Ophthalmic Surgery, Lasers and Imaging Retina

Clinical Science 

The Epidemiology of Retinopathy of Prematurity in the United States

Cassie A. Ludwig , MS, MD ; Tiffany A. Chen , BS ; Tina Hernandez-Boussard , PhD ; Andrew A. Moshfeghi , MD ; Darius M. Moshfeghi , MD

Abstract

BACKGROUND AND OBJECTIVE:

Retinopathy of prematurity (ROP) is a leading cause of blindness in premature and low birth weight infants. Here, the authors examine the incidence of ROP in the United States and evaluate risk factors associated with ROP development.

PATIENTS AND METHODS:

The National Healthcare Cost and Utilization Project Kids' Inpatient Database was queried for all newborns with and without ROP. Adjusted odds ratios were constructed for predictors of ROP using multivariate logistic regression modeling.

RESULTS:

The incidence of ROP increased from 14.70% in 2000 to 19.88% in 2012. Multivariate regression analysis indicated that female gender, birth weight, and gestational age predicted ROP. The frequency of ROP was 2.40% in newborns weighing more than 2,500 grams (g) and 30.22% in newborns with a birth weight between 750 g and 999 g.

CONCLUSIONS:

The authors' report examines a nationwide cohort of ROP infants and reveals an increase in the incidence of ROP from 2000 to 2012. This trend is inversely related to a simultaneous decline in newborn mortality.

[ Ophthalmic Surg Lasers Imaging Retina . 2017;48:553–562.]

Abstract

BACKGROUND AND OBJECTIVE:

Retinopathy of prematurity (ROP) is a leading cause of blindness in premature and low birth weight infants. Here, the authors examine the incidence of ROP in the United States and evaluate risk factors associated with ROP development.

PATIENTS AND METHODS:

The National Healthcare Cost and Utilization Project Kids' Inpatient Database was queried for all newborns with and without ROP. Adjusted odds ratios were constructed for predictors of ROP using multivariate logistic regression modeling.

RESULTS:

The incidence of ROP increased from 14.70% in 2000 to 19.88% in 2012. Multivariate regression analysis indicated that female gender, birth weight, and gestational age predicted ROP. The frequency of ROP was 2.40% in newborns weighing more than 2,500 grams (g) and 30.22% in newborns with a birth weight between 750 g and 999 g.

CONCLUSIONS:

The authors' report examines a nationwide cohort of ROP infants and reveals an increase in the incidence of ROP from 2000 to 2012. This trend is inversely related to a simultaneous decline in newborn mortality.

[ Ophthalmic Surg Lasers Imaging Retina . 2017;48:553–562.]

Introduction

Retinopathy of prematurity (ROP) is the leading cause of preventable blindness in premature and low birth weight (LBW) infants in the United States and occurs when retinal angiogenesis is disrupted. 1–2 The gold standard treatment of ROP is laser photocoagulation, in which the peripheral avascular retina is ablated to slow or reverse the growth of abnormal blood vessels. 3 The Early Treatment for Retinopathy of Prematurity (ETROP) clinical trial showed a reduction in unfavorable visual acuity and adverse structural outcomes from early detection and treatment of ROP. 4 Here, we report on the epidemiology of ROP in the United States using cross-sectional data from the Healthcare Cost and Utilization Project Kids' Inpatient Database (KID) for the years 2006, 2009, and 2012. Moreover, we aim to determine neonatal risk factors for the development of ROP using multivariate regression modeling and to compare our results to those from the earlier 1997 to 2005 Nationwide Inpatient Sample data. 5–6

Patients and Methods

Study Design

We performed a population-based, cross-sectional study using the KID to estimate the incidence of ROP and to determine predictors of ROP among at-risk newborns. All research adhered to the tenets of the Declaration of Helsinki. Institutional review board (IRB) approval was not required by the Stanford IRB, as this was a retrospective study that did not involve unique patient identifiers.

