Italian multicentre study on retinopathy of prematurity

The aim of this prospective multicentre study was to evaluate the influence of a number of perinatal factors on the development of ROP in high risk preterm infants with gestational age ≤30 weeks. All infants consecutively born in, or transferred to, one of the 14 participating centres from 1 January 1992 through 31 December 1993, who had a gestational age of 30 weeks or less and no congenital anomalies and survived to the age of 6 months, were included in the study. Of the 380 infants with mean ± SD gestational age of 28.4 ± 1.6 weeks (range 23–30 weeks) and birth weight of 1157 ± 335 g (range 485–2480 g) that were eligible for the study, 82 (21.5%) developed ROP stage 1 or 2 and 57 (15%) ROP stage 3 or 3+. Step-wise logistic regression analysis showed that the following factors had a significant predictive value for the development of ROP stage 3 or 3+: gestational age (Odds Ratio (OR)=0.6144 for each increment of 1 week of gestational age), birth weight (OR=0.843 for each increment of 100 g of birth weight), prenatal steroids (OR 4.044 for lacking or incomplete prophylaxis), RDS (OR 2.294), oxygen dependency at 60 days (OR 2.085), necrotising enterocolitis (OR 2.597). Conclusion This study confirms the role of prematurity, low birth weight and RDS in the pathogenesis of ROP, and emphasises the importance of prenatal steroid prophylaxis of RDS in very preterm infants. Furthermore, our data suggest that infants with oxygen dependency at 60 days or necrotising enterocolitis are at very high risk of developing ROP. Received: 29 September 1996 and in revised form: 28 January 1997 / Accepted: 1 April 1997     

早产儿视网膜病遗传易患性及相关基因的研究进展

目前,早产儿视网膜病仍是儿童致盲和视力损害的主要原因.它是一个多因素引起的疾病,除了早产、低体重及吸氧等原因,该病也存在遗传易患性,并有大量的基因参与其发病,对于这方面的研究能深入了解早产儿视网膜病的发病机制,为防治该病提供新的临床思路.     

Home oxygen therapy in infants with bronchopulmonary dysplasia: a prospective study

We followed the clinical course of 21 infants with bronchopulmonary dysplasia enrolled in a prospective home O₂ therapy programme during a 4-year-period. Mean gestational age was 28.5 weeks (range, 25–36 weeks) and mean birth weight 1093 g (range 630–2750 g). Infants were regularly monitored to maintain pulse oximeter O₂ saturation over 94%–95%. The source of O₂ was liquid oxygen and was delivered by nasal cannula. During the follow up oxygenation was assessed by SatO₂ measurement, cardiac function by Doppler echocardiography and respiratory function by the occlusion technique. All patients had an ophthalmological follow up. The mean age of the infants at discharge was 3.7 months (range 1.7–8.6) and mean weight 2830 g (range 2150–3780 g). At discharge 8 infants had right ventricular hypertrophy (RVH) and four of them had pulmonary hypertension. Mean duration of home O₂ therapy was 97 days (range 15–320 days) and the mean age of discontinuation of O₂ was 6.9 months (range 3–14.7 months). The cardiological follow up was benign: the ECG signs of RVH disappeared by 12 months of age in six out of eight infants and the right ventricular pulmonary pressure, as measured by the Doppler method, normalised in the four patients in whom it was detected. No relationship was found between respiratory mechanics and the duration of O₂ therapy. Weight gain was poor with mean growth at the 3rd percentile for females and just below the 3rd percentile for males. Twelve of the 21 infants required 25 rehospitalizations. No one presented deterioration of retinopathy of prematurity that was present in 16 infants at discharge; at 12 months retinopathy was resolved in 14 infants. A total of 2025 hospital days were saved, representing a significant financial saving. Conclusion Home O₂ therapy permits the safe early discharge of O₂-dependent BPD infants and it reduces significantly the length of time spent in hospital which represents a considerable financial saving. Received: 17 December 1996 and in revised from: 15 April 1997 / Accepted: 29 April 1997     

