Abstract 420 Poster Session IV, Tuesday, 5/4 (poster 198)

Background: Cyclosporine (CsA) is a first line agent in the prevention of graft rejection in organ transplant recipients, and has contributed greatly to the improved survival of these patients. By 1997 an estimated 5000 pregnancies had occurred in transplanted women.

Of transplant recipients of childbearing age, approximately one in 50 women will become pregnant. CsA therapy must often be continued during pregnancy to maintain maternal health in transplanted women. The drug also has a role in the treatment of some autoimmune diseases. CsA crosses the placenta thereby exposing the fetus to potential teratogenic effect.

Objective: To determine whether cyclosporine exposure during pregnancy is associated with an increased risk of congenital malformations, premature deliveries, or low birth weight in live born infants.

Methods: Medline, EMBASE, IPA, Cochrane, and Toxline databases were searched to identify relevant articles from 1966 to the present. Articles selected for inclusion in the study were required to be free of any apparent selection bias and to report outcomes in at least 10 newborns exposed to CsA in utero. Additional articles were identified from the references of the retrieved studies. Article selection and data extraction was performed by two independent reviewers, with adjudication by a third in cases of disagreement.

To assess risks of CsA-exposure, a summary odds ratio was calculated. Prevalence of malformation, prematurity and low birth weight were calculated as rates for all cyclosporine-exposed live births.

Results: Thirteen studies met the inclusion criteria for congenital malformations; a control group was present in 6 of these studies. The calculated odds ratio of 3.47 (CI 0.86-14.04) did not achieve statistical significance. The overall prevalence of malformations in the CyA-exposed patients was 4.08%. Nine studies were included for prematurity analysis, of which four had a control group.

The calculated odds ratio was 1.47 (CI 1.00-2.15,P=0.06). The overall prevalence of prematurity was 58.9% in the CsA exposed group compared to 45.9% in the non-CyA group. Two of four studies included for low birth weight analysis had a control group. The odds ratio of 1.59 (CI 1.05-2.40) achieved statistical significance. The prevalence of low birth weight in the CyA-exposed group was 49.1% compared to 38.0% in the non-CyA group of organ transplanted women.

Conclusion: The results of this study indicate a statistically significant increase in the odds ratio for low birth weight in live born infants exposed to CyA in utero. No increased risk of malformation or prematurity was associated with the use of CyA during pregnancy in the population studied. More studies are needed to allow sufficient sample size for the risk of malformations and prematurity.

Supported by Novartis, Barcelona.