Data Source

The KID is maintained by the Agency for Healthcare Research and Quality as part of the Healthcare Cost and Utilization Project (HCUP). 7 It is the largest publicly available pediatric inpatient care database in the United States, incorporating discharge data from 2,500 hospitals across 22 states in 1997 to more than 4,100 hospitals across 44 states in 2012. The KID uses systematic random sampling to select 10% of uncomplicated in-hospital births and 80% of complicated in-hospital births and other pediatric cases from each frame hospital. The sample frame includes pediatric (20 years or less) discharges from community and nonrehabilitation hospitals in the participating HCUP Partner States. Using the KID database compiled for the three most recent years (2006, 2009, and 2012), we performed a retrospective analysis of all newborns diagnosed with ROP. Data compiled for the years 2000 and 2003 were also included to analyze trends in ROP incidence and in-hospital mortality over time. We excluded the data compiled for the year 1997, when the KID first started, as several changes were made to the database in 2000 that would cause a discontinuity between the 1997 and 2000 data, including revising the definition of total discharges. Missing data are reported for each variable. Mortality refers specifically to death during the hospitalization.

Case Identification

We performed a retrospective review of the KID for all reported cases of ROP as defined by the International Classification of Diseases, 9th Revision (ICD-9) medical diagnosis codes (Table A). We limited our population of interest to newborns with length of stay (LOS) longer than 28 days to limit the effect of mortality on the dataset, as most newborn deaths in premature infants occur within the first week. Furthermore, this allowed us to capture the population at greatest risk for ROP as a stay of this length indicates an unstable clinical course, one of the criteria for ROP screening. 8–9 Newborns who underwent laser photocoagulation, scleral buckle, and/or vitrectomy were counted as cases. Demographic data was recorded in the database. Birth weights, estimated gestational age (EGA), comorbidities, and surgical interventions were assessed by determining the weighted frequencies of the recorded ICD-9 codes.

ICD-9-CM and ICD-9-PCS of ROP, Birth Weight, Gestational Age, Comorbidities, and Surgical Treatments;

Table A :

ICD-9-CM and ICD-9-PCS of ROP, Birth Weight, Gestational Age, Comorbidities, and Surgical Treatments

Outcomes

Outcomes of newborns with and without ROP were examined, including LOS, inpatient mortality, and associated complications identified with ICD-9 codes: birth trauma, intrauterine hypoxia, chronic respiratory disease, respiratory distress syndrome (RDS), perinatal infection, fetal hemorrhage, intraventricular hemorrhage, necrotizing enterocolitis (NEC), periventricular leukomalacia, continuous invasive mechanical ventilation, noninvasive mechanical ventilation, lack of respiratory support, and blood transfusions (Supplemental Table). In patients with ROP, the proportions receiving laser photocoagulation, vitrectomy, and scleral buckle were calculated and stratified by birth weight.

Statistical Analysis

The data were analyzed with SAS Enterprise Guide 7.1 (SAS Institute, Cary, NC). Variables were tested for normality with the Kolmogorov-Smirnov test to assess for outliers and to determine the appropriate statistical test. Crude univariate (unadjusted) testing was used to compare the cohort with and without ROP and to calculate the odds ratio (OR) and 95% confidence interval (CI) as measures of the association between ROP and each potential risk factor. All continuous variables were analyzed by the Student t test while dichotomous variables were analyzed by the Rao–Scott Chi-square test.

Predictors of ROP were then assessed using multivariate logistic regression modeling performed based on crude univariate analysis and review of the available literature. The model included clinically significant predictors with a P value of less than .10 and less than 20% missing data in the univariate analyses. Backward selection was performed on the predictors and the final multivariate model retained predictors with a P value of less than .05. The final model, therefore, contained independent risk factors for ROP. We used the area under receiver operating characteristic curve (AUROC) to estimate the prognostic ability of the model to discriminate between patients with and without ROP. We adjusted for overfitting using 10-fold cross validation.

All data were weighted according to HCUP recommendations prior to analysis to calculate national estimates.

