The influence of diethylstilbestrol on the progress and outcome of pregnancy based on a comparison of treated with untreated primigravidas
1949 Study Abstract
In a clinical experiment aimed at determining the value of diethylstilbestrol in the prevention of the complications of late pregnancy, 387 primigravidous women in the prenatal clinic at the Boston Lying-in Hospital were given the drug in gradually increasing doses from the early part of pregnancy (weeks 12 to 20) to the thirty-sixth week. So far as was possible, alternate primigravidous women who presented themselves for prenatal care before the twentieth week were treated, the synchronous untreated patients, of whom there were 555, serving as controls. Except for stilbestrol administration, the obstetrical care of the two groups was identical.
The incidence of late pregnancy toxemia was very low (2.3 per cent) in the stilbestrol-treated patients. The difference between this figure and the 6.8 per cent incidence in the control series could not have occurred by chance. In the few cases that developed despite stilbestrol, the disease was later in onset and less severe than in the control group.
Analysis of the data on spontaneous premature delivery revealed that the premature infants of stilbestrol-treated mothers were unusually large and mature for their gestational ages. If prematurity is defined in terms of weight of the babies, the incidence of this abnormality was significantly less in the treated patients than in the controls. On the basis of week of delivery, on the other hand, there was no real difference between the two groups.
Postmaturity was significantly less frequent in the stilbestrol-treated patients than in the controls.
The incidence of unexplained stillbirth was 1.1 per cent in the controls and 0.5 per cent in the treated patients. This difference could have occurred by chance.
There were four fetal deaths in the stilbestrol-treated patients, an incidence of 1.0 per cent as against twenty-one, or 3.8 per cent, in the untreated patients; a highly significant difference. This reduction in fetal mortality would appear to be due largely to two factors: (1) the lower incidence and later onset of toxemia, and (2) the greater size and maturity of prematurely delivered infants.
A complete analysis of the data on the uncomplicated term pregnancies of the treated and control patients revealed no difference so far as the mothers were concerned (e.g., length of labor, uterine inertia, intrapartum or post-partum bleeding, weight gain). Analysis of the data on full-term infants, however, revealed that significantly more babies of stilbestrol-treated mothers weighed over eight pounds and were more than 21 inches long at birth.
Four years later, Dieckmann presented his prospective placebo controlled trial in an annual meeting of the American Gynecological Society (1953), the result of which contradicts the findings of Smith (above). During discussion time, Smith made a remark :
“Our experience with the use of stilbestrol continues to be satisfactory … we are convinced that it has reduced the complications of late pregnancy and saved many babies“.
Smith was at this time an authority in the field and the objective evidence provided by Dieckman was largely ignored. Doctors continued prescribing DES to several million women over the next 20 years despite controlled studies with contrary findings…
- American Journal of Obstetrics and Gynecology, 58, Issue 5 Pages 994–1009, November 1949. Free full text available via sci-hub.
- Drs. George and Olive Smith featured image apache.be.