Prednisolone

Toxicity to reproduction: other studies

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

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1968

Report date:

1968

Reference 2

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

Test material information

Constituent 1

Reference substance name:

Prednisolone

EC Number:

200-021-7

EC Name:

Prednisolone

Cas Number:

50-24-8

Molecular formula:

C21H28O5

IUPAC Name:

11,17,21-trihydroxypregna-1,4-diene-3,20-dione

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.