Results

Patient Demographics

Table 1 provides the demographic characteristics of the newborns in this study with and without ROP with an LOS greater than 28 days, compiled for the years 2006, 2009, and 2012. On univariate analysis, newborns with ROP were more likely to be female and to have been identified by their parents as black than non-ROP controls. Conversely, infants identified by their parents as Native American had lower odds of ROP development. Although the relationship between black race and ROP became nonsignificant after controlling for EGA, the relationship between Native American race and ROP remained significant even after controlling for sex, EGA, and birth weight. There was no difference in the type of insurance (private vs. other) between newborns with ROP and non-ROP controls. Newborns with EGA less than 36 weeks had an increased odds of ROP. The odds were highest in newborns with an EGA of 24 weeks.

�A;Baseline Characteristics of Newborns With and Without ROP With a Hospital LOS Greater Than 28 Days (Years: 2006, 2009 & 2012)�A; �A;Baseline Characteristics of Newborns With and Without ROP With a Hospital LOS Greater Than 28 Days (Years: 2006, 2009 & 2012)�A;

Table 1 :

Baseline Characteristics of Newborns With and Without ROP With a Hospital LOS Greater Than 28 Days (Years: 2006, 2009 & 2012)

Effect of Birth Weight on ROP and LOS

Newborns classified by the World Health Organization as extremely low birth-weight (ELBW; less than 1,000 grams [g]) and very low birth weight (VLBW; 1,000 g to 1,499 g) with a LOS greater than 28 days had significantly higher odds of developing ROP as compared to normal birth weight (Table 1 ). A peak frequency of ROP of 30.22% occurred in newborns between 750 g and 999 g. Table 2 shows the mean LOS in newborns with and without ROP stratified by birth weight. For the same birth weight, infants with ROP had a significantly higher LOS than newborns without ROP ( P < .0001) for all weight categories. The greatest discrepancy in LOS occurred between newborns weighing less than 500 g with and without ROP.

�A;Mean LOS (Days) by Birth Weight of Newborns With and Without ROP (Years: 2006, 2009 & 2012)�A;

Table 2 :

Mean LOS (Days) by Birth Weight of Newborns With and Without ROP (Years: 2006, 2009 & 2012)

Incidence of Retinopathy of Prematurity in Dataset

Of the 18,822,055 discharges recorded during the three representative years analyzed (2006, 2009, and 2012), 27,481 newborns were identified with ROP. Within our population of interest of 153,706 newborns with LOS of more than 28 days, the total incidence of ROP was 17.9%. Table 3 presents the incidence of ROP and in-hospital mortality during the following years of the KID database: 2000, 2003, 2006, 2009, 2012. The overall incidence of ROP has increased from 14.70% to 19.88%, whereas in-hospital mortality among newborns with ROP and LOS longer than 28 days has ranged from 0.92% in 2000 to 0.45% in 2012 ( Figure ).

�A;Trend of Incidence and In-Hospital Mortality of ROP During Each KID Study-Year Cohort With a Hospital LOS Greater Than 28 Days (Years: 2000, 2003, 2006, 2009 & 2012)�A;

Table 3 :

Trend of Incidence and In-Hospital Mortality of ROP During Each KID Study-Year Cohort With a Hospital LOS Greater Than 28 Days (Years: 2000, 2003, 2006, 2009 & 2012)

�A;Graph showing incidence of retinopathy of prematurity (ROP) among newborns with length of stay (LOS) longer than 28 days (left axis, blue) along with in-hospital mortality among newborns with ROP with LOS longer than 28 days (right axis, orange) in the same years.�A;

Figure. :

Graph showing incidence of retinopathy of prematurity (ROP) among newborns with length of stay (LOS) longer than 28 days (left axis, blue) along with in-hospital mortality among newborns with ROP with LOS longer than 28 days (right axis, orange) in the same years.

