title: Prenatal versus Postnatal Screening for Familial Retinoblastoma.
abstract: To compare overall outcomes of conventional postnatal screening of familial retinoblastoma and prenatal RB1 mutation identification followed by planned early-term delivery.
  
  
  
  Retrospective, observational study.
  
  
  
  Twenty children with familial retinoblastoma born between 1996 and 2014 and examined within 1 week of birth.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Departments of Ophthalmology & Vision Sciences, The Hospital for Sick Children, Toronto, Canada; Department of Ophthalmology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors.forename: Sameh E
authors.initials: SE
authors.lastname: Soliman
authors.affiliation: Departments of Ophthalmology & Vision Sciences, The Hospital for Sick Children, Toronto, Canada; Department of Ophthalmology & Vision Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada; Division of Clinical Public Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; Child Health Evaluative Sciences, SickKids Research Institute, Toronto, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Dimaras
authors.affiliation: Departments of Ophthalmology & Vision Sciences, The Hospital for Sick Children, Toronto, Canada; Department of Ophthalmology, Sankara Nethralaya Hospital, Chennai, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Khetan
authors.affiliation: Departments of Ophthalmology & Vision Sciences, The Hospital for Sick Children, Toronto, Canada; Department of Ophthalmology and Vision Science, University of British Columbia, Vancouver, Canada.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Gardiner
authors.affiliation: Division of Hematology and Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada; Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Helen S L
authors.initials: HS
authors.lastname: Chan
authors.affiliation: Departments of Ophthalmology & Vision Sciences, The Hospital for Sick Children, Toronto, Canada; Department of Ophthalmology & Vision Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada; Division of Visual Sciences, Toronto Western Research Institute, Toronto, Canada.
authors.forename: Elise
authors.initials: E
authors.lastname: Héon
authors.affiliation: Departments of Ophthalmology & Vision Sciences, The Hospital for Sick Children, Toronto, Canada; Department of Ophthalmology & Vision Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada; Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Canada; Departments of Molecular Genetics and Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Canada. Electronic address: brenda@gallie.ca.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Gallie
mesh_terms: D000649:Amniocentesis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D042241:Early Diagnosis; D015353:Eye Enucleation; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D011181:Postnatal Care; D011247:Pregnancy; D011296:Prenatal Diagnosis; D019572:Retinal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D012175:Retinoblastoma / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D056286:Retinoblastoma Binding Proteins / Q000235:genetics; D012189:Retrospective Studies; D016879:Salvage Therapy; D047929:Term Birth; D016896:Treatment Outcome; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D014792:Visual Acuity
chemical_list: C000606393:RB1 protein, human; D056286:Retinoblastoma Binding Proteins; D044767:Ubiquitin-Protein Ligases