PEDIATRICS Vol. 121 No. 1 January 2008, pp. 97-105 (doi:10.1542/10.1542/peds.2007-0644)
ARTICLE |
Treatment for Retinopathy of Prematurity in Denmark in a Ten-Year Period (1996–2005): Is the Incidence Increasing?
a Departments of Ophthalmology
c Neonatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
b Department of Ophthalmology, Copenhagen University Hospital, Glostrup Hospital, Copenhagen, Denmark
d National Board of Health, Copenhagen, Denmark
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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OBJECTIVE. The objective of this study was to analyze the population incidence of retinopathy of prematurity treatment in Denmark in the 10-year period from 1996 to 2005.
METHODS. Patient charts of infants treated for retinopathy of prematurity and the national birth registry provide information about neonatal parameters. These parameters, along with birth in the latter half of the period (2001–2005), were analyzed as risk factors for retinopathy of prematurity. The national registry for blind and visually impaired children was accessed to obtain information about visual impairment attributable to retinopathy of prematurity in both treated and untreated infants.
RESULTS. The study population consisted of 5467 Danish preterm infants born in 1996 to 2005, with a gestational age of <32 weeks, who survived for 
5 postnatal weeks; 2616 were born in 1996 to 2000, and 2851 were born in 2001 to 2005. The incidence of treated retinopathy of prematurity cases increased significantly from 1.3% in 1996 to 2000 to 3.5% in 2001 to 2005. Significant risk factors for retinopathy of prematurity treatment were low gestational age, small for gestational age, male gender, and multiple birth. Other, yet unknown factors contributed to the increased incidence in the latter half of the period. Of the study population, 0.6% were registered as visually impaired because of retinopathy of prematurity within 2 years after birth (early-detected visual impairment). The incidences were not significantly different between 1996 to 2000 and 2001 to 2005. Of all of the early-detected, visually impaired children, 16% had not been treated for retinopathy of prematurity and were considered screening failures.
CONCLUSIONS. The incidence of retinopathy of prematurity treatment in Denmark has more than doubled during the past half-decade. This increase could not be fully explained by increased survival rates for the infants or by changes in the investigated neonatal risk factors.
Key Words: incidence • preterm delivery • retinopathy of prematurity • retinal ablation therapy • low gestational age • low birth weight • small for gestational age • gender • multiple birth
Abbreviations: ROP—retinopathy of prematurity • GA—gestational age • BW—birth weight • NBR—national birth registry • NRBVIC—national registry for blind and visually impaired children • PNA—postnatal age • SGA—small for gestational age • T-ROP—threshold retinopathy of prematurity
Each country has its own profile of retinopathy of prematurity (ROP), depending on local living standards and the medical care infrastructure.1 Among highly developed countries, the population incidence of ROP treatment has been reported to vary from 1.9 to 8.1 cases per 10000 live-born infants.2,3 Studies have described increasing local incidences of ROP treatment, especially among the most immature infants.4,5 In Denmark, all infants with a gestational age (GA) of <32 weeks are screened for ROP. The screening begins at the beginning of the fifth postnatal week. The screening and subsequent treatment are provided free of charge by the public health system. All ROP treatments are centralized at one referral center, namely, the National University Hospital (Rigshospitalet). Since 2001, we observed an increasing annual number of infants treated for ROP in Denmark. As neonatal care continuously improves, an increasing number of surviving extremely immature infants is a possible explanation.5,6 However, other (preventable) factors also might play a role. The present study was conducted to verify our hypothesis that the observed increase in ROP treatment is statistically significant and, if it is, to determine whether known neonatal risk factors for ROP treatment can explain it.
In Denmark, there is a national birth registry (NBR) that registers all newborn infants. It contains information about GA at delivery, birth weight (BW), gender, and single/multiple birth. There also exists a national registry for blind and visually impaired children (NRBVIC), to which reporting is compulsory when the best corrected visual acuity of the better eye in a child is suspected not to exceed 6/18 (0.33).
