The study of Incidence and Risk Factors of Retinopathy of Prematurity In NICU.

Dinesh Kumar Vuppu*, Venugopal Reddy I¹, Upendra Kumar DJ²

 

1. Medical Director and Consultant Pediatrician, Ovum Hospital, Bangalore.
2. Pediatrician.

 

*Correspondence to: Dinesh Kumar Vuppu, Consultant Pediatrician and Neonatologist, Ovum Hospital, Bangalore.

Copyright

© 2023 Dinesh Kumar Vuppu. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 12 June 2023

Published: 01 July 2023

 

Introduction

Retinopathy of prematurity (ROP), which was previously called as Retrolental Fibroplasia (RFL), is a vaso-proliferative disorder of the retina. Preterm infants are more  prone  for this disease  especially  low birth weight  (LBW)  neonates  who are exposed  to  large  amount  of  oxygen  (O2).  It is  the  major  cause  of  preventable blindness in infants.1

The World Health Organisation (WHO) programme of Vision 2020 targeted against ROP mentioned that the incidence of ROP can be reduced by early screening and   referral   for   treatment.2    Spectrum   of   ROP   is   broad   and   ranges   from   a spontaneously recovering stage to a vision threatening sequelae. In infants with birth weight (BW) less than 1000grams,  the risk of ROP is 82%, and 9.3% of them are potentially under the risk of blindness.3

Initially there was a low incidence of ROP in developing countries like India because  there  was  no adequate  screening  and reporting  and there  was  inadequate awareness  regarding  the  grave  consequences  of the  disease.  But  now  there  is an apparently increasing incidence with better screening protocols, more availability of assisted ventilation services and increased survival of preterms in newborn units.4

The pathogenic process involved in causation of ROP is multifactorial5. It is attributed to many possible risk factors like prematurity, hyperoxia, sepsis, necrotising enterocolitis, intraventricular hemorrhage (IVH), low birth weight (LBW), prolonged exposure  to O2, severity  of neonatal  illnesses,  severe respiratory  distress  requiring mechanical ventilation, shock, hypoxia, prolonged ventilatory support, need for blood transfusion, acidosis, anemia, high ambient light and vitamin E deficiency where as breast feeding was proposed to be having a protective effect.5,6

Materials and Methods

Preterm babies  with  GA  of  less  than  34wk  or  BW  of  less  than  1750gm admitted to our NICU in Ruby hall clinic,Pune. The duration of the study was from 1st April 2014 to 30th September 2015.

A minimum sample size calculation of 80 preterm neonates was done.

 

Method of collection of data:

Inclusion Criteria: Preterm babies with GA of less than 34wk or BW of less than 1750gm delivered in (inborn babies) to the NICU of Ruby hall clinic,Pune

Exclusion Criteria:  Children with suspected chromosomal anomalies.

Place of Screening

After  taking  informed consent from the parents, babies were assessed for the risk factors of ROP and recorded in  a  predesigned  proforma.  All the inborn neonates involved in the study were screened at the NICU in Ruby hall clinic,Pune.

The babies who developed any stage of ROP were taken as cases and the babies who did not have ROP were taken as controls.   Laser treatment was performed based on the Early Treatment Guidelines for ROP (ETROP)

 

Method of Study

The study was a descriptive and observational study. A total of 80 preterm neonates satisfying the inclusion criteria were included in the study. As soon as the baby fulfilling inclusion criteria was admitted to NICU, the details were entered in a predesigned proforma which includes assessment of the risk factors. Informed consent was taken from the parents and baseline data were collected for each baby regarding date of birth, sex, single or multiple births, intrauterine growth retardation and other antenatal insults. During the stay, heart rate, blood pressure, apnea monitoring and O2 saturation was done by continuous pulse oximetry. Clinical assessments and lab investigations for identifying the risk factors were carried out as follows.

 

Defining risk factors:

1. Oxygen exposure: Number of hours on oxygen, flow rate of oxygen and mode of oxygen delivery were noted for each child.

