As premature babies fight for life, another battle is raging behind their tiny eyelids — an eye disease that ultimately blinds up to 2,000 of these infants a year.
Now scientists are exploring two promising new ways to save preemies' eyesight: strictly maintaining the babies' oxygen levels at a constant but slightly lower level than usual which apparently slashed blindness at one major hospital — and giving the smallest babies an eye-important growth hormone they lack.
Preventing the blinding disease — called retinopathy of prematurity, or ROP — is a major goal because once it hits there's no sure way to save vision. Today's best treatment, laser therapy, decreases the chance of blindness by only a quarter, and many babies who don't go blind still will never see well enough as adults to drive.
The smaller the preemie, the bigger the risk of getting ROP. So with doctors saving more and more of the 40,000 babies born every year who weigh under 2.6 pounds, new ways to battle ROP are crucial.
"It's very devastating," says Dr. Lois Smith of Harvard Medical School, describing watching preemies survive only to lose their sight. Smith, who discovered the growth-hormone connection, calls today's ROP treatment "medieval ... but we just do what we can."
Very premature babies don't have properly formed blood vessels in the retina, the eye's innermost layer. Sudden exposure to oxygen as doctors attempt to save these babies is believed to cut off further blood vessel formation. Then there's a backlash: Blood-starved retinal tissue sends out an urgent call for help that results in sudden growth of abnormal blood vessels, eventually causing vision-blocking retina scars and even detachment.
To cut off that abnormal growth, doctors use a laser to destroy part of the retina emitting the distress call. That destroys some working eye tissue in hopes of saving the rest, but it can't restore lost sight.
Preventing ROP would be far better. In the 1950s, doctors tried drastically cutting preemies' oxygen levels. Death and brain damage rose, however, so hospitals today strive for moderate oxygen levels and hope for the best.
Now two experiments point to possible new solutions:
Cedars-Sinai Medical Center in Los Angeles set preemie oxygen levels about 10 percent lower than normal for a healthy person, based on research showing uterine oxygen pressure is low. Neonatal intensive care workers also were ordered to keep each baby's levels as constant as possible, in contrast to the common day-to-day raising and lowering of levels.
"You've got to have guts and keep the oxygen low but not too low," says Dr. Kenneth Wright, who developed the policy.
The hospital's incidence of severe ROP dropped from 12.5 percent in 1997 — higher than the national average of 9.8 percent — to a mere 3.7 percent last year, without harming survival or increasing brain damage.
Wright can't yet recommend the policy for all hospitals. One reason: He didn't give any preemies standard care as a comparison to prove the oxygen change really caused the ROP improvement. Wright now is discussing a multi-hospital study with the National Institutes of Health to prove his findings.
Oxygen isn't the only player. While oxygen levels help regulate a protein called VEGF that is important in blood vessel growth, Harvard's Smith discovered that another growth hormone called IGF-1 also is crucial.
Fetuses normally absorb IGF-1 from the placenta and amniotic fluid. Limit IGF-1 levels in baby mice and they develop ROP-like disease. Smith then studied 80 human preemies and found those with ROP had the lowest IGF-1 levels. Next year she hopes to begin testing to determine whether giving premature infants doses of IGF-1 right after birth can protect them.
Both experiments are generating cautious excitement. Vanderbilt University's Dr. John Penn says Wright's work supports his own research that keeping oxygen levels stable seems vital. And he calls Smith's work intriguing, noting that because IGF-1 is a body-produced protein and not a synthetic chemical, it should be safe enough to test in vulnerable preemies.
For now, there's little advice to offer anxious parents except to be sure their preemie is treated in a neonatal intensive care unit and gets examined for ROP four to six weeks after birth, Wright says.
But he says it can't hurt to ask right away about ROP and how closely the baby's oxygen levels are being monitored: "It'll make the house staff and neonatologists aware that this is a sophisticated parent and they'd better watch their p's and q's."