Prenatal versus Postnatal Screening for Familial Retinoblastoma

Purpose To compare overall outcomes of conventional postnatal screening of familial retinoblastoma and prenatal RB1 mutation identification followed by planned early-term delivery. Design Retrospective, observational study. Participants Twenty children with familial retinoblastoma born between 1996 and 2014 and examined within 1 week of birth. Methods Cohort 1 included spontaneously delivered neonates examined within 1 week of birth and confirmed postnatal to carry their family's RB1 mutant allele. Cohort 2 included infants identified by amniocentesis to carry their family's RB1 mutant allele, and therefore scheduled for early-term delivery (36–38 weeks' gestation). Treatment for retinoblastoma was performed at the Hospital for Sick Children, Toronto, Canada. Main Outcome Measures Age at first tumor in each eye, eye stage, treatments given, ocular salvage, treatment success (defined as avoidance of enucleation, external-beam irradiation, or both), visual outcome, number of anesthetics, pregnancy or delivery complications, and estimated treatment burden. Results Vision-threatening tumors were present at birth in 4 of 8 infants in cohort 1 and in 3 of 12 infants in cohort 2. Eventually, all infants demonstrated tumors in both eyes. At the first treatment, 1 of 8 infants in cohort 1 had eyes in stage cT1a/cT1a or cT1a/cT0 (smallest and least vision-threatening tumors), compared with 8 of 12 infants in cohort 2 ( P = 0.02). Null RB1 germline alleles induced earlier tumors than low-penetrance alleles ( P = 0.03). Treatment success was achieved in 3 of 8 children in cohort 1 compared with 11 of 12 children in cohort 2 ( P = 0.002). Acceptable vision (better than 0.2 decimal) was achieved for 8 of 16 eyes in cohort 1 compared with 21 of 24 eyes in cohort 2 ( P = 0.014). Useful vision (better than 0.1, legal blindness) was achieved for 8 of 9 children in cohort 1 compared with 12 of 12 children in cohort 2. There were no complications related to early-term delivery. Median follow-up was 5.6 years, cohort 1 and 5.8 years, cohort 2. Conclusions When a parent had retinoblastoma, prenatal molecular diagnosis with early-term delivery increased the likelihood of infants born with no detectable tumors, better vision outcomes, and less invasive therapy. Prenatal molecular diagnosis facilitates anticipatory planning for both the child and family.