Prenatal diagnosis of thalassemia major by fetal blood analysis: Experience with 1000 cases

In this report we have summarized our experience with the prenatal diagnosis of β-thalassemia in 1000 pregnancies followed at least until 12 months after birth. In the majority of these cases, the thalassemia lesion was the nonsense mutation at the codon corresponding to amino acid 39, which produces the hematological phenotype of β-thalassemia. Fetal blood sampling was carried out by placental aspiration, by which a sufficient amount of fetal blood for analysis was obtained in the majority of cases (99 per cent). The fetal mortality associated with fetal blood sampling was 6·3 per cent. Those placental samples contaminated by maternal cells were successfully purified by Ørskov lysis. Fetal blood was analysed by globin chain synthesis on CM–52 columns, which gave reliable results. Two misdiagnoses (0·2 per cent) have been made of which one was due to a non-globin protein co-migrating with the β-chains while the other resulted from a misclassification of the type of thalassemia segregating in the family.     

Prenatal paternity testing by dna analysis

Prenatal paternity testing was evaluated by DNA analysis in chorionic villus biopsies obtained during the 7th-22nd weeks of gestation. Using highly polymorphic variable number of tandem repeats (VNTR) probes, we analysed four cases consisting of mother/child/alleged father trios. In all cases, we were able to detect maternal and paternal alleles and could establish or exclude paternity. The application of DNA analysis represents a new important diagnostic aid for all cases that require a prenatal identification of paternity.     

The prognostic factors in the prenatal diagnosis of the echogenic fetal lung

The prenatal diagnosis of an echogenic fetal lung (EFL) is now often made in the early second trimester using high-resolution ultrasound. This ultrasound appearance is usually caused by a congenital cystic adenomatoid lung malformation (CCAM), an intrapulmonary lung sequestration or obstruction of a major airway. In order to provide prognostic guidelines to parents who may be considering termination of a fetus with these findings, we have analysed a series of 11 cases diagnosed in our centre over the past 2 years in conjunction with 60 cases from major published series. The data suggest that in the absence of non-immune hydrops fetalis (NIHF) or other anomalies, the outcome for the fetuses is excellent, with over 90 per cent survival. Neither early diagnosis (24 weeks) nor the presence of mediastinal shift is a poor prognostic indicator. In addition, it appears that if NIHF is absent at diagnosis, the chance that it will develop as the pregnancy continues is small (6 per cent). Furthermore, there is a significant (up to 30 per cent) chance that this ultrasound finding will resolve in utero. The development of in utero fetal surgical techniques may be the only hope for those hydropic fetuses who appear to have a dismal prognosis.     

Schizencephaly: Prenatal diagnosis by computed sonography and magnetic resonance imaging

Magnetic resonance (MR) imaging was performed at 29 weeks of pregnancy after ultrasonographic detection of an abnormal cleft in the fetal brain. Fetal neuromuscular blockade was induced by pancuronium bromide injected into the umbilical vein under continuous ultrasound (US) guidance. MR images supported the echotomographic diagnosis of schizencephaly improving the visualization of symmetrical broad clefts connecting the lateral ventricles with the subarachnoid space. Schizencephaly was finally confirmed by neonatal US, computed tomography, and MR.     

An embryogenic model to explain cytogenetic inconsistencies observed in chorionic villus versus fetal tissue

While the fetus and placenta have a common ancestry, chorionic villus tissue does not always reflect fetal genotype. Data are presented from 15 CVS subjects in whom cytogenetic inconsistencies were observed when comparing (1) cultured chorionic villi, (2) direct chromosome preparations of intact villi, and (3) cultured fetal tissue. Embryogenic models are presented to explain these discrepancies. Mosaicism confined to direct chromosome preparations was the most commonly observed inconsistency. This can be explained by postzygotic non-disjunction limited to cytotrophoblast. In all but one instance, the abnormal cell line was limited to the placenta, with the normal cell line reflecting fetal genotype. Analysis of direct chromosome preparations from multiple individually processed villus fragments may be helpful in recognizing mosaicism confined to the placenta. While both direct chromosome preparations and villus cultures can be misleading, the latter are more likely to reflect fetal genetic status since they are derived from the extraembryonic mesoderm.     

OEIS complex (cloacal exstrophy): Prenatal diagnosis in the second trimester

OEIS complex (exstrophy of the cloaca) is an association of fetal malformations that includes omphalocele, exstrophy of the bladder, imperforate anus, and spinal defects. Most cases should be prenatally detectable by maternal serum alpha-fetoprotein screening, but an accurate diagnosis is essential for appropriate counselling of the family.     

Prenatal diagnosis of chromosomal abnormalities from chorionic biopsy samples: Improved success rate using a modified direct method

Several methods for fetal chromosome analysis using chorionic biopsy samples were compared. A modified direct method for culturing villi was considered to be the method of choice and details are presented of 186 pregnancies tested prenatally. The success rate in obtaining a fetal karyotype with the direct method was 93 per cent. The fetal loss rate in the prenatal series was 4.3 per cent and congenital abnormalities in the babies already born did not differ from the expected incidence.     

Creatine kinase estimation in pure fetal blood samples for the prenatal diagnosis of duchenne muscular dystrophy

This paper compares the results of a survey of plasma creatine kinase (CK) activity measured in fetuses at-risk for Duchenne muscular dystrophy (DMD) with a reliable control series. Only pure fetal blood samples obtained by fetoscopy at between 17–24 weeks gestational age were used. Of the at-risk group 19 male pregnancies, mostly at low risk for DMD, proceeded to term with a normal outcome; there was no significant difference between their fetal plasma CK activities and the control group. Another 21 male pregnancies were terminated. This group included the highest risk mothers and hence was expected to contain a significant proportion of affected fetuses. The fetal plasma CK activity range was overlapping but significantly higher than the control group. No grossly elevated CK value was obtained. We conclude that, on average, DMD fetuses at this gestational age have higher plasma CK activity than controls. The problems of applying this finding to the prenatal diagnosis of DMD are discussed.     

Admixture of maternal metaphases in first trimester direct chromosome preparations?

The autoradiographic labelling of different cell types in chorionic villi and decidual tissue was investigated after [³H]-thymidine incorporation in vitro. Although the extent of labelling was found to be lower in decidual than in villus tissue the possibility that direct chromosome preparations may contain maternal metaphases should be considered. The need for careful selection of villi for direct cytogenetic analysis was stressed.     

Misdiagnosis of omphalocele associated with Edwards syndrome and congenital heart disease

We present a case in which an apparent omphalocele, diagnosed at 30 weeks gestation ultrasound, led to identification of fetal trisomy 18 and congenital heart disease. At delivery, the fetus had the features of trisomy 18 and congenital heart disease but the omphalocele was absent. We suggest that the appearances seen are easily confused with a small omphalocele and could potentially result in unnecessary further investigations being performed.