Fetal liver alanine: Glyoxylate aminotransferase and the prenatal diagnosis of primary hyperoxaluria type 1

Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the hepatic peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT, EC 2.6.1.44) (Danpure and Jennings, FEBS Lett., 201 , 20–24, 1986). The activity of AGT has been measured in fetal livers of gestational age 14–21 weeks. Activity increases up to 17 weeks and then levels off between 17 and 21 weeks. At this time, the mean AGT activity is about 30 per cent of the mean normal postnatal level. As in adult liver, the AGT enzyme activity and the AGT immunoreactive protein are peroxisomal. Prenatal diagnosis has been performed by measuring AGT enzyme activity and immunoreactive AGT protein on liver biopsies from two fetuses at risk for primary hyperoxaluria type 1. One was unaffected and one was affected.     

Incidence of fetal chromosome abnormalities in 2264 low-risk women

Among a population of 6305 pregnant women, aged 25 to 34 years and estimated to be at no increased risk of genetic disease in the fetus, 4606 women participated in a randomized controlled trial of genetic amniocentesis between 1980 and 1984. In the study group having amniocentesis (2264 women), 23 fetal chromosome abnormalities (1.0 per cent) were found: eight autosomal aneuploidies, seven sex chromosome aneuploidies, seven balanced structural rearrangements and one case of a marker some. The structural rearrangements and the marker chromosome were all shown to be inherited. The study group seemed representative for the whole population of younger women at low genetic risk. Therefore, a 1.0 per cent total rate of fetal chromosome abnormalities, consisting of one-third autosomal aneuploidies, one-third sex chromosome aneuploidies and one-third structural rearrangements, may be expected in the second trimester in younger low-risk women. In the same period of time, 562 women in the same age group were offered amniocentesis because of an estimated increased risk of fetal genetic disease. The total rate of fetal chromosome abnormality in this ‘high-risk’ group was 0.9 per cent and thus no different from the rate in the low-risk group.     

Prenatal diagnosis of gall bladder anomalies—report of 17 cases

We describe here 17 cases of fetal gall bladder anomalies, detected as early as the 14th week of gestation, out of 10 016 fetal systemic examinations performed by us in the last 6 years (015 per cent). In seven cases, agenesis of the fetal gall bladder was detected. The diagnosis was confirmed by post-abortal examination in five cases and in two post-partum. In six other cases, a left-sided gall bladder and in one case, a ‘floating’ gall bladder were detected at 15 weeks' gestation. In two cases, a septated or bilobed gall bladder was visualized. None of these 15 cases was dyskaryotic, but in five cases, two with agenesis and three left-sided gall bladders were associated with other fetal malformations. In two other cases, the gall bladder appeared dysmorphic on sonographic examination and in both of them intrauterine growth retardation and other anomalies were detected. Trisomy 18 was diagnosed by amniocentesis in one of them. According to our experience, failure to visualize the fetal gall bladder by the 15th gestational week is diagnostic of its absence and should raise the differential diagnosis between gall bladder atresia, which has a good prognosis, and external biliary atresia, which has a poor prognosis. Further experience is needed to characterize the various gall bladder malformations and their prognosis.     

Central nervous system damage and other anomalies in surviving fetus following second trimester antenatal death of co-twin. Report of four cases and literature review

Four cases of multiple gestation with second trimester death of one fetus and subsequent damage to a survivor are reported. Monochorionic placentation was documented in three of the cases. Central nervous system lesions occurred in all cases, and bowel injury was noted in two of the damaged fetuses. Although rare maternal clotting problems have been reported in similar situations, none was noted in any of these four cases. Prior reports have indicated that losses in the first half of gestation were of no consequence to the surviving fetuses. These four cases contradict this suggestion, and indicate that close sonographic observation of the survivors is important in any multiple gestation where one fetus has died.     

Visualization of fetal intra-abdominal organs in second-trimester severe oligohydramnios by intraperitoneal infusion

Fetal intraperitoneal infusion of saline was performed in two patients with severe oligohydramnios at 24 and 25 weeks' gestation in order to enhance visualization of intra-abdominal organs. Renal agenesis was easily diagnosed. The technique can be considered as an alternative to artificial instillation of amniotic fluid in the differential diagnosis of conditions associated with severe oligohydramnios.     