The purpose of the current study was to investigate the incidence of ROP treatment in our study population of Danish infants born in 1996 to 2005, with GA of <32 weeks, who survived 5 weeks. A priori, we divided the study decade into 2 periods, namely, 1996 to 2000 and 2001 to 2005. Our hypothesis was that the incidence increased significantly in 2001 to 2005, compared with 1996 to 2000, and the increase could not be explained by changes in the known risk factors for ROP in the study population. We used a multivariate analysis to estimate birth in 2001 to 2005 as an independent risk factor for ROP treatment, adjusting for the following known risk factors for ROP: low GA, small for GA (SGA), male gender, and multiple births. Another purpose of this study was to investigate the incidence of registration as blind or visually impaired because of ROP among our study population. Our hypothesis was that the incidence of blindness or visual impairment attributable to ROP increased from 1996 to 2000 to 2001 to 2005.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Study Design
This study was a retrospective chart review of all infants treated for ROP in Denmark in 1996 to 2005, combined with a national register study of all newborn infants in Denmark, as well as a national register study of visually impaired children in Denmark. Information obtained from these data sources was linked by using the unique Danish civil registration numbers. At birth, each Danish citizen is assigned a civil registration number, which is issued and administered by the National Board of Health in Denmark.
Identification of Treated Infants
Because ROP treatment in Denmark is centralized to the eye department of Rigshospitalet, current listings of treated infants could be cross-checked against the hospital registry for the disease code (International Classification of Diseases, 10th Revision, code) for ROP and the treatment codes for laser treatment or cryotreatment, as well as vitrectomy and scleral buckling surgery. All identified patient charts were reviewed, and the case was included if the patient was born within the study period (1996–2005), had parents with a permanent address in Denmark, and was treated for ROP. From the chart review, we recorded data on the treatment and neonatal parameters, including GA, BW, gender, and single/multiple birth. We excluded infants born to mothers with a permanent address outside Denmark, in Greenland, or in the Faroe Islands. For all treated infants, we calculated the postnatal age (PNA) of the infant at the time of first treatment. We also calculated the corresponding postconceptional age, defined as the sum of GA and PNA.
Identification of Premature Infants
The NBR of the National Board of Health records demographic data on all live-born infants in Denmark, with the exception of infants with parents with a permanent address outside Denmark, in Greenland, or in the Faroe Islands. The registry is based on compulsory reporting of live births by physicians and midwives. Registration is almost complete, because the registry contains information on 99.7% of all live-born infants in Denmark. A child may falsely not be entered in the registry if the mother is without a permanent address in Denmark at the time of the child's birth but subsequently lives in the country. The NBR contains information on infants' GA, BW, gender, single/multiple birth, and date of death (in cases of nonsurviving infants). Registration of death includes death on the day of birth, but the NBR does not contain information about whether the death took place in the delivery room or elsewhere. We searched the NBR for infants born during the study period (1996–2005). We included infants with either GA of <32 weeks or BW of 1500 g (for comparison, with a similar denominator). We excluded infants with missing information about either GA or BW. To minimize errors attributable to faulty coding (such as a missing 0 in BW), we used the previously established relationship between GA and BW for Danish children and calculated the expected BW from the recorded GA.7,8 If the recorded BW was <300 g or more then twice the expected BW, then the entry was considered erroneous and excluded. For each included infant, we calculated whether the recorded BW was <76% of the estimated mean BW; such entries were labeled SGA.7,8
Identification of Children With Blindness or Visual Impairment Attributable to ROP
The NRBVIC records all children in Denmark with a visual acuity of 
6/18 (0.33) in the better seeing eye. Law mandates reporting to this registry if a child is suspected of being visually impaired. When a child is reported, it is ensured that an ophthalmologist has examined the child and established the diagnosis that is entered into the registry. We accessed the registry on February 23, 2007, and searched for visually impaired children born within the study period and entered with the diagnosis of ROP. We excluded children born outside Denmark, as well as children born in Greenland and the Faroe Islands. To make comparisons over the study period, we also excluded children entered into the registry >2 years after birth.
