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ORIGINAL ARTICLE
Year : 2021 | Volume
: 10
| Issue : 1 | Page : 31-36
Retinopathy of prematurity: Incidence and perinatal risk factors in a tertiary hospital in Saudi Arabia
Huda Khalid Ahmedhussain1, Waleed W Khayyat2, Bashaer M Aldhahwani3, Abdullah Omar Aljuwaybiri4, Nooran Osama Badeeb5, Muhammad Anwar Khan6, Mansour Abdullah Al-Qurashi7, Hashem S Almarzouki8
1 Department of Ophthalmology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
2 College of Medicine, King Saud bin Abdulaziz University for Health Sciences; King Abdullah International Medical Research Center, Jeddah; King Khalid Eye Specialist Hospital, Riyadh, Saudi Arabia
3 Department of Ophthalmology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
4 Department of Ophthalmology, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
5 Department of Ophthalmology, University of Jeddah, Jeddah, Saudi Arabia
6 College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
7 College of Medicine, King Saud bin Abdulaziz University for Health Sciences; King Abdullah International Medical Research Center; Department of Neonatology, King Abdulaziz Medical City, National Guard Hospital, Jeddah, Saudi Arabia
8 College of Medicine, King Saud bin Abdulaziz University for Health Sciences; King Abdullah International Medical Research Center; Department of Ophthalmology, King Abdulaziz Medical City, National Guard Hospital, Jeddah, Saudi Arabia
Correspondence Address:
Dr. Huda Khalid Ahmedhussain
Department of Ophthalmology, King Abdul Aziz University Hospital, Jeddah, P.O Box 80215 Jeddah 21589
Saudi Arabia
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/jcn.jcn_171_20
Purpose: This study aims to estimate the incidence of retinopathy of prematurity (ROP) and investigate its perinatal and neonatal risk factors in a tertiary hospital in Saudi Arabia. Methodology: This was a retrospective cohort study of premature infants admitted to a neonatal intensive care unit at a tertiary hospital in Jeddah, Saudi Arabia, from January 2016 to December 2017. Participants who met the screening criteria for ROP were included and followed up until spontaneous recovery or laser treatment. Results: A total of 119 infants screened, the incidence of ROP was 21.8% (26/119). A plus disease was diagnosed in 15.4% (4/26) of the ROP infants. For most, 80.7% (21/26) of the ROP regressed spontaneously, and 19.2% (5/26) required a laser intervention. The mean gestational age (GA) of infants diagnosed with ROP was 25.62 ± 1.58 weeks and the median birth weight (BW) 750 (interquartile range: 280) g. Lower GA, lower BW, prolonged oxygen therapy, and mechanical ventilation (MV) were significantly related to ROP disease and severity. Requiring resuscitation at birth, a lower Apgar score at 1-min, poor weight gain proportion at 6 weeks, and requiring a blood transfusion were significantly associated with ROP disease. Conclusion: Compared to other local studies, the incidence of ROP was lower in our population. Lower GA, low BW, prolonged oxygen therapy and MV, and poor weight gain at 6 weeks are well-documented risk factors. We recommend close monitoring of weight gain and oxygen therapy and modifying risk factors in preterm infants to lower the incidence and the severity of ROP.
Keywords: Premature neonate, retinopathy of prematurity incidence, retinopathy of prematurity risk factors, retinopathy of prematurity, Saudi Arabia
Retinopathy of prematurity (ROP) is a vasoproliferative disease affecting the retinal vascularization of premature infants due to disturbance in multiple factors, including the oxygen level in the retina, vascular endothelial growth factor, and systemic insulin-like growth factor 1 (IGF-1); this disease has a vision-threatening late sequelae if not detected and treated promptly.[1],[2] The literature from tertiary centers in Saudi Arabia showed that the incidence of ROP ranged from 23% to 56% from 1995 to 2018.[3],[4],[5],[6],[7],[8] We aimed to investigate the incidence of ROP and some of the perinatal and neonatal risk factors of ROP that were not studied previously in Saudi Arabia.