2. Hypoxia and  hyperoxemia:  Arterial  blood  gas  analysis  was  done  as  per  unit protocols  and  episodes  of  hyperoxia  and  hypoxia  was  monitored.  Continuous pulse oximetry was done in all babies who required any form of supplemental O2. Any values of SpO2  less than 85% and more than 92% was noted. 85-92% of oxygen saturation is taken as the reference range.79

3. Apnea: Apnea was defined as a cessation of respiration for more than or equal to 20seconds or less than this duration accompanied by bradycardia (heart rate  less than 100 beats per minute) or cyanosis.80

4. Hyperglycemia: Heperglycemia was defined as whole blood glucose level of more than 125 mg%. Daily RBS monitoring was done thrice a day with a glucometer. Any  glucometer  reading  more  than  125  mg%  was  confirmed  by  checking  the blood glucose levels by laboratory method.81

5. Thrombocytopenia:  Thrombocytopenia was defined  as  platelet  count  less  than 1.5 lakhs cells/cumm.82

6. Severe   respiratory    illness    requiring    mechanical    ventilation:    Duration    of mechanical ventilation in hours, mode of ventilation, proximal inspiratory pressure. (PIP), peek end expiratory pressure (PEEP) and fraction of inspired O2 (FiO2), was monitored for each case.

7. Severity of illness: RDS, surfactant administration, necrotizing enterocolitis, apnea of   prematurity, pulmonary   hemorrhage,  patent   ductus   arteriosus,   hypoxic ischaemic  encephalopathy  and IVH were considered  as severe illnesses  for the study.

8. Septicemia:  Blood culture positivity for bacterial or  fungal  sepsis  was  noted. Clinical manifestations suggestive of pneumonia, meningitis, pyelonephritis, osteomyelitis, septic arthritis, shock, sclerema,  necrotizing  enterocolitis, disseminated intravascular coagulation were noted. Laboratory criteria like white blood cell count less than 5000cells/mm3,  absolute  neutrophil  count  less  than 1000/mm3 and band neutrophil ratio more than 0.2 were also considered.83

9. Anemia:  Anemia was defined as hematocrit  or  hemoglobin  level  more  than 2 standard deviations below the mean value for the age.84Since hematocrit is more reliable than haemoglobin for assessment of anemia, hematocrit was checked for all cases which were pale clinically or had a haemoglobin level below the mean.

10. Amount of blood transfusion:  Number of  units  and  ml/kg  of  whole  blood transfused shall be noted. Amount of other blood products transfused like packed red blood cells, fresh frozen plasma and platelets were noted.

11. Duration of stay: Duration of stay in the hospital in days was calculated for each case.

 

Preparation And Precautions

All the precautions were taken as per the AAP 2013 guidelines.69  Since ROP screening examinations can have short-term effects on blood pressure, heart rate and respiratory  function  in  the  premature  baby,  examinations  were  kept  as  short  as possible and precautions taken to ensure that emergency situations were 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 pre treatment  of the eyes with a topical Proparacaine  and swaddling  the baby. Babies  were  fed  at  least  one  hour  before  examination  to  avoid  vomiting  and aspiration.  Hand  washing  was  done  and  asepsis  maintained.  Neonatologist  was available throughout the procedure in anticipation of any complications.

 

Time of 1st screening of Screening for ROP

Every case was screened as per the AAP 2013 guidelines for ROP screening  (table: 3)69

 

PROCEDURE

Instruments used: The following instruments were used for screening:

  1.   Indirect ophthalmoscope

 2.   Pediatric wire speculum.

  3.   Scleral indentor.

Dilatation   of   the   pupil:   Pupils   were   dilated   with   Phenylephrine   2.5%   and Tropicamide 0.5%. One drop of Tropicamide was instilled every 10-15 minutes for 4 times starting 1 hour before the scheduled time for examination. This was followed by Phenylephrine, one drop just before examination. Phenylephrine which is available in 10% concentration was diluted 4 times before use in neonates. Repeated instillation of Phenylephrine was avoided for the fear of hypertension.

 

Screening

Screening of ROP was done with Retcam Shuttle (Clarity MSI, USA) by an experienced ophthalmologist in our NICU. After instilling a topical anaesthetic drop like Proparacaine, a wire speculum was inserted to keep the eye-lids apart. First the anterior  segment  of  the  eye  was  examined  to  look  for  tunica  vasculosa  lentis, pupillary dilation, and lens/media clarity; followed by the posterior pole to look for plus disease; followed by sequential examination of all clock hours of the peripheral retina. A scleral depressor was used to indent the eye externally to examine areas of interest, rotate and stabilize the eye.

