AIM: To compare the efficacy of intravitreal injection of ranibizumab(IVR)and intravitreal injection of conbercept(IVC)in children with retinopathy of prematurity(ROP).METHODS: Retrospective study. A total of 1 100 eyes with ROP treated with intravitreal anti-VEGF at our hospital from January 2015 to June 2023 were included. According to the different therapeutic drugs, the children were divided into two groups: IVR group and IVC group. According to the degree of ROP, the patients were divided into three groups: aggressive ROP(A-ROP), Zone Ⅰ type 1 ROP and Zone Ⅱ type 1 ROP. The reactivation and retreatment between the two groups were compared after propensity score matching(PSM)analysis, and they were followed-up for at least 3 mo after surgery.RESULTS: In Zone Ⅱ type 1 ROP, there was a statistically significant difference in the rates of reactivation and retreatment between the IVR and IVC groups(P<0.05); however, in A-ROP and Zone I type 1 ROP, there were no statistically significant differences in the rates of reactivation and retreatment between the two groups(P>0.05). The risk of reactivation and retreatment of Zone I type 1 ROP was higher than the Zone II type 1 ROP. Furthermore, the use of drugs and corrected gestational age of first treatment were influencing factors of lesion recurrence and retreatment.CONCLUSION: There is a significant difference in the initial cure effect between the two drugs in Zone II type 1 ROP, with the reactivation and retreatment rates of the IVC group being much lower than those of the IVR group.

Objective:We applied a hypoxia-induced model of human fetal retinal microvascular endothelial cell (RMEC) to study the effect of carbonic anhydrase 9 (CA9) on cell proliferation.Methods:The eyeballs of spontaneously aborted fetuses in Guangdong Women and Children's Hospital were obtained, and the retinas were isolated. RMEC was obtained by trypsin and collagenase two-step enzyme digestion, and endothelial cells were identified by CD34. The fetal RMEC and the purchased adult RMEC were cultured in normoxic and hypoxic incubators (1%O 2+5%CO 2+94%N 2), and the expression of CA9 was detected by qPCR and Western blot. After knocking down the CA9 by small interference RNA technique, the cell proliferation was detected by CCK-8 method, and the cell viability was detected by CCK-8 after adding CA9 inhibitor U-104. Results:The primary RMEC was extracted successfully. Immunofluorescence staining showed the percentage of CD34 positive cells in the third-generation cells was nearly 100%. The expression of CA9 mRNA in immature fetus and adult RMEC under hypoxia culture was higher than that under normoxic culture (fetal 1% O 2 group vs. fetal 21% O 2 group: 67.80±10.31 vs. 1.00±0.04, P<0.001; adult 1% O 2 group vs. adult 21% O 2 group: 1.72±0.22 vs. 1.00±0.02, P=0.014). Western blot analysis showed significantly increased expression of CA9 in the fetal RMEC exposed to hypoxia, which aligned with the expression of CA9 mRNA. When fetal RMEC was transfected with siCA9 20 nM, the knockdown rate of CA9 was 95% ( P<0.001). CCK-8 assay showed significantly lower proliferation of fetal RMEC cells in siCA9 group compared to siNC group (0.57±0.05 vs. 0.90±0.03, P<0.001), which was reflected by the OD value. With the addition of 100 μM CA9 inhibitor U-104, the viability of fetal RMEC in the treated groupwas significantly lower than that in the untreated group (99.16%±3.82% vs. 119.10% ±1.72%, P=0.002). Conclusions:The expression of CA9 differed between adult and preterm fetus in our hypoxia-induced RMEC model. Inhibiting CA9 can inhibit the proliferation of retinal microvascular endothelial cells of preterm fetus.

Hypoxia-inducible factor-1 (HIF-1) is an essential transcription factor, which mediates the transcription of multiple target genes to adapt the body for hypoxia.Oxygen-induced retinal neovascularization (RNV) is an important pathological process of retinopathy of prematurity (ROP). By mediating the transcription of vascular endothelial growth factors, angiopoietin and platelet-derived growth factors, HIF-1 can promote RNV and then lead to ROP.Therefore, HIF-1 plays a vital role in the pathological process of ROP.In this paper, the recent research progress on the role of HIF-1 in oxygen-induced RNV was summarized in order to further the understanding of ROP pathogenesis and treatment.