Data Analyses
Because the risk of ROP is confined to a relatively short period in postnatal life, we operationally defined the cumulated 1-year incidence (henceforth denoted incidence) of ROP treatment as the number of individuals treated in 1 eye in a given period divided by the number of infants born in that period who survived until the risk of ROP commences (ie, until the end of the fifth postnatal week). The incidence of visual impairment attributable to ROP was operationally defined as the number of infants registered as visually impaired because of ROP within 2 years after birth (early-detected visual impairment) and born in a given period divided by the number of infants born in the same period who survived 5 weeks. Although not a Kaplan-Meier estimate, this is in keeping with the methods used in other reports.3,9,10
Statistical analysis was performed by using SigmaStat (Systat Software, San Jose, CA). In the logistic regression analysis, the significance of the estimated parameters was assessed by using the Wald statistic. In the analysis of survival, the Grehan-Breslow test was used. Comparisons of proportions were performed by using the 
2 test. Before comparisons between continuous variables were performed, we tested for normality of the data set with the Kolmogorov-Smirnov test. If the data were normally distributed, then the unpaired t test was used; if not, then the Mann-Whitney test was used. Throughout the study, we used a significance level of 5%. For variables that followed a normal distribution, results are presented as mean ± SD. For other variables, results are presented as median and range.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Infants Treated for ROP
From the database in Rigshospitalet, we identified 140 infants who were treated for ROP and were born in Denmark during the present 10-year period. Of those infants, we excluded 5 infants whose mothers had permanent addresses abroad, in Greenland, or in the Faroe Islands at the time of birth. The remaining 135 infants' patient charts were evaluated. We found 30 infants who underwent cryotherapy, 104 who received laser treatment, and 1 who presented primarily retinal detachment and underwent vitrectomy. In July 2000, cryotherapy was abandoned in favor of 810-nm diode laser photocoagulation. None of the cryotherapy-treated infants was subjected to additional surgery, whereas this was the case for 4 infants who progressed to retinal detachment despite retinal ablation therapy. They all subsequently underwent vitrectomy. Throughout the study period, the indication for retinal ablation therapy was the presence of threshold ROP (T-ROP), as defined in the Cryotherapy for Retinopathy of Prematurity study.11 The same senior consultant (Dr Fledelius) participated in making the recommendation for almost all treated infants and supervised nearly all ROP treatments. Because international criteria for intervention changed during the study period,12 we reviewed the treated infants' charts to assess whether T-ROP was present in all treated infants. In 1996 to 2000, 35 infants were treated, 30 bilaterally and 5 unilaterally. Of the 30 bilaterally treated patients, 3 had T-ROP in only 1 eye and 1 did not have T-ROP in either eye. In 2001 to 2005, 100 infants were treated, 91 bilaterally and 9 unilaterally. Of the bilaterally treated patients, 13 had T-ROP in only 1 eye and 3 did not have T-ROP in either eye. Of the 9 unilaterally treated patients, 1 did not have T-ROP in the treated eye. Of the 256 eyes treated in the 2 periods, 9% had only subthreshold disease. There was no statistically significant difference between the numbers of treated nonthreshold eyes in the 2 periods (
2 test, P = .6). Treatment for ROP was administered at PNA of 69 ± 16 days (mean ± SD) and at postconceptional age of 256 ± 14 days (mean ± SD). Among the treated infants in the entire 10-year period, 63.7% were male and there was a large proportion of multiple birth (43.7%). Of all of the treated infants, 35.6% were SGA, and those infants had a significantly higher GA than did infants not SGA (median GA: SGA infants, 191 days; infants not SGA, 181 days; Mann-Whitney test, P < .001) (Fig 1). The median GA of the treated infants was 183 days (range: 165–222) (Fig 1). The BWs of the treated infants ranged from 480 to 1500 g, with a median of 800 g (Fig 2). The highest BW in a treated infant was exactly 1500 g. That infant was born in 1997, had a GA of 207 days, and was treated with cryotherapy at PNA of 37 days. There was no significant difference in BW among single- and multiple-birth infants (Mann-Whitney test, P = .4) (Fig 2). The proportion of SGA infants among the treated infants decreased as the GA decreased (Figs 1 and 3). Of the 135 treated infants, 25 (18.5%) had been screened for ROP at Rigshospitalet, and the remaining part had been referred for ROP treatment from elsewhere in the country. There were no significant differences between the proportions of treated infants screened at the Rigshospitalet between the first half of the period (17.1%) and the second half of the period (19.0%; 2 test, P = .8). Two (1.5%) of the treated infants died within their first year, at PNA of 225 and 271 days.
