The ductus venosus in early pregnancy and congenital anomalies

The ductus venosus (DV) is a tiny vessel leading oxygenated blood from the placenta to the fetal heart and its flow assessment has been used as an indicator of fetal acidemia. At 11 to 14 weeks, the fetuses with increased nuchal translucency also showing an abnormal DV blood flow were consistently found to be aneuploid. Early cardiac dysfunction, signaled by abnormal DV blood flow, was suggested as the underlying cause of increased nuchal translucency. Detection rates for aneuploidy with the use of DV blood flow studies range from 59 to 93% with 2 to 21% false-positive rates. In fetuses with normal karyotype, an abnormal DV flow pattern signals cardiac defects or adverse perinatal outcome. Copyright © 2004 John Wiley & Sons, Ltd.     

Trisomy 13 mosaicism: study of serial cytogenetic changes in a case from early pregnancy to infancy

We report a patient whose chorionic villus sampling showed a nonmosaic trisomy 13 [46,XX,der(13;13)(q10;q10)]. Subsequent amniocentesis and cordocentesis showed varying percentages of abnormal cells (77 and 78% in two amniocentesis; 14% in cordocentesis) and mosaic trisomy 13 was impressed. Prenatal fetal ultrasound scanning revealed only mild structural abnormalities (echogenic cardiac foci, transient lemon head, transient skin oedema). The mother chose to continue the pregnancy. Karyotyping of the cord blood, peripheral blood, umbilical cord, urine, and chorion were performed postpartum. The process of correction appeared to exist in the placenta (indirect evidence from coexistence of trisomy 13 [46,XX,der(13;13)(q10,q10)], euploidy [46,XX], aneuploidy [46,XX,–13, +mar], and monosomy 13 [45,XX,–13] in the chorion at birth). The baby had survived beyond eight months of age at the time of submission. Few structural abnormalities except low-set ears, absence of the 12th rib, and cardiomegaly with ventricular septal defect, were noted postnatally. The growth reached 95th percentile at the age of one month. Development milestones were not delayed at serial evaluations. Her ventricular septal defect was corrected surgically at the age of six months. Karyotypes of her skin fibroblasts, blood lymphocytes, and cardiac tissue were all normal [46,XX] at the time of surgery. Difficulties of the genetic counseling are also discussed. Copyright © 2004 John Wiley & Sons, Ltd.     

Down syndrome maternal serum marker screening after 18 weeks' gestation

Women having access to prenatal care late in pregnancy may still wish to benefit from maternal serum screening for Down syndrome. Therefore, we established reference values for α-feto protein (AFP) and free β-human chorionic gonadotrophin (β-hCG), and assessed the diagnostic value of maternal serum marker screening at 18–35 weeks' gestation based upon a series of 4072 sera from unaffected pregnancies and 118 sera from pregnant women with fetuses affected by Down syndrome. Using a 1/250 risk cut-off, a detection rate of 72.9% (95% CI = 71.5–74.3%) was achieved with a false-positive rate of 7.51% (95% CI = 6.71–8.3%). This was not significantly different from the percentages observed in our 14–17 weeks routine screening (50 596 patients): 71.9% (95% CI = 71.5–72.3%) and 6.48% (95% CI = 6.28–6.68%), respectively. Detection and screen-positive rates were, respectively, 51.3% (95% CI = 35.6–67.0%) and 5.95% (95% CI = 5.12–6.68%) in women aunder 35 years of age, and 84.8% (95% CI = 76.9–92.7%) and 24% (95% CI = 20.7–27.3%) in women aged 35 years and over. In conclusion, maternal serum marker screening is feasible at 18 weeks' gestation and later, which may be of interest in selected cases. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal diagnosis of autosomal dominant polycystic kidney disease using flanking DNA markers and the polymerase chain reaction

A prenatal diagnosis was carried out on a 9-week-old fetus at risk for autosomal dominant polycystic kidney disease (ADPKD). Ten members of the family were previously typed using five DNA markers linked to the PKD1 locus on chromosome 16, and one marker linked to the putative PKD2 locus on chromosome 2. The polymerase chain reaction (PCR) was used to amplify the D16S125 locus. Pairwise and multipoint lod scores indicated that the family was most likely segregating a PKD1 mutation. The fetus inherited the disease haplotype from the affected parent. Diagnostic accuracy was greater than 99 per cent, taking into account the possibility of genetic heterogeneity.     