Complications and Comorbidities Associated with Newborns with ROP

The complications and comorbidities in newborns with and without ROP and with an LOS of longer than 28 days are shown in Table 4 . On univariate analysis, compared to newborns without ROP, newborns with ROP had an increased odds of chronic respiratory disease, RDS, perinatal infection, fetal hemorrhage, intraventricular hemorrhage, continuous invasive mechanical ventilation, noninvasive mechanical ventilation, and blood transfusions. Compared to newborns without ROP, newborns with ROP had a lower odds of birth trauma, intrauterine hypoxia, NEC, and lack of respiratory support. There was no significant difference in the odds of periventricular leukomalacia between newborns with and without ROP. The most common comorbidities in both ROP and non-ROP newborns were RDS, continuous invasive mechanical ventilation, and perinatal infection.

�A;Complications and Comorbidities in Newborns With and Without ROP With a Hospital LOS Greater Than 28 Days (Years: 2006, 2009 & 2012)�A;

Table 4 :

Complications and Comorbidities in Newborns With and Without ROP With a Hospital LOS Greater Than 28 Days (Years: 2006, 2009 & 2012)

Multivariate Logistic Regression

We assessed the following variables as possible risk factors in regression modeling based on crude univariate analyses and review of the current literature: sex, race, EGA, birth weight, continuous invasive mechanical ventilation, noninvasive mechanical ventilation, lack of respiratory support, RDS, and intraventricular hemorrhage (Table 5 ). Backward selection was performed on the predictors and the final multivariate model retained predictors with a P value of less than .05, including sex, EGA, birth weight, and lack of respiratory support. The AUROC for this model was 0.703, but 10-fold cross validation revealed a true AUROC of 0.695 (95% CI, 0.691–0.698). The overoptimism was 0.008, indicating a very low degree of overfitting. Newborns with female sex, EGA less than 36 weeks, and birth weight less than 2,000 g had significantly increased odds of developing ROP among infants with a LOS greater than 28 days. Significance of any one variable did not change after adjusting for in-hospital mortality.

�A;Multivariate Analysis of Predictors of the Development of ROP in Newborns With a Hospital LOS Greater Than 28 Days (Years: 2006, 2009 & 2012)�A;**

Table 5 :

Multivariate Analysis of Predictors of the Development of ROP in Newborns With a Hospital LOS Greater Than 28 Days (Years: 2006, 2009 & 2012)

Surgical Interventions for ROP

Overall, 8.31% (2,284 of 27,481) of newborns required treatment of ROP prior to discharge from the hospital. Of these newborns, 8.21% (2,257 of 27,481) underwent laser photocoagulation, 0.18% (49 of 27,481) underwent pars plana vitrectomy, and 0.03% (nine of 27,481) underwent scleral buckle. Incidence of laser photocoagulation in infants with ROP was highest in infants with weight less than 500 g (45.19%; 156 of 345), followed by infants weighing between 500 g and 749 g (29.03%; 1,144 of 3,941).

Discussion

Our study represents the most updated report of ROP using a nationwide cohort of newborns. In contrast to previous retrospective analyses using the National Inpatient Sample (NIS) database, which includes patients of all ages, our current study uses the KID sample, the largest publicly-available inpatient care database in the United States focusing on the pediatric population. The design of the KID, with an emphasis of sampling complicated in-hospital births from each frame hospital, makes it ideal for research on rare pediatric conditions requiring hospitalization, including ROP. 10

Our cohort represents the largest group of premature newborns in this time period with ROP that has been examined (more than 26,000 infants with ROP out of 18.8 million discharges over three study years). Our final predictive model had an AUROC of 0.695, demonstrating that the model can successfully distinguish between the diseased and healthy subpopulations in our study cohort.

