Pregnancy outcomes in female patients exposed to cyclosporin‐based versus tacrolimus‐based immunosuppressive regimens after liver/kidney transplantation: A systematic review and meta‐analysis

Abstract

What is known and objective: Pregnancy after transplantation is a challenge owing to the high risk of adverse maternal and foetal outcomes, and immunosuppressants may further impact these outcomes. There are no head-to-head randomized controlled trials comparing influences of cyclosporin and tacrolimus on pregnancy outcomes. Thus, we systematically reviewed and meta-analysed observational studies assessing the comparative influences of these two drugs on pregnancy outcomes in liver/kidney transplant recipients. Methods:Relevant studies comparing pregnancy outcomes with tacrolimus and cyclosporin head-to-head were searched in PubMed, EMBASE and Web of Science (from 1 January 2000 to 20 March 2020). The weighted mean difference and odds ratio (OR) were calculated to compare continuous and dichotomous variables, respectively, with 95% confidence intervals (CIs). Publication bias was estimated using funnel plots. The study quality was assessed according to the modified Newcastle-Ottawa scale.Results and discussion: Overall, 10 observational studies of low quality, including a total of 1080 post-liver or kidney transplant pregnancies, were identified. Tacrolimustreated recipients experienced a lower risk of gestational hypertension (28.0%; OR: 1.74; 95% CI: 1.27-2.39; p < 0.01). Cyclosporin-treated recipients showed a lower incidence of caesarean section (40.3%; OR: 0.62; 95% CI: 0.46-0.82; p < 0.01).Additionally, cyclosporin performed better in terms of the live birth rate (78.0%; OR: 1.38; 95% CI: 1.02-1.88; p = 0.04). No significant differences in the incidences of preeclampsia, gestational diabetes, preterm delivery and birth weight were observed.What is new and conclusion: Tacrolimus performed better in patients with gestational hypertension, while cyclosporin was associated with a lower incidence of caesarean section and a higher incidence of live birth. The findings are based on relatively lowquality evidence, but may provide a reference for clinicians in their clinical monitoring and obstetric care for post-transplant pregnancies. | 745 GONG et al.

Planned Pregnancy in Kidney Transplantation. A Calculated Risk

“…Hypertension and preeclampsia have been reported to occur at higher incidence in transplanted women taking calcineurin inhibitors [48,49]. A systematic review and meta-analysis could not find any difference in the rate of preeclampsia between transplant pregnant women taking cyclosporine or tacrolimus [50].…”

Type of donor liver transplant does not affect pregnancy outcomes—a systematic review and meta-analysis

“…This systematic review and meta-analysis evaluated 438 female patients who underwent LT, including 806 total pregnancies after LT. While there have been multiple systematic reviews and meta-analyses of pregnancy outcomes in LT patients, this is the first study to assess and delineate the effect of undergoing LDLT on pregnancy outcomes 7,24–28 . Our study showed that there were no differences in pregnancy outcomes between women who have undergone LDLT compared to DDLT.…”

“…[43] The majority of the literature studying the effect of different immunosuppressive regimens after LT on pregnancy outcomes did not include stillbirths as an outcome. [25,[44][45][46] In a small kidney transplant population, the rate of stillbirths was not different based on the type of immunosuppressive regimen. [47] Unfortunately, the field of obstetric outcomes following LT is limited, and therefore, there are many remaining unknowns about the factors that impact pregnancy outcomes.…”

Pregnancy and neonatal outcomes in women receiving calcineurin inhibitors: A systematic review and meta‐analysis

“…These Tacrolimus and cyclosporine have different pharmacokinetic characteristics and serum binding mechanisms. 1,50 Previous investigations demonstrated that tacrolimus has a lower nephrotoxicity and a weaker vasoconstrictive effect compared with cyclosporine. 51,52 A recent systematic review and meta-analysis showed an incidence of gestational hypertension was 47.5% in cyclosporin-treated patients and 28.0% in tacrolimus-treated patients.…”

“…Tacrolimus and cyclosporine have different pharmacokinetic characteristics and serum binding mechanisms 1,50 . Previous investigations demonstrated that tacrolimus has a lower nephrotoxicity and a weaker vasoconstrictive effect compared with cyclosporine 51,52 .…”