Objective:To study the insulin-like growth factors-1 (IGF-1) and lipid level of term small for gestational age (SGA) infants within 24 hours postnatally and to explore the correlation between IGF-1 and blood lipids.Methods:A prospective study was conducted on singleton term SGA and appropriate for gestational age infant (AGA) who were delivered and admitted to the neonatal ward of Guangdong Women and Children Hospital within 24 hours after birth from May 2020 to January 2021, and the infants were divided into SGA and AGA groups to compare the differences in IGF-1 and lipid levels within 24 hours after birth and to analyze the correlation between IGF-1 and lipids.Results:A total of 95 cases in the SGA group and 84 cases in the AGA group were included in the study. The proportion of infants with IGF-1 <25 ng/ml was significantly higher in SGA group (87.4%) than in the AGA group (52.4%). It was also found that the proportion of infants with IGF-1 <25 ng/ml in SGA was significantly higher than that in AGA within different gender composition groups, early-term and full-term births groups. The triglyceride (TG) level was higher in the SGA group than that in the AGA group, but the high-density lipoprotein cholesterol (HDL-C) level was lower than that in the AGA group ( P<0.05). IGF-1 level within 24 hours postnatally in SGA and AGA was positively correlated with HDL-C levels ( P<0.01) and negatively correlated with TG ( P<0.01), and HDL-C level was a predictor of IGF-1. Conclusions:Compared with term AGA, SGA term infants showed insufficient IGF-1 and HDL-C secretion and high TG within 24 hours after birth. Nutritional support for SGA should be given promptly after birth to avoid hypoglycemia and to stimulate IGF-1 secretion.

Objective:To explore the incidence, diagnosis and treatment of retinopathy of prematurity(ROP) in preterm infants born in the Guangdong Women and Children′s Hospital and transported from other hospital.Method:s Clinical data of 755 premature infants with ROP at Neonatal Intensive Care Unit, Guangdong Women and Children′s Hospital from January 2013 to December 2015 were retrospectively analyzed.There were 239 cases born in the hospital and 516 cases transported from other hospitals.Their gestational age, birth weight, gender, severity of ROP lesion and clinical data were collected and compared.Result:s The birth weight in the group of transported from other hospital was lower than that in the group of born in the hospital[(1 290.64±392.87) g vs.(1 586.21±512.74) g], and the difference was statistically significant( P<0.001). The ROP diagnosis of gestational age in the group of transported from other hospital was higher than that in the group of born in the hospital[(35.53±2.81)weeks vs.(34.51±2.17)weeks], and the difference was statistically significant( P<0.001). On the proportion of severe condition [such as lesion area Ⅰ, aggressive posterior retinopathy of prematurity(AP-ROP) and plus combined lesions], in the group of transported from other hospital was higher than that in the group of born in the hospital, and the differences was statistically significant( P<0.001). In the comparison of the proportion of laser photocoagulation, vitreous injection, combination of the two operations and supplementary laser therapy, in the group of transported from other hospital were higher than those in the group of born in the hospital[60.1%(310/516 cases) vs.20.9%(50/239 cases); 10.9%(56/516 cases) vs.2.5%(6/239 cases); 8.1%(42/516 cases) vs.1.7%(4/239 cases); 4.5%(23/516 cases) vs.1.3%(3/239 cases)], and the differences were statistically significant(all P<0.001). Conclusions:Premature infants with ROP transported from other hospitals have lower birth weight, severe ROP lesions and high surgical intervention rate.Improving ROP screening level in primary hospitals, timely diagnosis and efficient transportation can help to effectively prevent the deterioration of ROP in premature infants and improve their quality of life.

With the development of modern perinatal medicine, the incidence rate and survival rate of small for gestational age(SGA) infants significantly increased.But the surviving SGA infants tend to be associated with a lot of health problems and sequelae.SGA infants not only have a risk of perinatal adverse outcome, but also have a high risk of growth retardation, cognitive dysfunction, adult metabolic syndrome and psychosocial dysfunction.Now, the present status and research progress of growth and development of SGA infants are expounded, in order to provide evidence for early identification, diagnosis, effective intervention and follow-up strategy, and further to improve the prognosis of SGA infants and the quality of life, easing the burden of society.

