H. Cuckle

AMNIOTIC-FLUID ACETYLCHOLINESTERASE AS A POSSIBLE DIAGNOSTIC TEST FOR NEURAL-TUBE DEFECTS IN EARLY PREGNANCY

Raised levels (greater than or equal to 4.5 munits/ml) of acetylcholinesterase (AChE) activity in amniotic fluid at 14--23 weeks of pregnancy were significantly associated with open fetal neural-tube defects. Out of 72 pregnancies correctly classified by the amniotic-fluid alpha-fetoprotein (A.F.P.) test, 2 of 56 without neural-tube defects and all 16 with open neural-tube defects (8 with anencephaly and 8awith open spina bifida) had raised levels of AChE. Out of 5 pregnancies misclassified by the A.F.P. test (4 without neural-tube defects and 1 with open spina bifida), only 1 was misclassified by the AChE test--namely, one of those without a neural-tube defect. Thus, only 3 of the 77 pregnancies tested were misclassified by the quantitative AChE test. A qualitative test for an isoenzyme of AChE found in cerebrospinal fluid correctly classified these 3 pregnancies. These findings suggest that the analysis of AChE in amniotic fluid may be a useful test in the diagnosis of open neural-tube defects.

MATERNAL SERUM-ALPHA-FETOPROTEIN AND LOW BIRTH-WEIGHT

High maternal serum-alpha-fetoprotein (A.F.P.) concentrations in the first half of pregnancy were associated with prematurity and high perinatal mortality. 94 singleton pregnancies without neural-tube defects but with A.F.P. levels equal to or greater than three times the normal median resulted in the birth of infants weighing, on average, 357 g less than controls (P less than 0-001). The mean head circumference of the infants was also smaller than that of the controls. The 1 stillbirth and 3 neonatal deaths yielded a mortality-rate more than three and a half times that for singleton births without neural-tube defects at the same hospital in the years 1974-76. The results suggest that some pregnant women who will deliver low-birth-weight infants at high risk of perinatal death may be identified by means of serum-A.F.P. measurement early in pregnancy.

SMALL BIPARIETAL DIAMETER OF FETUSES WITH SPINA BIFIDA: IMPLICATIONS FOR ANTENATAL SCREENING

The biparietal diameter of 20 fetuses with spina bifida was measured during pregnancy by ultrasound scanning, mainly in the second trimester. The mean result was 0.83 cm smaller than the value based on 186 unaffected pregnancies at the same gestational ages (P<0.001), suggesting that spina bifida fetuses are growth retarded. The practical consequence of this finding is that the routine use of ultrasound in pregnancy will increase the sensitivity of AFP screening for open spina bifida at 16 to 18 weeks gestation from 79 per cent as estimated by the UK Collaborative AFP Study to about 90 per cent or more.

ANTENATAL SCREENING IN OXFORD FOR FETAL NEURAL TUBE DEFECTS

Between May 1975 and the end of 1977, 6443 antenatal patients were screened mainly between 16 and 22 weeks of pregnancy for neural tube defects (NTDs) at the John Radcliffe Hospital, Oxford, by maternal serum alpha‐fetoprotein (AFP) measurement; a take‐up of 72 per cent. Seventeen out of 18 (94 per cent) patients with open NTD pregnancies (9 out of 9 with anencephaly and 8 out of 9 with open spina bifida) had positive screening tests, and all except one were offered and accepted a termination of pregnancy. Two hundred and forty‐five (3.8 per cent) patients with unaffected pregnancies also had positive screening tests, although only 1 4 per cent had an amniocentesis. Following ultrasonography, about 50 per cent of patients with unaffected pregnancies with positive screening tests were not offered an amniocentesis because they had a multiple pregnancy or their gestational age had been underestimated. The odds of having a fetus with an NTD among the women who had an amniocentesis was about 1 to 6 (1 to 11 for open spina bifida alone). Two apparently normal pregnancies were terminated. A survey of the acceptability of the screening programme among a consecutive sample of 73 patients who knew that they had a positive screening test revealed that all except one had no objection to screening in general, and 68 (93 per cent) wanted to be tested again in a future pregnancy. The approximate direct cost of the programme was £2 to £3 per patient screened, or about £l000 per NTD detected (about £2200 per open spina bifida detected).