Notes were made after each ROP examination, detailing zone, stage and extent in terms of clock hours of any ROP and the presence of any pre-plus or plus disease. These notes included a recommendation for the timing of next examination and were kept with the medical record. After screening, the cases were classified as per ICROP on the basis of vascularization of the retina and characterized by its position (zone), severity (stage), and extent (clock hours).

 

Follow up.

Follow up was done as per the recommended by the ICROP67.

 

Ethical Issues

Informed consent  of  parents  was  taken  after  explaining  in  detail  about the   methods   and   procedures   involved   in  the   study   in  their   own   vernacular language. Institutional Ethical Committee Clearance was taken before the study was undertaken.

 

Results

INCIDENCE OF ROP AMONG STUDY SUBJECTS (n = 80)

Overall incidence of ROP in the study group was 21.3% (17 babies). Out of them, 7 babies (41.2%) had stage-1 ROP and 10 babies (58.8%) had stage-2 ROP.

 

DISTRIBUTION OF SEX AMONG CASES AND CONTROLS

There was no  statistically  significant  difference  in  sex  distribution  among cases and controls. Hence, cases and controls were approximately similar in terms of sex distribution.

SEX RATIO: The sex ratio in the study group was 1.29:1[Male: Female]

 

MODE OF DELIVERY AMONG CASES AND CONTROL

11.8% of cases and 1.6% of controls were delivered vaginally. 88.2% of cases and 98.4% of controls were delivered by caesarean section (P value =0.113). The same is also depicted in Table 3.

 

CLASSIFICATION OF  CASES  BY  STAGE  AND  ZONE  OF  ROP  AS  PER ICROP.

 Of 7 babies who had stage 1 ROP, 2 babies had zone 2 and 5 babies had zone 3 disease. Of 10 babies who had stage 2 ROP, 5 had zone 2 and 5 had zone 3 disease. The same is depicted in table 4 and figure 4.

 

DISTRIBUTION OF BIRTH WEIGHT AMONG CASES AND CONTROLS

The BW of the ROP babies ranged from 620gm-1700 gm while that of non- ROP  babies  ranged  from  1100gm-1750gm.  Maximum  number  of  cases  had  BW ranging  from  1000gm-1499gm  where  as  maximum  number  of  controls  had  BW ranging from 1500gm-1750gm.  LBW was significantly associated with increased incidence of ROP (p<0.001). Table 5 and figure 5 depict the same.

 

MEAN BIRTH WEIGHT AMONG CASES AND CONTROLS

The mean birth weight of the ROP babies was 1255.3gm ± 302.8 gm, while that of non-ROP babies the mean birth weight was mean 1480gm ± 170.4gm. Low birth weight was significantly associated with increased incidence of ROP on univariate analysis. (p value<0.001) The same is depicted in the form of table 6 and figure 6 below:

 

MEAN GESTATIONAL AGE AT BIRTH AMONG CASES AND CONTROLS

The  mean  GA  of  the  cases  was  30.12wk  ±  2.29wk  and  the  controls  was 32.43wk ± 0.96wk. Cases had significantly lower mean GA when compared to controls which was statistically significant (P-value<0.001).

The GA ranged from 25wks to 34wks among cases and 29wk to 34wk among controls. Of the total number of ROP cases, maximum number (82.4%) was amongst babies born with a GA of less than 32 wk, whereas among controls only one baby had a GA of less than 32wks, which was highly significant (p<0.001). The same is shown in table 8 and figure 8a below.

Stage  1  ROP  was  distributed  amongst  babies  with  GA  at  birth  ranging between  29 wk-34  wk,  where  as  stage  2  ROP  was  found  amongst  babies  with  a lower mean GA at birth ranging from 25wk-32wk. This is shown in the Table 8 and figure8b which follows.

 

GESTATIONAL  AGE OF STUDY GROUP AT IST  OPHTHALMOLOGICAL EVALUATION.