MethodologyThis was a retrospective cohort study conducted from January 2016 to December 2017. Data were retrieved from the records of preterm infants admitted to the neonatal intensive care unit at a tertiary center in Jeddah, Saudi Arabia. The data included:
Perinatal data: gender, maternal information (age and maternal disease), birth weight (BW), gestational age (GA), delivery type, plurality, Apgar score, and resuscitation at birthNeonatal course: Need of surfactant, oxygen therapy and mechanical ventilation (MV) duration, blood transfusion total volume, and weight at 4 and 6 weeksNeonatal complications: respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), sepsis, neonatal jaundice, patent ductus arteriosus (PDA), hydrocephalus, and intraventricular hemorrhage (IVH)ROP examination: stage, zone, plus disease, extent, treatment, and outcome.We included all infants who met the screening criteria according to the American Academy of Pediatrics Screening Guidelines 2013, which include an infant born at 30 weeks of gestation or earlier, or a BW of <1500 g, a BW between 1500 and 2000 g, or a GA of more than 30 weeks with an unstable clinical course, including those requiring cardiorespiratory support, who are believed by their attending pediatrician or neonatologist to be at high risk of ROP.[9]
The ROP screening examination is done by a retinal specialist or a pediatric ophthalmologist, based on the ROP schedule of examination, which was at 31 weeks of gestation or 4 weeks after birth, whichever was later. During a dilated fundus examination, the ROP's staging was done according to the most advanced stage at the time of the eye examination, following the International Classification of ROP in staging the disease.[10] Laser treatment was provided for infants classified as Type 1 prethreshold ROP as recommended by the Early Treatment for ROP Cooperative Group Trial guidelines.[11] Type 2 ROP was carefully observed for progression to Type 1 ROP. The research was ethically approved by the Institutional Review Board of King Abdullah International Medical Research Center.
Statistical analysis was done using the Statistical Package for the Social Sciences version 22 IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. (Armonk, NY: IBM Corp.). Simple descriptive statistics were used to present the general data. A Chi-square test (or Fisher's exact test) was used to determine the association of categorical variables between different groups of patients. An independent t-test (or Mann–Whitney test) was used to compare continuous variables between two groups of patients. The variables that were statistically significant with ROP, identified with the univariate analysis, were included in a multivariable regression analysis, where the backward elimination method was applied to decide the most predictive factors. P < 0.05 was considered as a cutoff for statistical significance. The weight gain proportion was calculated as the amount of increase in weight at 4 or 6 weeks ÷ BW. A result of <50% at 6 weeks was defined as low birth weight gain (WG) proportion.[12]
ResultsOne hundred and nineteen preterm infants met the screening criteria and included in the study. The majority (58%, n = 96) were male, 77 (64.7%) were delivered by cesarean section, 39 (32.8%) were products of multifetal gestation, the mean GA was 27.13 ± 1.84 weeks, and the median BW was 920 (interquartile range [IQR]: 420) g.
ROP was detected in 26 (21.8%) infants, of which 9 (34.6%) had Stage 1, 14 (53.8%) Stage 2, and 3 (11.5%) Stage 3. The majority (84.6%) had involvement of zone 2, and four patients had the plus disease (15.4%). For the group with ROP, 21 (80.7%) regressed spontaneously, and 5 (19.2%) required laser treatment.
[Table 1] compares the ROP versus non-ROP groups based on multiple variables. In terms of the neonatal factors, lower mean GA, lower BW, hydrocephalus, PDA, and sepsis were significantly associated with ROP. Regarding the clinical course, the ROP group had a lower Apgar score at 1 min after birth. A more significant proportion of the ROP group required resuscitation at birth compared to the non-ROP group. The ROP group required a longer duration of oxygen therapy and MV. Higher proportions of the ROP group required a blood transfusion, however, the median volume of the required blood transfusions was not statistically different. The mean weight gain proportions at 4 and 6 weeks were significantly lower for the ROP group.
