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 assessment of anterior abdominal wall defects and their prognosis

Eighty-eight cases of abdominal wall defect with and without other lesions were ascertained by reviewing all labour room records in the West of Scotland, all surgical admissions to the Royal Hospital for Sick Children, Yorkhill, and all post mortems at Royal Hospital for Sick Children between 1978 and 1981. The affected cases comprised 39 terminations of pregnancy (17 of anterior abdominal wall defect without neural tube defect). 20 spontaneous stillbirths and 29 livebirths. All 10 cases of body stalk anomaly, 37.5 per cent of 16 gastroschisis cases and 53 per cent of 62 exomphalos cases had additional severe abnormalities. Abnormal karyotypes were present in seven out of 19 exomphalos cases but all karyotypes from 10 gastroschisis and 6 body stalk anomaly cases were normal. No correlation was found between the maternal serum AFP levels, the amniotic AFP levels and acetylcholinesterase results and the size of the lesion. It is proposed that anterior abdominal wall defects detected prenatally should have chromosome analysis and careful ultrasound to exclude associated severe anomalies before coming to a decision about termination. This policy was implemented in six pregnancies complicated by fetal gastroschisis without severe associated anomalies which were identified in the second trimester and continued to term. Immediate surgical repair was achieved in each case, although two of the infants succumbed from later complications of gastroschisis closure and one from respiratory distress syndrome. The remaining three infants made a satisfactory recovery.     

Early sonographic diagnosis of body stalk anomaly

Ultrasonographic features of a fetus at 18 weeks of gestation suggesting a body stalk anomaly are presented. These included a large abdominal anterior wall defect in apparent continuity with the placenta, severe kyphoscoliosis of the lower spine, the absence of one kidney, and a very short umbilical cord with only one umbilical artery. The amniotic fluid was reduced and the fetus was almost immobile at short-interval ultrasound examinations. The pregnancy was terminated and autopsy of the fetus showed abnormalities compatible with maldevelopment of both cephalic and caudal embryonic folds.     

Omphalocele—What should we tell the prospective parents?

An omphalocele is a congenital defect in the abdominal wall characterized by absent abdominal muscles, fascia, and skin. The characteristic ultrasound appearance includes a midline defect with herniation of abdominal contents into the base of the umbilical cord. Other anatomic abnormalities are seen in approximately 50% of cases, most notably cardiac defects (19%–32%). Approximately, 50% of cases are associated with genetic and multiple malformation syndromes including trisomy 13/18, pentalogy of Cantrell and Beckwith–Wiedemann syndrome. Therefore, a thorough evaluation is recommended, including detailed anatomic survey, fetal echocardiogram, genetic counseling, and prenatal diagnostic testing. Overall prognosis depends on the size of the omphalocele, genetic studies, and associated anomalies. Early prenatal diagnosis remains important in order to provide parental counseling and assist in pregnancy management. Delivery should occur at a tertiary care center. Timing and mode of delivery should be based on standard obstetric indications with cesarean delivery reserved for large omphalocele (>5 cm) or those that involve the fetal liver. Neonatal management involves either primary or staged reduction, both of which can be associated with a prolonged neonatal hospitalization.     

Gastroschisis: sonographic diagnosis,associations, management and outcome

Gastroschisis is a defect in the abdominal wall, typically on the right side of a normally inserted umbilical cord through which bowel and other abdominal contents herniate. Classically, no membrane covers the herniated abdominal contents, which distinguishes the defect from exomphalos, an important differential diagnosis. Gastroschisis is usually diagnosed prenatally using ultrasound examination. The prevalence is increasing worldwide from approximately 0.1 per 10 000 total births in the 1970s to over 5 in the early 2000s. The reasons for this are unknown, but factors such as maternal smoking, recreational drugs and young maternal age are strongly associated with the defect. The increasing prevalence is causing concern because the cost of treating gastroschisis is high. Neonatal morbidity depends on significant complicating factors such as bowel atresia or necrosis and prolonged post-operative ileus. Foetuses with gastroschisis are more likely to be born premature and with intra-uterine growth restriction, both of which contribute to the morbidity. Gastroschisis requires early surgery after birth, often followed by prolonged neonatal care. However, advances in surgical and post-operative care in the last decade have meant that currently 90% of affected neonates survive, with few long-term problems. Copyright © 2008 John Wiley & Sons, Ltd.     