GA of the cases at first ophthalmological examination ranged from 30 wk to 38 wks where as the controls had a GA ranging from 31wk to 37wk.

The GA at first ROP screening examination and distribution among cases and controls, and among stage 1 and stage 2 ROP is as shown in the table 9 and figure 9 that follows.

 

MEAN GESTATIONAL AGE AT 1ST OPHTHALMOLOGICAL EXAMINATION FOR SCREENING OF ROP.

The mean GA at first examination in cases was at 34.04wk  ± 2.10wk and the mean GA at first examination among controls was at 34.3wk ± 1.53wk. There was no significant difference in the mean age at first screening examination of the cases and the controls. (P value= 0.512). The same is depicted in Table10 and Figure 10 below.

 

STAGE OF ROP AND THE GESTATIONAL AGE AT COMPLETE VASCULARIZATION  OF RETINA  AMONG  THE STAGES  OF ROP AND CONTROLS

All the controls attained full vascularization  by 45wk of GA. Among cases, all stage 1 ROP cases attained full vascularization by GA of 46wk where as stage 2

ROP cases took up to GA of 49wk for full vascularization. The same is depicted in

Table 11 and Figure 11 below.

 

MEAN GESTATIONAL AGE  AT  COMPLETE  VASCULARIZATION AMONG CASES AND CONTROLS

Mean  GA  at  which  complete  vascularization  of  retina  was  evident  was 43.06wk ±2.63wk for cases where as the controls attained complete vascularization at a mean  GA  of 40.48wk±2.50wk  which  was  significantly  earlier  than  the ROP  cases (P value<0.001). The same is shown in table 12 and figure 12.

 

NEED FOR OXYGEN ADMINISTRATION

Ten babies among the cases (58.8%) and 15 babies among the controls (23.8%)  needed  oxygen  therapy  by  any  of  the  modes  like  through  oxygen  hood, oxygen prongs, bubble CPAP (continuous  positive airway pressure)  or mechanical ventilation.  The  requirement  for  oxygen  was  significantly  more  among  the  cases when compared to the controls (P value <0.001) as shown in table 18.

 

COMPARISON OF VARIOUS PARAMETERS OF OXYGEN ADMINISTRATION AMONG CASES AND CONTROLS

For all the babies in the study group who required oxygen, the duration of oxygen requirement, the minimum and the maximum duration of saturation of arterial oxygen (SpO2) attained and the duration of the maximum and minimum SpO2  were continuously  recorded  using transcutaneous  pulse oximetry  technique  by using the trend setter mode and significance assessed between the documented values among cases and controls.

The mean  duration  of oxygen  administered  was 70.00± 48.96  hours  among the cases and 49.60 ± 23.39 hours among controls. (P-value<0.05) the same is shown in table14 and figure 14a.

The mean of maximum SpO2  attained in the cases was 98.76%±1.20%  and that in the control was 97.53%±1.41% (P-value=0.012). The mean of minimum SpO2 was significantly lower in the cases (81.88%±7.36%) when compared to the levels in the controls (87.87%±4.05%) (P Value =0.009). These 2 data showed that the cases were  exposed  to  significantly  wider  levels  of  fluctuation  in  the  arterial  oxygen saturation than the controls. The same is shown in table 14 and figure 14b.

 

UNIVARIATE ANALYSIS OF VARIOUS RISK FACTORS

COMPARISON  OF  THE  DISTRIBUTION  OF  APGAR  SCORES  AMONG CASES AND CONTROLS

In the present study groups, no case or control had one minute APGAR score less than 3, but cases had a lower APGAR at both 1 and 5 minutes when compared to the  controls.  There  was  a statistically  significant  difference  in  the  distribution  of APGAR score between cases and controls recorded at first and fifth minute of life (P value <0.01 for both).

The mean APGAR score at 1 minute of the cases was 7.06 ±0.83 and the controls was 6.32± 0.95.( p<0.01) The mean APGAR score at 5 minutes of the cases was 8.88 ± 0.33 and the controls was 8.46 ± 0.62 (p<0.01).

Mean  APGAR  scores  at  1minute  and  5  minutes  were  significantly  lower among case when compared to the controls, signifying that neonates with perinatal asphyxia are at risk of ROP. The same shown in table 15 and figure  15.

