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Incidence of retinopathy of prematurity in Lothian, Scotland, from 1990 to 2004
  1. C Dhaliwal1,
  2. B Fleck2,
  3. E Wright3,
  4. C Graham4,
  5. N McIntosh5
  1. 1
    Centre for Reproductive Biology, Queens Medical Research Institute, Edinburgh, UK
  2. 2
    The Royal Hospital for Sick Children, Edinburgh, UK
  3. 3
    Princess Alexandra Eye Pavilion, Edinburgh, Scotland
  4. 4
    Wellcome Trust Clinical Research Facility, University of Edinburgh, Western General Hospital, Edinburgh, UK
  5. 5
    Department of Child Life and Health, Edinburgh, UK
  1. Dr C Dhaliwal, Room W1.12, Centre for Reproductive Biology, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK; cdhaliwa{at}staffmail.ed.ac.uk

Abstract

Background: To report the trends in incidence of retinopathy of prematurity (ROP) within Lothian, a geographically defined region in southeast Scotland over a 15-year period from 1990 to 2004.

Methods: This was a prospective observational study of all infants born with gestational age <32 weeks and/or birth weight <1500 g who were born to mothers resident in Lothian between 1 January 1990 and 31 December 2004. Eligible infants underwent eye screening by two experienced paediatric ophthalmologists (BF and EW). Lothian population data were obtained from the Scottish Health Service. The trends in survival rates, incidence and treatment of ROP were analysed from 1990 to 1994, 1995 to 1999 and 2000 to 2004.

Results: Lothian population data showed a steady decline in the number of live births from 1990 to 2004. The proportion of babies born with birth weight <1500 g and/or gestational age <32 weeks remained constant (p = 0.271 using χ2 test), although the proportion of these babies surviving to 42 weeks corrected gestation increased from 1990 to 2004 (p<0.001 using χ2 test for trend). There was a statistically significant linear trend towards a reduction in the number of babies undergoing treatment for ROP throughout the study period (p<0.01 using χ2 test for trend). A reduction in the incidence of any degree of ROP and severe (stage 3 or greater) ROP was also observed although this did not reach statistical significance.

Conclusions: There was a significant increase in survival of infants with birth weight <1500 g and/or gestational age <32 weeks together with a significant reduction in the number of infants treated for ROP in the Lothian region of southeast Scotland from 1990 to 2004.

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Retinopathy of prematurity (ROP) is a disorder of retinal vascular development in premature infants. It is a major cause of childhood blindness worldwide.1 The trends in incidence of ROP over time have been the subject of much debate. Since ROP was first described in 1942,2 there have been two notable epidemics within the developed world.36 The first was seen in the early 1950s and was associated with exposure to high oxygen concentrations for prolonged periods of time.3 The second epidemic developed in the 1980s and was related to increased survival of very low birth weight (BW<1500 g) infants associated with advances in neonatal medicine.47 Many centres have reported a decline in the incidence of ROP in the 1990s and early 2000s.8 11 Since then, there has been an increasing body of evidence demonstrating that a modest reduction in target oxygen saturation levels is associated with a reduction in the incidence of severe ROP.1215 There has, however, been a marked lack of population-based studies, which will report the longer term trends in incidence of ROP most accurately.1621

We report the trends in incidence of ROP within Lothian, a geographically defined region in southeast Scotland over a 15-year period from 1990 to 2004.

MATERIALS AND METHODS

Subjects

This was a prospective observational cohort study. The population of the study consisted of all infants eligible for eye screening who were born to mothers’ resident within the Lothian region of southeast Scotland during the study period of 1 January 1990 – 31 December 2004. All infants born with gestational age <32 weeks and/or birth weight <1500 g who survived until eye screening commenced were eligible. Eligible Lothian babies born outside Lothian and transferred back into Lothian during eye screening were included.

The total population of Lothian increased steadily from approximately 745 000 in 1990 to 790 000 in 2004. There were approximately 9800 livebirths in 1990 which decreased over the years to 8300 in 2004. During the study period infants were born at one of three hospitals:

  • The Simpson Memorial Maternity Pavilion/the New Royal Infirmary, Edinburgh: Level 3 South East Scotland Regional Neonatal Unit with over 6000 live births per year. Approximately 520 infants admitted to neonatal unit each year. Hospital moved to the site of the New Royal Infirmary, Edinburgh in summer 2002.

