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sponse and augment the proposed "adaptive process" duringthe late stages of pre-eclamptic pregnancy.Division of Internal Medicine,University of Calgary,Calgary, Alberta, Canada R. M. LEWKONIA

HUMAN PLACENTAL LACTOGEN IN LATEPREGNANCY

SIR,-Dr Letchworth and his colleagues (May 6, p. 955)suggest that human placental lactogen (H.P.L.) in serum beroutinely screened in late pregnancy. We have been doing thisbut occasionally have met problems.One such case was that of a 26-year-old primigravida who,

after stopping oral contraceptives 2 years before conception,had had normal 28-day menstrual cycles. The early pregnancywas uneventful and fetal movements were felt at the 21stweek. Between the 20th and 33rd week the patient put on 5.5 5kg. A routine serum-H.P.L. in the 33rd week was less than 2.0mg/1 (H.P.L. immunoassay kit, Radiochemical Centre, Amer-sham). Clinically the size of the uterus and the fetus appearednormal for the gestation; the blood-pressure was normal.H.P.L. values at weeks 34 and 35 were 1.1 and 1.0 mg/1, re-spectively. Because of these low H.P.L. levels the patient wasadmitted for observation. During the 34th week the 24 h urin-ary excretion of oestrogens was 129 mol. Twice-weekly 24 hurinary oestrogen determinations from then on showed a pro-gressive rise, and by the 38th week reached a peak of 240mol. Oestrogen excretion fell to 198 tmol/24 h at the 39thweek. A repeat H.P.L. at 39 weeks was again below 2.0 mg/1.The fetal biparietal diameter at that time was normal for thegestational age. The placenta had some calcification from the36th week onwards but was of normal size. The patient wasinduced empirically at term and after a labour lasting 15 h shehad a forceps delivery of a male infant weighing 3.42 kg. Theonly sign of fetal distress was a rapid fall in the fetal heart-rateto 80 beats/min at the beginning of the second stage of labour.The Apgar score was 2 at 1 min and 8 at 5 min. The placentaweighed 550 g and had scattered areas of calcification but nodefinite infarcts. The subsequent progress of both mother andbaby was uneventful.

Serum-H.p.L. rises progressively with gestation, and failureto reach the expected concentrations in the 3rd trimester ofpregnancy has been found to be an index of placental insuffi-ciency. In this patient’s serum H.P.L. was almost undetectable.We do not know why. The conventional assay kit is one wehave used in many pregnancies without encountering this

problem. H.P.L. has a dimeric form,’ but the dimer is moreactive than the monomer in the radioimmunoassay. The H.P.L.produced by our patient may have had altered immunologicaldeterminants in the molecule. Another possibility is that H.P.L.production was defective. Saxena et al.2 suggested that lowH.P.L./H.C.G. ratios are helpful in distinguishing neoplasmsfrom normal trophoblasts during early pregnancy because ofthe impaired production of H.P.L. by trophoblastic neoplasms.In our patient there was no evidence that the placenta wasabnormal, the pregnancy was uneventful, and follow-up hasbeen unremarkable. Another possible explanation may be thatdestruction of H.p.L. was more rapid than normal.

This case shows that very low H.P.L. values may be foundin the last trimester of normal pregnancy. This biochemical

finding prompted close monitoring of the patient although thepregnancy and birth were normal.

Maternity Unitand Department of Chemical Pathology,

North Devon District Hospital,Barnstaple, Devon EX31 4JB

W. P. BRADFORDT. HARGREAVES

1. Schneider, A. B., Kowalski, K., Buchman, G., Sherwood, L. M. Biochim.biophys. Acta, 1977, 493, 69.

2. Saxena, B. N., Goldstein, D. P., Emerson, Jr. K., Selenkow, H. A. Am. J.Obstet. Gynec. 1968, 102, 115.

SIR,-Dr Letchworth and his colleagues recommend H.P.L.assay as a routine screening test to identify at-risk pregnancies.The prediction of danger to the life of the fetus would be themost important feature of such a test, but Letchworth et al.give no data on this aspect of pregnancy outcome.

Spellacy et al.’ in a large study, showed that of 71 pregnan-cies which ended with intrauterine death only 36 (51%) hadlow H.P.L. levels at or before fetal death. H.P.L. levels were lowin most pregnancies with severe toxaemia, but 18 out of 19 nor-motensive patients had normal H.P.L. levels. Toxocmia is a

major threat and affected patients receive intensive antenatalcare as a matter of course. Identification of patients who willhave a poor outcome of their pregnancy in the absence of clini-cal features associated with high risk is very important. In thisrespect H.P.L. was ineffective and misled the obstetrician.Our experience with H.P.L. assays in late pregnancy, with

the same kit method as Letchworth et al., is similar to that ofSpellacy et al. We have measured H.P.L. more than 4000 timesin some 2300 patients. We have H.P.L. data on 22 pregnancieswhich resulted in intrauterine death. Only 6 of these patientshad abnormally low H.P.L. levels (less than 4-0 mg/1). In 7 pa-tients the blood-sample was obtained after intrauterine deathand non-detection of fetal heart sounds; H.P.L. levels were nor-mal or higher. Clearly, maternal serum-H.P.L. values do not re-flect fetal health, and it is doubtful if H.P.L. levels bear a quan-titative relationship to placental function. We have foundmany pregnancies with abnormally low H.P.L. levels (less than2.0 mg/1) and a satisfactory outcome whereas intrauterinedeath could occur in the presence of normal H.P.L.We have recently measured oestriol in all plasma samples

submitted for H.P.L. assay and have to date comparable resultsin 10 pregnancies which resulted in intrauterine death. Oes-triol was found to be abnormally low in all cases, but H.P.L.was abnormally low in only 2. In 1 case oestriol fell progress-ively over three weeks before death of the fetus whereas H.P.L.actually increased slightly over the same period.Measurement of urinary cestrogens is a well-established pro-

cedure for screening large numbers of patients in late preg-nancy ; serum (or plasma) oestriol assay seems the obviouschoice if a further test is required. If H.P.L. assay is used as ascreening test an early warning of intrauterine death may bemissed in at least 50% of cases.

Bellshill Maternity Hospital,Bellshill, Lanarkshire ML4 3JN

L. G. S. RAOW. PLENDERLEITH

CONTROLLED TRIALS IN SURGERY

SIR,-In theory, reviewers of scientific papers impose stan-dards for acceptance based on the aim of all scientists-toreport a true result. For therapeutic trials a true result dependson the design-i.e., the results should reveal real treatmenteffects by measures which avoid bias in selecting patients andadministering therapy. Acceptance of the results for publica-tion implies merit, and without publication it is very difficultto establish a new treatment in practice. Medical journals thusbecome the filter through which properly studied treatmentscan go on to application but through which badly designedtrials should not be able to pass. While this has been increas-

ingly true for drugs it has not been the case for new surgicalprocedures and new applications of established procedures.Most journal reviewers, abstract referees for scientific meet-ings, and hospital research committees maintain high stan-dards for the design of medical therapeutic trials. Yet they donot impose equal standards for surgical trials. This is notbecause such trials cannot be done.

Prospective, controlled trials of surgical therapy, includingrandom allocation of patients, are feasible though perhaps

1. Spellacy, W. N., Buhi, W. C., Birk, S. A. Am. J. Obstet. Gynec. 1975, 121,835.