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Infants at Risk of Developing ROP
The total demographic 10-year sample consisted of 657787 live-born infants (1996–2005 birth cohort). In a search of the NBR, we found 6484 infants with a recorded GA of <32 completed weeks who were born within the study period. Of those, we excluded 241 because of likely errors in the recorded BW or GA. As described above, an entry was considered erroneous (not valid) if the recorded BW was either <300 g or more than twice the expected BW, as calculated from the recorded GA.7,8 Of the 241 erroneous entries (3.7%), the majority (n = 218) had a recorded BW of
2500 g and thus were probably not at risk for ROP at all. The sample of live-born infants with GA of <32 completed weeks thus consisted of 6243 infants with valid entries in the NBR. One of the treated infants could not be found in the NBR. That infant was born in 2005 with a BW of 670 g and a GA of 25 weeks (175 days) and was included in the sample, which then included 6244 infants born with GA of <32 completed weeks.
Of the 6244 infants born with GA of <32 weeks, 832 (13.3%) died within the first year after birth, with 93% of those deaths occurring within the first 5 weeks. For the 2 periods (1996–2000 and 2001–2005), Fig 4 shows the survival rates of infants born with GAs of <32 weeks, <28 weeks, and <26 weeks. In none of the GA groups did we find statistically significant differences between the survival rates of infants born in the 2 periods (Gehan Breslow test, P > .2). There was a slight tendency toward increased survival rates among infants with GA of <26 weeks in the latter period (Fig 4); however, this amounted quantitatively to an excess survival of only 20 infants.
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Because infants who die in the first 5 weeks are not at risk of ROP, they were excluded from the analysis of ROP incidences. Therefore, the population for the following analysis consisted of 5467 infants with GA of <32 completed weeks and postnatal survival time of
5 weeks (2616 born in 1996–2000 and 2851 born in 2001–2005).
Table 1 summarizes the distribution of GAs in the study population. No major changes were found in the numbers of live births and the numbers of preterm infants with GA of <32 weeks who survived 5 weeks through the study period. However, the proportions of extremely premature infants, that is, 5-week surviving infants with GA of <26 weeks and <28 weeks, increased significantly, by 58% and 26%, respectively, between 1996 to 2000 and 2001 to 2005 (2 test, P < .001).
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In Denmark, infants with GA of <32 weeks are screened for ROP. Therefore, we based our study population and subsequent analyses on such infants. However, to compare ROP incidences in Denmark with incidences in countries where BW of <1500 g or <1250 g is the main screening criterion, we also searched the NBR for infants born with BW of <1500 g, with valid data in the NBR (as defined above), who survived for
5 weeks. This yielded a population of 4748 infants with BW of <1500 g, which constitutes the denominator used for the calculations shown in Fig 5 and Table 2.