Objective To study the safety and efficacy of continuous intravenous infusion of fentanyl in laser photocoagulation of retinopathy of prematurity (ROP).Methods From March,2014 to January,2015,ROP infants hospitalized for laser photocoagulation in Guangdong Women and Children hospital were randomly (using envelope method)assigned into the fentanyl groupand the control group.In the fentanyl group,the patients were given fentanyl combined with topical anesthesia,while onlytropical anesthesiain the control group.Premature infant pain profile (PIPP)scores,heart rate,mean artery pressure and complications within 3 days after operation were recorded. The concentration of epinephrine, norepinephrine and cortisol in the blood were measured before and after the operation.Student′s t test,non-parameter rank and chi-square test were used to compare the differences between the two groups.Results A total of 82 infants were enrolled in the study,42 in the fentanyl group and 40 in the control group.In the fentanyl group,11 .9% infants had maximum PIPP score ≥6 and 70.0% in the control group,the difference was statistically significant (P <0.05).In the fentanyl group,the PIPP score at the beginning of operation, the maximum PIPP score during operation and the PIPP score at the end of operation were 2.0,3.0and 1 .5, respectively.In the control group,these scoreswere 8.0,8.0and 8.0 respectively.The differences were statistically significant (P <0.05 ).No significant differences existed between the concentration of epinephrine,norepinephrine and cortisol before and after operationin the fentanyl group.However,these concentrations were elevated after the operation than before the operation in the control group (P <0.05).The incidence of complications within three days after operation was 19.0% in the fentanyl group and 40.0% in the control group,and the difference was statistically significant (P <0.05 ).Conclusion Comparing with topical anesthesia,fentanyl combined with topical anesthesia has lower pain scores,less stress responses and fewer complications during ROP laser photocoagulation.Fentanyl combined with topical anesthesia is a safe and effective analgesic method during ROP laser photocoagulation.

Objective To study the differentially expressed genes and analyze its functional pathways of retinopathy of prematurity(ROP),in order to discover the pathogenesis and provide the theoretical basis for the prevention and treatment of ROP.Methods Fetal eyeballs of induced labor were obtained and retinal microvascular endothelial cells were isolated and cultured.The endothelial cells were divided into 7 groups according to the medium of cobalt chloride (CoC12) concentration (0 μ mol/L,100 μ mol/L,150 pμmol/L,200 μmol/L,250 pμmol/L,300 μmol/L,350 μmol/L),and 150 μmol/L CoCl2 was finally used to induce ROP model in vitro.Retinal microvascular endothelial cells were verified by adopting Ⅷ factor and CD31 antibody fluorescence staining.RNA purification,gene chip hybridization and signi-ficant analysis of microarrays were performed to screen differentially expressed genes.Genes functional pathways were studied by using gene ontology analysis software.Results (1) The proliferation activity of vascular endothelial cells decreased when CoCl2 ≥ 150 μmol/L(F =21,P ＜ 0.05).(2) In 150 μmol/L CoC]2 group,blue nucleus and green cytoplasm were visible in the second and the third generation vascular endothelial cells stained by factor Ⅷ antibody,and red fluorescence could also be observed in the cytoplasm by means of CD31 monoclonal antibody staining.However,only blue nucleus was detected in the group without CoCl2.(3)There were 326 genes differently expressed in retinal micro vascular endothelial cells induced by CoCl2 in vitro,among whom,198 genes were up-regulated and 128 genes were down-regulated.Up-regulated expression genes were 1.5 times more than those of the down-regulated genes.(4)Ten biological pathways including cell hypoxia,angiogenesis suppression and iron ion transport etc.may play important roles in ROP pathogenesis.Conclusions Hypoxic retinal microvascular endothelial cells induced by CoCl2 can successfully be used to induce cell model of ROP in vitro.Differentially expressed genes may play an important role in ROP development.Functional pathway such as hypoxic cells,inhibition of angiogenesis,iron ion transport may be associated with ROP pathogenesis.