早产儿视网膜病变筛查及相关因素分析

目的：分析我院早产儿视网膜病变( retinopathy of prematurity,ROP)的发病情况,探讨其相关因素。方法回顾性分析2013年9月至2014年9月我院新生儿科住院的182例早产儿(出生体重<2000 g或胎龄<37周)的临床资料。于生后第4~6周或纠正胎龄32周进行ROP筛查,并定期随访。结果182例早产儿中筛查出不同程度ROP患儿32例,占17.6％,其中单眼10例,双眼22例。ROP患儿平均出生胎龄为(29.3±1.5)周,平均出生体重为(1280±240)g,其中ROP 1期11例,2期5例,3期16例,附加病变5例,住院期间18例患儿行视网膜激光光凝手术,2例行Lucentis球内注射。ROP组患儿与非ROP组在出生体重、胎龄、吸氧、肺表面活性物质应用、感染、窒息、输血方面比较,差异有统计学意义(P<0.05)。 Logistic回归分析显示胎龄、吸氧、机械通气、肺表面活性物质应用对ROP的发生有明显影响( P<0.05)。结论胎龄、出生体重、吸氧、呼吸暂停、感染等因素与ROP的发生有关,出生体重及胎龄越低,ROP发病率越高。     

The apparent role of blood transfusions in the development of retinopathy of prematurity

During a 30-month-period, 184 very low birth weight infants from two Liverpool neonatal intensive care units were screened for evidence of retinopathy of prematurity (ROP). Seventeen clinical variables previously considered relevant to the development of ROP, blood gas and blood pressure data over the first 7 days, and the maximum stage of ROP reached in either eye were recorded, together with the need for cryotherapy and current visual status. Ninety-two infants developed any stage of ROP and 15 required cryotherapy or became blind. Logistic regression showed that only gestational age and frequency of blood transfusion were independently associated both with the risk of occurrence of ROP and its severity.     

The influence of early postnatal nutrition on retinopathy of prematurity in extremely low birth weight infants

Background

Retinopathy of prematurity(ROP) is the most common serious ophthalmic disease in preterm infants. Human milk may provide a protective effect for ROP; however, beneficial effects of human milk preclude randomized trials. Therefore, we conducted a retrospective analysis comparing early postnatal nutrition with ROP development.

Objective

Evaluate relationship between early postnatal nutriture and ROP surgery.

Design/methods

Nutrition data was collected for inborn AGA infants, BW 700-1000 g. ROP surgery was the primary outcome variable. A single pediatric ophthalmologist supervised examinations. All infants received triweekly IM vitamin A as chronic lung disease prophylaxis (Tyson: NEJM, 1999).

Results

BW and gestational age were 867 ± 85 g and 26.3 ± 1.2 weeks (n = 77, mean ± 1SD). ROP surgery infants(n = 11) received more parenteral nutrition, 1648 mL, and less human milk, 13.8 mL/kg-day, and vitamin E, 1.4 mg/kg-day, during the second postnatal week. Human milk was a negative predictor for ROP surgery, odds ratio = 0.94. Both groups met vitamin A recommendations; however, 74% was administered via IM injections. Neither group met vitamin E recommendations.

Conclusions

Human milk feeding, parenteral nutrition volume and vitamin E intake were predictors for ROP surgery. IM vitamin A injections provided the majority of vitamin A; vitamin E administration was insufficient. Improving human milk feeding rates and vitamin dosing options may affect ROP surgery rates.     

Macular pigmentary changes as a sequelae of retinal hemorrhages in premature infants with retinopathy of prematurity

PURPOSE: We assess the incidence of macular changes in ROP patients with retinal hemorrhages. PATIENTS AND METHODS: The premature group consisted of 360 children born 32 weeks gestation and/or with weight below 1,500 g. We used the RetCam-120 Digital Retinal Camera to document retinal changes. RESULTS: Of the 360 premature infants 241 (67%) had no ROP, and 119 (33%) had ROP. Of the preterm infants with ROP retinal hemorrhages were found in 46 (38%) children. Of the newborns with ROP and with retinal hemorrhages, macular pigmentary changes were found in 3 (6%) patients. Of these 3 patients, the first had pre-threshold ROP, the second threshold ROP and had underwent diode laser photocoagulation, and the third patient had stage 2 ROP. In the patients with pre-threshold and threshold ROP retinal hemorrhages appeared 6 weeks after birth and macular pigmentary changes were found 6 months after birth. In the patient with stage 2 ROP hemorrhages appeared 7-8 weeks after birth and macular pigmentary changes were detected 12 months after birth. CONCLUSIONS: Although macular hemorrhages almost always resorb without complications, our study allows the assumption that retinal hemorrhages may cause macular pigmentary changes in the macula, and thus may lead to deprivation amblyopia. Our results may suggest that the presence of the macular pigmentary changes may be related to the hemorrhage and not to the specific therapy or to the disease.     

