Preterm-associated visual impairment and estimates of retinopathy of prematurity at regional and global levels for 2010.

BACKGROUND: Retinopathy of prematurity (ROP) is a leading cause of potentially avoidable childhood blindness worldwide. We estimated ROP burden at the global and regional levels to inform screening and treatment programs, research, and data priorities. METHODS: Systematic reviews and meta-analyses were undertaken to estimate the risk of ROP and subsequent visual impairment for surviving preterm babies by level of neonatal care, access to ROP screening, and treatment. A compartmental model was used to estimate ROP cases and numbers of visually impaired survivors. RESULTS: In 2010, an estimated 184,700 (uncertainty range: 169,600-214,500) preterm babies developed any stage of ROP, 20,000 (15,500-27,200) of whom became blind or severely visually impaired from ROP, and a further 12,300 (8,300-18,400) developed mild/moderate visual impairment. Sixty-five percent of those visually impaired from ROP were born in middle-income regions; 6.2% (4.3-8.9%) of all ROP visually impaired infants were born at >32-wk gestation. Visual impairment from other conditions associated with preterm birth will affect larger numbers of survivors. CONCLUSION: Improved care, including oxygen delivery and monitoring, for preterm babies in all facility settings would reduce the number of babies affected with ROP. Improved data tracking and coverage of locally adapted screening/treatment programs are urgently required.

Retinopathy of prematurity and the oxygen conundrum: lessons learned from recent randomized trials.

Emerging data from randomised controlled trials of different pulse oximeter oxygen saturation (SpO(2)) target ranges shows that higher SpO(2) targets are associated with a higher risk of severe retinopathy of prematurity. However, the trials have also shown that higher SpO(2) targets are associated with improved survival. In the light of these results and pending the full results for long-term outcome, it is recommended that oxygen saturation targets for preterm infants of gestational age less than 28 weeks at birth should be maintained at or more than 90%.

Dr Mary Crosse, OBE, MD (1900-1972) and the premature baby.

On behalf of Birmingham's Department of Public Health, Dr Crosse developed the Sorrento Premature Baby Unit in 1931 and pioneered the modern care of these small newborn infants in Britain.

Optimal oxygen saturation for preterm babies. Do we really know?

Oxygen is the most commonly used 'drug' in neonatal units as an integral part of respiratory support. It has also been known for half of the century that it is easy to damage the eyes of preterm infants by giving too much oxygen especially in the first few weeks of life. Despite this knowledge there is still a wide variation in approaches to oxygen monitoring within neonatal units. A randomized controlled trial conducted more than 50 years ago first made clinicians aware of 'oxygen toxicity' in preterm infants, but no other controlled trial has ever been conducted since to clarify how much oxygen infants really need, or what oxygen saturation level is optimal in caring these preterm babies. Perhaps time has come for clinicians to resolve this 'uncertainty' by well-designed randomized trials.

The discovery of retrolental fibroplasia and the role of oxygen: a historical review, 1942-1956.

Nearly 50 years after it was thought to be conquered, retinopathy of prematurity (ROP) continues to cause vision disturbances and blindness among prematurely born infants. During the 1940s and early 1950s, researchers and caregivers first identified and struggled to eliminate this problem, which seemed to come from nowhere and was concentrated among the most advanced premature nurseries in the U.S. Research studies initially identified many potential causes, none of which could be proved conclusively. By the mid 1950s, oxygen was identified as the culprit, and its use was immediately restricted. The rate of blindness among premature infants decreased significantly. ROP was not cured, however. By the 1960s, it had reappeared. The history of ROP serves to remind us that, despite our best intentions, the care and treatment of premature newborns will always carry with it the possibility of iatrogenic disease. This caution is worth remembering as we work to expand the quality and quantity of clinical research.

The earliest case of retinopathy of prematurity?

Retinopathy of prematurity (ROP) is a well-recognized condition in premature babies born today and in the recent past. One would not normally expect to come across evidence of its existence among older patients. We present a case of apparent regressed ROP in a lady born in May 1939, prior to the documented reports of the first cases.

Oxygen monitoring in preterm babies: too high, too low?

A small randomised trial in 1952 showed that excess oxygen use might well be causing a major epidemic of retinal blindness in preterm babies. That single study of just 65 babies was enough to throw doubt on a longstanding treatment strategy of oxygen therapy and highlighted just how powerful a tool the randomised controlled trial could be. Confirmatory evidence from a co-operative trial 4 years later involving 212 babies banished all residual doubt and we should reproach ourselves that we have still not learnt after 50 years how to optimise oxygen delivery to the preterm baby, making further use of this powerful research tool. Two well-conducted trials have recently shown that avoiding subclinical hypoxaemia (a fractional SaO(2) of less than 92%) in babies more than a month old does nothing to improve later growth or development. It is now time the same question was asked of babies less than a month old. This is particularly important in babies of less than 28 weeks' gestation, who currently remain at serious risk of chronic lung disease and permanent retinal damage.