  • The Eastern General Hospital, Edinburgh: Level 2 neonatal unit with approximately 2200 live births and 250 babies admitted to the neonatal unit each year. This hospital closed in April 1998.

  • St Johns Hospital, Livingston: Level 2 neonatal unit with approximately 2400 live births and 170 admissions to the neonatal unit each year.

Nursing staff in these hospitals referred all eligible babies to the ophthalmology team. Ophthalmologists recorded the date of birth, sex, gestational age, birth weight and maximum severity of ROP reached in any one eye for every baby examined. This information was prospectively stored on a database. Each hospital throughout the period of study used oxygen saturation monitor thresholds of 86–94%.

Lothian population epidemiological data

Epidemiological data was obtained from the Information Services Division (ISD) of the Scottish Health Service, which accessed the Scottish Morbidity Record (SMR02). Their figures differ from our Lothian hospital data and our results are based on both sources. Unfortunately, we could not cross-check our data with ISD due to patient confidentiality and data protection legislation, thus a small discrepancy remains.

Eye examination schedule

Screening and treatment (if required) was carried out by two dedicated paediatric ophthalmologists (BF and EW). Eligible infants were first examined at 4–6 weeks chronological age, or 34 weeks corrected age, whichever was earlier. Screening was continued fortnightly until full retinal vascularisation. Examinations were performed weekly if “prethreshold” disease was found (see below for definition).

Eye examination technique

Pupils were dilated with topical phenylephrine 2.5% and tropicamide 0.5% applied 60 min and 30 min prior to eye examination. Indirect ophthalmoscopy was performed using a binocular indirect ophthalmoscope and 28 Dioptre lens. A lid speculum and scleral indenter were routinely used. The entire retina was examined, including the periphery throughout 360°. Retinopathy was graded according to the International Classification of ROP.22 The stage of ROP (1–5), zone of vascularisation, number of clock hours of ROP and presence or absence of “plus” disease was documented in both the eye logbook and patient medical notes. “Plus” disease represented significant dilatation and tortuosity of posterior pole blood vessels.22 “Threshold” ROP referred to five or more contiguous or eight or more cumulative clock hours of stage 3 ROP in zones 1 or 2 in the presence of “plus” disease.22 “Prethreshold” disease consisted of any stage 3 disease less extensive than threshold, or stage 2 disease in the presence of “plus”.22 All eyes examined with “threshold” ROP were treated with cryotherapy in 1990–1991 and with diode laser therapy from 1992 onwards. From January 2005 new treatment criteria were used following the publication of the Early Treatment For Retinopathy Of Prematurity (ETROP) study.23 The study was therefore terminated at the end of 2004.

Statistical analysis

For analysis, the maximum severity of ROP in either eye for an individual infant was recorded. The 15-year study period was divided into three 5-year epochs: 1990–4, 1995–9 and 2000–4. Statistical analysis was performed using the GraphPad InStat programme (GraphPad Software, California, USA). Contingency tables were analysed using the χ2 test (χ2) and χ2 test for trend (χ2 trend). As birth weights and gestational ages did not appear to follow a normal distribution, the Mann–Whitney test was used to compare the missing eligible babies with those of the study population. The Kruskal—Wallis test was used to compare the birth weights and gestational ages of the study population in each of the three epochs. In all cases a p value <0.05 was taken to indicate statistical significance.

The Lothian Research Ethics Committee were contacted and it was declared that no ethical approval was required for this research.

RESULTS

Lothian population epidemiological data—supplied by ISD (table 1)

The proportion of babies born with birth weight <1500 g and/or gestational age <32 weeks who survived to 42 weeks’ corrected gestational age (CGA) has increased from 1990 to 2004 (p<0.001 using χ2 trend). This increase in survival is evident despite the proportion of these babies being born remaining unchanged (p = 0.271 using χ2).

Study population—from Lothian hospitals data

During the study period, there were 1450 eligible babies registered for eye screening; 77 (5%) were discharged home prior to eye screening, or failed to attend outpatient eye screening. There were insufficient medical records from 10 (0.7%) babies. Thus complete data were available on 1363 infants (1363/1450, 94% of eligible population). ISD reported a total of 1636 babies from 1990 to 2004 with birth weight <1500 g and/or gestational age <32 weeks where the baby survived to CGA 42 weeks or more (table 1). Therefore, a discrepancy of 186 babies remains between our hospital data and ISD data. We could not access details on these babies due to patient confidentiality and data protection legislation and therefore could not cross-check our hospital records with ISD.

