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

J Clin Pharm Ther. 2021 Jun;46(3):744-753. doi: 10.1111/jcpt.13340. Epub 2021 Jan 2.

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. Tacrolimus-treated 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 pre-eclampsia, 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 low-quality evidence, but may provide a reference for clinicians in their clinical monitoring and obstetric care for post-transplant pregnancies.

Keywords: cyclosporine; immunosuppression; pregnancy outcomes; tacrolimus; transplantation.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Cesarean Section / statistics & numerical data
  • Cyclosporine / administration & dosage
  • Cyclosporine / adverse effects
  • Cyclosporine / therapeutic use*
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation / statistics & numerical data
  • Liver Transplantation / statistics & numerical data
  • Observational Studies as Topic
  • Pregnancy
  • Pregnancy Complications / epidemiology*
  • Pregnancy Outcome
  • Tacrolimus / administration & dosage
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use*

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Tacrolimus