 

EVALUATION OF MATERNAL AND FETAL RISK FACTORS AMONGST CASES AND CONTROLS

17.6% of the cases had maternal pregnancy induced hypertension compared to

22.2% of the controls, which was not statistically significant.

7.4% of cases had maternal antepartum hemorrhage compared to 15% in the controls which was not significant.

Non from the cases had antenatal steroid exposure compared to 20.6% in the controls which was not statistically significant.

None from.  The cases   had   meconium  stained   amniotic   fluid   indicating intrauterine asphyxia compared to 33.3% of the controls, which was statistically significant.

 

COMPARISON   OF  VARIOUS   NEONATAL   COMPLICATIONS   AMONG CASES AND CONTROLS

The following are the various neonatal complications which were significant on univariate analysis of cases and controls:

1.   Respiratory  distress  syndrome:  58.8%  of  the  cases  had  respiratory  distress syndrome compared to 23.8% in the controls which had a high significance (p=<0.001).

2.   Clinical sepsis: Clinical sepsis was present in 70.5% of the cases where as it was present only in 49.2% of the controls (p=0.171).

3.   Hypoxic   ischemic   encephalopathy   was   present in 100.0% of cases and  90.4% of controls (p=0.417).

4.   Acute kidney injury: Acute kidney injury was considered in the study group if oliguria (urine output <1ml/kg) is present and/or if serum creatinine was elevated2 standard deviation above the mean value for gestational age or rise in value was ≥0.3mg/dl/day. 5.9% of the cases had acute kidney injury where as 6.3% of the controls had it, which was not significant (p=0.999).

5.   Convulsions: Presence of convulsion during the period of admission was a very significant  factor among  cases (5.9%)  when compared  to the controls  (6.3%) (p=0.517).

6.   Hypotension: 17.6% of the cases had hypotension requiring inotropic support of atleast  one  drug.  Among  controls  there  were  only  12.7%  of  the  babies  who required the same. Presence of hypotension was not significant risk factor among the cases (p=0.693)

7.   Transfusion  of blood  and  blood  products:  Transfusion  of whole  blood  or any blood products like packed red blood cells, platelet concentrate and fresh frozen plasma  transfusion  was considered  here. 17.6% of case required  any one of the above were as only 14.3% of the controls required it. (p=0.711)

 

VARIOUS     NEONATAL     COMPLICATIONS      WHICH     WERE     NOT SIGNIFICANT ON UNIVARIATE ANALYSIS OF CASES AND CONTROLS

Neonatal hyperbilirubinemia,  Surfactant  administration,  patent  ductus arteriosus, intraventricular hemorrhage, necrotising enterocolitis, hemorrhagic disease of newborn, anemia, thrombocytopenia, requirement of exchange transfusion, bacterial and fungal sepsis and hypothermia were not significant on univariate analysis.

 

COMPARISON  OF VARIOUS PARAMETERS  OF SEPSIS AMONG CASES AND CONTROLS

Distribution of CRP did not differ significantly between cases and controls     (P-value =0.750).

Distribution of Plate count differs significantly between cases and controls       (P-value =0.041).

Distribution of Mean Hb did not differ significantly between cases and controls       (P-value =0.751).

Distribution of Fungal sepsis did not differ significantly between cases and controls    (P-value =0.999).

Distribution of bacterial sepsis did not differ significantly between cases and controls    (P-value =0.749).

 

MULTIPLE LOGISTIC REGRESSION ANALYSIS

On multivariate analysis, GA, duration of hospital stay, day of establishment of feeds, apnea, need for resuscitation and duration of oxygen administration were found to be independent risk factors.

 

NEED FOR RESUSCITATION AMONG CASES AND CONTROLS

47.1% of the cases needed resuscitation compared to 17.5% of the controls. Resuscitation was a significant and independent risk factor of ROP (P-value = 0.021).

 

DISTRIBUTION OF APNEA AMONG CASES AND CONTROLS

58.8% of the cases had at least one episode of apnea. There was no episode of apnea among the controls. Apnea was an independent risk factor for ROP. Table 22 shows the same.

