The Epidemiological Survey Of Retinopathy Of Prematurity And Screening Of Wnt Signaling Pathway Related Genes In Advanced Retinopathy Of Prematurity

Objective：To analyze the incidence and severity of retinopathy of prematurity (ROP)in Shanghai China, and evaluate the effectiveness of the current ROP screeningguidelines; to analyze the relationship between various risk factors and ROP; toevaluate the possibility of genetic involvement in ROP.Methods：A prospective, neonatal units based study undertaken in two tertiary levelhospitals in Shanghai, China, from January1,2010to December31,2012. All infantswith birth weight (BW) of2000g or less and/or gestational age (GA) of34weeks orless were screened for ROP. ROP was treated in accordance with therecommendations of the Early Treatment for Retinopathy of Prematurity CooperativeGroup. The general situation of all enrolled infants in the perinatal and neonatalperiod was evaluated and detailed recorded. For some of the analyses, infants weredivided into three groups: no ROP; mild ROP i.e. developed ROP that did not requiretreatment; and severe ROP which required treatment. Statistical analysis wasperformed using Statistical Package for the Social Sciences (SPSS) Version17.0(IBM Corporation, Armonk, NY). Significance level was set at less than0.05.Peripheral blood was obtained from96severe ROP patients and96premature infantswithout ROP. Genomic DNA from each baby was subjected to PCR and directsequencing of the NDP, FZD4, LRP5, and TSPAN12genes.Results：A total of2825(93.7%) of3014eligible infants were screened and ROP wasdiagnosed in503infants (17.8%). The mean GA of ROP patients was29.9±2.1weeks and their mean BW was1425±266g.191infants (6.8%) had type1or worseROP and were treated with laser or vitrectomy. Infants who needed treatment for ROPhad a mean GA of29.3±2.1weeks and mean BW of1331±330g. Among thesetreated infants,18infants (9.4%) exceeded the UK’s screening criteria, and28(14.7%)exceeded the criteria used in the US. If narrower criteria as GA≤33w and/orBW≤1750g were adopted, almost16.9%fewer infants would not have been examined without missing any infant that required treatment. Low gestational age, low birthweight, multiple birth, mechanical ventilation and intraventricular hemorrhage wereclosely related to the occurrence of ROP. We identified two missense mutations and3synonymous mutations in the coding region of either the FZD4gene (p.G530E) or theLRP5gene (p.A1330V, c.3375G>A, c.4089C>T and c.3600T>C). No such changeswere found in the NDP and TSPAN12gene.Conclusions：The detection rate of ROP in Shanghai is consistent with the resultsobtained in previous studies of other developed area in China. Larger, older infantsare at risk in China compared with developed countries. Premature birth, low birthweight, multiple birth, mechanical ventilation and intraventricular hemorrhage areindependent risk factors of ROP. The mutations found in ROP patients suggest thatgenetic changes in the Wnt signaling pathway associate to the development of severeROP.