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 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.


CONCLUSIONS
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.
Nulman
Irena
I
The Motherisk Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. irena.nulman@sickkids.ca
Sgro
Michael
M
Barrera
Maru
M
Chitayat
David
D
Cairney
John
J
Koren
Gideon
G
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002652:Child Behavior / Q000187:drug effects; D002657:Child Development / Q000187:drug effects; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects; D015331:Cohort Studies; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007360:Intelligence / Q000187:drug effects; D007361:Intelligence Tests; D016030:Kidney Transplantation; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications; D047928:Premature Birth / Q000209:etiology; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies; D012923:Social Class
D007166:Immunosuppressive Agents; D016572:Cyclosporine