Effects of mid-trimester induced abortion on the subsequent pregnancy

The outcome of the pregnancy following (a) a mid-trimester termination of pregnancy (TOP) for fetal neural tube defect (NTD) (77 women=group 1); (b) mid-trimester TOP for fetal Down's syndrome (13 women=group 2); (c) delivery of a baby with NTD (119 women=group 3) was studied. The prenatal fetal loss was relatively high in all groups. In group 1 it was similar to that found in other studies after first trimester TOP, in group 2 it was associated with advanced maternal age and the unexpected finding in group 3 was not attributable to advanced maternal age. It is suggested that a previous NTD per se might increase the risk of fetal loss in the next pregnancy. A previous mid-trimester TOP for NTD was not associated with an increase in premature labour, small for dates babies or congenital abnormality in the next pregnancy, but there was a slight increase in the number of babies weighing less than 2500 g.     

The impact of screening for open neural tube defects in England and Wales

Using information derived from the voluntary system of notification of congenital malformations in England and Wales, the birth prevalence of anencephaly and spina bifida was estimated to have declined by 80 per cent from 31.5 to 6.2 per 10 000 between 1964–1972 and 1985. Over the same period, notified terminations of pregnancy with a suspected fetal central nervous system abnormality increased from less than 1 per cent to 56 per cent of neural tube defect births and central nervous system terminations combined, accounting for 31 per cent of the decline in births. Routinely collected national statistics provide a method for monitoring the impact of screening for open neural tube defects. However because they are incomplete and lack detail an alternative method of monitoring is needed. This paper includes an outline of such a method, together with the results of a pilot study designed to assess the feasibility of monitoring screening in the Oxford Region.     

Detection of fetal structural abnormalities at the 11–14 week ultrasound scan

The aim of this study was to evaluate the detection of fetal structural abnormalities by the 11–14 week scan. 2853 pregnant women were submitted to a routine ultrasound scan between the 11th and 14th week and the fetal skull, brain, spine, abdominal wall, limbs, stomach and bladder were examined. Following the scans the patientes were examined in the second or third trimester of pregnancy. An isolated increased nuchal translucency was not considered an abnormality. However, these patients had an early echocardiography assessment. Fetal structural abnormalities were classified as major or minor and of early or late onset. A total of 130 (4.6%) defects were identified and 29 (22.3%) of these were diagnosed at the 11–14 week scan, including nine cardiac defects associated with increased nuchal translucency. The antenatal ultrasound detection rate was 71.5%, and 31.2% were detected in the first-trimester assessment. 78.8% of the major defects were diagnosed by the prenatal scan and 37.8% by the 11–14 week scan. Fetal structural abnormalities at the 11–14 week scan were detected in approximately 22.3% of the cases, therefore, a second-trimester anomaly scan is important in routine antenatal care to increase the prenatal detection of fetal defects. Copyright © 2002 John Wiley & Sons, Ltd.     

Amniotic fluid acetylcholinesterase in the prenatal diagnosis of open neural tube defects and abdominal wall defects: A comparison of gel electrophoresis and a monoclonal antibody immunoassay

Stored amniotic fluid samples collected in Oxford and East Birmingham as part of the Collaborative Acetylcholinesterase Study were assayed for the presence of acetylcholinesterase (AChE) using a monoclonal antibody (4F19) enzyme antigen immunoassay. These results were compared with the results of a gel AChE which had been performed earlier. A total of 5689 samples from singleton pregnancies were analysed (including 36 with anencephaly, 77 with open spina bifida and 17 with anterior abdominal wall defects). The gel test yielded detection rates of 97% for anencephaly, 99% for open spina bifida and 94% for abdominal wall defects; the false positive rate (excluding pregnancies associated with serious abnormalities, miscarriages and intrauterine deaths) was 0·24%. The monoclonal test yielded similar results; using appropriate cut-off values to allow for differences in acetylcholinesterase levels in blood stained and clear samples, a similar false-positive rate of 0·22% was associated with detection rates of 97%, 95 % and 71 % respectively for the three types of defect. Although the detection rates and the false positive rate were slightly higher for the gel test, a result that might be explained by a decrease in AChE activity caused by storage of the samples, the monoclonal test has the advantages of requiring less interpretative expertise, it can be performed on a larger number of samples a day and it is not affected by contamination with fetal calf serum.     

