|Year : 2017 | Volume
| Issue : 3 | Page : 197-202
A comparative study of the incidence of retinopathy of prematurity between small-for-gestational-age and appropriate-for-gestational-age preterm babies in North Kerala
Ratheesh Raj, NV Latha, AV Asha, Twinkle Ann George, Shamin Jacob, KK Praveena
Department of Ophthalmology, Academy of Medical Sciences, Kannur, Kerala, India
|Date of Web Publication||30-Jan-2018|
Dr. N V Latha
Department of Ophthalmology, Academy of Medical Sciences, Pariyaram, Kannur - 670 503, Kerala
Source of Support: None, Conflict of Interest: None
Purpose: The purpose of this study is to compare the incidence of retinopathy of prematurity (ROP) in small-for-gestational-age (SGA) infants with appropriate-for-gestational-age (AGA) infants.
Materials and Methods: A hospital-based prospective descriptive study was conducted on all cases of preterm babies <34 weeks of gestation and/or <1500 g of birth weight admitted in a tertiary care center, who were sent for ROP screening. Babies were divided into two groups using Lubchenco growth chart. Group 1 consisted of all AGA preterm babies. Group 2 consisted of SGA preterm babies. Screening and staging of ROP were done. Babies were managed appropriately. Data were entered and analyzed.
Results: Out of the 300 babies examined, 67 babies were SGA and rest 233 were AGA. The overall incidence of ROP was 29% and it was increased in SGA group to 40% compared to AGA group, which was 25.8%. SGA had a significant association with ROP. Other significant factors were oxygen delivery, mechanical ventilation, sepsis, respiratory distress syndrome, surfactant, apnea, blood transfusions, and acidosis. Maternal factors such as oligohydramnios, premature rupture of membranes, and preeclampsia were also associated with ROP significantly. On multivariate analysis, apnea, blood transfusion, low partial pressure of oxygen, lower gestational age, and maternal gestational diabetes mellitus were independent risk factors.
Conclusion: The incidence of ROP is higher in SGA compared to AGA. Being small for gestation is a risk factor for developing ROP.
Keywords: Appropriate for gestational age, incidence, preterm, retinopathy of prematurity, risk factors, small for gestational age
|How to cite this article:|
Raj R, Latha N V, Asha A V, George TA, Jacob S, Praveena K K. A comparative study of the incidence of retinopathy of prematurity between small-for-gestational-age and appropriate-for-gestational-age preterm babies in North Kerala. Kerala J Ophthalmol 2017;29:197-202
|How to cite this URL:|
Raj R, Latha N V, Asha A V, George TA, Jacob S, Praveena K K. A comparative study of the incidence of retinopathy of prematurity between small-for-gestational-age and appropriate-for-gestational-age preterm babies in North Kerala. Kerala J Ophthalmol [serial online] 2017 [cited 2018 May 25];29:197-202. Available from: http://www.kjophthal.com/text.asp?2017/29/3/197/224305
| Introduction|| |
Retinopathy of prematurity (ROP) is a vasoproliferative disease, affecting the retina of premature infants, ranging from mild disease without any visual loss to advanced disease leading to irreversible blindness.
In India, the initial low incidence of ROP is increasing due to the better screening protocols and increased survival of preterm babies.,, Some studies observed that the incidence of ROP is more in small-for-gestational-age (SGA) babies compared to appropriate-for-gestational-age (AGA) babies,, but others noted no difference., In view of the paucity of clinical studies on the incidence of ROP in SGA babies, our study was to compare the incidence of ROP in SGA and AGA babies.
This study aimed to compare the incidence of ROP in SGA preterm infants with AGA preterm infants.
| Materials and Methods|| |
Our study was a hospital-based descriptive study conducted in the newborn neonatal Intensive Care Unit (NICU) from April 1, 2014 to September 30, 2016. All preterm babies <34 weeks of gestational age (GA) and/or <1500 g of birth weight admitted in NICU and sent for ROP screening were included in the study.
