ASCERTAINMENT OF MALFORMATIONS

222

Thirty cells were found accurately counted:

in which chromosomes could be

46 chromosomes,

8 cells fully analysed of which 4 contained 3 contained 45 chromosomes, and 1 contained 44+2 double

fragments. Cells with 46 chromosomes showed a normal male karyotype with 22 autosomes and sex chromosomes XY. Cells with 45 chromosomes showed 22 autosomes with sex chromosomes XO. Buccal smears were chromatin negative, and in addition the 17-ketosteroid excretion (March 15, 1961) was 7-5 mg. in 24 hr. The patient died on Jan. 6, 1962, and postmortem was refused. Not only is this case of interest as a phenotypic male XY/XO mosaic but also because of the neoplasia in the male gonad and in the uterus, separated by seventeen years. A full report of this

case

is

being prepared

for

publication. F. J. W. LEWIS J. P. MITCHELL G. L. Foss.

RUBELLA BEFORE CONCEPTION AS A CAUSE OF FŒTAL ABNORMALITY

SIR,-Has not Mr. Whitehouse (Jan. 19) misinterpreted his data and thereby complicated what we know of the effect of rubella virus on the embryo ? It is quite possible that the primigravida’s history was not accurate; that her last menstrual period of June 10 was a decidual bleed; and that conception occurred during early May. The embryo would thus have been subjected to the effects of rubella in the mother "in late May ". The weight of an abnormal foetus may not be a good measure of its maturity; nevertheless a 28-week foetus weighs 1080 g. and a 32-week fcetus 1670 g.,! so that this macerated foetus, weighing 1240 g. was at least 28 and probably more than 30 weeks old. Gross maceration would occur after death in utero during the second week of December and before evacuation in January. The disparity between the true age of the foetus and the estimate of 24-26 weeks obtained from palpation of the fundus might be due to oligohydramnios, associated with agenesis of the kidneys,2 found on pathological examination. A more valid conclusion would be that intrauterine death occurred in a foetus with several malformations. Anephregenesis and associated oligohydramnios were found and the developmental abnormalities were possibly due to maternal rubella at a very early stage of pregnancy.

A.

J. JOUHAR.

ASCERTAINMENT OF MALFORMATIONS SIR,-The special article by Dr. Leck and Dr. Smithells (Jan. 12) is very timely. There is one point which I wish to question. Their series includes 33 infants with major limb defects as compared with an expected figure of 18-20 calculated from the Ministry of Health figures. They say there is a chance of less than 1 in 200 of obtaining a figure so much greater than that expected as a result of random variation (my italics). The incidence of limb malformations presumably bears relation to the amount of thalidomide prescribed. The sale of this drug in different regions cannot have been made in a random fashion, because, amongst other factors, it must have depended on the enthusiasm of local representatives and the attitude of hospital physicians in recommending the drug to general practitioners. 3-7% of Scottish births 1. 2.

Arey, L. B. Developmental Anatomy. Philadelphia, 1949. Baird, D. Combined Textbook of Obstetrics and Gynæcology. Edin-

burgh,

1950.

in Stirlingshire, but 11 infants with major limb defects whose mothers took, or may have taken, thalidomide were born alive in this area out of a total of 511 in Scotland-i.e., 22%. This extreme variation makes the random distribution of these cases even less likely. I agree with Dr. Leck and Dr. Smithells, however, that the national figures are unsatisfactory, especially as they tend to be invested with an air of authority. For instance, it is odd that all the deaths in Scotland should have occurred in Stirlingshire. Thus, according to the official figures, of 51 infants born to mothers who took, or may have taken, thalidomide, 14 are still alive. Of the 11 such infants liveborn in this area, only 4 are still alive.

occur

Royal Infirmary, Stirling.

A. L. SPEIRS.

PITFALLS IN TESTS FOR TERATOGENICITY

SIR,-The statement of Dr. Fraser and others2 that the of malformations depends on several interacting factors is undoubtedly of great importance. Nevertheless, I think that from a practical standpoint-i.e., in screening the possibly teratogenic drug-this is of minor interest.

frequency

The question is not quantitative but exclusively qualitative. Whether one finds 6% or 72% of malformations, the conclusion must be the same: the drug should not be released for clinical use. In fact, the pitfall is that, having found no teratogenic effect in a " sufficient number of different species of laboratory animals ", one can still not be sure of the effect on the human foetus, which is always the ultimate purpose of investigation.

MOGENS NYMARK. MECLOZINE AND FŒTAL ABNORMALITIES SIR,-The Fetal Life Study,3 a prospective survey of pregnancy, began to record in February, 1953, the nature and amount of drugs utilised. On the weekend of Nov. 24, 1962, several articles appeared in the New York City lay

Press reporting concern that meclizine (see figure) (or’meclozine as it is known in Britain) might be con-

tributing

faetal

to

mal-

formations. A preliminary report of the epidemic observation unit of the College of General Practitioners4 and a letter circulated bv the Swedish Medical Board have expressed caution in the use of meclizine during pregnancy. Weicker et al. have pre1. 2. 3.

Lancet, 1962, ii, 986. ibid.p. 1116. McIntosh, R., Mellin, G. W. Bull. Sloane Hosp. Women, December, 1956, 2, 95. 4. Watson, G. I. Brit. med. J. 1962, ii, 1446. 5. Weicker, H., Bachmann, K. D., Pfeiffer, R. A., Gleiss, J. Dtsch. med. Wschr. 1962, 87, 1597. TABLE I-PROPRIETARY NOMENCLATURE

Meclizine : Ancolan Bonamine Bonine Navicalm Neo-Istafene Postafene Meclizine and pyridoxine: Ancoloxin Bonadoxin Postadoxin

Cyclizine:

Marezine Marzine

Dimenhydrinate: Amosyt Anautine

Andramine Diamarin Dramamine Dramarin

Dramyl Gravol

Menhydrinate Nevamin Travelin Travelmin Xamamina