 

DURATION    OF   STAY   IN   THE   HOSPITAL    AMONG    CASES    AND CONTROLS

Majority of the cases (82.4%) had duration of hospital stay more than 13 days but the most of the controls (77.8%) had a period of stay less than 13 days.

 

COMPARISON    OF    MEAN    DURATION    OF    ESTABLISHMENT     OF FEEDING AMONG CASES AND CONTROLS

Any  type  of  enteral  feeding  of  breast  milk  in  the  form  of  nasogastric  or orogastric feeding, pallada or direct breastfeeding was established at a significantly earlier period among controls when compared to the cases (P value<0.01).

 

Discussion

Significance of ROP screening lies in the fact that ROP is the most common cause of childhood blindness which is preventable. The primary prevention of ROP can be done by limiting the exposure  to antenatal,  natal and postnatal risk factors which are proposed  to contribute  to the increased  incidence as well as severity of ROP. Secondary prevention of ROP is done by timely screening and early treatment to prevent blindness that can occur in severe ROP which were missed at the screening and are not treated. So the secondary prevention of ROP is given utmost importance in the WHO. VISION 2020 programme.2

In  this  era  of  improving  standards  of  neonatal  care,  ROP  is  becoming  a significant problem in developing countries like India. Though there are data from the different urban and rural areas of India, reports from large randomised multicentric trials are lacking from our country. So there is a scarcity of data on the epidemiology of ROP from the Indian sub continent.85

Studies  from  developed  countries  have  reported  that  although  the  clinical spectrum  and incidence  of ROP is not similar  in all the units, there is an overall decrease in the incidence of the disease wherever there is an ongoing surveillance programme.86 So timely screening is a very important aspect in management of ROP. Incidence of ROP

The incidence  of ROP in the present  study is 21.3%  Various  studies  have shown that about 9.4%-25.4% of babies with gestational age 32wk or less develop some degree of ROP.

Studies in the literature usually use a cut-off point of a BW of 1,250gm or 1,500gm or 1,750gm, a GA of 28wk or 32 wks, or both. Using a BW of 1750gm or less, a GA of 34 wk or less, or both as criteria for inclusion in this study, explains the similar incidence of ROP when compared to other Indian studies.

The  overall  incidence  of ROP  in  the  present  study  is 21.3%.  Patil24   et  al reported the overall incidence of ROP as 17.5% and there were no cases of severe ROP. They  studied  40  babies  with  <32wk  or  <  1250gm.  Maheshwari23   et  al.  in  1996 reported overall incidence as 20% and severe ROP as 7%. They studied 66 babies with <35wk or < 1500gm. Gupta et al in 2003 reported overall incidence as 21.7% and severe ROP as 5%. They studied 60 babies with ≤ 35wk or ≤1500gm. Dutta25 et al screened 108 babies of ≤32 wk or ≤1700gm and reported overall incidence as 21%.  However,  in  most  instances  it  is  not  possible  to  compare  studies,  as  the inclusion  criteria  are  different.

 The  incidence  of  ROP  in  our  study  would  have increased if the screening was done only in babies weighing <1300gm or in babies <32wk of GA at birth. Screening of babies with a GA of <34wk and/or <1750gm BW in this study has made the incidence of ROP comparable to other Indian studied.

Inclusion criteria of ROP Screening if changed to lower limit of GA or BW (≤30wk and ≤1250gm) would make screening more cost effective and detect the more severe stages of ROP easily enough to permit treatment, reduce unnecessary examinations  and  avoid  wastage  of  time  and  manpower.87,88   But  there  are  high chances of missing ROP cases which can lead to sequelae which are avoidable with screening and early treatment. In the present study all the babies who were ≤ 28wk of GA developed ROP. All the babies who had a BW ≤1000gm developed stage 2 ROP which was the maximum stage of ROP in this study.

 

SEVERITY OF ROP

Most  of  the  studies  consider  stage  3  and  above  as  severe  ROP.     The percentage of severe ROP among various stages of ROP is depicted in the box below.

In our study there were no stages of ROP above stage 2, which was similar to study conducted by Patil et al. This could be explained by the fact that the screening programme and surveillance for the risk factors was good in our hospital.