Patients were divided into two groups using Lubchenco growth chart. Group 1 consisted of all preterm babies with weight AGA. Group 2 consisted of preterm babies born with weight <10th percentile over GA called SGA.
ROP screening examinations can have short-term effects on blood pressure, heart rate, and respiratory function in the premature baby. Hence, the examinations were kept as short as possible and precautions were taken to ensure that emergency situations are dealt with promptly and effectively. Eye examination during screening lasts several minutes and may cause considerable pain to the neonate. Discomfort to the baby was minimized by pretreatment of the eyes with a topical proparacaine and swaddling the baby. Babies were not fed just before examination to avoid vomiting and aspiration. Handwashings were done and asepsis was maintained.
Screening procedure was done by three experienced ophthalmologists. Pupillary dilation is done using eye drops tropicamide 0.4% and phenylephrine 2.5%. First the anterior segment of the eye was examined to look for tunica vasculosa lentis, pupillary dilation, and lens/media clarity. Binocular indirect ophthalmoscopy was done using a 20 D lens, and scleral depression was done, when necessary, to identify peripheral retinal alterations. Retinopathy would be graded based on the International Classification of ROP. Maturity of retina, zone of retinopathy, clock hours involved, presence of plus disease, and stage of ROP were recorded. Appropriate treatment was initiated for indicated babies. Data were then analyzed and recorded.
Approval for the study was granted by the hospital's institutional review board comprising Ethical and Research Committee. Written informed consent was obtained from the parents of babies before enrollment.
Statistical analysis was done using SPSS version 24 (SPSS Inc., Chicago, IL, USA). P < 0.05 was considered statistically significant.
| Results|| |
Out of the 300 babies, who were included in the study group, 67 babies belong to the SGA group and rest 233 babies were appropriate for age (AGA). GA ranges from 25 weeks +5 days to 36 weeks +5 days with a mean GA of 32 weeks [Table 1]. Birth weight ranges from 590 to 2500 g with mean birth weight of 1418.9 g [Table 2]. Average APGAR score at 1 min was 6.23 and at 5 min was 7.43. Among the 300 babies, 143 babies were females and 157 were males [Figure 1].
|Figure 1: Frequency of small-for-gestational age and appropriate-for-gestational age babies|
Click here to view
Twenty-nine babies were born with single type of gestation and 71 were multiple gestation babies [Figure 2].
The overall incidence of ROP was 29% and it was increased in SGA group to 40%. ROP incidence in AGA was 25.8% [Figure 3].
|Figure 3: Frequency of retinopathy of prematurity in small for gestational age babies|
Click here to view
Out of the 600 eyes, 59 eyes had Stage 1 ROP, 75 eyes had Stage 2 ROP, and 9 eyes had Stage 3 ROP. There was no ROP in Stages 4 and 5. Twelve eyes received treatment for ROP.
On Chi-square test, the association between ROP and SGA was found to be statistically significant (P = 0.021) [Figure 4].
|Figure 4: Retinopathy of prematurity and small-for-gestational-age association|
Click here to view
Oxygen delivery to baby showed a very significant association with ROP in this study (P<0.001). Out of the 26 babies who received oxygen more than 10 days, 24 babies developed ROP [Figure 5].
Other important factors found to have significant association with ROP include infant respiratory distress syndrome (P < 0.001), surfactant (P < 0.001), blood transfusion (P < 0.001), sepsis (P = 0.042), mechanical ventilation (P < 0.05), anemia (P = 0.005), congenital heart disease (P = 0.028), necrotizing enterocolitis (P < 0.05), apnea (P < 0.001), respiratory acidosis (P = 0.04), metabolic acidosis (P < 0.001), intrauterine growth retardation (P = 0.014), pregnancy-induced hypertension (P = 0.005), gestational diabetes mellitus (GDM) (P = 0.041), oligohydramnios (P = 0.014), and premature rupture of membranes (P < 0.001).
On multivariate analysis, GA (P = 0.05), blood transfusion (P = 0.001), low partial pressure of oxygen (pO2) (P =0.001), apnea (P =0.025), and GDM (P =0.025) were found as independent risk factors [Table 3].