Objective To explore the effects of perinatal infection on retinopathy of prematurity (ROP).Methods A retrospective cohort study was performed to analyzed the clinical data of 238 preterm infants at gestational age ≤32 weeks who were delivered in Guangdong Women and Children Hospital from November 2014 to October 2015 and ROP screening examinations.Observation was not terminated until they were 45 weeks of corrected gestational age.Mild ROP was defined as having stage 1 or stage 2 ROP in zone Ⅱ or Ⅲ without additional disease,and severe ROP was defined as stage 3 or higher,any ROP in zone Ⅰ,prethreshold/threshold,with additional disease,and aggressive posterior retinopathy of prematurity (AP-ROP).Medical records of eligible preterm infants were retrospectively reviewed and analyzed.Occurrences of ROP,severe ROP,and clinically significant ROP requiring surgical treatment were assessed.Results The mean gestational age of the cohort was (30.10 ± 1.34) weeks (25.29-32.00 weeks) and the mean birth weight was (1 373 ± 272) g(720 ～2 330 g).ROP was diagnosed in 76 of 238 infants (31.9％),including 39 cases with mild ROP (16.4％) and 37 cases with severe ROP (15.5％).Surgical treatment was performed on 22 infants (9.2％).In the patients with ROP,the time to develop ROP from birth was (35.16 ± 14.26) d and the mean time of its most serious stage was (44.62 ± 18.99) d.In 22 patients with ROP who required surgical treatment,the time of surgical treatment was (50.27 ± 17.24) d.In univariate analysis,maternal perinatal infection disease was found to be associated with ROP occurrence (x2 =7.891,P =0.005) and ROP progression requiring surgical treatment (x2 =4.494,P =0.034).Small gestational age,low birth weight and long-term oxygen therapy were found to be asso ciated with ROP occurrence and severe ROP (gestational age:t =-5.803,P ＜ 0.001;t =-5.290,P ＜ 0.001;t =-4.150,P ＜ 0.001;birth weight:t =-4.942,P ＜ 0.001;t =-4.058,P ＜ 0.001;t =-3.126,P =0.002;the duration of oxygen therapy:t =2.351,P =0.020;t =2.473,P =0.018).Apgar scores ≤ 7 at 1 min and 5 min were found to be associated with severe ROP (x2 =4.803,P =0.028).Neonatal sepsis and neonatal fungal infection were found to be associated with ROP occurrence (x2 =6.071,P =0.014;x2 =4.070,P =0.044).Neonatal fungal infection was also found to be associated with severe ROP (x2 =5.479,P =0.019).Multivariate regression analysis indicated that maternal perinatal infection disease was associated with an increased risk of ROP and ROP progression requiring surgical treatment (OR =2.837,P =0.023;OR =4.087,P =0.012).Maternal preeclampsia was also associated with an increased risk of ROP (OR =2.506,P =0.040).Gestational age was an important risk factor for the development of ROP.The smaller the gestational age was,the higher the rate of occurring ROP and severe ROP (OR =0.518,0.508,0.520,all P ＜ 0.001).Conclusions Both fetal and neonatal exposure to infection appear to contribute to the increase of ROP risk in the preterm infants at gestational age ≤ 32 weeks.Maternal perinatal infection disease and maternal preeclampsia were independently associated with ROP occurrence and ROP progression in the preterm infants at gestational age ≤32 weeks.

Objective To analyze the risk factors of aggressive posterior retinopathy of prematurity (AP-ROP). Methods A retrospective case-control study was applied. Questionnaire was designed through literature research to collect data of AP-ROP and ordinary ROP(except for AP-ROP)from March,2012 to September, 2014 in the department of neonatology in Guangdong Women and Children′s Hospital. Based on the ratio of 1:2 , the two groups were selected with the matching conditions:the closest date of admission in hospital,ordinary ROP children,collection and analysis of the data. Results Univariate analysis:gestational age(P<0.05),birth weight(P<0.05),oxygen therapy days(P<0.05),days of mechanical ventilation(P<0.05),gestational age<32 w(P<0.05),birth weight<1250 g(P<0.05),oxygen(P<0.05),oxygen≥14 d(P<0.05),mechanical ven-tilation(P < 0.05),mechanical ventilation ≥ 14 d(P < 0.05),PS(P < 0.05),neonatal anemia(P < 0.05), blood transfusion≥2 times(P<0.05),RDS(P<0.05),neonatal pneumonia(P<0.05),apnea(P<0.05), BPD(P < 0.05),intracranial hemorrhage(P < 0.05),metabolic acidosis(P < 0.05),and retinal hemorrhage (P < 0.05) were related to AP-ROP. Multivariate analysis with conditional logistic regression analysis indicated that blood transfusion ≥2 times(OR:14.956,95%CI:4.328~51.684)and apnea(OR:7.590,95%CI:2.507~22.978)were regarded as the independent risk factors for AP-ROP. Conclusions AP-ROP is associated with low gestational age,low birth weight,oxygen therapy and related complications including RDS and retinal hemorrhage. Blood transfusion and apnea are important independent risk factors of AP-ROP.