Table 1 Lothian population epidemiological data (supplied by ISD Scotland)

The median gestational age for the Lothian hospitals study population (1363) was 29 weeks, (interquartile range 28–31), median birth weight was 1240 g (interquartile range 965–1490). The study population comprised 54% boys. The median gestational age of the missing eligible babies (enough data only from 77 discharged babies) was 31 weeks (interquartile range 30–32) and median birth weight was 1467 g (interquartile range 1340–1675). Using the Mann–Whitney test we found that the 77 babies had a significantly higher gestational age (p<0.001) and also a higher birth weight (p<0.001). These baseline characteristics were expected as only the more mature and heavier babies would have been discharged prior to commencement of eye screening.

The baseline characteristics of infants in the three time epochs, 1990–4, 1995–9 and 2000–4, were also calculated. There was no evidence of statistically significant differences in birth weight (Kruskal–Wallis, p = 0.48) or gestational age at birth (Kruskal–Wallis, p = 0.09) between the three cohorts.

Incidence and severity of ROP in Lothian hospitals study population (table 2)

Table 2 Incidence of retinopathy of prematurity (ROP) in Lothian hospitals study population (1363 babies)

One baby in 1999 developed stage 4 ROP after laser treatment. No babies developed stage 5 ROP during the study period. The heaviest baby treated weighed 1190 g at birth and the most mature baby treated was 30 weeks’ gestation at birth.

Incidence and severity of ROP in Lothian hospitals study population for birth weight categories (tables 3 and 4)

Table 3 Incidence of retinopathy of prematurity (ROP) in Lothian hospitals study population with birth weight <750 g and 750–999 g
Table 4 Incidence of retinopathy of prematurity (ROP) in Lothian hospitals study population with birth weight 1000–1249 g and 1250–1499 g

From Lothian hospitals study population data, a total of 1032 babies with birth weight <1500 g underwent eye screening from 1990 to 2004. The remaining 331 babies had gestational ages <32 weeks but birth weights >1500 g and were not included in this analysis. A trend towards a greater proportion of babies with birth weight <750 g having no ROP (p = 0.03) was observed, and a reduced proportion of these babies required treatment (p<0.01). The incidence of severe ROP in babies with birth weight 1000–1249 g and 1250–1499 g was consistently low and there was a trend towards fewer 1250–1499 g birth weight babies having any ROP (p = 0.04). No statistically significant trends from 1990 to 2004 were observed for babies with birth weight 750–999 g and 1000–1249 g.

Incidence and severity of ROP in Lothian hospitals study population for gestational age categories

Similar trends were observed when considering the babies in gestational age categories (see data supplement online).

DISCUSSION

What is already known on this topic

  • Many centres are now reporting a reduction in the incidence of retinopathy of prematurity (ROP).

  • However very few population-based studies have been published which accurately report the longer-term trends in ROP incidence.

What this study adds

  • This 15-year population-based study shows a significant increase in survival of infants with birth weight <1500g and/or gestational age <32weeks together with a significant reduction in the number of infants undergoing treatment for ROP.

  • There was also a trend towards a reduced number of infants with any stage of ROP and severe (stage 3 or greater) ROP.

The changing trends in the incidence of ROP have been the cause of much debate. Improved survival rates for premature infants led to the concern that the incidence of ROP might increase.6 24 Conversely, improved neonatal care led to a reported decrease in the incidence of ROP in some centres.8 1315 Our prospective population based study has found a significant reduction in the number of babies treated for ROP from 1990 to 2004. A reduction in the overall incidence of any degree of ROP and severe ROP was also observed. We have also seen an increase in overall survival in babies with birth weight <1500 g or gestational age <32 weeks.