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Incidence of ROP Treatment
From the data in Table 1, it can be calculated that, in the 10-year period of 1996 to 2005, the incidence of ROP treatment was 2.1 cases per 10000 live-born infants. Among the sample of premature infants with GA of <32 weeks in 1996 to 2005, this incidence was 2.5% (135 of 5467 infants). It can be seen from Table 1 that the incidence of ROP treatment among such infants increased statistically significantly, from 1.3% in 1995 to 2000 to 3.5% in 2001 to 2005 (
2 test, P < .001). For the subgroups of infants with GA of <26 weeks and <28 weeks, these numbers were 7.3% and 5.0% in 1996 to 2000 and increased statistically significantly to 21.4% and 11.8%, respectively, in 2001 to 2005 (2 test, P < .001). Figure 5 shows the annual incidence of ROP treatment in the study period according to GA and BW. It is apparent that more-immature infants were treated for ROP in the latter half of the study period. To assess the contribution of demographic factors for the increased risk of ROP treatment, including increased immaturity in the latter half of the study period, we performed a multivariate analysis. In this analysis, we included birth in 2001 to 2005 as a risk factor, as well as the known risk factors for ROP treatment, that is, low GA, SGA, male gender, and multiple birth. The results of this analysis are shown in Table 3. The analysis confirmed a significant association of the already known risk factors with ROP treatment. However, even with adjustment for these risk factors, birth in the latter part of the study period was a highly significant risk factor, with an odds ratio of 2.4. Of the 100 infants treated for ROP in the latter part of the study period, the demographic neonatal parameters in the model accounted for 46 infants. The remaining 54 infants are to be explained by other, yet unknown, risk factors in the latter 5-year period.
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Visual Impairment Attributable to ROP
The search in the NRBVIC yielded 37 children born within the study period and registered with the diagnosis of ROP. We excluded 1 child not born in Denmark. To make comparisons over the study period, we excluded 5 children registered as visually impaired >2 years after birth (late detection). The population with early-detected visual impairment attributable to ROP among children born in Denmark in 1996 to 2005 thus consisted of 31 children. The population incidence of early-detected visual impairment caused by ROP in 1996 to 2005 was 5 cases per 100000 births in the general population, or 0.6% of the sample of premature infants who were born in the period with GA of <32 weeks and survived for
5 weeks (31 of 5467 infants). The early-detected sample consisted of 18 children born in 1996 to 2000 and 13 born in 2001 to 2005. No statistically significant difference in the proportions of early-detected, visually impaired children among premature infants was found between the 2 periods (2 test, P > .2). Of the 31 visually impaired children, 15 had recorded visual acuity of >0.1 in the better-seeing eye, 13 had visual acuity of 0.1 in the better-seeing eye, and exact information about the visual acuity was missing for the remaining 3. Of the 13 blind children (visual acuity of 0.1), 6 were born in 1996 to 2000 and 7 were born in 2001 to 2005. There was no statistically significant difference in the proportions of blind children among premature infants between the 2 periods (2 test, P > .5). Among the visually impaired children, 5 had never received treatment for ROP and were considered screening failures. These children had GAs between 25 and 31 weeks and BWs between 805 and 885 g. The screening failures represented 16% of early-detected visual impairment attributable to ROP. In the first half of the period, 18 children were entered in the registry, 4 (22%) of whom were screening failures; in the latter half of the period, 13 children were entered, with 1 (7%) screening failure. The proportions of screening failures in the population of premature, 5-week survivors did not differ significantly between the periods of 1996 to 2000 and 2001 to 2005 (2 test, P > .1). |
DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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In this study, we determined the most-recent 10-year incidence of ROP treatment in Denmark. The Danish treatment incidence corresponds well to that found in a neighbor Nordic country.13 The international ROP incidences reported previously depend critically on the selection criteria used to define the background population. Table 2 compares the incidences of T-ROP found in the present study with those found in recent international studies from other highly developed countries. For each study listed, we calculated the incidences of ROP treatment in our study population by using the selection criteria used in that previous study. The Early Treatment for Retinopathy of Prematurity study is included for comparison, although the end point, prethreshold disease, was different from the end point used in the other studies.12 It can seen from Table 2 that studies based on both centralized referral in geographically defined populations2,3,5,14,15 and studies based on single-center or multicenter populations reported incidences of ROP treatment are quite similar to ours, when common denominators are used.4,6,14,16,17 It is possible that infants with GA of
32 weeks but BW of <1500 g developed treatment-demanding ROP without receiving treatment and subsequently being registered in the NRBVIC and therefore remained undetected. However, for populations that are screened for ROP with a criterion of BW of <1500 g, Table 2 might underestimate the true Danish incidence. We found a more than twofold increase in the incidence of treated ROP cases in 2001 to 2005, compared with 1996 to 2000. This increase was most pronounced for the smallest infants (Fig 5). This confirms our hypothesis that the number of ROP treatments has increased since 2001. A similar trend was found in other recent studies, particularly for the smallest infants.3–6,18 In the 1990s, in contrast, the incidence of severe or treated ROP was reported to be constant or even declining.16,19–22
The incidence of early-detected visual impairment attributable to ROP found in the present study is similar to other reported values.9,10 Given the increased incidence of ROP treatment in 2001 to 2005, compared with 1996 to 2000, it is surprising that the number of children with visual impairment or blindness attributable to ROP did not increase, although the numbers are small and the possibility of a type II error cannot be excluded. There are several possible explanations for the present increase in the incidence of ROP treatment.
There was a tendency toward increased survival rates for the most-immature infants (GA of <26 weeks) in the latter half of the study period (Fig 4). Although this amounted to an excess survival of only 20 infants, these infants may be frailer, and thus have a higher risk of ROP than infants with similar GAs in the first half of the study period. Also, more extremely premature infants survived 5 postnatal weeks in the latter half of the study period (Table 1).
A multivariate analysis was performed to determine whether the increased number of extremely premature infants and changes in known risk factors for severe ROP could explain the increased incidence of ROP treatment found in 2001 to 2005, compared with 1996 to 2000. This analysis confirmed that low GA, male gender, and multiple birth were significant risk factors for ROP treatment.23–26 Because GA and BW are confounded (Fig 3), we did not include both parameters in the analysis, because it would be rather arbitrary whether the model assigned the risk of ROP treatment to low GA or low BW. Instead, we investigated SGA, which adds information about growth retardation. SGA was found to be a major significant risk factor for ROP treatment, as indicated previously.18,27,28 The multivariate analysis showed that birth in the latter half of the study period was a significant risk factor for ROP treatment, after adjustment for all other risk factors. The analysis also showed that only 17% of the increase in the incidence of ROP treatment could be accounted for by the observed changes in immaturity and other known risk factors. Therefore, the majority of the increased number of infants treated for ROP could not be explained by changes in investigated risk factors for ROP in the study population.
A slackening in the indications for treatment could also contribute to the increased incidence of ROP treatment in the latter half of the study period. Despite the appearance of the Early Treatment for Retinopathy of Prematurity study, it was our deliberate intention to maintain the T-ROP criterion for treatment throughout the study period.11,12 The same senior pediatric ophthalmologist (Dr Fledelius) participated in making the recommendation for ROP treatment in almost all cases. This ensured consistency in the indications for treatment throughout the period. The treatment reports in the infants' charts confirmed that no fundamental changes occurred in the indications for treatment during the 10-year period, as also indicated in a previous investigation.29 Occasional lack of adherence to this criterion was mainly attributable to difficulties in transport or local follow-up monitoring of the infant.