The factors which failed to show significant association with ROP include sex of the baby, multiple gestation, neonatal jaundice, hypocalcemia, intraventricular hemorrhage, maternal infection, and antenatal steroids.
| Discussion|| |
Prematurity and oxygen exposure are considered as the most important risk factors for ROP. One of the other known risk factors is low birth weight. Birth weight may reflect the GA of the baby if the baby has grown AGA. For SGA babies, the prenatal growth restriction results in abnormally low birth weight. SGA babies comprise a significant proportion of NICUs and have high morbidity and mortality rates. SGA infants with low GA encounter adverse in utero environment and postnatal period, which may lead to increased morbidity among them. SGA status and prematurity have additive effect during postnatal life.,,
ROP is one among the morbidities of SGA babies in the postnatal period. However, there are conflicting reports regarding the risk of developing ROP in SGA babies compared to the AGA babies. Factors contributing to these disparities may be the different definitions of SGA and the different growth charts to identify SGA. The common definition of SGA is having a birth weight that is either more than two standard deviations below the mean weight for GA or below the 10th percentile for GA. Hence, heavier infants can also be classified. Commonly using growth charts are based on the weights recorded at birth in large populations, some of them are corrected for sex and others are not.
There are many reports, which shows the risk of any stage of ROP and SGA compared to AGA. In addition, some authors studied the association of severe stages of ROP in SGA compared to AGA. Many studies used the criteria as two standard deviations below the mean weight for GA.,, In our study, we used the criteria as birth weight below the 10th percentile for GA.
ROP is a disease which occurs during the postnatal life and associated with so many risk factors including both maternal and environmental factors. Hence, we studied the associations of some of these risk factors, which is commonly seen in our institution.
In our study, the mean GA of SGA, 238.5 days (34 weeks), was higher than the AGA infants, 219.2 days (31 weeks +2 days), which is similar to other studies. The mean age of SGA (34 weeks) reminds the importance of including more mature babies under currently accepted screening criteria. In the SGA group, more females were involved, opposite to the AGA group, where males were more than females. The overall incidence of ROP in the entire population was 29%, which can be compared with other similar present studies and lower than older studies.,,, The incidence of ROP in SGA group (40%) was higher compared to the AGA group (25%). Bardin et al. and Darlow et al. described that SGA babies have an increased risk of developing ROP. The large population study done in Israel among babies with GA between 24 and 31 weeks reported that SGA infants have 2-fold increased risk of developing Stage 3–4 ROP. Darlow et al. described that the more growth restricted the infant, the greater the severity of ROP. In a study from Canada, Bardin et al. reported higher incidence of ROP in SGA in extremely preterm infants. Dhaliwal et al. found that SGA infants with GA 26–32 weeks had more chances of developing any ROP and Stage 3–5 ROP compared to the AGA groups. SGA and growth restriction (<25th percentile for a given age) were reported to be risk factors for developing threshold ROP by Allegaert et al. In some studies, Shah et al., Fortes Filho et al., and Giapros et al. reported no difference in the incidence of ROP between SGA and AGA.,, It may be due to the insufficient data and unequal comparison.
On univariate analysis, there were multiple risk factors emerged resulting in ROP. A significant association was observed between oxygen delivery and ROP in our study, which is a well-known factor from previous studies.,,,,, Low partial pressure oxygen was associated with ROP in our study. Infant respiratory syndrome was associated with ROP in this study. Shah et al. and Procianoy et al. noted an increased incidence of ROP in infant respiratory syndrome. Supplementation of surfactant for the baby was a risk factor and Seiberth andLinderkamp  and Maheshwari et al. found similar results. Blood transfusions were associated with increased ROP incidence and it is confirmed by other studies like Shohat et al., Seiberth andLinderkamp, and Maheshwari et al.
