Bilateral Retinoblastoma Not Affected By Maternal Age, Birth Order

Ophthalmologist writing a prescription for the pregnant patient
Doctor wearing protective mask when writing prescription for her
Country income status also appears to have no impact on the development of the condition, compared with the unilateral presentation.

Advanced maternal age, birth order, and country income status do not appear to influence the risk of developing bilateral retinoblastoma for children, according to research published in Eye (Lond).

Researchers conducted a retrospective cohort study to assess the influence of advanced maternal age, birth order, and income status of the mother’s country (as gross domestic product [GDP] per capita) on the ratio of bilateral retinoblastoma cases vs unilateral retinoblastoma cases. A statistically significant association would suggest that these factors influence the development of de novo germline pathogenic variants in the RB1 gene.

The team used data from 689 patients who were treated or offered treatment for retinoblastoma at 11 centers in 10 countries. Unilateral and bilateral retinoblastoma was present in 67% and 33.1% of patients, respectively. Maternal age was younger than 20 years for 8.33%, between 20 and 25 years for 26.75%, between 26 and 30 years for 20.18%, and older than 33 years for 1.32% of patients. Birth order was first for 40.79%, second for 34.65%, third for 13.16%, fourth for 6.14%, and later than fourth for 5.26% of patients. GDP per capita ranged from $772.30 USD in Ethiopia to $62,886.80 USD in the United States.

Using a stepwise conditional logistic regression model, the researchers found no associations between advanced maternal age (P =.534), birth order (P =.201), or GDP per capita (P =.067) and the ratio of bilateral to unilateral retinoblastoma cases. 

Limitations of this study included those inherent to retrospective studies, lack of a group of healthy control participants, lack of genetic testing, and a family history of retinoblastoma in 3 children.


Lloyd P, Westcott M, Kaliki S, et al. The role of maternal age & birth order on the development of unilateral and bilateral retinoblastoma: a multicentre study Eye (Lond). Published online March 31, 2022. doi:10.1038/s41433-022-01992-w