Within our population of interest for newborns with a LOS greater than 28 days, the ROP incidence increased by one-third from 15.6% between 1997 and 2005 to 17.9% in our study spanning the years 2006 to 2012. 5 One important factor leading to this jump may be the widespread implementation of the American Academy of Pediatrics and American Academy of Ophthalmology ROP screening guidelines in 2006. The guidelines recommended that all infants with weights less than or equal to 1,500 g, who have an EGA equal to or less than 32 weeks (now less than 30 weeks with revised 2013 guidelines), and who have an unstable clinical course or are at high risk for developing ROP as determined by an attending pediatrician or neonatologist should be serially evaluated until the criteria for screening termination are met. 8–9 Furthermore, advancements in life-preserving technologies have led to increased survival of premature and LBW babies. 11 As EGA and LBW are both well-known to be inversely related to ROP risk, 12–15 these developments in neonatal care have increased the population of babies at risk for ROP. 16–18 In addition to contributing to the increasing incidence of ROP with more systematic screening guidelines and advancements in neonatology, these factors may also play a role in decreasing the overall in-hospital mortality in newborns with ROP (Table 3 ).

In our analysis, premature infants with ROP were significantly more likely to be female. This held true even after adjustment for EGA and birth weight. This is consistent with the 1997 to 2005 NIS data, 5 but differs from the CRYO-ROP results in which no difference in sex was found in patients with or without ROP. 19 Further evaluation is warranted to conclusively determine the relationship between sex and ROP.

As in prior studies, EGA, VLBW, and ELBW were strongly associated with ROP (Table 1 ). 5–6,12–15 In this study, 30% of patients diagnosed with ROP were 1,250 g or greater. This is almost a 50% increase in ROP incidence in this weight category compared to the 1997 to 2005 NIS study 5 and illustrates the importance of evaluating newborns who meet the age criteria for ROP screening regardless of their birthweight. 8–9 Of note, we identified a small percentage of normal-weight infants with ROP, which has increased by more than 60% from the 0.19% reported in the 1997 to 2005 NIS study. 5 Infants in this group were likely to satisfy EGA criteria for ROP screening, as they were on average of lower EGA than VLBW and ELBW infants. 8–9

Univariate analysis showed that the newborns in our sample with ROP and a LOS of longer than 28 days had significantly higher incidence of intraventricular hemorrhage (IVH), perinatal infection, blood transfusion, and mechanical ventilation than newborns without ROP. However, all relationships were nonsignificant after controlling for birth weight and EGA. Our results did indicate that babies not exposed to oxygen therapy had lower odds of developing ROP, which is consistent with previous studies. 20–24

Several complications and comorbidities had a significantly lower incidence in our population of interest as compared to all newborns with LOS longer than 28 days, including birth trauma, intrauterine hypoxia, and necrotizing enterocolitis. The mechanisms of action to explain these trends have not been studied, and prior studies examining comorbidities have shown conflicting results, making it difficult to interpret the significance of these associations. 5,25–28 One possibility is the suggestion by Lad et al. that aggressive treatment of comorbidities may explain the negative association with ROP. 6

The overall percentage of newborns with ROP and a LOS greater than 28 days who required treatment prior to discharge (8.31%) is similar to the percentage reported in the 1997 to 2005 NIS study (> 8.18%). 5 In contrast, an Australian study found that approximately 17% of patients diagnosed with ROP from 1992 to 2009 required laser therapy. 29 The discrepancy may be a result of greater use of nonsurgical treatment options for ROP, namely the anti-VEGF inhibitors bevacizumab (Avastin; Genentech, South San Francisco, CA) and ranibizumab (Lucentis; Genentech, South San Francisco, CA). 30–37 The KID does not have records of any newborns receiving intravitreal injections of bevacizumab or ranibizumab. However, we believe this is due to the lack of an accurate ICD-9 code for off-label use of these drugs, or that providers were using CPT codes instead, which are not captured by the KID.

