July 1998, VOLUME102 /ISSUE Supplement 2


  1. Mary Ellen Avery, MD
  1. 1From the Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.

All neonatologists must be pioneers by definition, because we are now looking after infants who would not have survived before. Every year is a new experience as we have the pleasure of seeing more and more low birth weight infants survive, and we accept the challenge of reducing their continuing morbidities.

Modern neonatology begins in the 1940s. One of the reasons it began, I think, was post World War II construction, new facilities, and, alas, a tragedy—the emergence of the leading cause of blindness in children in the United States; we now call it retinopathy of prematurity. In the late 1940s, it was called retrolental fibroplasia and was the leading cause of blindness among children in the United States. Recognition, in the 1950s, that the cause was hyperoxia led to better monitoring of oxygen delivery and a near elimination of the problem among infants weighing >1800 g.

In 1940, there was a 50% survival rate of infants whose birth weights were <1800 g at 28 days. The overall neonatal mortality rate was 29 per 1000 live births. In comparison, in 1994 it was 5 per 1000 live births. This 50% survival rate was a function of multiple events.

New premature nurseries were built and people were putting an emphasis on the needs of newborn infants after World War II. We began to have better instrumentation. We went through a misadventure with restricted oxygen use in the 1950s and most infants died of respiratory distress. There were no ventilators and no blood gas measurements. Pathologists played an enormously important role by saying over and over again these infants' lungs had something that looked like hyaline membranes and atelectasis.

Pathologists such as Peter Gruenwald, George Anderson, Benjamin Landing, Edith Potter, Kurt Benirschke, and many others wondered why these infants had this 3-day disease with such a high mortality. Twenty-five percent of the infants died, and this was the leading cause of death of liveborn, low birth weight infants. This eventually led to the establishment of regionalization and transport to centers where ventilators were available in the 1960s and 1970s.

Micromethodology developed with both chemistries and blood gases leading to the application of some scientific principles to the management of the small infants. The increased respect for the reproductive rights of women also increased the number of infants we were caring for.

The liberalization of the cesarean section was yet another big advance. I do not know what the right numbers are, but the 5% in the 1950s was surely too few; we very rarely see battered infants anymore from difficult deliveries. Today's 20% to 25% section rate is being continually reviewed but surely has been a major force in giving us healthier newborns to look after.

Glucocorticoids and surfactant replacement have made a difference, although not major compared with what one must think of as continuum of advances. My mentor, Dr Alexander Shaffer, and his colleague, Dr Milton Markowitz, were among those who paid a lot of attention to newborn infants in the 1950s. Concurrently physiologists, particularly in England including the work of McCance, Widdowson, Dawes, Barcroft, and Barron, led the way to the experimentation on animals, particularly the lamb, illuminating the adaptations to extrauterine life.

Later clinical trials were recognized as an important way to evaluate interventions when they were not based on certainty. The comparisons of efficacy and safety of new interventions in randomized, prospective, controlled, blinded, clinical trials have been an enormously important advance. Concurrent with all of this, Spock, Brazelton, and colleagues made a great impact on the way in which infants were treated more gently and carefully.

The work of all these scientists has led to one of the most significant recent concepts—that mechanical ventilators can be quite lethal and probably play a major role in the induction of the chronic lung disease of low birth weight infants through barotrauma. Jen Wong from Columbia and others have proven that permissive hypercapnia is important. With PCO2s in the 50 mm Hg range, or even in the 60 mm Hg range means lower airway pressures are possible. My own bias is that chronic lung disease is an effective reaction to injury, much of which is related to barotrauma and the increased requirements for oxygen engendering oxygen toxicity as well.

We learned about temperature regulation. We learned about amniotic fluid testing for prenatal diagnosis, and many other advances. What were the forces that drove this record of achievement?

Some of the advances came after misadventures. We learned a lot from our mistakes. It is a sort of tragedy to have to admit that, but it is perfectly clear that it mattered a lot. What about hyperoxia, chloramphenicol, and hexachlorophene? We knew a long time ago that the very immature infant absorbed most anything across the thin skin. But it is only in the October 1996 issue of Pediatrics that you will read that antiseptics with iodine in them can lead to toxic levels of serum iodine. We have had serum soap, we have had serum iodine, but none of these findings were planned. They happened because we did things without making sure that there was some kind of scientific basis controlled clinical trial to guide us.

I do not like to think about these misadventures too much, but we must because it is from them that we will be very careful about what we put on the skin of our 500-, 600-, and 700-g infants, who are now our responsibility.

Observant people have made most of the difference in outcome of low birth weight infants, not just pediatricians. It was also interaction with obstetricians thinking about prenatal events and understanding much more about neonatal adaptations. Also, the cell biologists with their capacity to identify major malformations through chromosome identification in amniotic fluid, and molecular biologists who are now giving us a whole new world to observe by knock-out mice with their inborn errors that reflect the same kinds of things we have seen and puzzled about for so many years.

People mattered and our interdisciplinary research (now called translational research) mattered. Neonatologists have been doing translational research for the last 25 years, and now it is being taken up by others as a good thing to do. And there's a lot we need to know. I will suggest that translational research has been our bag for many years, and we must continue it. Fortunately, we have lived in times when society has backed our efforts. I cannot underestimate the importance of the National Institutes of Health in my own personal life. It has been totally essential for our research and training for >30 years.

The improved standard of living that has resulted from an emphasis on nutrition, the awareness now that pregnant women should certainly not be smoking and should be careful about what they eat or drink is most important. During the periconceptual period they should be sure they are getting enough folic acid because that has clearly reduced the number of neural tube defects and has been an extraordinary advance.


The prematurity rate in this country really has not changed. It has been between 6% or 7% year after year. Sometimes the population changes, such as more teen pregnancies now than in the past. We must understand this. We must understand much more about what initiates labor, what induces its premature onset, and the separation of the placenta, for example.

I am pleased now to see the placenta is reaching center stage. Even molecular biologists are getting excited about it. After all, it is a remarkable organ. It had to go from a fertilized egg, had to stimulate enormous amounts of angiogenesis, and has to become a critical endocrine organ for all of the hormones of pregnancy. It is the lungs, intestines, and kidneys of the fetus. I presume it has a lot to do with the timing of delivery, because it has to undergo aging, too. Somebody will be talking about apoptosis of the placenta one of these days. In fact, it's likely to be a hot topic.

With that I am going to conclude this little exercise in sound bites and headline news, because, after all, that is what we are all attuned to now. I want to leave you with one thought, probably the only one you'll remember from this. If you ever see a turtle on a fence post, it didn't get there by itself.