Parental reaction and adaptability to the prenatal diagnosis of fetal defect or genetic disease leading to pregnancy interruption

The objective of the study was to evaluate the psychological reaction of two groups of parents to a pregnancy termination after they had undergone a prenatal diagnostic procedure. The analysis involved interviews with a study group of 76 patients who were at risk of giving birth to a child with a genetic disease or defect and a comparison group of 124 who had a pregnancy termination after a major anomaly had been detected by routine ultrasound and who were not at known risk for a genetic disease. Only patients in the study group had received counselling before the prenatal diagnosis and were aware that the fetus could be affected. The overall reaction of the comparison group was one of shock, denial of fetal abnormality, and guilt over ‘abandoning the fetus’. A feeling of guilt was expressed by patients in the comparison group (73 per cent versus 29 per cent) in the period immediately following the interruption. One-third of patients in both groups felt obliged to undergo a therapeutic abortion. More patients in the study group than in the comparison group expressed the need to see a psychiatrist at the time of the study (19 per cent versus 7 per cent) and viewed future pregnancies as a replacement for the lost pregnancy (63 per cent versus 19 per cent). The recommendations of the study focus on information sessions to personnel, nursing support, analgesia during the expulsion period, an atmosphere of respect that should be present at the time that the fetus is viewed, the anticipation of mourning, and the long-term follow-up of the couple to ensure that counselling for future pregnancies and psychological support are provided when needed.     

Mosaicism and accuracy of prenatal cytogenetic diagnoses after chorionic villus sampling and placental biopsies

Discrepant chromosome findings in placenta and fetus (false negative and false positive) after chorionic villus sampling (CVS) are mainly due to confined mosaicism. Non-mosaic normal or abnormal chromosome counts after direct preparation and culture nearly always correctly reflect the fetal chromosome constitution. False-negative results have almost exclusively been restricted to cytotrophoblast cells not representing a fetal chromosome abnormality. Diagnosis of placental mosaicism definitely requires an adequate follow-up by amniocentesis, fetal blood sampling, or sonography before a pregnancy is terminated. When direct preparations and cultured cells are used for cytogenetic diagnoses and placental mosaicism is not taken as proof for a chromosomal abnormality in the fetus, CVS is an accurate diagnostic tool.     

Alpha-fetoprotein and acetylcholinesterase activity in first-and early second-trimester amniotic fluid

Normal ranges of amniotic fluid alpha-fetoprotein (AFP) and acetylcholinesterase activity (AChE) are described for gestational weeks 11–14 using rocket gel immunoelectrophoresis for AFP quantitation and a monoclonal antibody (4F19) enzyme antigen immunoassay for AChE activity measurement. The normal ranges were established by the examination of 281 amniotic fluid samples from 281 normal pregnancies. AFP was found to increase from a median level of 14.0 MIU/1 at 11 weeks to a maximum at 13 weeks (median=18.0 MIU/l) (P<0.05), thereafter falling (not significant). No AChE test result exceeded 4.8 nkat/l. In addition, AFP and AChE values for three cases of fetal malformation, identified by the biochemical analyses of amniotic fluid, are given. These cases included two fetuses with a neural tube defect and one fetus with an abdominal wall defect. Amniocentesis was performed at 10, 11, and 14 weeks, respectively. The AFP and AChE values were all high.     

Ultrasound observation of amnion dysmorphism at 14.5–16 weeks

The presence of chorio-amniotic separation and amnion anomalies was recorded in 9500 patients referred for vaginal ultrasound examination at 14.5–16 weeks' gestation. In all patients with a change in the amnion, a search for fetal anomalies was performed and pregnancy outcome was checked. Amnion dysmorphism was observed in 30 cases. The main findings were a floating membrane which changed its configuration when the uterus was tilted and multiple intrauterine amniotic sheets. In no case was attachment of the fetus to the membranes noted. There was no fetal abnormality and pregnancy outcome was favourable in all patients. In conclusion, ultrasound visualization of amnion dysmorphism in early pregnancy is not associated with an adverse pregnancy outcome.     

