348

B.T.P. IN 70 SAMPLES OF AMNIOTIC FLUID DURING THE 14THTO THE 33RD WEEKS OF GESTATION

disorders than alpha-fetoprotein (A.F.P.), it is interestingto note the case of a 17th-week amniotic-fluid sample froma patient who subsequently had a spontaneous abortion;here, the concentration of A.F.P. was greater than 250 mg.per litre, while B.T.P. was 6-7 mg. per litre-a not abnormalfinding. However, an amniotic-fluid sample from a 38-week anencephalic fetus had concentrations of 6-3 mg.B.T.P. and 3-5 mg. A.F.P. per litre.

B.T.P. is not specific for C.S.F., it being also present innormal serum (2-6-6-0 mg. per litre, independent of adultage)1’ and urine 18,19 with a daily excretion below 9-5 mg.,20as well as in various organ extracts-e.g., brain, pancreas,kidney, and urogenital tissues.19,21,22 An impressive bodyof quantitative data has been compiled enabling the useof A.F.P. for prenatal diagnosis of grave fetal disorders, inparticular, open neural-tube defects. The commercial

availability of A.F.P. calibration solutions and anti-A.F.P. isalso advantageous. Quantitative investigations into theuse of B.T.P. as a marker for neural-tube defects in amnioticfluid are being continued.Department of Neurology,

University Hospital,S-22185, Lund, Sweden. JAN E. OLSSON.

Blood Centre and Departmentof Clinical Chemistry, MICHAEL S. SHERMAN.

Department of Obstetrics andGynæcology,

University Hospital,S-750 14 Uppsala, Sweden. BERNDT KJESSLER.

NEURAL-TUBE DEFECTS ANDSUBFERTILITY

SIR,-While studying another problem, I had an

opportunity to ask mothers of babies born with anencephalyand spina bifida whether for any pregnancy they hadactively tried to conceive for a period longer than sixmonths. The starting population of 339 subjects wasobtained from entries appearing on live-birth and fetal-death certificates in up-State New York in 1970-72. Forvarious reasons only legitimate maternities in Whitewomen were included in the study. Controls (two foreach case) were taken from the same source and matchedfor race, legitimacy, county of residence, child’s date ofbirth, and pregnancy outcome (fetal death or live birth).

17. Olsson, J. E., Link, H., Nosslin, B. ibid. 1973, 21, 1153.18. Hochwald, G. M., Thorbecke, G. J. Proc. Soc. exp. Biol. Med.

1962, 109, 91.19. Laterre, E. C., Heremans, J. F., Carbonara, A. Clinica chim. Acta,

1964, 10, 197.20. Ericsson, J., Link, H., Zettervall, O. Neurology, Minneap. 1969, 19,

606.21. Penny, R., Osserman, E. F. Aust. J. exp. Biol. med. Sci. 1971, 49,

111.22. Olsson, J. E., Nord, L. J. Neurochem. 1973, 21, 625.

Before interviewing by telephone (by the Birth DefectsInstitute, New York State Health Department) the familyphysician’s approval was obtained, and the mothers werethen informed about the study by letter. 265 case mothersand 549 control mothers were interviewed.

In their responses most women answered " yes " or" no ", but a few were " unsure " (see table). Since

" unsure " probably meant they were uncertain if they hadwaited six months, such responses were combined with"

yes ". The resultant relative risk of 1-30 agrees with thefinding of James 1 but is not statistically significant(x2=2.50). If, however, the subfertility is related to

EXPERIENCE OF 6-MONTII PERIOD OF INFERTILITY

* Significant at 0-01 level.

subnormal pituitary production of gonadotrophin thenone could predict that the relative risk in the accompanyingtable would be highest in younger mothers and would fallwith increasing maternal age. This is inferred from theclaims that the level of urinary gonadotrophin tends to

increase monotonically with age in premenopausal women,3and that subfertility related to gonadotrophin deficiencyshould therefore be proportionately more prevalentamong younger women. A breakdown of the overallresults in the table shows a tendency for the relative riskto decrease with age, as predicted. The risk is nearlydouble for both younger age-groups, but statisticallysignificant only for women in the 25-29 age-group.

These results are subject to the usual uncertaintiesassociated with case/control studies. In the case of memorybias, however, it is difficult to see how it would have

apparently affected younger mothers exclusively. Con-

ceivably (but in my opinion unlikely) it could be related toyounger mothers having to recall events over shorter

periods. Misunderstanding of the question has also to beraised as a possibility, although this might reasonably beexpected to have occurred at random. Surprisingly,perhaps, the proportion of subfertile mothers declines

among both cases and controls aged 35 and over-a featurewhich may also be discerned in the Growth of AmericanFamilies Study, 1960.4 This seems to be explained by theprevalence of sterility tending to increase with increasingage and the exclusion of women known to be sterilefrom the present study.

Office of Epidemiology andBiometry,

National Institute of Child Healthand Human Development,

National Institutes of Health,Bethesda, Maryland 20014, U.S.A. PHILIP S. SPIERS.

1. James, W. H. Lancet, 1973, ii, 916.2. Spiers, P. S. ibid. p. 1149.3. Albert, A., Randall, R. V., Smith, R. A., Johnson, C. E. in Hormones

and the Ageing Process (edited by E. T. Engle and G. Pincus);p. 49. New York, 1956.

4. Kiser, C. V., Grabill, W. H., Campbell, A. A. Trends and Varia-tions in Fertility in the United States; p. 33. Harvard, 1968.