Retinopathy of prematurity in Rwanda: a prospective multi-centre study following introduction of screening and treatment services

Objectives: To investigate risk factors for retinopathy of prematurity (ROP) in a newly established ROP screening and management programme in Rwanda, Africa. Methods: In this multi-centre prospective study 795/2222 (36%) babies fulfilled the inclusion criteria (gestational age (GA) < 35 weeks or birth weight (BW) < 1800 g or unstable clinical course), 424 (53%) of whom were screened for ROP. 270 died before the first screening. ROP and treatment-warranted ROP were classified using the revised International Classification of ROP (2005). Data on maternal and perinatal risk factors were collected from daily neonatal notes. Results: 31 babies (7.3%, CI 5.0–10.2) developed any ROP, 13 of whom (41.9%, CI 24.5–60.9) required treatment. ROP was seen in six neonates with GA > 30 weeks and BW > 1500 g, one of whom required treatment. In univariate analysis the following were associated with any ROP: increasing number of days on supplemental oxygen (OR 2.1, CI 1.5–3.0, P < 0.001), low GA (OR 3.4, CI 1.8–6.4, P < 0.001), low BW (OR 2.3, CI 1.5–3.4, P < 0.001), at least one episode of hyperglycaemia ≥ 150 mg/dl (OR 6.6, CI 2.0–21.5, P < 0.001), blood transfusion (OR 3.5, CI 1.6–7.4, P < 0.001) or sepsis (OR 3.2, CI 1.2–8.6, P = 0.01). In multivariate analysis longer exposure to supplemental oxygen (OR 2.1, CI 1.2–3.6, P = 0.01) and hyperglycaemia (OR 3.5, CI 1.0–12.4, P = 0.05) remained significant. Conclusions: ROP has become an emerging health problem in Rwanda, requiring programmes for screening and treatment. ROP screening is indicated beyond the 2013 American Academy guidelines. Improved quality of neonatal care, particularly oxygen delivery and monitoring is needed. A risk factor study was nested within the prospective observational study carried out in the NICUs of three tertiary hospitals in Rwanda from September 2015 to July 2017. Two NICUs were located in the capital city Kigali, i.e. King Faisal Hospital (KFH) and University Teaching Hospital of Kigali (CHUK), and one in Huye, University Teaching Hospital of Huye (University of Rwanda campus Butare, CHUB).The study population were all preterm babies admitted to these NICUs who fulfilled the inclusion criteria, i.e. GA < 35 weeks or birth weight (BW) < 1800 grams (g) or an unstable clinical course, as indicated by the paediatrician. Data on potential risk factors were extracted from daily neonatal progress notes throughout hospital admission on a weekly basis. BW and GA were defined as categorical variables. Exposure to supplemental oxygen was assessed as the number of days in supplemental oxygen (categorical variable) and method of administration, i.e. nasal cannula, continuous positive airway pressure (CPAP) or ventilator [10]. In cases of nasal cannula, supplemental unblended oxygen was delivered. Initially oxygen saturation was recorded but was felt to be too unreliable as a study variable. Sepsis was defined as early or late (starting 3 or more days after birth), necessitating antibiotic treatment for ≥ 5 days on clinical grounds and/or on the basis of a positive blood culture, if available. Blood transfusion was defined as the administration of adult red blood cells on one or more occasions. Hyperglycaemia was defined as serum glycemia ≥ 150 mg/dl sampled before a meal. The first eye examination took place 4 weeks after birth. At the beginning of the study six local ophthalmologists were trained in ROP screening by an expert ophthalmologist during joint screening sessions. Quality control on the screening process took place during follow-up visits. Both monocular and binocular indirect ophthalmoscopy were performed using a 20 or 30 dioptre lens and indentation or Missotten–Fabri neonatal lens (Fabrilens, Lommel, Belgium), depending on the preference of the attending ophthalmologist. This lens serves both as a magnifier and speculum to keep the eyelids open. Retinal changes were classified by stage, zones and the presence of plus disease using standard photographs based on the International Classification of ROP and Early Treatment for ROP studies [14, 15]. The maximum severity of ROP in either eye was the level assigned to each infant. ROP-screening was at least every 2 weeks until vascularisation reached zone III or until 41 weeks postmenstrual age. Weekly screening was scheduled if the vessels ended in zone I or posterior zone II, or if there was any plus disease, or any stage 3 disease in any zone. Treatment-warranted ROP (TW-ROP) was defined Type 1 ROP i.e. ROP in Zone I, stage 3 without plus disease or in Zone I, any stage with plus disease, or ROP in Zone II, Stage 2 and 3 with plus disease [15]. Data were entered into a Microsoft Access database and analysed using STATA-software 9.2 (STATA Corp, College Station, TX). Statistics were presented overall and for the subgroups any ROP, TW-ROP and no ROP. Statistical analysis compared infants with any ROP with those without. Further analysis compared infants with TW-ROP with those without ROP. Potential risk factors were evaluated in univariate logistic regression analyses calculating odds ratios (OR) and 95% confidence intervals (CI) at 0.05 level of significance. Variables which were statistically significant were entered into a multivariate logistic regression model using a backward stepwise method. Assuming a prevalence of any ROP of 15% among exposed and 5% among non-exposed to potential risk factor, a sample size of at least 380 babies was needed to achieve 90% power at the 5% level of significance. The study was conducted in accordance with the Declaration of Helsinki and was approved by the Rwandan National Ethics Committee. An information sheet was read out to parents/caregivers in Kinyarwanda, after which they signed a consent form. All medical eye care related to ROP was provided free of charge. This densely populated country with a reasonably good main infrastructure has a compulsory health insurance system, which facilitates access to health care even for the poor.