Cystic hygroma: Prenatal diagnosis and genetic counselling

Six cases of cystic hygromas detected during second trimester ultrasound examination are reported: 4 fetuses (67 per cent) had a 45, X karyotype, 1 fetus had trisomy 18, 1 fetus had a normal karyotype (46,XX) and at autopsy multiple anomalies were observed. In the latter case the family history suggested an autosomal recessive pattern of inheritance. In order to reach a definite diagnosis and give proper genetic counselling when a fetus is found to have cystic hygroma, a fetal karyotype as well as a family and reproductive history should be obtained.     

Prenatal diagnosis of abdominal cystic hygroma

We present a case of fetal abdominal cystic hygroma that presented at 19 weeks of gestation. Ultrasonographic evaluation of the fetus revealed soft tissue enlargement of the left leg and a retroperitoneal mass in the left pelvis and abdomen. This represents the first reported case of prenatal diagnosis of abdominal cystic hygroma.     

Prenatal diagnosis of giant cystic hygroma: Prognosis,counselling, and management; case presentation and review of the recent literature

Cystic hygromas have historically been associated with a grim prognosis when discovered during prenatal sonographic study of the fetus. This same grim prognosis is not observed by the paediatric surgeon who evaluates the neonate or paediatric patient. We present a fetal patient with a massive anterior cystic hygroma discovered in the third trimester prior to 30 weeks. This case and a review of the literature suggest tailoring the prognosis by category when counselling patients: (1) first trimester, normal karyotype-good; (2) first trimester, abnormal karyotype-poor; (3) second trimester and early third-poor to guarded; and (4) mid to late third trimester-good.     

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.     

Evaluation of prenatal diagnosis by a registry of congenital anomalies

Prenatal diagnosis performed by fetal karyotype and ultrasound scan is now a routine part of antenatal care in many countries. How many fetal anomalies are actually detected by these procedures? We have used our registry of congenital malformations to answer this question. In our region, prenatal diagnosis was performed in 23.1 per cent of fetuses with a chromosomal aberration and in 20.1 per cent of fetuses with non-chromosomal anomalies. Only 6.9 per cent of the pregnancies with fetuses with non-chromosomal anomalies were terminated. The sensitivity of prenatal diagnosis by ultrasonographic examination was much lower for isolated malformations (fetuses with only one anomaly) than for multiple malformed children, 15.3 and 48.3 per cent respectively, chromosomal anomalies excluded.     

Amniotic band syndrome in second trimester associated with fetal malformations

The Possibility of severe fetal malformations, including neural tube defects, secondary to early amniotic rupture followed by formation of fibrous bands (amniotic band syndrome) is a well-known entitity. The fact that these pregnancies are usually uneventful makes prenatal diagnosis difficult, but routine determination of serum alphafetoprotein, followed by ultrasound scanning, may detect some of the malformations. We present a case, where detection of a neural tube defect led to induced second trimester abortion of a fetus severely affected by this syndrome. There appeared to be a causal relationship between maternal trauma and the amniotic rupture.     

Prenatal ultrasound diagnosis of fetal scoliosis with termination of the pregnancy: Case report

Gross scoliosis of the fetal thoracic spine was diagnosed at 18 weeks gestation. The pregnancy was terminated and the fetus found to have webbing of the neck and an imperforate anus in addition to vertebral defects.     

Transvaginal sonography—detection of findings suggestive of fetal chromosomal anomalies in the first and early second trimesters

Over a 4-year period, 14 dyskaryotic fetuses were diagnosed by amniocentesis, performed after early detection of malformations using transvaginal sonography (TVS). These 14 dyskaryotic fetuses were detected out of 4878 sonographic screenings performed by TVS between 9 and 16 weeks' gestation. Twenty-eight per cent of the referrals were at high risk and 72 per cent were at low risk for fetal malformations. Two hundred and twenty-nine fetuses (4.7 per cent) of the screened population had 265 anomalies, 39 per cent of them being transient. In 7 of the 14 dyskaryotic fetuses (50 per cent), the sonographically detected anomalies were transient, being undetected by follow-up sonographic screenings at later gestational ages (⩾18 weeks). Postponing the first sonographic scan aimed at malformation detection to a later gestational age may lead to transient anomalies and their associated dyskaryosis being missed.     