Table 1: Univariate analysis of risk factors between the retinopathy of prematurity and nonretinopathy of prematurity groupsIn multivariable regression analysis, lower GA and needing resuscitation at birth were found to independently predict the development of ROP. The rest of the variables showed low predictivity in the regression analysis [Table 2].
Table 2: Multivariable regression analysis of risk factors for the retinopathy of prematurity and nonretinopathy of prematurity groupsFor the ROP group, the severity of the disease was significantly associated with a lower GA and lower BW. The actual weight remained significantly different between the two groups (Stage 1 vs. Stage 2 or 3) until 4 and 6 weeks, but there was no statistical difference in the mean weight gain proportion at 4 and 6 weeks. Patients with more severe disease required a longer duration of oxygen therapy and MV. The mean maternal age was significantly higher for the more severe cases [Table 3].
Table 3: Univariate analysis of risk factors and retinopathy of prematurity severity Discussion The incidence of ROP in the contemporary study was 21.8% (26/119), four had plus disease (15.4%), and five required laser treatment (19.2%). The incidence is lower than previous local studies [Table 4]. Similar studies from Iran, the United Arab Emirates, Egypt, and Japan reported different incidence rates. A lower ROP incidence rate was reported by Sabzehei et al. (17.14%, 71/414).[13] In contrast, Nugud et al., Hadi and Hamdy, and Uchida et al. studies reported a higher rate of ROP diagnosis (27%, 44/163; 34.4%, 152/52; and 46%, 182/84, respectively).[14],[15],[16]
ROP is a multifactorial disease, and in terms of neonatal factors, the mean GA is significantly different between the non-ROP and ROP groups (non-ROP = 28.90 ± 2.17 weeks, ROP = 25.62 ± 1.58 weeks). Furthermore, the BW (750 g, IQR = 280) was significantly lower in the ROP group (P < 0.001). These findings are lower compared to regional studies: Mgharbil et al. (GA: 27.2 + 1.7 weeks, BW: 916.5 + 241.4 g), Al-Qahtani et al. (GA: 27 + 2.4 weeks, BW: 938.4 + 257.9 g), Amer et al. (GA: 27.8 + 2 weeks, BW: 961.7 + 237.4 g), and Al-Amro et al. (GA: 26.7 + 2.2 weeks, BW: 856.5 + 177.3 g).[3],[5],[7],[8] Another study by Binkhathlan et al. included much older and heavier infants (30.2 weeks, 1325.7 g, respectively).[4]
In the multivariable analysis, only the GA (odds ratio [OR] = 3.78, confidence interval [CI] = 1.71–8.46, P = 0.001) and the need for resuscitation at birth (OR = 9.20, CI = 4.53–12.82, P = 0.001) were the most predictive risk factors for ROP development. GA was a significant independent risk factor in the multivariable analysis in Al-Qahtani et al. and Binkhathlan et al. studies.[4],[7]
Resuscitation at birth has not been investigated previously in Saudi Arabia. In a contemporary study, this factor showed a significant correlation to ROP. A similar finding was reported in the literature by Shariati et al. (2019), Bas et al. (2018), and Sabzehei et al.[13],[17],[18] The ROP group had a lower Apgar score at 1 min after birth (P = 0.029), and a similar finding was reported in Al-Qahtani et al. study and studies from Iran, Singapore, and Japan.[7],[16],[18],[19],[20]
Respiratory complications (RDS and BPD) and requiring surfactant therapy were insignificant in our study, but the duration of oxygen therapy and MV was statistically significant. Similar findings were reported in Al-Amro et al., Binkhathlan et al., Al-Qahtani et al., and Nugud et al.[3],[4],[7],[14] In contrast to the Turkey studies, where Bas et al. reported a significant correlation between RDS, surfactant therapy, and the duration of oxygen therapy and MV to ROP, however, Akkoyun et al. described comparable findings to Bas et al., but the prophylactic surfactant therapy did not show any significance.[17],[21]
In the contemporary study, the neonatal comorbidities that were significantly associated with ROP were PDA, sepsis, and hydrocephalus but not IVH and neonatal jaundice. This finding was supported in an Iran study in 2013, reporting an association between ROP and PDA but not with IVH.[13] However, a local study by Waheeb and Alshehri indicated that both IVH and PDA were associated with ROP.[6] Requiring a blood transfusion is a major risk factor for ROP in the literature.[6],[7],[13]