Sepsis in the postnatal period is an important risk factor for developing ROP. We had a similar association between ROP and sepsis, which was seen in the other studies like Maheshwari et al. and Hakeem et al. Mechanical ventilation using ventilator or continuous positive airway pressure was associated with increased ROP. Similar results were obtained in other studies by Seiberth andLinderkamp  and Tae Kim et al. Anemia was associated with ROP in our study, most of the anemic babies received blood transfusions also. Congenital heart disease was another risk factor for ROP in our study, Shah et al. obtained similar results. Apnea was found to be a strong risk factor for developing ROP, which was confirmed by studies done by Shah et al. Shohat et al., and Tae Kim et al.
Other important risk factors include the necrotizing enterocolitis, which is described as a risk factor for ROP in very few studies. Metabolic abnormalities such as metabolic acidosis and respiratory acidosis were associated with increased ROP, but alkalosis was not associated with ROP in our study. Acidosis is described as an important factor of ROP in some studies. Intrauterine growth restriction was seen as a risk factor in this study, which shows conflicting results in the literature., Maternal growth factors such as preeclampsia, GDM, oligohydramnios, and premature rupture of membrane were also found to be associated with ROP in our study.,,,,,
On multivariate analysis, apnea, blood transfusion, low pO2, and lower GA were independent significant risk factors, which were identified in previous studies.,, Maternal GDM was found to be an independent risk factor in our study, but only very limited data are available in the literature supporting this.
| Conclusion|| |
The study was aimed to compare the incidence of ROP between SGA and AGA preterm babies. We observed that the incidence of ROP is higher in SGA babies compared to AGA babies. Being small for gestation is associated with ROP, but we could not predict it as an independent risk factor for developing ROP. More studies should be conducted in this regard. We confirmed the role of known risk factors such as apnea, low pO2, and lower GA in causing ROP. We observed that blood transfusion and maternal GDM are also risk factors for ROP. To conclude, SGA babies need special attention and the screening should also include more mature babies who are small for gestation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rekha S, Battu RR. Retinopathy of prematurity: Incidence and risk factors. Indian Pediatr 1996;33:999-1003.
Varughese S, Jain S, Gupta N, Singh S, Tyagi V, Puliyel JM, et al.
Magnitude of the problem of retinopathy of prematurity. Experience in a large maternity unit with a medium size level-3 nursery. Indian J Ophthalmol 2001;49:187-8.
] [Full text]
Maheshwari R, Kumar H, Paul VK, Singh M, Deorari AK, Tiwari HK, et al.
Incidence and risk factors of retinopathy of prematurity in a tertiary care newborn unit in New Delhi. Natl Med J India 1996;9:211-4.
Bardin C, Zelkowitz P, Papageorgiou A. Outcome of small-for-gestational age and appropriate-for-gestational age infants born before 27 weeks of gestation. Pediatrics 1997;100:E4.
Darlow BA, Hutchinson JL, Henderson-Smart DJ, Donoghue DA, Simpson JM, Evans NJ, et al.
Prenatal risk factors for severe retinopathy of prematurity among very preterm infants of the Australian and New Zealand Neonatal Network. Pediatrics 2005;115:990-6.
Fortes Filho JB, Valiatti FB, Eckert GU, Costa MC, Silveira RC, Procianoy RS, et al.
Is being small for gestational age a risk factor for retinopathy of prematurity? A study with 345 very low birth weight preterm infants. J Pediatr (Rio J) 2009;85:48-54.
Shah VA, Yeo CL, Ling YL, Ho LY. Incidence, risk factors of retinopathy of prematurity among very low birth weight infants in Singapore. Ann Acad Med Singapore 2005;34:169-78.
McIntire DD, Bloom SL, Casey BM, Leveno KJ. Birth weight in relation to morbidity and mortality among newborn infants. N Engl J Med 1999;340:1234-8.
Giapros V, Drougia A, Krallis N, Theocharis P, Andronikou S. Morbidity and mortality patterns in small-for-gestational age infants born preterm. J Matern Fetal Neonatal Med 2012;25:153-7.
Regev RH, Lusky A, Dolfin T, Litmanovitz I, Arnon S, Reichman B, et al.
Excess mortality and morbidity among small-for-gestational-age premature infants: A population-based study. J Pediatr 2003;143:186-91.