Amniotic fluid microvillar enzyme activities in the early detection of fetal abnormalities

Measurement of the microvillar enzymes, γ-glutamyltranspeptidase (GGTP), aminopeptidase M (APM) and alkaline phosphatase (ALP), in amniotic fluid supernatant has been proposed as a method for the early prenatal diagnosis of cystic fibrosis. The activities of these enzymes in a series of other fetal abnormalities have now been examined. GGTP activities were below the 5th percentile in 28 out of 54 cases of trisomy 21 and 9 of 14 cases of trisomy 18, while APM values were below this cut-off in 26 of 54 cases of trisomy 21 and 8 of 14 cases of trisomy 18. Abnormal ALP isoenzyme ratios were found in 6 of 54 cases of trisomy 21 and 4 of 14 cases of trisomy 18. If prenatal cytogenetic studies are routinely carried out on amniotic fluid cells, the occasional confounding effect of abnormal microvillar enzymes associated with fetal trisomies rather than with cystic fibrosis should be avoided.     

Isolating fetal cells in maternal circulation for prenatal diagnosis

Fetal cells unequivocally exist in and can be isolated from maternal blood. Erythroblasts, trophoblasts, granulocytes and lymphocytes have all been isolated by various density gradient and flow sorting techniques. Chromosomal abnormalities detected on isolated fetal cells include trisomy 21, trisomy 18, Klinefelter syndrome (47,XXY) and 47,XYY. Polymerase chain reaction (PCR) technology has enabled the detection of fetal sex, Mendelian disorders (e.g. β-globin mutations), HLA polymorphisms, and fetal Rhesus (D) blood type. The fetal cell type that has generated the most success is the nucleated erythrocyte; however, trophoblasts, lymphocytes and granulocytes are also considered to be present in maternal blood. Fetal cells circulate in maternal blood during the first and second trimesters, and their detection is probably not affected by Rh or ABO maternal-fetal incompatibilities. Emphasis is now directed toward determining the most practical and efficacious manner for this technique to be applied to prenatal genetic diagnosis. Only upon completion of clinical evaluations could it be considered appropriate to offer this technology as an alternative to conventional invasive and non-invasive methods of prenatal cytogenetic diagnosis.     

Autosomal recessive polycystic kidney disease. Problems of prenatal diagnosis

Autosomal recessive polycystic kidney disease (ARPKD) is characterized by different proportions of cystic dilated collecting ducts invariably associated with congenital hepatic fibrosis. Because of the nearly regular arrangement of nephrons and collecting ducts, disturbances have been postulated to act rather late on embryological grounds. Prenatal diagnoses seem to confirm this observation, as can be demonstrated in our cases and those reported in the literature. Increased echogenicity and renal enlargement are the main ultrasonographic signs of ARPKD; oligohydramnios is characteristic but not always present. Repeated sono-graphic measurements of the kidney length seem to be the most useful parameter. As differential diagnoses, autosomal dominant polycystic kidney disease as well as Meckel syndrome have to be taken into consideration. The prognosis of cases with oligohydramnios is usually poor. In genetic counselling, the possibility of prenatal diagnosis in the second trimester of pregnancy should be given with caution.     

Prenatal detection of the autosomal dominant type of congenital hydronephrosis by ultrasonography

We report a family with clearly defined two generation, and probable four generation uropathy due to a congenital malformation of the genitourinary system. There appears to be variation in expression within this family and a severely affected fetus was detected by ultrasonography at 31 weeks gestation.