We found that the more severe forms of ROP occurred in infants with a lower GA and lower BW, consistent with other reports.[3],[5],[15],[17],[19] Oxygen therapy and the duration of MV were also associated with more severe forms of ROP (Stage 2 and 3 vs. Stage 1). Al-Amro et al. study had similar results, reporting that the group needing treatment had a longer duration of oxygen therapy.[3] Bas et al. support these findings.[17] The cautious use of ventilation and oxygen therapy could be a potential strategy to minimize the incidence and severity of ROP in these vulnerable infants.[15]
Regarding postnatal weight gain, Hellstrom et al. and Smith et al. found that the deficiency of systemic IGF-1 has a role as a predisposing factor to ROP.[1],[2],[22] However, a serum IGF-1 is not a routine blood test performed on preterm babies, and the postnatal weight gain thought to reflect the level of serum IGF-1, as it is related to the infant's postnatal growth.[23] To our knowledge, this is the first study reporting that poor WGs from birth to both 4 and 6 weeks of life were potential risk factors for ROP in Saudi Arabia. Although the association was not significantly related to ROP severity, the ROP group had a poor postnatal WG proportion of <50% (46% for Stage 1 and 31% for Stages 2 and 3 at 6 weeks), reported as clinically significant by Wallace and Fortes.[12],[24] Poor WG is indicated as a predictive risk factor for ROP development in the literature.[12],[24],[25],[26],[27]
In 1995, Hall et al. first described the theory in four survivors of quintuples with the same GA and BW.[28] In 2000, Wallace et al. investigated retrospectively the postnatal WG in 111 neonates and reported the significance of poor postnatal WG to the threshold of ROP.[24] In a prospective cohort study published in 2008, Fortes Filho et al. investigated the low weight gain from birth to 6 weeks and concluded that the WG proportion under 51.2% of BW at 6 weeks of life was a significant risk for a severe form of ROP.[12] Aydemir et al. and Wang et al. studied the relative weight gain at 4 and 6 weeks of life and showed a significant association of poor postnatal WG at 4 weeks to ROP but not at 6 weeks.[25],[29] Anuk-Ince et al., in 2013, reported a significant association of a low WG at 4 and 6 weeks to Stage 3+ ROP.[30] In these studies, the recommendation was to closely monitor infants with poor WG in the first 6 weeks of life. Due to the previous theory, multiple predictive models were recently developed in several countries, aimed at identifying infants with a higher risk of developing treatable ROP.[31]
The limitation of our study is the relatively small sample size. However, despite the small sample size, we identified two significant risk factors reported in Saudi Arabia for the first time, including resuscitation at birth and poor WG proportion at 6 weeks of life. These findings may shed light on new risk factors and could change neonatal management locally.
ConclusionROP causes blindness; earlier detection and intervention is vital. The incidence of ROP in our sample was lower relative to other local studies. In addition to the known risk factors in the literature locally, resuscitation at birth and poor weight gain in the first 6 weeks were found to be significant in our study. However, additional studies are required regionally to explore these and other modifiable risk factors. We recommend close monitoring of weight gain and oxygen therapy and modifying known risk factors in preterm infants to lower the incidence and the severity of ROP further.
Acknowledgment
We would like to thank Dr. Mohamed Eldigire Ahmed for his data management assistance. We also thank Dr. Susanna Wright for her help in reviewing the manuscript.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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