Long-term neurodevelopment of children exposed in utero to ciclosporin after maternal renal transplant

Background: Immunosuppressant therapy is essential in the prevention of organ transplant rejection. Objective: To evaluate the long-term neurodevelopmental outcomes of children following in utero ciclosporin (cyclosporine) exposure after maternal renal transplantation. Methods: 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). Results: 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 lowbirthweight, high rates of perinatal complications, and instrumental deliveries. Relative to fullterm 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 childrens IQ (p < 0.001 and p = 0.03, respectively). Therewere no statistically significant differences in exposed childrens IQwho were andwere not breastfed. Conclusion: 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 childrens 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 childs profile

Neurocognitive outcomes following fetal exposure to chemotherapy for gestational breast cancer: A Canadian multi-center cohort study

Background: Limited knowledge exists on outcomes of children exposed prenatally to chemotherapy for breast cancer (BC). The purpose of this study was to compare long-term neurocognitive, behavioral, developmental, growth, and health outcomes of children exposed in-utero to chemotherapy for BC. Methods: This is a multi-center matched cross-sectional cohort study involving seven cancer centers across the region of Southern Ontario (Canada), and the Hospital for Sick Children (Toronto, Ontario). Using standardized psychological and behavioral tests, we compared cognitive and behavioral outcomes in children exposed to chemotherapy during pregnancy for BC to age-matched pairs exposed to known non-teratogens. Results: We recruited 17 parent-child pairs and their matched controls. There were more preterm deliveries in the chemotherapy-exposed group compared to controls (p < 0.05). Full Scale IQ of children in the chemotherapy group was significantly confounded by maternal IQ and prematurity. Exposed children born at term were not different in cognitive outcomes. Children from both groups were similar in their developmental milestones, pediatric anthropometric measurements and health problems. There were no cases of autoimmune cytopenia. Conclusions: This is the first Canadian prospective comparative study designed to assess pediatric cognition following prenatal exposure to chemotherapy for BC. Chemotherapy was not found to be neurotoxic in this cohort and did not affect pediatric health. The decision to plan a preterm birth for initiating or continuing chemotherapy treatment must be taken into consideration in context of pediatric implications. While these results may assist in such decision making, replication with a larger sample is needed for more conclusive findings