Fetal diagnosis of toxoplasmosis in 190 women infected during pregnancy

One hundred and ninety women who contracted toxoplasmosis after the seventh week of pregnancy underwent antenatal diagnosis, including ultrasound examination and biological tests. Tests included Toxoplasma isolation in fetal blood and amniotic fluid by mouse inoculation, specific IgM and IgA in fetal blood, and non-specific tests. Twenty fetuses had positive specific as well as non-specific tests for Toxoplasma infection. At birth, four of these presented with clinical congenital toxoplasmosis and 12 with subclinical forms. Antenatal diagnosis enabled the detection of 83 per cent of the infected fetuses. Under specific conditions, cordocentesis permits early diagnosis and considerably reduces the number of terminations of pregnancy.     

The time of appearance and disappearance of fetal DNA from the maternal circulation

A single copy Y-chromosome DNA sequence was amplified using the polymerase chain reaction (PCR) from the peripheral blood of 30 women who had achieved a pregnancy through an in vitro fertilization (IVF) programme. The time of conception was known precisely and was confirmed by serial ultrasound scans. Conceptions were dated as the number of weeks after fertilization plus 2, to give a time equivalent to the obstetric menstrual dating of the pregnancy (LMP). Y-chromosome-specific DNA was detected in all pregnancies with a male fetus (18/30). The earliest detection was at 4 weeks and 5 days, and the latest at 7 weeks and 1 day. Y-chromosome-specific sequences were no longer detected in any of the male pregnancies 8 weeks after delivery. No Y-chromosome sequences were detected in any of the pregnancies where only female babies were delivered. This demonstrates that fetal DNA appears in the maternal circulation early in the first trimester, that it can be identified in all pregnancies tested by 7 weeks, that it continues to be present throughout pregnancy, and that it has been cleared from the maternal circulation 2 months after parturition. Early non-invasive prenatal diagnosis for aneuploidies and inherited disorders will be possible in all pregnancies if fetal cells can be isolated free from maternal contamination (or identified accurately in the presence of maternal cells) without problems of contamination from previous pregnancies.     

Prenatal diagnosis of a left ventricular aneurysm

In a fetus with ventricular extrasystoles a congenital aneurysm of the left ventricle was diagnosed prenatally. At 32 weeks of gestation, echocardiography showed a large apical left ventricular aneurysm with a thin, hypokinetic wall. Congestive heart failure did not occur. Prenatal and postnatal examinations did not detect the aetiology of the aneurysm, but excluded the majority of possible causes. The 2-year-old child is now asymptomatic and normally developed. Neither medication nor surgical treatment have been necessary, except for antithrombotic prophylaxis with low-dose aspirin.     

Abnormal immunological development in fetuses with trisomy 18

Flow cytometry was used to enumerate the lymphocyte subpopulations in fetal blood obtained by cordocentesis from eight trisomy 18 fetuses at 20–36 weeks' gestation. Compared with values in chromosomally normal fetuses, in trisomy 18 the mean T- and natural killer (NK) cell counts were significantly lower (t= − 7·63, P<0·001 and t= − 3·58, P<0·01, respectively); the mean B-cell count was not significantly different (t= − 1·32). These findings demonstrate that in trisomy 18 there is abnormal intrauterine development of the immune system.     

The causes and natural history of fetal ascites

The purpose of this study was to examine the natural history and differential diagnosis of ultrasound-detected, isolated fetal ascites. Retrospective review of our patient data base, from 1989 to 1993, revealed 18 patients with fetal ascites diagnosed sonographically. Fetuses presenting with generalized hydrops were excluded. One of the 18 fetuses with ascites had a chromosomal abnormality (trisomy 21), four fetuses had intrauterine infections, seven had gastrointestinal processes, two had genitourinary tract abnormalities, and four were labelled as ‘idiopathic’ (all four resulting in normal neonates). Seventeen of 18 fetuses survived; there was one fetal demise secondary to active syphilis. One fetus with parvovirus infection required intrauterine transfusion and did well. Two infants are developmentally retarded, including one with trisomy 21 and one with microcephaly secondary to cytomegalovirus infection. Fourteen of 18 fetuses had documented in-utero resolution of the ascites. Eleven of the 18 were associated with polyhydramnios sometime during fetal life. None of the fetuses developed hydrops. In conclusion, fetal ascites can result from many different aetiologies, including gastrointestinal and genitourinary anomalies. Chromosomal abnormalities and viral aetiologies must also be considered. Fetuses who have isolated ascites can have a good outcome with resolution of the ascites antenatally.     