Ferritin-Bearing Lymphocytes in the Diagnosis of Breast Cancer

Four hundred forty‐seven women attending a breast clinic because of either suspicious lesions, anxiety about breast cancer, follow‐up after the removal of a benign breast lesion, or a family history of breast cancer had a routine test for percentage of ferritin‐bearing lymphocytes (FBL) in their peripheral blood. Among patients who received surgery following physical examination in the clinic and/or mammography, the test was positive in 40 of the 45 (89%) with Stage I; II carcinoma, 3 of 3 with Stage IV carcinoma, and only in 29 of the 97 (37%) with benign breast disease. The possible reasons for the poorer detection rate in Stage III carcinoma are discussed. The test, however, identified 2 cases of Stage I carcinoma, 1 of breast lymphoma, and 12 with premalignant lesions in those who were found normal on physical examination and mammography. Ferritin‐bearing lymphocyte results tended to become negative after surgical removal of the lesion, and became positive on recurrence of the tumor and appearance of metastases. The detection rate was maximized by combining the FBL test with the clinical modes of detection.

MATERNAL SERUM ALPHA‐FETOPROTEIN AND BIRTH WEIGHT IN TWIN PREGNANCIES

In 102 twin pregnancies the mean birth weight of each pair showed a statistically significant negative association with maternal serum alpha‐fetoprotein (AFP) levels early in pregnancy. Women with AFP levels of four or more times the median value for singleton pregnancies gave birth to infants with a median birth weight 660 g less than that of infants born to women with AFP levels between 1·0 and 1·5 times the median for singleton pregnancies. Maternal serum AFP has been shown to be an early predictor of low birth weight delivery in singleton pregnancies. Our results indicate that this is also true in twin pregnancies.

CLINICAL DILEMMAS ARISING FROM THE ANTENATAL DIAGNOSIS OF NEURAL TUBE DEFECTS

Eight case histories are presented which demonstrate clinical problems associated with the antenatal screening for and diagnosis of neural tube defects. It is suggested how some of these problems might be avoided in future.

Evidence against oral contraceptives as a cause of neuraltube defects

Summary. Information on oral contraceptive (OC) use, collected at the first antenatal visit, was abstracted from the medical notes in respect of 107 index pregnancies resulting in the delivery of an infant with a neural‐ tube defect (NTD) and 214 unaffected controls. The relative risk of having an NTD infant for women who had at any time used OCs was 0.82 (95% confidence interval 0.52,1.32) compared with that in women who had never used OCs. For women who stopped OC use less than 3 months before becoming pregnant or who continued in early pregnancy, the relative risk was 1.18 (95% confidence interval 0.70, 1.98) compared with women who had used OCs at any other time. An analysis restricted to those women who had at any time used OCs did not suggest an association between NTD risk and the interval between stopping OC use and becoming pregnant. None of our analyses therefore provided any evidence that OCs cause NTDs and if a risk exists it can only be small.

Maternal serum alpha-fetoprotein levels in triplet and quadruplet pregnancy.

Maternal serum alpha‐fetoprotein (AFP) levels were higher in six triplet pregnancies and three quadruplet pregnancies than in control singleton pregnancies matched for maternal age, parity and time of gestation at which the serum sample was taken. Between 12 and 23 weeks of pregnancy, the average AFP levels among the triplet pregnancies was three times that found in the singleton pregnancies, and the level in the quadruplet pregnancies was even higher. Maternal serum AFP levels appear to be associated with the number of fetuses in utero.

BIRTH WEIGHT OF INFANTS WITH SPINA BIFIDA CYSTICA

The mean birth weight of 189 singleton infants with spina bifida cystica (including 21 with encephalocele) was statistically significantly less than the mean birth weight of 3816 singleton infants without neural tube defects, 0·20 kg less among male infants and 0·24 kg less among female infants. Most, if not all, of this difference in birth weight was due to the spina bifida infants being light for their gestational age. The difference could not be explained by differences in parity or social class.