Detecting neural tube defects by amniocentesis between 11 and 15 weeks' gestation

Forty-two open neural tube defects (NTDs) were identified in our series of 7440 amniocenteses tested between 11 and 15 weeks of gestation. Using a cut-off of ≥2.0 MOM, the detection rate for open NTDs was 95 per cent; 100 per cent each for anencephaly and spina bifida; and 78 per cent for encephalocele. Two encephaloceles had AFP levels less than 2.0 MOM and negative AChEs. Thirty-four (81 per cent) of these NTDs were tested between 13 and 15 weeks and 8 (19 per cent) before 13 weeks. There were 0.6 per cent false positives by AFP (excluding serious abnormalities and fetal death) and 0.1 per cent after AChE. The likelihood of an open NTD after an elevated AFP (≥2.0 MOM) was 24 and 77 per cent for any serious abnormality. These results, when combined with an earlier study, indicate that amniotic fluid AFP appears to be as sensitive a test for open NTDs between 13 and 15 weeks as between 16 and 20 weeks. Additional experience is necessary to determine this before 13 weeks.     

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.     

Amniotic fluid fibrinolytic system in fetal neural tube defects

Second trimester amniotic fluid fibrinolytic system was examined in normal pregnancies and those complicated by anencephaly, spina bifida and fetal chromosome abnormalities. No significant difference was demonstrated between the fibrinolytic systems from normal pregnancies and those complicated by fetal chromosome abnormalities. In pregnancies complicated with anencephaly and spina bifida no significant difference was demonstrated for alpha-1-antitrypsin, alpha-1-antichymotrypsin and urokinase. Plasminogen was significantly lower (p < 0.02) and plasmin significantly higher (p < 0.001) than levels from normal amniotic fluid. Alpha-2-macroglobulin, fibrinogen, FDP-D and FDP-E were detected only in pregnancies complicated with anencephaly and spina bifida.     

False-negative amniotic fluid acetylcholinesterase in a case of meningo-encephalocele

We describe a patient with a significantly elevated serum alphafetoprotein (AFP) concentration at 17 weeks of gestation, who showed only a marginally increased amniotic fluid AFP and lacked the second rapidly migrating band of acetylcholinesterase electrophoresis. Ultrasound examination revealed an encephalocele and ventriculomegaly. Autopsy showed that the encephalocele was not covered by skin.     

Vitamins,folic acid and neural tube defects: Comments on investigations in the United States

No clear answer concerning whether multivitamin/folate supplementation prevents neural tube defects (NTDs) is provided by three studies in the United States. All these studies are occurrence in nature, no recurrence studies having been conducted. The Atlanta Birth Defects Study is subject to pronounced memory and recall biases, the length between event and interview being as long as 16 years. In a second study (Boston University), objections can be raised to certain aspects of the experimental design, and the claim that 22 per cent of women started vitamins sufficiently early after pregnancy diagnosis to influence NTD formation is suspicious. Our NICHD case control study of 541 women in California and Illinois revealed no evidence for multivitamins or folic acid preventing NTDs. U.S. public policy-makers face difficulties in applying results of recurrence or occurrence studies in high-risk areas to low-risk areas in the U.S.     

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.     

Neural tube defects in trisomy 18

In a retrospective survey, the incidence of neural tube defects in liveborn trimsomy 18 was found to be 6·2 per cent. Based on these data one would expect to find trisomy 18 in 1 of the 117 patients with myeloidysplasia; the incidence of trisomy 18 in dysraphic fetuses would be anticipated to be higher. These observations underscore the need for amniocentesis karyotyping of fetuses with neural tube defects, and the importance of careful examination of infants born with neural tube defects.     

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.     

The use of amniotic fluid AFP action limits in diagnosing open neural tube defects

An analysis is made of alphafetoprotein (AFP) concentrations in 3630 amniotic fluids submitted for prospective prenatal diagnoses over a 7-year period. There were 89 cases of anencephaly, 74 of open spina bifida and 3467 with normal singleton outcomes. The AFP data were expressed in both standard deviations above the mean and multiples of the normal median for individual weeks of gestation. False positive and false negative rates were comparable in the two systems at selected cut-offs. It is concluded that either system may be used in setting action limits for the primary distinction of unaffected pregnancies from those in which an open neural tube defect is present.