Insights into the pathogenesis and natural history of fetuses with multicystic dysplastic kidney disease.

To better delineate the natural history of multicystic displastic kidney disease (MCDKD) and provide insights into the pathogenesis of this condition, we report our experience in 102 prenatally detected cases. MCDKD is most commonly an incidental finding on prenatal ultrasound examination. The abnormality may be unilateral (76 per cent) or bilateral (24 per cent). In unilateral cases, abnormality of the contralateral kidney is common (33 per cent). Associated non-renal abnormalities occur frequently with both unilateral (26 per cent) and bilateral (67 per cent) MCDKD, and increase the risk for an abnormal chromosome study. Males are more likely to be affected than females with a ratio of 2.4:1, but females are twice as likely to have bilateral MCDKD and associated non-renal abnormalities, and four times more likely to have an abnormal chromosome study. We suggest that the option of chromosomal analysis should be discussed with all patients diagnosed with MCDKD in their fetus, if there is bilateral renal involvement or if an associated non-renal abnormality is present. Unilateral MCDKD without associated renal or non-renal abnormalities was not associated with an abnormal chromosome study, and resulted in favourable outcomes. While unilateral MCDKD, lack of associated anomalies, normal chromosome study and adequate amniotic fluid are all reassuring findings, a complete neonatal urologic work-up should be performed in all newborns. We believe the evaluation should include voiding cystourethrography to rule out vesicoureteral reflux. Our findings allow more precise counselling of patients regarding prognosis, and subsequent management of the fetus found to have MCDKD.

Preconception genetic counseling.

The purpose of this chapter has not been to be all-inclusive, but to raise awareness of the benefits of preconception consultation in the prevention of birth defects. If there is to be a significant decrease in the incidence of congenital malformations, it will come only by intervention that occurs prior to organogenesis, and that opportunity is lost by the first prenatal visit. For the practitioner interested in a more in-depth analysis of the subject of preconception counseling, the two books listed as supplementary reading provide a wealth of information essential to the care of the patient planning a pregnancy.

Gorlin syndrome (naevoid basal cell carcinoma syndrome): prenatal detection in a fetus with macrocephaly and ventriculomegaly.

The Gorlin (naevoid basal cell carcinoma) syndrome is an autosomal dominant disorder consisting principally of naevoid basal cell carcinomas, odontogenic keratocysts, skeletal abnormalities, and intracranial calcification. We report the prenatal detection of the Gorlin syndrome by ultrasonography in a fetus with macrocephaly and mild ventriculomegaly.

Increased echogenicity in the fetal abdomen: use of DNA analysis to establish a diagnosis of cystic fibrosis.

The sonographic finding of increased echogenicity within the fetal abdomen presents a diagnostic dilemma, with a differential diagnosis ranging from normal variation to CF. We report the diagnostic evaluation of four cases, two of which were found to be the result of CF. On the basis of this experience, we believe that persistence of an echogenic bowel pattern, especially with bowel dilation, after 20 weeks' gestation should prompt an evaluation for CF. Using DNA analysis, approximately 75% of the cases involving CF can be detected with noninvasive studies of the parents, and confirmation by amniocentesis is performed only in those cases in which both parents are carriers of known mutations.

Prenatal diagnosis of cytomegalovirus (CMV) infection: a preliminary report.

Eight patients were referred for prenatal diagnosis for suspected fetal cytomegalovirus infection (CMV): six for documented first-trimester infection and two for abnormal ultrasound evaluation suggestive of fetal infection. Three methods of diagnosis were employed: (1) amniotic fluid viral cultures and CMV-specific IgM in fetal serum; (2) amniotic fluid cultures and detection by polymerase chain reaction amplification of CMV-specific DNA in chorionic villi; and (3) detection of CMV-specific DNA in villus samples only. Amniotic fluid cultures detected all cases of infection, but CMV-specific IgM was not a reliable indicator of infection in any case. DNA analysis correlated well with both culture results and clinical outcome.

Congenital nephrosis: detection of index cases through maternal serum alpha-fetoprotein screening.

Congenital nephrosis is an autosomal recessive disorder with an incidence of 1 in 8000 in Finland, but it is quite rare in non-Finnish populations. In families known to be at risk, prenatal detection is possible by means of maternal serum and/or amniotic fluid alpha-fetoprotein levels. We report the antenatal diagnosis of four cases of congenital nephrosis, three of which were index cases, through maternal serum alpha-fetoprotein screening. The diagnosis was confirmed at birth in two infants. Two patients elected to terminate their pregnancies, and the diagnoses were confirmed pathologically (obliteration of foot processes on electron microscopy of fetal glomeruli) in both. In cases of elevated maternal serum alpha-fetoprotein, with unexplained and marked elevations of amniotic fluid alpha-fetoprotein and normal acetylcholinesterase levels, the diagnosis of congenital nephrosis must be considered regardless of ethnic origin.

Chorionic villus sampling: the University of Maryland experience.

The University of Maryland was the first program in the state to offer chorionic villus sampling (CVS). Since the program's beginning in 1984, 998 patients have been seen with successful sampling in 99.1 percent, using both transcervical and transabdominal approaches. The overall loss rate was quite low (2.3 percent), and no increased risk of birth defects was seen. These observations demonstrate that CVS provides a safe and accurate alternative to amniocentesis.

Transcervical chorionic villus sampling and amniocentesis: a comparison of reliability, culture findings, and fetal outcome.

We evaluated the reliability, culture findings, and fetal outcome after transcervical chorionic villus sampling or amniocentesis in a group of 860 patients. All procedures were performed for the indication of advanced maternal age with consistent procedure and laboratory techniques. Successful procedures were completed in 97.7% (420/430) of patients in the chorionic villus sampling group, compared with 99.5% (428/430) in the amniocentesis group (p less than 0.01). Success was more frequent with only one attempt in the amniocentesis group (427/428) versus 354 of 420 in the chorionic villus sampling group (p less than 0.001). Culture failure was more common after chorionic villus sampling (p less than 0.001). Pregnancy loss rates through 28 weeks' gestation and the entire gestation were not significantly different. The prevalence of preterm delivery did not vary between groups, but birth weights of infants in the chorionic villus sampling group were significantly greater. In summary, the present investigation supports previous findings that chorionic villus sampling is a safe alternative to amniocentesis and is not associated with long-term pregnancy complications.

Chorionic villus sampling.

Chorionic villus sampling in the first trimester of pregnancy has the potential to become a major tool in the prenatal diagnosis and therapy of genetic disorders. Villus samples can be used for cytogenetic and biochemical studies as well as DNA analysis. However, little is known about the effects of chorionic villus sampling on a continuing pregnancy, or the long-term effects on the subsequently delivered infants. Despite these limitations, chorionic villus sampling appears to be a major breakthrough in prenatal diagnosis.