Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Department of Internal Medicine, Division of Gastroenterology, Hepatology and Motility, University of Kansas, KS, USA.
Br J Clin Pharmacol. 2022 Sep;88(9):3950-3961. doi: 10.1111/bcp.15414. Epub 2022 Jun 3.
Calcineurin inhibitors (CNIs) are often used for solid organ transplantation recipients or patients with immune-mediated diseases. This systematic review and meta-analysis aims to understand how CNIs affect pregnancy and neonatal outcomes.
Electronic databases were searched for observational studies assessing pregnancy and neonatal outcomes in CNI-treated patients. The pooled rate of each outcome was determined. Metaregression was conducted to identify contributing factors to the outcomes.
We analysed 98 studies with a total of 5355 pregnancies in 4450 CNI-treated patients. The pooled rates of live birth and spontaneous abortion were 82.1% (95% confidence interval [CI] 76.7-86.4%) and 11.7% (95% CI 8.7-15.5%), respectively. The rates of preterm delivery (33.2%, 95% CI 29.2-37.5%), low birth weight (35.8%, 95% CI 27.7-44.8%) and preeclampsia (13.5%, 95% CI 9.4-19.2%) were 3-4 times higher than the rates of general population. Nearly half of the CNI-treated patients required caesarean delivery (43.5%, 95% CI 36.9-50.3%). The rates of stillbirth, neonatal and maternal death were 4.2% (95% CI 2.8-6.2%), 2.9% (95% CI 1.8-4.8%) and 2.3% (95% CI 1.3-4.1%), respectively. Metaregression showed that preeclampsia was significantly associated with the risks of preterm delivery and low birth weight. Older maternal age, prepregnancy hypertension and cyclosporine use increased the risk of preeclampsia.
Given the higher mortalities in CNI-treated patients and their children than the general averages, their pregnancy is considered high risk. The risks of preterm delivery and low birth weight were primarily attributed to preeclampsia. Since prepregnancy hypertension increased its risk, an appropriate preconception blood pressure management may improve their outcomes.
钙调神经磷酸酶抑制剂（CNI）常用于实体器官移植受者或免疫介导性疾病患者。本系统评价和荟萃分析旨在了解 CNI 如何影响妊娠和新生儿结局。
检索评估 CNI 治疗患者妊娠和新生儿结局的观察性研究，确定每种结局的汇总率。进行荟萃回归以确定结局的影响因素。
我们分析了 98 项研究，共纳入 4450 例 CNI 治疗患者的 5355 例妊娠。活产率和自然流产率的汇总率分别为 82.1%（95%置信区间 [CI] 76.7-86.4%）和 11.7%（95% CI 8.7-15.5%）。早产率（33.2%，95% CI 29.2-37.5%）、低出生体重率（35.8%，95% CI 27.7-44.8%）和子痫前期率（13.5%，95% CI 9.4-19.2%）分别是一般人群的 3-4 倍。近一半的 CNI 治疗患者需要剖宫产（43.5%，95% CI 36.9-50.3%）。死胎、新生儿和产妇死亡率分别为 4.2%（95% CI 2.8-6.2%）、2.9%（95% CI 1.8-4.8%）和 2.3%（95% CI 1.3-4.1%）。荟萃回归显示，子痫前期与早产和低出生体重的风险显著相关。产妇年龄较大、孕前高血压和环孢素使用增加了子痫前期的风险。
鉴于 CNI 治疗患者及其子女的死亡率高于一般人群，其妊娠被认为是高危妊娠。早产和低出生体重的风险主要归因于子痫前期。由于孕前高血压增加了其风险，适当的孕前血压管理可能会改善其结局。
