First-trimester prenatal diagnosis of severe alpha-thalassemia

By means of chorion biopsy together with restriction endonuclease analysis of fetal DNA, first trimester diagnoses were successfully made in 33 fetuses at risk for Bart's hydrops fetalis. Seven pregnancies with Hb H or hydrops fetalis were therapeutically terminated before 4 months of gestation. Of the 26 pregnancies intended to continue, 18 have come to term with normal deliveries; one with threatened abortion was terminated at the end of the first trimester and, seven are progresssing normally.     

Activity of biotin-dependent and gaba metabolizing enzymes in chorionic villus samples: Potential for 1st trimester prenatal diagnosis

We have documented the presence of five mitochondrial enzymes in samples of chorionic villus tissue and measured the levels of activity. Three of the enzymes catalyse biotindependent reactions. These are propionyl-CoA carboxylase, 3-methylcrotonyl-CoA carboxylase and pyruvate carboxylase. the other enzymes. 4-aminobutyric acid aminotransferase and succinic semialdehyde dehydrogenase, are involved inthe degradation of the central inhibitory neurotransmitter GABA. Distinct diseases in whichthere is deficiency of each of these enzymes have been documented in man. Significant levels of activity were observed for all five enzymes in chorionic villus tissue. This methodology should permit early prenatal diagnosis of deficiencies of these enzymes by chorionic villus biopsy in the first trimester.     

Prenatal sex diagnosis: Testosterone and fsh levels in mid-trimester amniotic fluids

We studied the validity of mid-trimester amniotic fluid testosterone and FSH in the diagnosis of fetal sex in abnormal fetuses and in twins. It was found that the testosterone/FSH ratio, but not the level of the individual hormones, was an excellent criterion for fetal sex diagnosis. In a control group of 32 female and 34 male fetuses, the testosterone/FSH ratio was diagnostic. In two cases the values were indeterminate and fetal sex could not be predicted, but there were no false diagnoses. The abnormalities of the fetuses were diagnosed by karyotype analyses or raised levels of α-fetoprotein. It was found that neither autosomal trisomies nor X-chromosome aneuploidy or neural tube defect interfered with the diagnostic value of the hormonal approach. The twin study included 14 pairs, three of whom were discordant for sex. In all twins the fetal sex diagnosis was appropriate. In co-twins of the same sex the hormone levels were very close to each other.     

Mucolipidosis IV: Prenatal diagnosis by electron microscopy

Mucolipidosis IV (ML 1V) is a lysosomal storage disease presenting in infancy with cloudy cornea and psychomotor retardation. Our experience with 12 pregnancies at risk for ML IV, monitored by transmission electron microscopy (TEM) studies of cultured amniotic fluid cells, is presented. The prenatal diagnoses were confirmed in the 3 affected and the 8 un- affected pregnancies. In the one pregnancy where no definite diagnosis was reached the pregnancy was terminated. TEM examination of fetal tissues from this pregnancy showed no abnormal lysosomal storage bodies and a review of the cultured amniotic fluid cell sections revealed that the diagnosis of a normal fetus could have been made.     

Prenatal diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in a family with a previous fatal case of sudden unexpected death in childhood

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a potentially fatal inherited disease with a carrier frequency of approximately 1:100 in most Caucasian populations. The disease is implicated in sudden unexpected death in childhood. A prevalent disease-causing point mutation (A985G) in the MCAD gene has been characterized, thus rendering diagnosis easy in the majority of cases. Since the clinical spectrum of MCAD deficiency ranges from death in the first days of life to an asymptomatic life, there are probably other genetic factors—in addition to MCAD mutations—involved in the expression of the disease. Thus, families who have experienced the death of a child from MCAD deficiency might have an increased risk of a seriously affected subsequent child. In such a family we have therefore performed a prenatal diagnosis on a chorionic villus sample by a highly specific and sensitive polymerase chain reaction (PCR) assay for the G985 mutation. The analysis was positive and resulted in abortion. We verified the diagnosis by direct analysis on blood spots and other tissue material from the aborted fetus and from family members.     