A comparison of amniotic fluid alpha-fetoprotein and acetylcholinesterase in the prenatal diagnosis of open neural tube defects and anterior abdominal wall defects

Amniotic fluid samples received for routine prenatal diagnosis of open neural tube defects were used for a study to compare amniotic fluid acetylcholinesterase (AChE) determination using a monoclonal antibody (4F19) enzyme antigen immunoassay and amniotic fluid alpha-fetoprotein (AFP) measurement as diagnostic tests for open neural tube defects. The study was based on 9964 women with singleton pregnancies and known outcome (including 6 with anencephaly and 18 with open spina bifida) having an amniocentesis at 14–23 weeks of gestation. The AChE immunoassay yielded detection rates for anencephaly of 100 per cent (95 per cent confidence interval (CI) 54·07–100 per cent), for open spina bifida of 100 per cent (95 per cent CI 81·47–100 per cent), for anterior abdominal wall defects of 20 per cent (95 per cent CI 0-51-71-64 per cent), and a false-positive rate of 0·22 percent (95 per cent CI 0·14–0·34 per cent) excluding anencephaly, open spina bifida, and anterior abdominal wall defects. For similar detection rates the false-positive rate of the AFP test was significantly higher, 0·74 per cent (95 per cent CI 0·58–0·94 per cent). On the basis of these findings, it is recommended that the technically simple AChE immunoassay should be used on all samples; the AFP test should only be used on the 0·5 per cent of the samples with concentrations of AChE activity ⩾ 8·5 nkat/1 for clear samples and blood-stained samples becoming clear after centrifugation, and ⩾ 25·0 nkat/1 for blood-stained samples that are discoloured after centrifugation; an AFP cut-off level of 2·0 MOM is recommended for this policy. Thereby, the detection rates for anencephaly, open spina bifida, and anterior abdominal wall defects would be 100, 100, and 20 per cent, respectively (95 per cent CIs 54·07–100, 81·47–100, and 0·51–71·64 per cent, respectively), and the false-positive rate would be 0·08 per cent (95 per cent CI 0·03–0·16 per cent) (excluding anencephaly, open spina bifida, and anterior abdominal wall defects).     

Alphafetoprotein,cholinesterases and rapidly adhering cells in the prenatal diagnosis of neural tube defects

Amniotic fluid cholinesterases tested on polyacrylamide gel and rapidly adhering cell analysis were compared in their efficiency at diagnosing fetal neural tube defects in three cases where the alphafetoprotein results were equivocal. While rapidly adhering cells were also equivocal, the cholinesterases consistently gave a clear indication of fetal abnormality.     

The effect of the introduction of prenatal diagnosis on the reproductive history of women at increased risk from neural tube defects

The reproductive history of 45 couples at increased risk for neural tube defect (NTD) who came for genetic counselling in 1970 and 1971 were compared with a similar number counselled in 1975 and 1976, when prenatal diagnostic tests were freely offered. They were subsequently interviewed in their homes and had their reproductive history recorded to the end of 1973 and 1978 respectively. Nearly all had a previous child with an NTD and none of the women were pregnant at the time of counselling. The effect of prenatal diagnosis was to speed somewhat the decision about further pregnancies, but the number of couples deciding on no further children and on having further pregnancies were almost identical in the two groups. The average number of pregnancies was 2·8 per family, with only 1·2 surviving children. The pregnancy outcomes are discussed as are the reasons for not attempting further pregnancies in both groups, which included very high risk of recurrence, a surviving spina bifida child, inability to accept the tests or its implications. Ninety per cent of the second group had tests. Their reactions to the tests were favourable but all complained of the waiting time between amniocentesis and obtaining the results. They all would have tests again in any future pregnancy. The reason for women not having prenatal diagnostic tests included inability to accept termination. It is concluded that couples in South Wales decide either to have no more children or to have further pregnancies regardless of tests. but tests speed a decision and enable the women to enjoy the pregnancy after obtaining the results, and that an NTD greatly reduces the number of children per family. A termination for an NTD is much more acceptable to most than an NTD at term. The reasons for this are discussed.     