Our study draws from a large, nationwide pediatric database to report the incidence of ROP in the United States. The KID has several advantages over the NIS, including its emphasis on sampling complicated in-hospital births from each frame hospital, making it ideal for study of rare diseases. However, the KID is similarly limited by its capture of inpatient data alone, failing to record morbidity and mortality that occurs outside of the hospital setting. Furthermore, analysis of the database is limited by accurate and consistent classification of ICD-9 codes by providers. Likewise, the severity of several comorbidities and the extent and duration of exposures is often not captured by ICD-9 codes. For instance, the volume of blood transfusions or duration of oxygen therapy, which are both known risk factors for ROP, were not addressed in our study as the data is not recorded through ICD-9 codes. Moreover, the KID does not capture longitudinal data on individual patients, so long-term outcomes and efficacy of treatments are also not available. Lastly, as with any retrospective study, missing data within the KID prevent a complete assessment of the entire population of interest, and may affect calculated odds ratios.

ROP is a devastating disease that can lead to childhood blindness if not detected and treated early. In the present study, we surveyed more than 18 million live births in the United States between 2006 and 2012, with an overall ROP incidence of 17.9% among newborns with a length of stay greater than 28 days. Our results confirm existing knowledge that LBW and EGA are important risk factors for the development of ROP, and suggest that sex and lack of respiratory support are independently associated with ROP. Finally, we show that the incidence of ROP has been increasing from 14.70% in 2000 to 19.88% in 2012, a trend inversely related to the decline in newborn mortality in the United States in the same time period.

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Baseline Characteristics of Newborns With and Without ROP With a Hospital LOS Greater Than 28 Days (Years: 2006, 2009 & 2012)

Characteristic + ROP (n = 27,481) − ROP (n = 126,225) Odds Ratio (95% CI) P Value
Sex (% Female)
  Female 13,930 50.69% 58,795 46.58% 1.18 (1.14–1.22) < .0001
  Male 13,546 49.29% 67,397 53.39% Reference -
  Missing 5 0.02% 33 0.03% - -
Race
  White 10,579 38.50% 50,661 40.14% 0.84 (0.79–0.89) < .0001
  Black 6,488 23.61% 23,131 18.33% 1.30 (1.20–1.40) < .0001
  Hispanic 4,655 16.94% 20,841 16.52% 0.96 (0.89–1.04) .3572
  Asian or Pacific Islander 983 3.58% 3,991 3.16% 1.07 (0.96–1.20) .2087
  Native American 149 0.54% 933 0.74% 0.69 (0.54–0.90) .0053
  Other 1,638 5.96% 6,706 5.31% 1.06 (0.95–1.19) .2746
  Missing 2,988 10.87% 19,963 15.82% - -
Private Insurance
  Yes 11,722 42.65% 52,763 41.80% 1.04 (0.98–1.09) .2058
  No 15,736 57.26% 73,273 58.05% Reference -
  Missing 23 0.08% 189 0.15% - -
Gestational Age (Weeks)
  <24 583 2.12% 1,155 0.92% 33.87 (19.66–58.36) < .0001
  24 1,545 5.62% 2,624 2.08% 39.48 (23.22–67.12) < .0001
  25 to 26 5,024 18.28% 9,574 7.58% 35.20 (20.73–59.79) < .0001
  27 to 28 7,012 25.52% 16,409 13.00% 28.67 (16.90–48.62) < .0001
  29 to 30 7,322 26.64% 27,806 22.03% 17.66 (10.36–30.11) < .0001
  31 to 32 3,911 14.23% 28,942 22.93% 9.07 (5.33–15.41) < .0001
  33 to 34 422 1.54% 11,544 9.15% 2.45 (1.44–4.16) .0009
  35 to 36 101 0.37% 4,584 3.63% 1.48 (0.83–2.63) .808
  >36 22 0.08% 1,500 1.19% Reference Reference
  Missing 1,539 5.60% 22,086 17.50% - -
Birth Weight (Grams)
  <500 345 1.26% 766 0.61% 18.37 (13.21–25.57) < .0001
  500–749 3,941 14.34% 8,282 6.56% 19.42 (14.25–26.46) < .0001
  750–999 6,526 23.75% 15,068 11.94% 17.67 (13.08–23.88) < .0001
  1,000–1,249 6,491 23.62% 19,491 15.44% 13.59 (10.08–18.32) < .0001
  1,250–1,499 5,263 19.15% 21,413 16.96% 10.03 (7.44–13.52) < .0001
  1,500–1,749 2,342 8.52% 17,955 14.22% 5.32 (3.94–7.19) < .0001
  1,750–1,999 742 2.70% 10,860 8.60% 2.79 (2.05–3.78) < .0001
  2,000–2,499 258 0.94% 8,574 6.79% 1.23 (0.91–1.67) .1827
  >2,500 85 0.31% 3,454 2.74% Reference Reference
  Missing 1,489 5.42% 20,361 16.13%

