Can 5-minute Apgar score be considered as an additional independent risk factor for screening of retinopathy of prematurity?

Introduction Retinopathy of prematurity (ROP) is a multifactorial disorder with vasoproliferative nature that affecting premature neonates with low birth weight (LBW) and very low birth weight (VLBW). ROP is considered the main cause of preventable but untreatable blindness in children throughout the world.1-4 Many risk factors can lead to the development of ROP; their leaders are gestational age and birth weight. Other factors described in the articles are oxygen therapy, male gender, apnea, sepsis, cerebral hemorrhages and anemia. The role of these risk factors has not yet been fully elucidated. Instead, preeclampsia and respiratory system maturation due to prenatal steroids therapy have been shown to have a protective role.5-9 Since the survival rate of premature infants’ increases, recent articles have shown a significant decrease in the incidence of ROP, which is possible to improved neonatal care and better determining the causes of ROP. Identifying other effective risk factors and prognostic factors which can be easily evaluated can reduce the number of unnecessary examinations. Because we observed cases of ROP in routine examinations of neonates who had no risk factor for screening we concluded that other measurable risk factors other than gestational age and weight should be considered for screening. Perhaps the first measurable risk factor that predicts the probability of oxygen therapy is the Apgar score. Our first objective in this study was to determine whether the Apgar score is an independent risk factor or not and in the following of this study, what score can be considered as a risk factor.


Introduction Introduction
Retinopathy of prematurity (ROP) is a multifactorial Retinopathy of prematurity (ROP) is a multifactorial disorder with vasoproliferative nature that affecting disorder with vasoproliferative nature that affecting premature neonates with low birth weight (LBW) and premature neonates with low birth weight (LBW) and very low birth weight (VLBW). ROP is considered the very low birth weight (VLBW). ROP is considered the main cause of preventable but untreatable blindness in main cause of preventable but untreatable blindness in children throughout the world. children throughout the world. 1-4 1-4 Many risk factors can lead to the development of ROP; Many risk factors can lead to the development of ROP; their leaders are gestational age and birth weight. Other their leaders are gestational age and birth weight. Other factors described in the articles are oxygen therapy, male factors described in the articles are oxygen therapy, male gender, apnea, sepsis, cerebral hemorrhages and anemia. gender, apnea, sepsis, cerebral hemorrhages and anemia. The role of these risk factors has not yet been fully The role of these risk factors has not yet been fully elucidated. Instead, preeclampsia and respiratory system elucidated. Instead, preeclampsia and respiratory system maturation due to prenatal steroids therapy have been maturation due to prenatal steroids therapy have been shown to have a protective role. shown to have a protective role. 5-9 5-9 Since the survival rate of premature infants' increases, Since the survival rate of premature infants' increases, recent articles have shown a significant decrease in the recent articles have shown a significant decrease in the incidence of ROP, which is possible to improved neonatal incidence of ROP, which is possible to improved neonatal care and better determining the causes of ROP. care and better determining the causes of ROP.
Identifying other effective risk factors and prognostic Identifying other effective risk factors and prognostic factors which can be easily evaluated can reduce the factors which can be easily evaluated can reduce the number of unnecessary examinations. number of unnecessary examinations.
Because we observed cases of ROP in routine Because we observed cases of ROP in routine examinations of neonates who had no risk factor for examinations of neonates who had no risk factor for screening we concluded that other measurable risk screening we concluded that other measurable risk factors other than gestational age and weight should be factors other than gestational age and weight should be considered for screening. Perhaps the first measurable considered for screening. Perhaps the first measurable risk factor that predicts the probability of oxygen therapy risk factor that predicts the probability of oxygen therapy is the Apgar score. Our first objective in this study was to is the Apgar score. Our first objective in this study was to determine whether the Apgar score is an independent risk determine whether the Apgar score is an independent risk factor or not and in the following of this study, what score factor or not and in the following of this study, what score can be considered as a risk factor. can be considered as a risk factor.