Diagnosis and significance of cystic hygroma in the first trimester

Thirty cases of cervical cystic hygroma were diagnosed in the first trimester of pregnancy. Karyotype analysis was available in 29 (97 per cent). Fifteen (52 per cent) had a chromosomal abnormality. The ultrasound appearance was described as posterior cervical, lateral cervical, or cervical hygroma with hydrops. Of the 14 euploid embryos, six were electively aborted, two are undelivered, and six have been delivered as phenotypically normal infants. In cases in which the chromosomes were normal and the pregnancy continued, all lesions resolved by 18 weeks.     

Prenatal diagnosis and management of anterior abdominal wall defects in the West of Scotland

An attempt was made to identify all the cases of abdominal wall defects occurring in the West of Scotland over a 7-year period to determine the current incidence, prenatal diagnosis, management, and prognosis for fetuses and neonates with abdominal wall defects. Cases were identified because they presented either for prenatal diagnosis, or to the Department of Pathology following termination or spontaneous pregnancy loss, or as neonates to the Neonatal Surgical Department. The incidence of abdominal wall defects was found to be 1 in 2500 births. Exomphalos was diagnosed before birth in 66 per cent of cases, and in 30 per cent of cases it was associated with another major abnormality. There was a 20 per cent intact survival in the cases diagnosed prenatally who had no fetal anomaly and who opted to continue with the pregnancy. Gastroschisis was diagnosed before delivery in 70 per cent of cases, and in the group who continued with the pregnancy there was an intact survival of 77 per cent. Body stalk anomalies were all diagnosed prenatally and terminated. Maternal serum alpha-fetoprotein was elevated in 89 per cent of the cases with exomphalos and in 100 per cent of the cases with gastroschisis and body stalk anomalies in which it was tested.     

Prenatal diagnosis of cystic fibrosis: I. Prospective study of 51 pregnancies

A prenatal diagnosis was performed in 51 pregnancies with a 1-in-4 risk of having a child with cystic fibrosis. The criteria for determining an affected fetus were based on the results of alkaline phosphatase (ALP) residual activity after inhibition by phenylalanine and by homoarginine, of total ALP activity, and of gamma-glutamyltranspeptidase (GGTP) activity in the amniotic fluid taken between 16 and 19 weeks of pregnancy. The chromosomal analysis of amniotic fluid cells showed trisomy 13 in one case which was excluded from the analysis of biochemical assays. The biochemical assays were in the normal ranges in the amniotic fluid of 35 pregnancies: 26 have reached term and a normal infant has been born, 9 are still in progress. A deficiency of the ALP phenylalanine-inhibitable form, depressed values of total ALP and GGTP were observed in the amniotic fluid of 15 pregnancies: one pregnancy went to term and the infant had CF, in 14 cases the pregnancy was terminated, and meconium ileus was observed in ten of these cases. It was observed that the changes towards abnormal values became more significant with advancing gestational age and that 18 weeks appeared to be the optimum time for diagnostic amniocentesis.     

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.     

Measurement of cholinesterases in amniotic fluid using a naphthyl acetate as substrate: A possible initial test for prenatal diagnosis of open neural tube defects

A quantitative method for cholinesterases in amniotic fluid using the non-specific substrate α naphthyl acetate and the cholinesterase-specific inhibitor, eserine, is described. This assay was used to test 671 samples of amniotic fluid. The diagnoses for fetal ONTDs, based on the levels of AChE + ChE, were compared with those made for the same samples by the AFP method. Correct diagnoses were made by both methods with amniotic fluid from 35 women carrying fetuses with ONTDs and 631 carrying normal fetuses. There were five false-positive test results for normal fetuses by both methods when the cut-off points were 5 standard deviations above the mean for AFP and above the upper limit of the normal range (7. 5 milliunits) for cholinesterase (AChE + ChE). None of the false-positive samples from either method had the acetylcholinesterase band of activity characteristic of ONTDs after gel electrophoresis. In addition to the above 671 samples, 37 pregnancies with serious fetal abnormalities other than ONTDs were tested. Two were identified by both the AFP and AChE + ChE methods, two more by AFP assay and one other by the AChE + ChE assay.     

