performed in monochorionic pregnancies all resulted in pregnancy loss. Among 183 potentially viable deliveries, 7 occurred before 28 weeks, 19 at 29 to 32 weeks, 41 at 33 to 36 weeks, and 93 at > or = 37 weeks. Gestational age at delivery was not influenced by the technique used or the indication but was negatively correlated with gestational age at the time of selective termination. No coagulopathy or ischemic damage was observed in survivors. There was no maternal morbidity. CONCLUSIONS: (1) Selective termination in experienced hands for a dizygotic abnormal twin is safe and effective when done with potassium chloride. A total of 83.8% of viable deliveries occurred after 33 weeks and only 4.3% at 25 to 28 weeks. (2) Gestational age at the procedure correlated positively with loss rate and inversely with gestational age at delivery; this emphasizes the need for early diagnosis in multifetal pregnancies. (3) Coagulopathy tests are probably unnecessary.
OBJECTIVES: To precisely evaluate fetal renal function in cases of bilateral fetal urinary tract obstruction, we analyzed fetal urine metabolites by nuclear magnetic resonance spectroscopy. STUDY DESIGN: Fifty-six specimens of fetal urine samples in utero were retrospectively analyzed by proton nuclear magnetic resonance. Group 1 (n = 21) consisted of survivors for > or = 1 year with normal serum creatinine (< 50 mumol/L), for group 2 (n = 17) of survivors with abnormal serum creatinine (> 50 mumol/L), and group 3 (n = 18) of those with bilateral histologic dysplasia associated with fetal (termination of pregnancy) or neonatal death. RESULTS: A specific nuclear magnetic resonance profile was obtained for each of the three groups of renal function. A two-dimensional representation of alanine-valine and valine-threonine concentrations allows clear differentiation between the three degrees of renal function, with a sensitivity and specificity of 88% and 86%, respectively. CONCLUSIONS: In fetal bilateral urinary tract obstruction a fetal urine nuclear magnetic resonance profile allows an accurate identification of renal function at birth.
OBJECTIVES: Two major approaches for multifetal pregnancy reduction have been developed over the past several years: transabdominal potassium chloride by injection and pelvic procedures by either transcervical aspiration or transvaginal potassium chloride injection or by an automated spring-loaded puncture device. The purpose of this study was to create the largest database from among the world's largest centers to assess possible differences in efficacy and complication rates by transabdominal or transcervical or multifetal pregnancy reduction. STUDY DESIGN: Data on over 1000 completed pregnancies that underwent multifetal pregnancy reduction by both methods from major centers with among the highest worldwide experience were combined. Transabdominal cases were divided temporally (1986 through 1991 and 1991 through 1993). RESULTS: Transabdominal multifetal pregnancy reduction was successfully performed on 846 patients and transcervical or transvaginal on 238 patients. Transcervical or transvaginal reduction is performed earlier and starts and finishes with fewer embryos. In 12.6% of cases transcervical or transvaginal reduction left a singleton as opposed to 4.4% for transabdominal reduction. Pregnancy losses (up to 24 weeks) were observed in 13.1% of transcervical or transvaginal cases and in 16.2% of transabdominal cases early in the series and 8.8% of late transabdominal cases. Transcervical or transvaginal reduction may be safer very early in gestation and transabdominal safer later in the first trimester. Premature deliveries were comparable, with only about 5% delivered between 25 and 28 weeks. The smaller starting numbers for transcervical and transvaginal reduction may explain a slightly higher term delivery rate. The transabdominal route tends to reduce the fundal embryos and the transcervical and transvaginal the lower ones. The significance of this is not clear. CONCLUSIONS: (1) Multifetal pregnancy reduction by either method is a relatively safe and efficient method for improving outcome in multifetal pregnancies. (2) More than 84% are delivered at > 33 weeks. (3) The experience and preference of the operator are probably the key determinants for an individual patient. (4) An inverse relationship of starting and finishing number to loss rates and gestational age at delivery suggests that there still is a cost of iatrogenic multifetal pregnancies, even if multifetal pregnancy reduction can be successfully performed.
The specificities of autoantibodies directed against the acetylcholine receptor (AChR) for embryonic and adult muscle AChR were studied in 22 mothers with myasthenia gravis (MG) and in their newborns using human fetus and normal adult muscle AChR preparations. 12 mothers had transmitted MG to their neonates with, in three cases, antenatal injury. A clear correlation was found between occurrence of neonatal MG (NMG) and the high overall level of anti-AChR antibodies (embryonic or adult muscle AChR). However, a strong correlation was also found between occurrence of NMG and the ratio of anti-embryonic AChR to anti-adult muscle (Te/Ta) AChR antibodies (P < 0.0002). Taken together, these data suggest that autoantibodies directed against the embryonic form of the AChR could play a predominant role in the pathogenesis of NMG. Paradoxically, the three cases with antenatal injury presumably the most severe form of NMG, were not associated with high Te/Ta. At the clinical level, these observations could prove helpful in the prediction of transmission of NMG.
In order to evaluate renal function, fetal urine was sampled in 27 fetuses with urinary tract obstruction diagnosed by ultrasonography. Amino acid concentrations were measured retrospectively. On histological examination performed after termination of pregnancy, five fetuses were found to have bilateral renal dysplasia (group 1). Eleven fetuses developed renal failure after birth: at one year, plasma creatinine concentration was over 50 mumol/l (group 2). Renal function was normal in the 11 other infants (group 3, plasma creatinine concentration at one year < 50 mumol-1). Statistically significant between-group differences were seen in fetal urine amino acids concentrations. However, there was an overlap of values in the three groups and individual amino acid concentrations could not be used predictively.