Trisomy 12 mosaicism in amniocytes and dysmorphic child despite normal chromosomes in fetal blood sample

Trisomy 12 mosaicism (44 per cent) was detected prenatally in cultured amniocytes. A cordocentesis was performed to confirm the result. Only normal cells were found in the fetal blood sample. The fetus was estimated to be at a low risk of having a chromosomal abnormality and the pregnancy continued. Eight days after birth, a congenital heart defect was detected in the child. Several dysmorphic features were also evident. Further karyotyping of different tissues revealed normal blood and urinary cells but trisomic cells in the placenta (100 per cent) and in skin fibroblasts (25 per cent). The child died at 5 weeks of age. In this case, the fetal blood sample failed to reveal the real chromosome constitution of the fetus.     

A survey of diagnostic amniocenteses in Oxford from 1974–1981

A survey was conducted of the results of mid-trimester diagnostic amniocenteses in the Oxford Region from 1974 to 1981. The survey used data relating to all 4357 singleton pregnancies in which an amniocentesis was performed during this period. Follow-up information on outcome was obtained in respect of 4284 (98 per cent) pregnancies. A cell culture to determine karyotype and an alpha-fetoprotein determination was carried out in all cases. From 1974 to 1981 amniocenteses became increasingly common, rising from 2 to 32 per 1000 births. The most common indication for amniocentesis was a high risk of a chromosome abnormality–56 per cent of all amniocenteses. Within this group advanced maternal age was responsible for 89 per cent of the cases. The next most common indication was a high risk of a neural tube defect (37 per cent of all amniocenteses)–in 1974 a raised maternal serum alpha-fetoprotein level accounted for only 4 per cent of these; by 1981 this had risen to 67 per cent. There were seven false-positive and 132 true-positive diagnoses of neural tube defect; since 1981, with the introduction of amniotic fluid acetylocholinesterase determination as a secondary diagnostic test for neural tube defects, there have been no further false-positive diagnoses. In 1981 76 per cent of women aged 35 years or more did not have an amniocentesis. It is not known to what extent this was due to not offering women in this age group amniocentesis or to women not accepting such an offer.     

The psychosocial sequelae of a second-trimester termination of pregnancy for fetal abnormality

A retrospective study to investigate the psychosocial sequelae of a second-trimester termination of pregnancy (TOP) for fetal abnormality (FA) is described. After appropriate consent was obtained, 84 women and 68 spouses were visited 2 years after the event and asked to complete an extensive questionnaire. Most couples reported a state of emotional turmoil after the TOP. There were differences in the way couples coped with this confusion of feelings. After 2 years about 20 per cent of the women still complained of regular bouts of crying, sadness, and irritability. Husbands reported increased listlessness, loss of concentration, and irritability for up to 12 months after the TOP. In the same period, there was increased marital disharmony in which 12 per cent of the couples separated for a while and one couple obtained a divorce. These problems could be attributed to a lack of synchrony in the grieving process. Confusing and conflicting feelings led to social isolation and lack of communication. Difficulties in coming to terms with the fetal loss were not found to be linked to the type of fetal abnormality or religious beliefs but were related to parental immaturity, inability to communicate needs, a deep-rooted lack of self-esteem before the pregnancy, lack of supporting relationships, and secondary infertility. Suggestions for improved management are given.     

The importance of late pregnancy scans for renal tract abnormalities

A 12-month prospective population study of antenatal patients was undertaken in a large district general hospital to assess ultrasound scanning in late pregnancy for the detection of non-lethal fetal renal abnormalities. The rate of false-negative antenatal scans during the study period was also assessed. Both 18–20 and 28–32 weeks' gestational scans were performed on 6497 pregnant women. Forty fetuses with a suspected abnormality were referred for postnatal examination and 29 neonates were found to have renal abnormalities. Of these, 21 were significant and eight were likely to be extrarenal pelves. In six, there was evidence of an abnormality at the early scan. Nine children, seven with reflux, presented within the study period, all with preceding normal antenatal scans. The incidence (0·46 per cent) of structural renal abnormalities is similar to that reported previously. A late scan is necessary for the antenatal detection of non-lethal renal abnormalities.     