Significance of septations in isolated fetal cystic hygroma detected in the first trimester

Recent reports have indicated an increased risk for fetal chromosome abnormalities, especially autosomal trisomy, in fetuses with isolated cystic hygroma, or prominent nuchal membranes, detected by ultrasonography during the first trimester. However, these reports present contradictory information regarding the prognostic significance of septations within the cystic hygroma. We evaluated, in blind fashion, 55 consecutive cases of isolatd fetal cystic hygroma detected at or before 13·9 weeks' gestation to determine the association between septations and fetal chromosome complement. Septations were associated (P<0·05) with an increased risk for fetal chromosome abnormalities. However, the incidence of chromosome abnormalities was also increased (12·5 per cent) among cases not characterized by septations. Thus, we believe it prudent to offer invasive prenatal testing to all women found to be carrying fetuses with cystic hygroma, irrespective of the presence or absence of septations.     

Prenatal screening and diagnosis of neural tube defects in England and Wales in 1985

A survey was carried out to determine the effect of prenatal screening and therapeutic abortion on births in 1985 with anencephaly and spina bifida in England and Wales. Maternal serum alpha-fetoprotein tests were done on 399 288 women (60 per cent of pregnant women): 4 per cent were reported as being screen-positive and 1 per cent had an amniocentesis. An estimated 534 pregnancies associated with anencephaly were terminated and an estimated 445 pregnancies associated with spina bifida (but without anencephaly) were terminated. Most (63 per cent) of the anencephalic pregnancies were first suspected from an ultrasound examination; 57 per cent of the spina bifida pregnancies were first suspected from a positive maternal serum alpha-fetoprotein test, 35 per cent by ultrasound, and the remaining 8 per cent by other means. The birth prevalence of anencephaly declined by 94 per cent between 1964–1972 and 1985, but when the terminations of pregnancy on account of having a fetus with anencephaly are added to the births the decline in prevalence was only 50 per cent. The birth prevalence of spina bifida declined by 68 per cent over the same period but when the terminations were added to the births the decline in prevalence was only 32 per cent. Among births with anencephaly 66 per cent had had no screening or diagnostic tests in early pregnancy, but in those that did nearly all were positive–usually in twin pregnancies where one fetus was affected but not the other. Among births with spina bifida, 48 per cent had no tests and in those that did the results were mainly negative. We conclude that in order to monitor adequately the national screening programme for anencephaly and spina bifida a special neural tube defects register should be formed.     

Serum alpha-fetoprotein and neural tube defects in the first trimester of pregnancy

As part of the Medical Research Council randomized trial of vitamin supplementation in the prevention of neural tube defects (NTDs), maternal serum alpha-fetoprotein (AFP) was available for 19 NTD pregnancies. Each of these was matched with four unaffected controls, by maternal age, participating centre, and duration of sample storage. The samples came from women whose gestational age ranged from 6 to 14 completed weeks. The median AFP level in the affected pregnancies was 1·2 multiples of the median value in unaffected pregnancies of the same gestational age (95 per cent confidence interval (CI) 0·83–1·59). This confirmed the view that serum AFP measurement is of no practical value in the detection of NTDs in the first trimester of pregnancy. The study also showed that folic acid supplementation, used as a method of preventing NTDs, had no effect on the concentrations of maternal serum AFP up to 14 weeks of pregnancy.     

Prenatal diagnosis of hemoglobinopathies in twin pregnancies by double simultaneous fetoscopy

A new technique for sampling fetal blood in twin pregnancies using two fetoscopes simultaneously is described. Two fetoscopes were inserted, one after the other, into both amniotic cavities and fetal blood samples were obtained from either the chorionic plate vessels or the umbilical cord insertion area. The observation of the bright tip of the second fetoscope behind the septum using the first fetoscope assured the successful entry of the two fetoscopes into the two different amniotic sacs. This technique was performed on 15 out of 17 patients. In all patients the fetuses were at risk of β-thalassemia major. Sampling was successful in all cases. Double simultaneous fetoscopy seems to be a safe and accurate technique without technical problems or complications. The simultaneous use of two fetoscopes opens new possibilities in intrauterine fetal surgery and research.