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The three epidemics of ROP: A growing public health problem

Epidemiology of retinopathy of prematurity - past and present.
Epidemiology is the study of the magnitude, distribution, determinants, and application of interventions to control diseases and conditions within a population. It can be used to answer four important questions about a disease or condition. How many people in the population are currently affected, and how many new cases might occur in the future, who is the most affected, what are the underlying causes and risks for developing the condition, and what can be done to control the condition? Understanding the epidemiology of retinopathy of prematurity can help programs improve how they prevent, detect, and treat sight-threatening ROP. Let’s consider the four questions in turn. Question one, part a, how many preterm infants are at risk of developing ROP?
Each year approximately 15 million babies are born preterm, that is with a gestational age of less than 37 weeks. Being born preterm raises the risk of ROP. Preterm births are grouped by gestational age into three categories, moderate or late; between 32 and 36 weeks, very preterm; between 28 and 32 weeks, and extreme preterm babies; who are born before 28 weeks gestational age. Almost 2.3 million preterm babies are born very or extremely preterm each year, that is before 32 weeks gestational age or eight or more weeks preterm.
South Asia is the region with the largest number of preterm births, over 5 million each year.
The countries with the largest number of preterm births are India, China, Nigeria, Pakistan, Indonesia, and the USA. The preterm birth rate measures the number of live births before 37 completed weeks per 100 live births.
The highest preterm birth rates are in the sub-Saharan African and southern Asian regions, where they reach 15%. Question one; b, how many preterm babies develop ROP? To estimate the global burden of ROP, researchers used a meta-analysis. This combines data from multiple sources to create a model of the risk of ROP and of subsequent visual impairment for surviving preterm babies. The researchers applied 2010 data on live preterm birth and survival rates from 184 countries to the model. The analysis estimated that globally around 850,000 preterm infants survived neonatal care in 2010. Of these, about 185,000 babies developed some degree of ROP. Almost 54,000 developed ROP which needed treatment, that is sight-threatening ROP.
And about 32,300 infants became blind or visually impaired from ROP. These estimates are likely to be conservative and an underestimate.
All regions of the world are affected by ROP. East Asia, Southeast Asia, and the Pacific are the regions with the highest number of preterm babies who survive and the highest number who develop visual loss from ROP. Across some regions of the world, such as sub-Saharan Africa and some of the least developed countries in Asia, improving survival rates for preterm babies is also placing more infants at risk of vision loss from ROP. In other regions, the number of ROP cases may fall as the quality of neonatal care improves and ROP screening and treatment become the standard of care.
Question 2, which preterm infants are most affected by ROP? Prematurity is responsible for 18% of under five mortality worldwide, which is the single biggest cause of death in newborns. Governments around the world have responded to this alarming issue by increasing the provision of neonatal services. However, significant gaps in coverage, equity, and quality of care remain, between and within countries. As survival rates increase, the risk of developing ROP, particularly sight-threatening ROP, increases with increasing prematurity. This risk also increases if the quality of the neonatal care of preterm babies receive is less than ideal.
Epidemiological studies have found regional patterns of birth weight and gestational age amongst babies who develop sight-threatening ROP.
In high-income countries, approximately 20% of babies born with a gestational age of less than 32 weeks develop some degree of ROP. And about 2% to 3% of these babies develop sight-threatening ROP. In middle- and low-income settings, approximately 40% of babies born with a gestational age of less than 32 weeks develop some degree of ROP. And studies in middle income countries have found that more than 10% of babies with some ROP go on to develop sight-threatening ROP. A study compared global ROP data from 1996 to 2002 against the standard ROP screening criteria used in high-income countries. These standards recommend screening for ROP in preterm infants with birth weight less than 1,500 grams and gestational age less than 32 weeks.
The study found that infants who develop sight-threatening ROP in low- and middle-income countries show different patterns of birth weight and gestational age than in high-income countries. The implication of these findings is that screening guidelines developed for high-income countries will not suit all situations.
Low- and middle-income countries have a wider range of birth weights in infancy developed ROP. This often means that larger babies develop sight-threatening ROP. They also have a wider range of gestational ages than inference in high-income countries. This results in gestationally older infants developing sight-threatening ROP than in high-income countries. The main reason for the regional differences seen in the levels of sight-threatening ROP is the variation in the quality of neonatal care. In units providing very high quality care, only extremely preterm infants, weighing less than 1,000 grams at birth, develop sight-threatening ROP, as seen in high-income countries. In units which provide less good care, extremely preterm infants are much more likely to die.
And larger and more mature babies can also develop sight-threatening ROP as seen in middle income countries. The implications of this are twofold. Firstly, much can be done to reduce the risk of sight-threatening ROP by improving the quality of neonatal care. And secondly, bigger more mature infants need to be screened for ROP in low- and middle-income countries, as well as in high-income countries. Question 3, what are the underlying causes of ROP? The single most important risk factor for ROP is prematurity. The more preterm the infant, the greater the risk for ROP, as they have less well-developed retinal blood vessels and are also likely to be sicker or unstable.
The other risk factors for ROP are defined as occurring before birth, prenatal, or in the first few hours, days, or weeks of life after birth, postnatal. Prenatal risk factors for ROP are linked to the medical management of pregnant women. For example, lack of corticosteroids to reduce the threat of preterm delivery.
The postnatal risk factors for ROP are: poorly administered supplemental oxygen from immediately after birth; sepsis, whether early within 48 hours of birth or late; failure to gain weight, transfusion with adult blood, and factors which make babies unstable, such as low body temperature, pain, loud noise; and lack of supportive care, such as kangaroo care, swaddling, and nesting.
Improving the quality of neonatal care has the potential to greatly reduce the risk of sight-threatening ROP, particularly in more mature infants in middle income countries. Question 4, what can be done to control ROP, that is to prevent or to treat it? There are three broad public health strategies to reduce the risk of vision loss from ROP.
Primary prevention: interventions which prevent ROP from occurring in the first place.
Secondary prevention: early detection, particularly in high risk infants; high quality treatment of sight-threatening ROP; and follow-up for other complications, such as myopia, short-sightedness.
Tertiary prevention: low vision interventions short-sightedness, which improve visual function or rehabilitation for irreversibly blind children.
To prevent blindness from ROP requires action across the health service; from good antenatal services, to quality of neonatal care, early detection of ROP, prompt treatment and follow-up. This requires a well-informed team approach, using a standard guideline along with parental support. In the UK, the recorded incidents of ROP increased tenfold between 1990 and 2011 from 12.8 to 125.5 per 1,000 low birth weight babies. Several factors contributed to this, an increasing number of preterm babies born and surviving and an increased recognition of ROP and the use of protocols for screening. ROP treatment in the UK over the same period saw a nine-fold increase, similar to that seen in ROP itself. This highlights the importance of strengthening ophthalmic care alongside neonatal services.
In summary, the risk of ROP increases with increased prematurity. Improved survival rates for preterm babies are likely to increase the incidence of ROP. This is clearly seen in many parts of Southeast Asia and Africa. Infants developing sight-threatening ROP in low- and middle-income countries have a wider range of birth weights and gestational ages than in high-income countries. Improving the quality of neonatal care can greatly reduce the risk of sight-threatening ROP, particularly in more mature infants in low- and middle-income countries This highlights the need to take a team approach to ROP prevention. Public health strategies are needed to reduce the risk of vision loss from ROP.