Mean LOS (Days) by Birth Weight of Newborns With and Without ROP (Years: 2006, 2009 & 2012)

Birth Weight (Grams) + ROP Mean (Median) LOS − ROP Mean (Median) LOS P Value
<500 121.39 (116.25) 104.63 (103.89) < .0001
500–749 104.13 (99.78) 97.58 (94.19) < .0001
750–999 79.59 (75.73) 77 (72.17) < .0001
1,000–1,249 59.44 (55.85) 56.30 (52.06) < .0001
1,250–1,499 47.92 (44.24) 45.38 (40.95) < .0001
1,500–1,749 43.13 (39.74) 40.61 (36.32) < .0001
1,750–1,999 41.07 (37.35) 39.53 (34.5) < .0001
2,000–2,499 45.01 (37.84) 41.85 (34.90) < .0001
>2,500 52.98 (46.36) 46.54 (37.35) < .0001
Missing * 76.99 (67.19) 57.92 (44.23) < .0001

Trend of Incidence and In-Hospital Mortality of ROP During Each KID Study-Year Cohort With a Hospital LOS Greater Than 28 Days (Years: 2000, 2003, 2006, 2009 & 2012)

2000 2003 2006 2009 2012 Total P Value
Total Weighted Discharges 6,351,352 6,468,925 6,578,068 6,393,803 5,850,184 38,035,077
Incidence of ROP Among Newborns With LOS >28 days 6,201/42,178 (14.70%) 5,509/42,929 (12.83%) 7,368/48,535 (15.18%) 9,630/52,451 (18.36%) 10,483/52,720 (19.88%) 42,323/38,035.077 (16.41%) < .0001
In-Hospital Mortality Rate of Newborns With ROP 57/6,201 (0.92%) 29/5,507 (0.53%) 54/7,368 (0.74%) 46/9,625 (0.47%) 47/10,483 (0.45%) 233/39,184 (0.59%) .0186

Complications and Comorbidities in Newborns With and Without ROP With a Hospital LOS Greater Than 28 Days (Years: 2006, 2009 & 2012)

Complication / Comorbidity + ROP (n = 27,481) − ROP (n = 126,225) Odds Ratio (95% CI) P Value
Birth trauma 241 0.88% 1,365 1.08% 0.81 (0.69–0.95) .0113
Intrauterine hypoxia 84 0.30% 524 0.42% 0.73 (0.54–0.99) .0453
Chronic respiratory disease * 5,995 21.82% 17,766 14.07% 1.70 (1.58–1.83) < .0001
Respiratory distress syndrome 19,782 71.98% 70,996 56.25% 2.00 (1.87–2.14) < .0001
Perinatal infection 11,389 41.44% 49,228 39.00% 1.11 (1.04–1.18) .0010
Fetal hemorrhage 6,002 21.84% 22,313 17.68% 1.30 (1.24–1.37) < .0001
Intraventricular hemorrhage 5,302 19.29% 18,127 14.36% 1.43 (1.35–1.51) < .0001
Necrotizing enterocolitis 1,529 5.56% 7,775 6.16% 0.90 (0.83–0.97) .0068
Periventricular leukomalacia 441 1.60% 1,742 1.38% 1.17 (0.96–1.41) .1220
Continuous invasive mechanical ventilation 19,407 70.62% 71,321 56.50% 1.85 (1.74–1.97) < .0001
Noninvasive mechanical ventilation 9,568 34.82% 37,862 30.00% 1.25 (1.15–1.35) < .0001
No respiratory support 4,456 16.21% 37,599 29.79% 0.46 (0.42–0.49) < .0001
Blood ransfusion 9,544 34.73% 30,309 24.01% 1.68 (1.57–1.81) < .0001