Methods Methods
This retrospective cross-sectional study was performed This retrospective cross-sectional study was performed from March 2017 to January 2018. The study population from March 2017 to January 2018. The study population consisted of newborns admitted to the neonatal intensive consisted of newborns admitted to the neonatal intensive care unit (NICU) at Al-Zahra hospital of Tabriz. For the care unit (NICU) at Al-Zahra hospital of Tabriz. For the cases of gestational age ≤32 weeks or birth weight ≤150 cases of gestational age ≤32 weeks or birth weight ≤1500 g or receive oxygen therapy for more than 2 days, then screening for ROP started between 4 and 6 weeks after birth and re-examined from 7 to 14 days according to the to 14 days according to the fundus exam until complete vascularization of the retina fundus exam until complete vascularization of the retina was obtained also treatment was performed in all cases was obtained also treatment was performed in all cases with type 1 ROP. with type 1 ROP.
A single drop of tropicamide (1%) and phenylephrine A single drop of tropicamide (1%) and phenylephrine (2.5 mg/mL) was instilled into each eye to obtain (2.5 mg/mL) was instilled into each eye to obtain full mydriasis 1 hour and 30 minutes before starting full mydriasis 1 hour and 30 minutes before starting examination. An ROP expert investigator examined the examination. An ROP expert investigator examined the fundus using a Topcon indirect ophthalmoscope and a fundus using a Topcon indirect ophthalmoscope and a VOLK Pan Retinal 2.2D lens in NICU of Alzahra hospital VOLK Pan Retinal 2.2D lens in NICU of Alzahra hospital or Nikukary eye center if permission from NICU. If retinal or Nikukary eye center if permission from NICU. If retinal vascularization was completed without any stage of ROP, vascularization was completed without any stage of ROP, then the infant was registered to the non-ROP group. then the infant was registered to the non-ROP group. Upon the witness of any stage of ROP, the infant was Upon the witness of any stage of ROP, the infant was registered to ROP group. registered to ROP group.
These parameters were examined and recorded: These parameters were examined and recorded: gestational age, gender, birth weight, duration and gestational age, gender, birth weight, duration and method of treatment with oxygen, Apgar score at 5 method of treatment with oxygen, Apgar score at 5 minute. All infants with the following characteristics were minute. All infants with the following characteristics were excluded from the study: multi gestational pregnancy, excluded from the study: multi gestational pregnancy, blood transfusion or exchange, phototherapy, underlying blood transfusion or exchange, phototherapy, underlying disease, cerebral hemorrhage, hypothermia, chronic lung disease, cerebral hemorrhage, hypothermia, chronic lung disease, sepsis, jaundice, pulmonary hemorrhage and disease, sepsis, jaundice, pulmonary hemorrhage and pneumothorax also infants who did not receive regular pneumothorax also infants who did not receive regular follow-up until complete retinal vascularization. follow-up until complete retinal vascularization.
SPSS, version 23 was used for statistical analysis. SPSS, version 23 was used for statistical analysis. Descriptive statistics were performed with independent Descriptive statistics were performed with independent samples t tests and Kolmogorov-Smirnov tests were used samples t tests and Kolmogorov-Smirnov tests were used to assess the normality of data distribution. The coefficient to assess the normality of data distribution. The coefficient level of this study was 0.95 and a difference with P < 0.05 level of this study was 0.95 and a difference with P < 0.05 was considered statistically significant. was considered statistically significant.

Results Results
One hundred and sixty-five neonates have inclusion One hundred and sixty-five neonates have inclusion criteria but 15 infants excluded because their families criteria but 15 infants excluded because their families change their location. Finally, 150 neonates were included change their location. Finally, 150 neonates were included in the study. 47 infants (31.3%) developed ROP in their in the study. 47 infants (31.3%) developed ROP in their examination and 103 infants (68.7%) never developed examination and 103 infants (68.7%) never developed any stage of ROP. The mean gestational ages in the any stage of ROP. The mean gestational ages in the ROP and non-ROP groups were 27.83 ± 1.70 weeks and ROP and non-ROP groups were 27.83 ± 1.70 weeks and 29.07 ± 1.55 weeks, respectively (P value 29.07 ± 1.55 weeks, respectively (P value < 0.001). The < 0.001). The mean birth weight in the ROP and non-ROP groups mean birth weight in the ROP and non-ROP groups were 1180.53 ± 495.12 g and 1079.45 ± 190.45 grams, were 1180.53 ± 495.12 g and 1079.45 ± 190.45 grams, respectively (P value = 0.64) and the mean Apgar scores respectively (P value = 0.64) and the mean Apgar scores were 5.4 ± 2.3 in ROP group and 6.2 ± 2.1 in non-ROP were 5.4 ± 2.3 in ROP group and 6.2 ± 2.1 in non-ROP group, respectively (P value = 0.041) (Table 1). group, respectively (P value = 0.041) ( Table 1).