Our observed changes are based on a complete population rather than single hospital data and therefore referral and inclusion bias should be eliminated. Interobserver variation should be minimal for detection of severe ROP as only two examiners examined the population over the 15-year period and both were experienced paediatric ophthalmologists. The methods of ophthalmoscopic examination for ROP and the classification system used were the same for the whole study period. We have not, however, analysed our incidence of mild (stage 1 or 2) ROP, as these data are less robust due to likely inherent observer error in scoring these lesser grades. There may have been an under-reporting of “any degree of ROP” and a related over-reporting of “no ROP” as a consequence of failure to detect minor degrees of ROP. The context of this prospective data acquisition was as a clinical service rather than a precisely defined epidemiological project as in other studies.17 We did not formally record ethnicity but results from the 2001 census in Scotland report the Scottish population as being 98% Caucasian, 1.4% Asian and 0.6% African Caribbean and other ethnic background.25 There was minimal movement of babies between different centres. Oxygen saturation monitors were introduced in the late 1990s and the target limits have always been 86–94%. Arterial catheters were infrequently used throughout the study period with the target partial pressure of oxygen being 6–10 kPa.

Recent population studies report differing trends in the incidence of ROP. Chiang et al report a 20.3% incidence of any ROP in infants with birth weight <1500 g born in New York State between 1996 and 2000 which is a similar incidence to the present Lothian study.20 Larsson et al compared ROP rates during 1988–90 and 1998–2000 in Sweden and found no change in incidence of any ROP and no change in severe ROP in infants with birth weight <1500 g.26 Todd et al studied the incidence and treatment of severe ROP in New South Wales and the Australian Capital Territory from 1992 to 2002.19 They found a considerable increase in severe ROP in infants ⩽24 weeks’ gestation (42% to 54%) together with an increase in treatment for severe ROP (19% to 24%). In infants of 25–26 weeks’ gestation there was a marked decrease in severe ROP (26% to 19%) and there was no change in infants with gestational age 27–29 weeks. In the most recent population-based study to be carried out in the UK, Hameed et al21 reported on severe ROP in Leicestershire from 1990 to 1999 in infants with birth weight ⩽1250 g. They found an increase in severe ROP from 4% in 1990–4 to 12% in 1995–9. This increase in severe ROP was also observed in infants with birth weight <750 g. This is very different from our findings as we observed a reduction in the incidence of severe ROP in babies <750 g. The reason for the different outcomes is unknown but the incidence of severe ROP may be influenced by relatively minor changes in neonatal care policies and practice.

The papers discussed above are all population studies although most incidence papers published have observed the trends in either a single hospital or a group of hospitals. These findings can be difficult to relate to the population as a whole due to local regional differences in survival rates, neonatal management and ethnicity, but large hospital-based studies over long periods of time still provide useful information. Rowlands et al found a significant reduction in the incidence of severe ROP from 1989 to 1998 in a level 2 neonatal unit in London.9 Hussain et al reported on a similar time period (1989–97) from a level 3 neonatal unit in the USA and found an incidence of 21% for any stage ROP and 5% for severe ROP.8 These are very similar to our findings.

In the past decade, several publications have highlighted the role of oxygen free radicals in several neonatal disease processes, as well as ROP.2729 As a result, many neonatal units have implemented new oxygen saturation policies to reduce the amount of supplemental oxygen given to premature babies. Several large centres have reported a significant decrease in the incidence of severe ROP following introduction of lower oxygen saturation targets.12 14 15 We did not change our oxygen saturation policy throughout the period of the study.

In summary, we have seen an increase in survival of preterm infants, a reduction in the incidence of any degree of ROP, severe ROP and a marked reduction in treatment for ROP in Lothian from 1990 to 2004. The past 20 years have seen dramatic advances in obstetric and neonatal care with routine administration of antenatal corticosteroids for premature labour, use of surfactant therapy, new methods of neonatal mechanical ventilation, introduction of continuous pulse oximetry, use of computerised monitoring systems and advances in neonatal nutritional support. It is highly probable that these advances are responsible for the overall decreasing incidence of ROP.

Acknowledgments

Many thanks to the charity Piggybankkids, which funds the Jennifer Brown Research Laboratory and the work done by CD. Thanks to M Fleming, E Shanks and other members of the ISD team for providing us with the population data.

REFERENCES

Footnotes

  • Competing interests: None.

  • Funding: The charity Piggybankkids pays CD’s salary via the University of Edinburgh; BF: NHS Scotland; EW: retired May 2007; CG: the University of Edinburgh; NMc: retired May 2007.

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