Wold SW, Sommerfelt K, Reigstad H, Rønnestad A, Medbø S, Farstad T, et al
. Neonatal mortality and morbidity in extremely preterm small for gestational age infants: A population based study. Arch Dis Child Fetal Neonatal Ed 2009;94:F363-7.
Dhaliwal CA, Fleck BW, Wright E, Graham C, McIntosh N. Retinopathy of prematurity in small-for-gestational age infants compared with those of appropriate size for gestational age. Arch Dis Child Fetal Neonatal Ed 2009;94:F193-5.
Gopal L, Sharma T, Ramachandran S, Shanmugasundaram R, Asha V. Retinopathy of prematurity: A study. Indian J Ophthalmol 1995;43:59-61.
] [Full text]
Maini B, Chellani H, Arya S, Guliani BP. Retinopathy of prematurity: Risk factors and role of antenatal betamethasone in Indian preterm newborn babies. J Clin Neonatol 2014;3:20-4.
] [Full text]
Chaudhari S, Patwardhan V, Vaidya U, Kadam S, Kamat A. Retinopathy of prematurity in a tertiary care center – Incidence, risk factors and outcome. Indian Pediatr 2009;46:219-24.
Kavurt S, Özcan B, Aydemir O, Bas AY, Demirel N. Risk of retinopathy of prematurity in small for gestational age premature infants. Indian Pediatr 2014;51:804-6.
Allegaert K, Vanhole C, Casteels I, Naulaers G, Debeer A, Cossey V, et al.
Perinatal growth characteristics and associated risk of developing threshold retinopathy of prematurity. J AAPOS 2003;7:34-7.
Chan-Ling T, Gock B, Stone J. The effect of oxygen on vasoformative cell division. Evidence that “physiological hypoxia” is the stimulus for normal retinal vasculogenesis. Invest Ophthalmol Vis Sci 1995;36:1201-14.
Madan A, Penn JS. Animal models of oxygen-induced retinopathy. Front Biosci 2003;8:d1030-43.
Lucey JF, Dangman B. A reexamination of the role of oxygen in retrolental fibroplasia. Pediatrics 1984;73:82-96.
Penn JS, Tolman BL, Lowery LA. Variable oxygen exposure causes preretinal neovascularization in the newborn rat. Invest Ophthalmol Vis Sci 1993;34:576-85.
Procianoy RS, Garcia-Prats JA, Adams JM, Silvers A, Rudolph AJ. Hyaline membrane disease and intraventricular haemorrhage in small for gestational age infants. Arch Dis Child 1980;55:502-5.
Seiberth V, Linderkamp O. Risk factors in retinopathy of prematurity. A multivariate statistical analysis. Ophthalmologica 2000;214:131-5.
Shohat M, Reisner SH, Krikler R, Nissenkorn I, Yassur Y, Ben-Sira I, et al.
Retinopathy of prematurity: Incidence and risk factors. Pediatrics 1983;72:159-63.
Hakeem AH, Mohamed GB, Othman MF. Retinopathy of prematurity: A study of prevalence and risk factors. Middle East Afr J Ophthalmol 2012;19:289-94.
] [Full text]
Kim TI, Sohn J, Pi SY, Yoon YH. Postnatal risk factors of retinopathy of prematurity. Paediatr Perinat Epidemiol 2004;18:130-4.
Hellström A, Engström E, Hård AL, Albertsson-Wikland K, Carlsson B, Niklasson A, et al.
Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth. Pediatrics 2003;112:1016-20.
Prendiville A, Schulenburg WE. Clinical factors associated with retinopathy of prematurity. Arch Dis Child 1988;63:522-7.
Aucott SW, Donohue PK, Northington FJ. Increased morbidity in severe early intrauterine growth restriction. J Perinatol 2004;24:435-40.
Longo S, Bollani L, Decembrino L, Di Comite A, Angelini M, Stronati M, et al.
Short-term and long-term sequelae in intrauterine growth retardation (IUGR). J Matern Fetal Neonatal Med 2013;26:222-5.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]