Discussion Discussion
Gestational age and birth weight are traditionally Gestational age and birth weight are traditionally considered the main risk factors for development of considered the main risk factors for development of ROP; they used as screening criteria all over the world. ROP; they used as screening criteria all over the world. recommend criteria for ROP screening were; infants with recommend criteria for ROP screening were; infants with a birth weight of ≤1500 g or gestational age of ≤ 30 weeks a birth weight of ≤1500 g or gestational age of ≤ 30 weeks and with a birth weight of 1500-2000 grams or gestational and with a birth weight of 1500-2000 grams or gestational age of >30 weeks with an unstable clinical course.10 age of >30 weeks with an unstable clinical course.10 It must be consider that these criteria vary in different It must be consider that these criteria vary in different countries depending on socioeconomic conditions, such countries depending on socioeconomic conditions, such as in our country (I.R. Iran) these limits are birth weight as in our country (I.R. Iran) these limits are birth weight ≤2000 g and gestational age ≤34 weeks for screening of ≤2000 g and gestational age ≤34 weeks for screening of ROP. ROP.
Saving of more immature born neonates leads Saving of more immature born neonates leads to increases the population of infants in need of to increases the population of infants in need of ophthalmological screening, thus use other criteria can ophthalmological screening, thus use other criteria can reduce inessential aggressive fundus examinatio reduce inessential aggressive fundus examinations of low risk infants and consequently economical savings occur. ur.
In a study of 957 infants in 2011, Ke et al also found the In a study of 957 infants in 2011, Ke et al also found the low Apgar score at 5 minutes was an effective risk factor low Apgar score at 5 minutes was an effective risk factor for the ROP progression to stages requiring treatment. But for the ROP progression to stages requiring treatment. But they could not prove it as an independent factor.11 they could not prove it as an independent factor. 11 Abrishami et al, in a study in Mashhad with 122 cases Abrishami et al, in a study in Mashhad with 122 cases founded that Apgar score in ROP cases were lower than founded that Apgar score in ROP cases were lower than newborns without ROP but their study was multifactorial newborns without ROP but their study was multifactorial and they not isolated Apgar score as independent factor.12 and they not isolated Apgar score as independent factor.12 Another study done with Marinov et al in Bulgaria, they Another study done with Marinov et al in Bulgaria, they shown A low 5-minute Apgar score and an Apgar score shown A low 5-minute Apgar score and an Apgar score of six or less at 5 minutes were not statistically significant of six or less at 5 minutes were not statistically significant risk factors for increasing the incidence of ROP, but were risk factors for increasing the incidence of ROP, but were significant risk factor for the progression of low stage ROP significant risk factor for the progression of low stage ROP to stages requiring treatment.13 to stages requiring treatment. 13 Yang et al who conducted a retrospective study of 252 (VLBW) children (birth weight <1500 g) found that low eight <1500 g) found that low 5-minute Apgar score was an important risk factor for 5-minute Apgar score was an important risk factor for development of ROP requiring treatment.14 development of ROP requiring treatment.14 Our study shown that 5-minute Apgar score was Our study shown that 5-minute Apgar score was statistically an independent risk factor for the incidence statistically an independent risk factor for the incidence of ROP but given the very statistically close results, it may of ROP but given the very statistically close results, it may not be very strong criteria for screening of ROP but it is a not be very strong criteria for screening of ROP but it is a good predictor for progression to ROP. good predictor for progression to ROP.
Our study has shortcomings that need further studies Our study has shortcomings that need further studies to complete; we input any stage of ROP in case group to complete; we input any stage of ROP in case group but due to results it seems best to evaluate the different but due to results it seems best to evaluate the different stage of ROP separately. Also in our study gestational age stage of ROP separately. Also in our study gestational age ≤ 32 weeks was a risk factor for ROP but in infants with ≤ 32 weeks was a risk factor for ROP but in infants with birth weight ≤1500 g, birth weight not considered as a risk birth weight ≤1500 g, birth weight not considered as a risk factor for ROP. factor for ROP.

Conclusion Conclusion
Today, due to the great advances in the field of NICU and Today, due to the great advances in the field of NICU and neonatology care, more (VLBW) and extremely low birth neonatology care, more (VLBW) and extremely low birth weight infants survive so that the infants that need ROP weight infants survive so that the infants that need ROP screening are increasing and we should find additional screening are increasing and we should find additional criteria for decreasi criteria for decreasing the population of whom needs screening our study shown Apgar 5 score is risk factor for ROP but statically not a strong criteria for reducing screening population.

Conflict of Interest rest
There is no conflict of interest.
There is no conflict of interest.

Ethic approval Ethic approval
This research was approved by regional ethic committee This research was approved by regional ethic committee of Tabriz