Registration Dossier

Toxicological information

Toxicity to reproduction: other studies

Currently viewing:

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
other: Case report study.
Adequacy of study:
weight of evidence
Study period:
1968
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Case report study on humans should be considered sufficient to accept data from investigations which cannot be obtained through test guideline, but which are nevertheless well documented and scientifically acceptable.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1968
Report Date:
1968
Reference Type:
secondary source
Title:
MORPHOLOGIC CHANGES IN THE DEVELOPING RAT PLACENTA FOLLOWING PREDNISOLONE ADMINISTRATION.
Author:
BLACKBURN, W. R.; KAPLAN, H. S.; MCKAY, D. G.
Year:
1965
Bibliographic source:
BLACKBURN, W. R.; KAPLAN, H. S.; MCKAY, D. G. American journal of obstetrics and gynecology. 1965, 92, 234-46.

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
not specified
Type of method:
other: Case report study.

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Any other information on results incl. tables

 Case no. Age (yr.)  Parity  Disease  Daily dose of prednisolone (mg.)  Pregnancy, delivery, and fetal outcome(8 stillbirths, 11 babies "at risk", 16 normal healthy babies) 
 1  22  Primipara  Asthma  10  40 wk., acute fetal distress, stillbirth, 2.8 kg.
 2  37  G.5 P.3  Eczema  10  40 wk., anencephalic, stillbirth, 2.06 kg.
 3  21  Primipara  Ulcerative colitis  15  I.U.D., 32 wk., 1.56 kg.
 4  35  Primipara  Asthma  10  40 wk., fetal distress, stillbirth, 3 kg.
 5  23  G.2 P.1  Asthma  10  I.U.D., 33 wk., 1.02 kg.
 6  28  Primipara  Lupus erythematosus  5  P.E.T., I.U.D., 33 wk., 1.531 kg.
 7  27  P.1  Asthma  5 -20  40 wk., fetal distress, stillbirth, 2.381 kg.
 8  41  G.7 P.6  Lupus erythematosus  10 -30  Twins 35 wk., anencephalic, 2.1 kg.
 9  25  Primipara  Asthma  10 -30  Hypertension, 40 wk., placental insufficiency, fetal distress, L.S.C.S., 2.353 kg.
 10  28  P.2  Asthma  10 -30  Placental insufficiency, L.S.C.S., 35 wk., 1.814 kg.
 11  25  Primipara  Asthma  5  Placental insufficiency, L.S.C.S., 35 wk., 1.814 kg.
 12  37  P.1  Asthma  5 -10  Placental insufficiency, L.S.C.S., 37 wk., 2.693 kg.
 13  39  Primipara  Eczema  40  Placental insufficiency, failed induction, L.S.C.S., 40 wk., 2.6 kg.
 14  22  Primipara  Lupus erythematosus  30  38 wk., placental insufficiency, forceps, 2.38 kg.
 15  17  Primipara  Eczema  7.5 -15  40 wk., fetal distress, low forceps, 2.892 kg.
 16  23  G.2  Eczema  5 -10  40 wk., fetal distress, L.S.C.S., 3.006 kg.
 17  24  Primipara  Ulcerative colitis  5 -10  42 wk., fetal distress, L.S.C.S., 3.006 kg.
 18  28  Primipara  Asthma  10 -15  N.D., 38 wk., respiratory-distress syndrome, 3.09 kg.
 19  19  Primipara  Eczema  5  N.D., twins, 3.317 kg.
 20  27  G.3 P.2  Eczema  20  N.D., 39 wk., 3.09 kg.
 21  24  G.3 P.2  Asthma  10  N.D., 40 wk., 3.373 kg.
 22  31  G.3 P.2  Arthritis  2.5  N.D., 40 wk., 3.43 kg.
 23  33  G.8 P.7  Asthma  10  N.D., 38 wk., 3.034 Kg.
 24  34  G.2 P.1  Asthma  10  Breech, 40 wk., 2.5 kg.
 25  32  Primipara  Urticaria  10  N.D., 39 wk., 2.665 kg.
 26  24  G.2 P.1  Asthma  10  N.D., 40 wk., 3.062 kg.
 27  25  Primipara  Sarcoidosis  10  N.D., 41 wk., 4.252 kg.
 28  34  G.3 P.2  Rheumatoid arthritis  5 -10  N.D., 39 wk., 2.722 kg.
 29  28  G.3 P.2  Asthma  10  N.D., 40 wk., 2.949 kg.
 30  33  G.5 P.4  Asthma  2.5 -10  N.D., 40 wk., 3.373 kg.
 31  28  G.2 P.1  Asthma  20  N.D., 40 wk., 3.29 kg.
 32  33  P.1  Lupus erythematosus  5  N.D., 38 wk., 3.091 kg.
 33  34  P.1  Asthma  10  N.D., 40 wk., 3.26 kg.
 34  22  Primipara  Asthma  10  N.D., 40 wk., 2.75 kg.

G, gravid; p, para; I.U.D., intrauterine death; I.S.C.S., lower segment cesarean section; N.D., normal delivery; P.E.T., pre-eclamptic toxemia.

Applicant's summary and conclusion

Conclusions:
The cause of risk to the fetus appears to be that of failure of placental function, manifesting itself either as a chronic process with a small fetus or as acute hypoxia in labour. This effect is apparently a direct result of prednisolone, since fetal mortality in the control group (i.e., with similar disease but not on prednisolone) was low. The effect is not a disturbance of fetal adrenal function, since none of the babies gave clinical evidence of adrenocortical insufficiency. Experimental work suggests that placentation is damaged by glucocorticoids; Blackburn et al. (1965) found that the administration of prednisolone to pregnant rats inhibited placental growth, caused morphological changes resembling premature ageing of the placenta, and significantly increased the incidence of intrauterine deaths. The high incidence of fetal death and fetal risk attributable to a placental fault in our series suggest that a similar change may occur in pregnant women.
Executive summary:

Thirty-four pregnancies in thirty women receiving prednisolone in the course of treatment of a general disease resulted in eight stillbirths, and nine foetuses were judged to have been at risk during pregnancy or parturition. In contrast, thirty-four pregnancies in women not receiving glucocorticoids but with similar general diseases resulted in one stillbirth, three premature babies, and thirty healthy babies.