 

SIGNIFICANT RISK FACTORS IN VARIOUS STUDIES

Though accumulating evidence indicates that ROP is a multifactorial disease, immaturity of retina and a period of hyperoxia are the main contributing etiological factors in the pathophysiology  of ROP.25  In our study, the incidence  of ROP was significantly inversely proportional to both birth weight(p=0.001) and gestational age (p<0.001).

On  univariate  analysis,  the  duration  of  oxygen  administration,   mean  of maximum  and  minimum  SpO2,  need  for  oxygen  supplementation,  clinical  sepsis, apnea, RDS, HIE, mean APGAR at first and fifth minute of life, acute kidney injury, convulsions, positive CRP, administration of blood and its products and hypotension are significantly associated with development of ROP.

 

LOW BIRTH WEIGHT AND PREMATURITY

The prevalence  of ROP was more among  VLBW  neonates  and the risk is inversely proportional to BW and GA in studies conducted by Maheshwari   et al.23 The mean gestational age of the cases was 29.93wk ±2.18wk and the controls were 32.42wk± 0.89wk. The range of gestational age was 27 wks – 34wks among cases and 29wk-34wk among controls. Mean birth weight of the ROP cases were 1340gms and non ROP babies was 1480gms. Incidence and severity of ROP increased as the birth weight decreased.

 

OXYGEN ADMINISTRATION

The duration of oxygen administered was an independent risk factor for development of ROP (p=0.001). 23.8% of babies who received oxygen therapy developed ROP in the present study and nearly 50 %of the babies on oxygen therapy developed the disease in other studies.18,85  Though cases were exposed to hyperoxia and hypoxia more than the controls, it was not found to be a significant  factor in causing ROP. This can be explained due to the close monitoring of babies on oxygen therapy by pulse oximetry and arterial blood gas analysis in our unit. The causal link between ROP and supplemental oxygen has been confirmed by controlled trials and clinical studies.14,85 However, a safe level of oxygen usage has not been defined. Preliminary work has suggested that continuous oxygen monitoring may  reduce  the  incidence  of  ROP.  In  present  study  oxygen  administration  is  a significant risk factor for development of ROP but not an independent risk factor on multivariate analysis.

 

ANTENATAL MATERNAL STEROID INTAKE

A study conducted by Rosemary et al showed that antenatal steroid administration   by   the   mother   had   a   protective   effect   against   ROP   in   the neonates.16But in our study it was not a significant risk factor.

 

LOW APGAR SCORE AND HYPOXIC  ISCHAEMIC  ENCEPHALOPATHY (HIE)

Preterm babies who had a lower APGAR at 1 minute had a higher risk of having ROP in the study conducted by Shah et al.48 In our study Mean  APGAR  scores  at  1minute  and  5  minutes  were  significantly  lower among case when compared to the controls, signifying that neonates with perinatal asphyxia are at risk of ROP. Distribution of various stages of HIE was significant among the cases but was not an independent risk factor for ROP.

 

RDS

RDS is significant risk factor in the present study but not an independent risk factor on multivariate analysis. Gupta et al18 and associates reported ROP in 33.3% of babies with RDS. In our study, 40% of babies among cases had RDS, which is almost comparable to the other studies mentioned.

 

SURFACTANT ADMINISTRATION

Surfactant used to treat hyaline membrane disease has been shown to reduce the risk of ROP but it did not significantly  reduced  the incidence  of ROP in the present study (p=0.12). It may be due to the fact that very few cases among babies having RDS had surfactant therapy.

 

MULTIVARIATE ANALYSIS OF THE RISK FACTORS

In  study   conducted   by  Chaudhari26    et  al  septicemia   (P<0.001),   apnea (P=0.0001) and oxygen therapy (P=0.031) were independent risk factors In our study on multivariate  analysis, GA, duration of hospital stay, day of establishment of feeds, apnea, need for resuscitation and duration of oxygen administration were found to be independently significant risk factors.

 

EVALUATION OF NEED FOR TREATMENT AMONG CASES

In study by Austeng, 33.3% required treatment. In our study, four babies (23.5%) had stage 2 plus disease and both required laser treatment. This may be due to the fact that our study had wide screening criteria compared to the other study and also there was strict monitoring  for the avoidable  risk factors and appropriate  and timely screening as per the AAP.