Doctors and the health industry: a case study of transcutaneous oxygen monitoring in neonatal intensive care.

This case study presents an industry perspective on medical innovation. Introduced as a scientific breakthrough in the late 1970s, transcutaneous oxygen monitoring was rapidly adopted for routine use in neonatal intensive care. But plagued by technical problems, it was within a decade being replaced by pulse oximetry, a still more recent technology. Its use in efforts to prevent retinopathy of prematurity, an eye disease of preterm newborns often leading to blindness, proved disappointing. The project included interviews with executives and design engineers of companies marketing the device, with investigators who had pioneered the technology, and with senior practicing neonatologists. The findings, reflecting complexity and uncertainty, are relevant to issues concerning health care in the United States and other developed nations. They centre on the key role and ultimate responsibility of the medical profession, with a need for greater attention to the scientific training of health care workers, as perceived by members of the medical device industry. The views of senior investigators are integrated into the picture, with discussion of major challenges faced by the medical community.

Oxygen as a cause of blindness in premature infants: "autopsy" of a decade of errors in clinical epidemiologic research.

Several intellectual "autopsies" have recently reviewed errors in clinical epidemiologic studies of causation, such as the original claim that amyl nitrite "poppers" caused AIDS. The current autopsy was done to determine why it took more than a decade--1942 to 1954--to end an iatrogenic epidemic in which high-dose oxygen therapy led to retrolental fibroplasia (RLF) in premature infants, blinding about 10,000 of them. The autopsy revealed a museum of diverse intellectual pathology. When first noted, RLF was regarded as neither a new disease nor a postnatal effect. In early investigations, the ophthalmologists did not establish explicit criteria for diagnosis and confused RLF with malformations previously seen in full-term infants. Because the patients were not referred until months after birth, the ophthalmologists assumed that the lesion, which resembled an embryologic structure, must have occurred prenatally. Other events suggesting a prenatal cause for RLF were its strong statistical associations with fetal anomalies, multiple gestations, and maternal infections. Although these events were also associated with prematurity, it was ignored when the RLF cases were compared with controls who were mainly full-term infants. The postnatal timing of RLF was eventually recognized when investigators did cohort studies in premature infants and found that RLF could develop in eyes that were normal at birth. As the search for a cause turned to events occurring after birth, statistical associations were produced for agents such as light, vitamins, iron, vitamin E deficiency, and hypoadrenalism. Each study had its own methodologic flaws: controls were missing for light; co-maneuvers were ignored for vitamins and iron; objective diagnosis was not used for vitamin E deficiency; and the research on hypoadrenalism contained biases in susceptibility and detection as well as problems of a competing outcome event. When the role of oxygen administration was first considered, the statistical association with RLF was stronger for vitamin- and iron-therapy than for oxygen. In addition, many investigators were dissuaded by contradictory evidence from institutions in which RLF was either absent despite high-dose oxygen or persistent despite reduced dosage. The contradictory evidence was later regarded as erroneous because of unsatisfactory delivery systems for the oxygen or failure to check the actual oxygen concentrations. An alternative explanatory hypothesis, rejecting the role of high-dose and long-duration oxygen, was the idea that RLF was due to "relative hypoxia", produced by overly rapid weaning from oxygen therapy rather than the duration of oxygen treatment itself.(ABSTRACT TRUNCATED AT 400 WORDS)

[The Annette von Droste-Hülshoff syndrome]. / Das Annette von Droste-Hülshoff-Syndrom.

In the past, physicians interested in the great poetess Annette von Droste-Hülshoff argued as to whether she suffered from chronic tuberculosis or Graves' disease. We can now explain her physical appearance without any difficulty, thanks to our knowledge of the oculopathy of prematurity. Annette von Droste-Hülshoff was a premature infant delivered in the seventh or eighth month, and there is no doubt that she suffered from severe myopia and myopic exophthalmos. Moreover, she had a divergent pseudosquint, as can be seen in some portraits of her; this was very probably caused by a dragged disc or dragged retina (i.e., displacement of the macula). The increasing number of outstanding talents seen among premature infants, who now grow up thanks to the incubator, reminds us that Annette von Droste-Hülshoff's vast knowledge and her poetic genius were an expression of her prematurity, which is documented in biographies and by cryptic autobiographical evidence.