Body stalk anomaly associated with maternal cocaine abuse

A case of body stalk anomaly diagnosed prenatally by ultrasound during the 24th week of pregnancy in a cocaine abusing mother is presented. Accurate visualization of the fetal organs was difficult due to the severe oligohydramnios caused by premature rupture of membranes, probably related to the cocaine use. The sonographic findings were an omphalocoele, fetal attachment to the placenta, kyphoscoliosis, and absence of a floating umbilical cord. The prenatal diagnosis of the syndrome and the possible relationship with cocaine abuse are discussed.     

Early amniocentesis at 11–14 weeks' gestation for the diagnosis of fetal chromosomal abnormality—a clinical evaluation

Early arnniocentesis between 11 and 14 weeks' gestation was offered to 110 women at risk of a chromosomally abnormal fetus due to maternal age. Four were found to be unsuitable for the procedure, and 106 early amniocenteses were performed. In 102 cases, clear amniotic fluid was obtained with a single tap. There were two dry taps and two bloodstained tapis; sampling was repeated in three of these cases before 15 weeks. In the fourth case, placental biopsy was performed at 16 weeks. Thus, we were able to obtain a satisfactory sample in all but three cases(2.8 percent). Karyotyping of cells harvested from the early amniotic fluid samples was successful in all the 105 cases. Cell culture from the initial samples revealed a normal karyotype in 99 cases, two balanced translocations, two tetraploid karyotypes, and two cases of pseudomosaicism. Of the 105 pregnancies successfully sampled, there have been two losses to date (1–8 per cent). Two further patients presented with premature rupture of membranes, both pregnancies having successful outcomes. Sixty-two babies have delivered to date, with four congenital anomalies. There were no respiratory problems. Twenty-nine pregnancies are continuing without known complications, and details are not yet available on the remaining 12. The results indicate that early arnniocentesis may replace the traditional test at 15–17 weeks.     

Preimplantation diagnosis: A patient perspective

A new dimension in the prevention of birth defects will be achieved when genetic diseases can be routinely diagnosed in embryos prior to implantation. The impressions and attitudes towards preimplantation diagnosis were studied in prospective patients, women at high reproductive risk for a genetic disease. Their perspective highlighted not only the advantages and disadvantages of this new approach, but also those changes necessary in order for preimplantation diagnosis to become a useful and practical technique. The data presented are based on information obtained by a mailed questionnaire answered by 58 women. The main benefit of preimplantation diagnosis for these high-risk women would be the ability to undertake a pregnancy without having to be subjected to the physical and/or emotional trauma of elective termination. Their major concerns related to possible damage to the embryo following biopsy, the cost of the procedure, and the low success rate of completed pregnancies. Other issues to be addressed before preimplantation diagnosis could begin to compare favourably with existing forms of prenatal testing were that the methods of obtaining oocytes or embryos should be simple, well tolerated, highly efficient, and low in maternal risk, and that the genetic analysis of embryonic or extraembryonic cells should be unequivocally accurate.     

First and early second-trimester diagnosis of fetal urinary tract anomalies using transvaginal sonography

Urinary tract anomalies are common. Prenatal diagnosis is important and enables either special obstetric management or termination of pregnancy and probably in the future, intrauterine intervention. Transvaginal sonography (TVS) allows visualization of the normal and anomalous fetal urinary tract at an early stage. One thousand nine hundred and forty women were examined via TVS at an early stage of pregnancy between 10 and 16 weeks from the last menstrual period (LMP) and 35 anomalies (1·8 per cent) were clearly identified: 29 cases of low urinary tract obstruction, 2 cases of multicystic dysplastic kidney, 2 cases of polycystic kidney (infantile type), 1 case of double collecting system, and 1 case of horseshoe kidney. Potter syndrome could be ruled out in three patients who had delivered fetuses suffering from this anomaly in previous pregnancies. The concise and early identification of anomalies makes TVS an important aid in the hands of the obstetrician, ultrasonographer, and neonatologist.