早产儿视网膜病的高危因素分析

目的了解我院早产儿视网膜病（refinopathy of prematurity,ROP）的发病状况,并对其高危因素进行分析。方法对2010年1月至2012年12月在我院新生儿科住院的早产儿（胎龄≤36周,体重≤2．5kg）,于生后2周进行ROP筛查,并定期随访。将患儿全身状况及吸氧、母孕期吸氧、先兆子痫、胎盘早剥等因素进行分析。结果255例患儿全部完成了眼底筛查,在周边视网膜血管化或病变退化后终止随访,发现ROP16例（26只眼）,ROP患病率为6．3％（5．1％）,其中Ⅰ期12例,Ⅱ期3例,Ⅲ期1例。高危因素分析示胎龄、出生体重、吸氧时间,吸氧浓度、机械通气与ROP相关（P〈0．05）;母孕期吸氧、先兆子痫、胎盘早剥等因素与ROP发病无关。结论早产、吸氧浓度高、机械通气是ROP的主要危险因素。对早产儿适时进行ROP筛查,并对发现的ROP早期进行有效视网膜激光光凝术,可控制病变,降低早产儿的致盲率。     

Pilot study of the systemic effects of three different screening methods used for retinopathy of prematurity

PURPOSE: This pilot study compared the physiological and behavioural changes in premature infants undergoing three different methods of screening for retinopathy of prematurity (ROP). STUDY DESIGN: Prospective randomized cross-over pilot study. SUBJECTS AND METHODS: Fifteen premature infants requiring screening for ROP were recruited, and physiological and behavioural responses produced by three different methods of screening were compared. The screening methods employed a RetCam 120 and an indirect ophthalmoscope with and without an eyelid speculum. Physiological indices (change in pulse, mean blood pressure and oxygen saturation) and facial responses to pain (brow bulge, eye squeeze, nasolabial fold, mouth opening and the presence of cry) were recorded at five points: before, during and immediately after screening and 10 and 30 min after examination. RESULTS: Screening with the RetCam 120 and the indirect ophthalmoscope with a speculum both caused a greater change in pulse and mean blood pressure and an increase in facial responses to pain during and immediately after screening as compared to the indirect ophthalmoscope without the speculum. RetCam 120 screening caused greater desaturation than the other methods. CONCLUSIONS: Although this was a small sample which limits absolute conclusions, the study showed that screening using a RetCam or a speculum and indirect ophthalmoscope caused more stress to the infant, as indicated by physiological and behavioural changes, than simply screening using an indirect ophthalmoscope without a speculum. These effects should be considered when deciding on the appropriate screening method for examining particularly sick infants.     

Nasal continuous positive airway pressure and outcomes in preterm infants: A retrospective analysis

OBJECTIVE

The aim of the present retrospective study was to describe the use of nasal continuous positive airway pressure (NCPAP) and the prevalence of bronchopulmonary dysplasia (BPD).

STUDY DESIGN

Data from 1526 neonates with gestational age less than 32 weeks, admitted to Children’s and Women’s Health Centre of British Columbia (Vancouver, British Columbia) between period 1 (1996 to 2000) and period 2 (2000 to 2004) were analyzed. The use of respiratory therapies and outcomes were retrospectively compared before and after the introduction of a NCPAP approach to respiratory support.

RESULTS

A significant increase in the use of NCPAP was noted between periods 1 and 2 (60% versus 71%), as well as a significant reduction in the use of surfactant (50% versus 41%), postnatal steroids (30% versus 10%) and the need for mechanical ventilation (77% versus 64%). In period 2, there was a significant reduction in the prevalence of BPD at 28 days (33% versus 26%), higher prevalence of severe retinopathy of prematurity (3% versus 6%) and less periventricular leukomalacia (4% versus 2%).

