The Motherisk Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Paediatr Drugs. 2010 Apr 1;12(2):113-22. doi: 10.2165/11316280-000000000-00000.
Immunosuppressant therapy is essential in the prevention of organ transplant rejection.
To evaluate the long-term neurodevelopmental outcomes of children following in utero ciclosporin (cyclosporine) exposure after maternal renal transplantation.
A cohort study with matched controls using a prospectively collected database was conducted to assess neurocognitive and behavioral outcomes using standardized measures. Thirty-nine children exposed in utero to ciclosporin therapy following maternal renal transplantation were assessed (15 single pregnancies, 24 multiple pregnancies) and compared with 38 matched unexposed children. Intelligence, visuomotor abilities, and psychologic adjustment were measured using the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), the Beery Developmental Test of Visual-Motor Integration (VMI-4) and the Wide Range Assessment of Visual Motor Abilities (WRAVMA), and the Child Behavior Checklist (CBCL), respectively. Statistical analysis, including regression, was performed to determine the significant predictors for the main outcome, full-scale IQ (FIQ).
There were no significant differences in FIQ, verbal IQ (VIQ), performance IQ (PIQ) or behavioral outcomes between exposed and unexposed children or between single and multiple delivery groups. Thirty-three percent of exposed children were premature versus 0.5% in unexposed controls (p < 0.01). Prematurity was associated with low birthweight, high rates of perinatal complications, and instrumental deliveries. Relative to full-term children, premature, low birthweight children in the ciclosporin-exposed group had significantly lower FIQ and VIQ scores (101.04 vs 111.31 [p = 0.008] and 102.31 vs 113.08 [p = 0.021], respectively). Maternal IQ and socioeconomic status were positive and significant predictors for children's IQ (p < 0.001 and p = 0.03, respectively). There were no statistically significant differences in exposed children's IQ who were and were not breastfed.
In this cohort, there was no association between in utero exposure to ciclosporin and long-term neurocognitive and behavioral development in children after maternal renal transplantation. Maternal IQ and socioeconomic status are positive predictors for children's intelligence. However, maternal renal transplantation and associated co-morbidity is associated with higher rates of premature delivery and consequent poorer neurocognitive and behavioral outcomes. Proper management of maternal morbidity and improved obstetric care may improve the child's profile.
免疫抑制剂治疗对于预防器官移植排斥反应至关重要。
评估母体肾移植后胎儿环孢素（环孢素）暴露对儿童的长期神经发育结局。
使用前瞻性收集的数据库进行队列研究和匹配对照，使用标准化测量方法评估神经认知和行为结果。评估了 39 名在母体肾移植后胎儿暴露于环孢素治疗的儿童（15 名单胎妊娠，24 名多胎妊娠），并与 38 名未暴露的儿童进行了比较。使用韦氏学前和小学智力量表修订版（WPPSI-R）、比耶发育测试视觉运动综合能力（VMI-4）和广泛视觉运动能力评估（WRAVMA）评估智力、视动能力和心理调整，以及儿童行为检查表（CBCL）。进行了统计分析，包括回归，以确定主要结局（全量表智商[FIQ]）的显著预测因子。
暴露组和未暴露组之间以及单胎和多胎分娩组之间，FIQ、言语智商（VIQ）、表现智商（PIQ）或行为结果均无显著差异。暴露组有 33%的儿童早产，而对照组中无 0.5%的儿童早产（p<0.01）。早产与低出生体重、围产期并发症发生率高和器械分娩有关。与足月出生的儿童相比，环孢素暴露组的早产儿和低出生体重儿的 FIQ 和 VIQ 评分明显较低（101.04 与 111.31[P=0.008]和 102.31 与 113.08[P=0.021]）。母亲的智商和社会经济地位是儿童智商的积极且显著的预测因子（p<0.001 和 p=0.03）。在接受和未接受母乳喂养的暴露儿童的 IQ 方面，没有统计学上的显著差异。
在本队列中，母体肾移植后胎儿环孢素暴露与儿童的长期神经认知和行为发育之间没有关联。母亲的智商和社会经济地位是儿童智力的积极预测因子。然而，母体肾移植和相关合并症与较高的早产率和随之而来的较差的神经认知和行为结局有关。适当管理母体发病率和改善产科护理可能会改善儿童的情况。
