An alert English nurse in the middle '50s noticed that newborn infants lying in bassinets placeó near windows had less iaunóice than those in darker parts of- the nursery. Following up on the nurse's observation, a physician, R. J. Cremer, reported that by exposing babies to sunlight or artificial light, bilirubin levels were markedly reduced.1
There was nothing new about phototherapy. In 1903 a Nobel Prize was awarded to Niels R. Finsen of Denmark, who had developed light therapies to prevent pockmarks of smallpox and to treat a form of tuberculosis of the skin. But, as time went on, these treatments were supplanted by superior ones, and phototherapy acquired unsavory associations - with quacks, "magic-light boxes" and panaceas. This new application in England was clearly respectable. It spread rapidly and significantly reduced the use of difficult exchange transfusions. By 1974, 57 per cent of short-term general and maternity hospitals in the United States used phototherapy.
Hyperbilirubinemia of the newborn, with the attendant risk of bilirubin encephalopathy, is a major problem in nurseries throughout the world. Some jaundice is common in newborn infants, whose immature livers do not process bilirubin efficiently during the first few days of life. In premature, ill, and malnourished babies the levels of bilirubin may become so high that the infant suffers brain damage or dies. The specific risk to an individual infant, at any degree of bilirubinemia, is difficult to assess clinically, and there has been a tendency to prevent the condition altogether or to limit its degree. This tendency has been implemented by the easy availability of the treatment, its effectiveness, and low cost.
Short-term effects of the. treatment have been reported, particularly insensible water loss, rashes, loose stools, and temporary delay in growth in premature infants. Research has focused largely on these short-term effects and on the physiology and biochemistry of serum bilirubin. Light administered for a few days or a week seems to have no major deleterious effects. But serious questions remain. What is the optimum light environment for the infant, and how may it best be achieved? In fact, little is known about the light needs of infants. Hospital nurseries have not traditionally been designed with the infant's needs in mind but rather to provide sufficient light for the professional staff to examine, diagnose, and monitor. Many nurseries have no natural light at all.
Phototherapy is the simplest, most prevalent, and, at the same time, the least understood treatment available for hyperbilirubinemia. Only recently has there been appreciation that light is, indeed, a pharmaceutical agent for which the risk-benefit ratio must be determined under controlled conditions and that phototherapy units are medical devices whose light intensity, dosage, and appropriate wavelengths must be appraised.
Phototherapy invokes remarkable and desirable changes, but what else might it be doing over the long term? Precisely how does light reduce bilirubin? There is general agreement that it is prudent to minimize the exposure of the infant to phototherapy consistent with adequate therapy and that it is important to establish criteria to distinguish between the infant risk and the infant who is not.
The National Institute of Child Health and Human Development (NICHD) held a conference in 1974 to address these questions and soon afterward began a study to determine the short- and long-term benefits and risks of phototherapy for newborn hyperbilirubinemia. It is a cooperative, randomized clinical trial comparing treated with untreated infants under specific conditions. Babies were randomized by weight to phototherapy or non phototherapy. Infants 2,000 gm and above were admitted to the study when their bilirubin reached specified levels. All infants under 2,000 gm. were admitted. Physical, neurologic and mental development of these infants will be followed through six years of age.
The initial analysis of 1 ,339 newborn examinations has been completed, covering the general characteristics of the sample at entry, the immediate safety and efficacy of phototherapy, the course of the serum bilirubin during the study period, and the occurrence of death and exchange transfusions. The analysis of approximately 1,000 examinations of infants at one year of age is underway. The one-year follow-up data include physical, neurologic, ophthalmologic, audtologic, and laboratory information. Second- and third-year follow-up examinations are being coded and edited. The Biometry Branch of the NICHD serves as a data center and is also responsible for the analysis of data.
Principal investigators of the collaborative contract are Audrey Brown, State University of New York; Lawrence Gartner, Albert Einstein College of Medicine; Philip Lipsitz, Long Island Jewish-Hillside Medical Center; Harold Maurer, Medical College of Virginia; Joan Hodgeman and Paul Wu, University of Southern California Medical Center; and James Sutherland and William J. Keenan, University of Cincinnati.
The NICHD also supports other investigations related to hyperbilirubinemia of the newborn. Among them are several that include studies of phototherapy. Lawrence Gartner and his associates at Einstein College of Medicine are studying the effect of phototherapy on bilirubin binding by albumin.
David Lightner, at the University of Nevada, is studying the excretion of unconjugated bilirubin during phototherapy and the structure of bilirubin in various environments. Roger A. Yeary, at Ohio State, is working with rats to study the interaction of hyperbilirubinemia, phototherapy, and drugs.
Jean Jew, at the University of Iowa, is working with jaundiced Gunn rats raised from age two to 21 days and treated with phototherapy. They are watched for behavior changes as well as histologic changes in the brain.
At the Medical College of Wisconsin in Milwaukee, Albert T. Girotti is looking at damage in human red cell membranes that have been photosensitized in the presence of bilirubin.
Material for this column has been prepared by the staff of the National Institute of Child Health and Human Development, National Institutes of Health, specifically for readers of Pediatric annals.
1. Cremer, R. 1., Perryman, P. W., and Richards, D. H. Influence of light on the hyperbilirubinemia of infants. Lancet I (1958), 1094.