Another factor contributing to the increased incidence of ROP treatment might be a change in screening efficacy during the study period, leading to the discovery of more children in need of treatment. It is an inherent weakness in the current study that we cannot completely verify that each NICU in Denmark fully implemented the recommended ROP screening guidelines. Therefore, the denominator used to calculate the incidence of treated ROP is a study population of infants who should have been screened, rather than those actually screened. However, during the entire study period, screening at Rigshospitalet was performed according to the same criteria by the same senior pediatric ophthalmologist (Dr Fledelius). Significant changes in screening efficacy at this institution are therefore unlikely. If major changes in screening efficacy in the rest of the country had occurred, then an increased proportion of cases referred for ROP treatment, relative to cases identified at Rigshospitalet, would be expected. This was not the case; rather, the increase in the number of treated ROP patients was distributed evenly throughout the country (data not shown). It is therefore not likely that major changes in screening efficacy took place between the 2 parts of the study period. Furthermore, if the screening efficacy had increased in the latter half of the period, then the number of screening failures (ie, children who developed visual impairment attributable to ROP without having had treatment) would be expected to decrease in the latter half of the period. We did in fact find fewer screening failures in the latter part of the period (4 vs 1 cases), but this difference was not statistically significant. The numbers are quite small, however, and the possibility of a type II error definitely exists. Although we use the term screening failures, it should be noted that ophthalmologists in the NICUs had in fact seen all 5 children with early-detected visual impairment attributable to ROP. Although our 10-year incidence of screening failures of 16% seems high, and undoubtedly the Danish screening effort can be improved, other studies from the Netherlands and Finland found corresponding figures of 43% and 84%, respectively.9,10
The reliance on registry data, with their inaccuracies, is an inherent weakness of this study. The NBR lacked 0.3% of all live births in Denmark during the study period and, within the registry, we found 3.7% of the entries to have obvious errors, most likely in the registration of GA. However, errors of this magnitude had only marginal impact on the calculated incidences. Registration of visually impaired children in the NRBVIC is expected to have a high rate of compliance among all Danish health professionals, because this registration entitles the child and his or her family to social benefits and support. The visual acuity and diagnosis entered in this registry are assessed by an ophthalmologist and approved by the registry. Therefore, we considered this registry diagnosis reliable. We acknowledge that a few visually impaired children might not be registered.
Because neither changes in the number of surviving immature infants nor changes in single known risk factors for ROP treatment or screening efficacy could fully explain the observed increase in the incidence of ROP treatment, we suggest that changes in neonatal care might play a role. This is definitely an area in need of further study. Surfactant treatment and monitoring with pulse oximetry were introduced around 1990. Both were well implemented in 1996 and are unlikely to have a bearing on the increased incidence of treated ROP seen after 2001.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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This study highlights the importance of continuing surveillance of the incidence of ROP treatment. It also highlights the remarkable similarity of the incidences of ROP treatment across a number of highly developed countries, provided comparable denominators are used. We found that we are treating more infants for ROP now than we did a half-decade ago. The explanation lies partly in an increased number of surviving extremely premature infants and partly in increased numbers of infants being SGA, male, and part of multiple births. Other, yet unknown, neonatal risk factors in the latter half of the study period accounted for the majority of the observed increase in the incidence of treated ROP cases. Additional studies are warranted and currently are in progress.
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ACKNOWLEDGMENTS |
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This work was supported by grants from Værn om Synet Foundation, Velux Foundation, Dagmar Marshalls Foundation, Direktør Jacob Madsen og Hustru Olga Madsens Foundation, P. A. Messerschmidt og Hustrus Foundation, and Hede Nielsens Foundation.
We thank Erik Scherfig, MD, Medical Anatomic Institute, Panum Institute (Copenhagen, Denmark), for valuable discussion.
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FOOTNOTES |
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Accepted Jun 20, 2007.
Address correspondence to Carina Slidsborg, MD, Department of Ophthalmology (2061), National University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. E-mail: carinaslidsborg{at}hotmail.com
The authors have indicated they have no financial relationships relevant to this article to disclose.
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