Biochemical examination of fetal skin biopsy specimens obtained by fetoscopy: Use of the method for analysis of keratins and filaggrin

This paper describes a method for biochemical analysis of proteins from fetal skin biopsy samples. The method has wide potential application for diagnosis of disorders with a known protein abnormality detectable by protein staining or a specific antibody. Analysis requires a single 1 mm biopsy, is rapid (2 days) and extremely sensitive. In the present study, fetal skin biopsies from normal fetuses and a fetus at risk for lamellar ichthyosis were obtained. The epidermis or hairs with attached follicular cells were dissected from the remaining skin. Proteins were extracted and separated by SDS-polyacrylamide gel electrophoresis. Proteins from duplicate gels were transferred to nitrocellulose and immunostained for the acidic and basic keratins and for the keratin filament associated protein, filaggrin, using monoclonal antibodies. All samples contained keratins typical of fetal epidermis at 20 weeks gestation. Presence of filaggrin is variable at this age and depends on the presence of keratinized cells of hair canals. No keratin abnormalities in the fetus at risk for lamellar ichthyosis were detected, however, in one presumably normal biopsy, an abnormally low proportion of the 67 kd keratin and the presence of follicular keratins were evident. These results demonstrate that biochemical analysis of fetal biopsies is possible, thus increasing the diagnostic potential of the fetal biopsy procedure for disorders in which a known protein or antigen is altered in utero.     

Fetal two-dimensional doppler echocardiography (colour flow mapping) and its place in prenatal diagnosis

One hundred and fifty fetuses between 16 and 38 weeks of gestation were studied by fetal echocardiography using colour-coded two-dimensional Doppler echocardiography. Two-dimensional, M-mode, and Doppler spectral analyses were also performed. In 14 fetuses, structural and/or functional abnormalities were detected. Abnormalities were correctly ruled out in all the other fetuses. The advantages of two-dimensional Doppler echocardiography are (1) rapid screening for flow abnormalities in the fetal heart, and thus shortening of the Doppler examination time; (2) rapid diagnosis of valvular regurgitation, valvular stenosis, and abnormal shunting of blood across the interatrial and interventricular septa; and (3) facilitation of the diagnosis of complex congenital heart defects which in certain cases is possible only by using two-dimensional Doppler echocardiography.     

Catecholamine metabolites in amniotic fluid from fetuses with neural tube defects

Catecholamine metabolites were analysed in amniotic fluid from fetuses with neural tube defects and controls. HMPG (4-hydroxy-3-methoxyphenyl-glycol) assumed to originate mainly from the central nervous system and VMA (4-hydroxy-3-methoxymandelic acid) formed in the peripheral nervous system were determined by gas chromatography-mass spectrometry. The HMPG/VMA ratio was increased (more than 2 SD) compared with controls in ten out of fifteen cases of neural tube defects.     

Fetal granulocytes in maternal venous blood detected by in situ hybridization

Fetal male cells from maternal venous blood were detected by a non-radioactive in situ hybridization method using the biotinylated Y-specific DNA probe pY431. The hybridizations were performed on Ficoll-Paque-isolated nucleated blood cells obtained from 11 pregnant women in the seventh to 31st week of gestation. A Y-specific signal was detected in both granulocytes and lymphocyte-like cells in seven of the 11 women studied. These women gave birth to boys. In one of the four remaining cases, a Y-specific signal was detected in the lymphocyte-like cells but not in the granulocytes. This woman gave birth to a girl. The other three women had no cells with a Y-specific signal and all three gave birth to girls. Altogether, 83 500 nucleated cells were analysed. One hundred and three cells showed a Y-specific signal. Of these Y-specific cells, 62 per cent were granulocytes and 38 per cent lymphocyte-like cells. Our results suggest that fetomaternal transfer of granulocytes is common and that it occurs as early as in the seventh week of gestation. None of the ten non-pregnant female control samples showed positive cells with the Y-chromosome-specific probe; approximately 97 per cent of the cells from the five adult male controls showed a Y-specific signal. Our results indicate that in situ hybridization using a Y-specific DNA probe performed on granulocytes in maternal blood can be used for fetal male sex determination.     

Fetal bradyarrhythmia: Diagnosis and outcome

Seventeen patients were referred to our ultrasound unit because of fetal bradyarrhythmia (<100 bpm). Duration of pregnancy varied between 21 and 40 weeks. Bradyarrhythmia was diagnosed as atrioventricular block (n = 12), mild sinus bradycardia (n = 3), and irregular bradycardia (n = 2). The association with maternal collagen disease was 29 per cent and with cardiac structural defects 59 per cent. The overall mortality was 41 per cent. There were three abnormal karyotypes (17 per cent) and four cases of cardiac compromise (23 per cent). Prognosis depends on the nature of the bradyarrhythmia and recognition of associated pathology such as cardiac structural defects, abnormal karyotype and degree of cardiac compromise.