CONCLUSIONS

A significant increase in the use of NCPAP therapy in the neonatal unit has been associated with a decrease in the use of more invasive therapies. The incidence of BPD has decreased if defined as need for supplemental oxygen at 28 days of age, but not when the 36 weeks’ postconceptional age criterion was used. NCPAP therapy may decrease the use of more invasive therapies and may improve respiratory outcomes. The impact of this intervention on nonrespiratory outcomes warrants further investigation.     

Inhaled versus systemic steroids in chronic oxygen dependency of preterm infants

The speed of action and side-effects of systemic versus inhaled steroids was compared in infants with mild-moderate oxygen dependency. Forty infants (median gestational age 27 weeks) were randomized to receive either 10 days of dexamethasone (systemic group) or budesonide (100 μg qds) (inhaled group). At randomization, there was no significant difference in the gestational or postnatal age, inspired oxygen requirements or compliance of the respiratory system of the two groups. After 36 h of treatment, there were significant changes (P < 0.01) in both the inspired oxygen concentration and compliance of the respiratory system in the systemic but not the inhaled group. Only after 1 week of inhaled therapy were improvements in respiratory status noted but, even at that time, the inspired oxygen requirement was significantly lower in the systemic versus the inhaled group. In the systemic group only, however, were there significant increases in blood pressure. Conclusion Systemically administered rather than inhaled steroids appear to have a faster onset of action. Received: 22 December 1995 / Accepted: 27 May 1996     

Pathogenesis of retinopathy of prematurity and possible preventive strategies

Retinopathy of Prematurity (ROP) occurs when premature birth interrupts normal retinal vascular development. Postnatal tissue oxygen levels are significantly higher than those present in utero. Oxygen therapy further increases oxygen levels in the developing retina. Hypoxia driven, VEGF mediated, retinal endothelial cell proliferation is reduced. Low IGF-1 levels may also contribute to delayed retinal vascular development. The neural structures of the peripheral avascular retina continue to develop, and become more metabolically active. Complex, as yet poorly understood abnormalities of structural and molecular interactions between immature endothelial cells and immature astrocytes at the anterior "leading edge" of retinal vascular development leads to the development of an ROP ridge. VEGF produced by the hypoxic peripheral retina, along with structural abnormalities of cell relationships within, and at the vitreoretinal interface of the ROP ridge, results in extraretinal angiogenesis - stage 3 ROP. Stage 3 ROP may resolve spontaneously, or may progress to traction retinal detachment and blindness.     

本院出生和外院转运早产儿视网膜病发病情况的对比研究

目的探讨广东省妇幼保健院出生和外院转运早产儿视网膜病(ROP)的发病及诊治情况。方法回顾性分析2013年1月至2015年12月收入广东省妇幼保健院新生儿重症监护室并诊断为ROP的755例早产儿的临床资料。本院出生组239例,外院转运组516例。收集2组患儿的胎龄、体质量、性别、ROP病变程度及手术治疗等资料。结果外院转运组ROP早产儿出生体质量[(1290.64±392.87)g]低于本院出生组[(1586.21±512.74)g],差异有统计学意义(P<0.001);外院转运组ROP早产儿诊断胎龄[(35.53±2.81)周]高于本院出生组[(34.51±2.17)周],差异有统计学意义(P<0.001);外院转运组严重ROP[如病变Ⅰ区、急进性后部型早产儿视网膜病(AP-ROP)、合并Plus病变]所占比例高于本院出生组,差异均有统计学意义(均P<0.001);外院转运组ROP早产儿行激光光凝术、玻璃体注药术、二者联合术、补激光术治疗所占比例均高于本院出生组[60.1%(310/516例)比20.9%(50/239例);10.9%(56/516例)比2.5%(6/239例);8.1%(42/516例)比1.7%(4/239例);4.5%(23/516例)比1.3%(3/239例)],差异均有统计学意义(均P<0.001)。结论外院转运ROP早产儿出生体质量较低,ROP病变较重,手术干预率高。提高基层医院早产儿ROP筛查水平,及时诊断和高效转运可有效防止ROP进一步恶化,提高早产儿生活质量。     