Predictive value of amniotic acetylcholinesterase analysis in the diagnosis of fetal abnormality in 3700 pregnancies

The value of acetylcholinesterase (AChE) analysis as an adjunctive test to amniotic alpha fetoprotein (amAFP) for the diagnosis of fetal abnormality has been investigated in a series of 3785 amniotic fluid samples. Quantitative analysis of AChE performed retrospectively on a selected group of 541 amniotic fluid samples failed to discriminate between normal and open neural tube defect pregnancies. Qualitative analysis of AChE by polyacrylamide gel (PAG) electrophoresis in the same series of 541 fluids correctly identified 251 of the 255 pregnancies with open neural tube defect and 29 of the 31 pregnancies with false positive amAFP results. The failure of the test to diagnose 4 cases of open neural tube defect was probably attributable to the age and condition of the stored AF samples. Routine diagnostic testing of AChE isoenzymes in a further 3244 AF samples successfully identified all 170 cases of open neural tube defect and 20 cases with other fetal defects. Thirteen fluids gave false positive AChE results (0.4 per cent) compared to 59 of the series in which there were false positive amAFP results (1.8 per cent). Six of the 13 false positive AChE cases had AChE bands of low intensity which would not be regarded as diagnostic of fetal abnormality, and in five the AChE band may have been the result of significant blood contamination. False positive AChE results contributed to the decision to abort three apparently normal fetuses, but a normal AChE result undoubtedly helped to save a number of pregnancies with false positive amAFP results. Our experience suggests that repeating the amniocentesis may help in resolving the rare diagnostic difficulty of a positive AChE result with or without an elevated amAFP in the absence of ultrasound evidence of fetal abnormality, particularly where there is blood contamination of the amniotic fluid sample.     

Sex chromosome mosaicism not detected at amniocentesis

Amniocentesis was performed because of a fetal abdominal wall defect, and a 45,X karyotype was obtained. A near-normal male infant with no features of Turner syndrome was delivered. The karyotype of the infant was 45,X/46,X, dic(Y)(q11), with each of the cell lines present in approximately 50 per cent of the lymphocytes and fibroblasts examined.     

Cytogenetic results from the U.S. collaborative study on CVS

Cytogenetic data are presented for 11 473 chorionic villus sampling (CVS) procedures from nine centres in the U.S. NICHD collaborative study. A successful cytogenetic diagnosis was obtained in 99.7 per cent of cases, with data obtained from the direct method only (26 per cent), culture method only (42 per cent), or a combination of both (32 per cent). A total of 1.1 per cent of patients had a second CVS or amniocentesis procedure for reasons related to the cytogenetic diagnostic procedure, including laboratory failures (27 cases), maternal cell contamination (4 cases), or mosaic or ambiguous cytogenetic results (98 cases). There were no diagnostic errors involving trisomies for chromosomes 21, 18, and 13. For sex chromosome aneuploidies, one patient terminated her pregnancy on the basis of non-mosaic 47,XXX in the direct method prior to the availability of results from cultured cells. Subsequent analysis of the CVS cultures and fetal tissues showed only normal female cells. Other false-positive predictions involving non-mosaic aneuploidies (n = 13) were observed in the direct or culture method, but these cases involved rare aneuploidies: four cases of tetraploidy, two cases of trisomy 7, and one case each of trisomies 3, 8, 11, 15, 16,20, and 22. This indicates that rare aneuploidies observed in the direct or culture method should be subjected to follow-up by amniocentesis. Two cases of unbalanced structural abnormalities detected in the direct method were not confirmed in cultured CVS or amniotic fluid. In addition, one structural rearrangement was misinterpreted as unbalanced from the direct method, leading to pregnancy termination prior to results from cultured cells showing a balanced, inherited translocation. False-negative results (n = 8) were observed only in the direct method, including one non-mosaic fetal abnormality (trisomy 18) detected by the culture method and seven cases of fetal mosaicism (all detected by the culture method). Mosaicism was observed in 0.8 per cent of all cases, while pseudomosaicism (including single trisomic cells) was observed in 1.6 per cent of cases. Mosaicism was observed with equal frequency in the direct and culture methods, but was confirmed as fetal mosaicism more often in cases from the culture method (24 per cent) than in cases from the direct method (10 per cent). The overall rate of maternal cell contamination was 1.8 per cent for the culture method, but there was only one case of incorrect sex prediction due to complete maternal cell contamination which resulted in the birth of a normal male. The rate of maternal cell contamination was significantly higher in samples obtained by the transcervical sampling method (2. 16 per cent) than in samples obtained by the transabdominal method (0.79 per cent). From these data, it is clear that the culture method has a higher degree of diagnostic accuracy than the direct method, which should not be used as the sole diagnostic technique. The direct method can be a useful adjunct to the culture method, in which maternal cell contamination can lead to incorrect sex prediction and potentially to false-negative diagnostic results.