Multivariate Analysis of Predictors of the Development of ROP in Newborns With a Hospital LOS Greater Than 28 Days (Years: 2006, 2009 & 2012) **

Characteristic Adjusted Odds Ratios * (95% CI) P Value
Sex
  Female 1.09 (1.05–1.13) < .0001
  Male Reference
Gestational Age (Weeks)
  <24 16.30 (9.08–29.24) < .0001
  24 20.07 (11.33–35.55) < .0001
  25 to 26 18.52 (10.46–32.80) < .0001
  27 to 28 16.43 (9.23–29.27) < .0001
  29 to 30 12.59 (7.05–22.50) < .0001
  31 to 32 8.74 (4.91–15.55) .0203
  33 to 34 3.26 (1.84–5.78) < .0001
  35 to 36 2.47 (1.32–4.61) < .0001
  >36 Reference
Birth Weight (Grams)
  <500 3.83 (2.62–5.60) < .0001
  500–749 4.22 (2.96–6.03) < .0001
  750–999 4.08 (2.89–5.78) < .0001
  1,000–1,249 3.60 (2.55–5.09) < .0001
  1,250–1,499 3.14 (2.22–4.43) < .0001
  1,500–1,749 1.98 (1.41–2.80) .0002
  1,750–1,999 1.32 (0.93–1.87) < .0001
  2,000–2,499 0.79 (0.56–1.10) < .0001
  >2,500 Reference
No Respiratory Support 0.90 (0.83–0.99) .0227

ICD-9-CM and ICD-9-PCS of ROP, Birth Weight, Gestational Age, Comorbidities, and Surgical Treatments

ICD-9-CM/ICD-9-PCS Code Description
Live Birth V30–V38, V39
ROP 362.20–362.27
Estimated Gestational Age 765.20–765.29
Birth Weight (Grams) 765.00–765.19
Complications
  Birth Trauma 767.0–767.9
  Intrauterine Hypoxia 770.88
  Chronic Respiratory Distress 770.7
  Respiratory Distress Syndrome 769.00
  Perinatal Infection 771.0–771.83, 771.89
  Fetal Hemorrhage 772.0–772.9
  Intraventricular Hemorrhage 772.10–772.14
  Necrotizing Enterocolitis 777.50–777.53
  Periventricular Leukomalacia 779.7
  Continuous Invasive Mechanical Ventilation 31.1, 31.21, 31.29, 96.04, 96.70–96.72
  Non-Invasive Mechanical Ventilation 93.90
  No Respiratory Support Absence of 31.1, 31.21, 31.29, 96.04, 96.70–96.72, 93.90
  Blood Transfusion 990.0–990.4, 990.8
Surgical Treatments
  Laser Coagulation 142.4, 143.4, 145.4
  Scleral Buckle 144, 144.1, 144.9
  Vitrectomy 147.3, 147.4

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Authors

From Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA (CAL, TAC, DMM); California Pacific Medical Center, San Francisco (CAL); Stanford University School of Medicine — Stanford, Stanford, CA (THB); and the Department of Ophthalmology, USC Eye Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles (AAM).

The authors report no relevant financial disclosures.

Address correspondence to Darius M. Moshfeghi, MD, Byers Eye Institute, Horngren Family Vitreoretinal Center, Department of Ophthalmology, Stanford University School of Medicine, 2452 Watson Court MC, Palo Alto, CA 94303; email: dariusm@stanford.edu .

10.3928/23258160-20170630-06

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