浙江地区早产儿视网膜病筛查1225例分析

目的 了解早产儿ROP发病状况,探索早产儿ROP筛查的临床策略.方法 按照"早产儿治疗痒和视网膜病变防治指南"中的ROP筛查标准用间接眼底镜对浙江两家医院新生儿监护室(NICU)住院的早产儿进行ROP筛查.结果 2005年3月至2008年11月间共筛查1225例住院早产儿,发生ROP132例(10.8%),高风险阈前ROP12例(0.98%),阈值ROP4例(0.3%);其中未吸氧的早产儿65例,发生低风险阈前ROP1例(1.5%);两者差异有极显著性意义(x2=5.115,P＜0.01).有与无ROP组出生体重或胎龄的比较,差异均有极显著意义(分别F=26.39,19.73,P＜0.001);与出生体重或胎龄呈负相关(r=-0.145,-0.126,P＜0.000).不同出生体重或胎龄的早产儿发生ROP的比较,差异亦有极显著意义(x2=39.53,31.40,P＜0.001);体重≤1000 g的早产儿发生ROP是体重＞1000 g的3倍多,胎龄≤28周的早产儿发生ROP是＞28周的2.5倍.性别和多胎与ROP无明显相关性,差异无统计学意义(x2=0.279,3.449,P＞0.05).高风险阈前和阈值ROP与患儿反复呼吸暂停、多次窒息抢救及当地用氧抢救史相关(r=0.54,0.57,0.57,P＜0.05).阈值ROP患儿均有氧依赖、反复呼吸暂停及窒息.结论 ROP的发生与出生体重和胎龄负相关,体重≤1000 g或胎龄≤28周的有吸氧史的早产儿在筛查中要予以特别关注;通过筛查,ROP及时发现并在阈值期得到治疗,减少了盲童.     

早产儿视网膜病变相关因素分析

目的 探讨早产儿视网膜病变(retinopathy of prematurity,ROP)发病情况及相关危险因素.方法 回顾性分析2008年12月至2011年2月我院出生的1 356例体重2500 g以下或胎龄小于37周早产儿的临床资料,分为ROP组(n=208)和非ROP组(n=1148),分析全部早产儿自生后4～6周或矫正胎龄32周筛查眼底改变情况.结果 1356例早产儿中,208例发生ROP,发病率为15.34％,其中,严重病变36例(2.65％).与非ROP组相比,ROP组患儿在出生体重[(1 528 ±243)g vs(1 960±187)g]、胎龄[(30.92±0.72)周vs (32.87±1.28)周]、吸氧＞8d(123例vs 865例)、应用肺表面活性物质(18例vs 216例)、败血症(42例vs 154例)、宫内窘迫(63例vs 511例)、贫血(64例vs 237例)等方面比较,差异有统计学意义(P均＜0.05).Logistic回归分析结果显示出生体重、胎龄、吸氧＞8d、败血症及应用肺表面活性物质是ROP发生的高危因素(P＜0.05).同时,不同出生体重、不同胎龄患儿ROP发病率比较,差异均有统计学意义(P＜0.05).结论 出生体重及胎龄越低,ROP发病率越高,病变程度越严重.婴儿出生的成熟度越低,ROP尤其是严重ROP发病可能性越高.     

Perinatal infection, inflammation, and retinopathy of prematurity

The major known risk factors for retinopathy of prematurity (ROP) are extremely low gestational age, exposure to high levels of oxygen early after birth (phase I) and relatively lower oxygen levels later (phase II). In this review, we summarize recent data suggesting that exposure to perinatal infection/inflammation is associated with an increased risk for ROP. Part of this effect might be due to direct exposure of the developing retina to circulating products of infection and/or inflammation. Another potential mechanism that deserves exploration is that inflammation and/or oxidative stress can modify the known increased risk of oxygen-associated ROP. Taken together, accumulating evidence suggests that prenatal, perinatal, and postnatal systemic inflammation contribute to a 'pre-phase', sensitizing the pre-ROP retina for subsequent insults, setting the stage for what are now called phase I and phase II of ROP pathogenesis. Strategies targeting inflammatory responses might help reduce the risk for ROP in extremely low gestational age newborns.