Prenatal diagnosis of trisomy 9 mosaicism possibly limited to fetal membranes

In repeat amniotic fluid cultures mosaicism due to trisomy 9 was noted. Autopsy of the aborted female fetus showed a sinus urogenitalis and gonadal dysgenesis with absence of germ cells only. Fetal lymphocytes and skin fibroblasts had a normal karyotype but trisomy 9 was found in cells grown from placenta. It is likely that trisomic cells were limited to fetal membranes.     

Clues and pitfalls in the early prenatal diagnosis of ‘late onset’ infantile polycystic kidney

Infantile polycystic kidney disease (IPKD) is an autosornal recesive inherited disorder, IPKD has been previously diagnosed by us as early as the 14th week of gestation. ‘Late onset’ (third trimester) IPKD has been previously described by several authors. We present here a case of intrauterine detection of ‘late onset’ IPKD, suggesting that elongated hyperechogenic kidneys (with normal transverse and anteroposterior diameters) should be considered as an early sign of ‘late onset’ presenting IPKD.     

Trisomy 20 mosaicism

A further case of trisomy 20 mosaicism found at amniocentesis is presented. Pregnancy was terminated, the fetus showed facial dysmorphia and minor cardial and renal anomalies. 19 published reports of true trisomy 20 mosaicism at amniocentesis are reviewed. Five pregnancies resulted in obviously normal newborns. The significance of mostly minor anomalies found at autopsy of 7 fetuses remains unclear. With regard to genetic counselling the significance of trisomy 20 mosaicism is summarized as follows: (1) true trisomy 20 mosaicism in amniotic fluid cells reflects mosaicism of the fetus; (2) severe malformation is not a major feature of trisomy 20 mosaicism; (3) the risk of mental retardation is still undetermined, due to limited experience. However, there is no definite proof that the condition is harmful at all.     

Demonstration of spontaneously dividing male fetal cells in maternal blood by negative magnetic cell sorting and fish

We investigated a case of massive feto-maternal bleeding by using negative magnetic cell sorting (MACS) and fluorescent in situ hybridization (FISH). A 37-year-old pregnant woman had an uncomplicated amniocentesis for advanced maternal age at 16 weeks' gestation. The fetal karyotype was 46, XY. At 19 weeks' gestation, she had a minor car accident and slight vaginal bleeding. A subsequent Kleihauer-Betke test showed a 140 ml feto-maternal haemorrhage. Serial sonographic examinations indicated a normal fetus and placenta. We performed FISH analysis on maternal peripheral blood at 25 weeks. Anti-CD45 and MACS were used to deplete maternal leucocytes, enriching the proportion of fetal nucleated erythrocytes present. The isolated cells were analysed by using dual-colour FISH with X and Y specific probes. Approximately 65 800 nucleated cells were obtained after MACS depletion. A total of 234 cells were analysed by FISH. The results revealed that 70 of the nucleated cells (30 per cent) were male with one X and one Y signal. Among these cells, six male metaphases were observed in spontaneously dividing cells.     

Oligohydramnios with amnio-chorionic separation at 15–16 weeks' gestation

Nine patients with oligohydramnios and amnio-chorionic separation were identified out of 7000 women who underwent a vaginal ultrasound examination at 15–16 weeks' gestation. Oligohydramnios was defined as a reduced amount of amniotic fluid, a distance of more than 1 cm between the chorion and amnion, and a good turgor of the amnion without floating membranes or intrauterine sheets. Fetal malformations were observed in all nine cases. In four of six fetuses where chromosomal analysis was available, an abnormal karyotype was found. It is concluded that oligohydramnios in the early second trimester is associated with fetal abnormality.