The first ROP epidemic occurred in high-income countries in the 1940s and 1950s. It was associated with the improving survival rates of moderately preterm babies (32 to <37 weeks gestational age) with very low birth weights (<1,500 grams) who were being given unrestricted oxygen supplementation.

In the second ROP epidemic in the 1970s, the dominant feature was the extreme prematurity (< 28 weeks gestational age) of the affected babies. However, reported rates of ROP varied widely between different neonatal intensive care units (NICUs) including in high-income settings and after adjusting for case mix. This can be explained by differences in the quality of care being provided to preterm babies at the time, such as the variety of approaches taken to achieving and monitoring oxygen saturation targets.

In the early 1990s, an emerging third epidemic of ROP related blindness in children in low- and middle-income countries was initially detected by examining children in schools for the blind. This data was combined with global estimates of the prevalence of blindness to roughly calculate a global magnitude of ROP blindness of at least 50,000 children aged <15 years who were blind from ROP, with the highest proportion and numbers being in Latin America. In the late 90s, the risk of blindness from ROP in different regions and countries was predicted by plotting the proportion of blindness due to ROP against infant mortality rates. This showed that babies who develop ROP in low- and middle-income countries had a far wider range of birth weights and gestational ages than was the case in the UK, Canada or the USA.

Worryingly, the evidence suggests that this trend continues today. More accurate estimates have been derived from a 2010 systematic analysis of regional data which assessed:

  • The prevalence of preterm birth amongst live births
  • The number of preterm babies who received neonatal intensive care and survived
  • The number of these survivors who were estimated to have developed ROP, and
  • Those who were then affected by visual impairment.

The study found that, globally, 16% of preterm survivors (>184,700 babies) born at <32 weeks gestational age are estimated to have some degree of ROP, with 3% (32,300) developing associated visual impairment or blindness. The results also highlighted large regional differences in the distribution and severity of ROP.

Reasons for the third, ongoing epidemic of ROP blindness

  • Rates of preterm birth are often higher in middle income countries than in high income countries
  • A high proportion of women are delivered in health care facilities in middle income countries and premature babies are, therefore, likely to be admitted to neonatal intensive care
  • Rates of severe ROP are higher in preterm babies in low- and middle-income countries which suggests that they are being exposed to risk factors which are now largely controlled in high income countries.

The evidence indicates that ROP is a growing global public health problem and that a wide range of programmatic control measures are needed from before birth to detect and treat ROP in preterm babies.

Watch the video to learn more about the epidemiology of ROP – its magnitude, distribution, determinants (causes) and how it is controlled – and understand the global ROP data trends and future projections.

What ROP data is kept in your setting? How is it used to guide the control of ROP?

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Retinopathy of Prematurity: Practical Approaches to Prevent Blindness

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