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Pediatric Update

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Pediatric Update

 
Spring 2006

Corticosteroid Use in Pre-term Babies May Impair Development

Corticosteroids, long thought to be almost miraculous drugs, are now used more cautiously as recurrent courses and high doses have revealed serious side effects. Still, in situations of survival, steroids can provide amazing results.

For more than 30 years, use of prenatal steroids for pregnant mothers in pre-term labor has decreased the incidence of respiratory distress syndrome and increased survival for their premature babies. These steroids act primarily by increasing the surfactant production in the baby’s lungs. Many times, premature babies are born suddenly, before a mother can receive the steroids. In those cases, steroids have been given to babies to help improve respiratory function and get them off the ventilator faster.

If giving corticosteroids to mothers in pre-term labor worked so well, physicians surmised that similar results could be achieved by giving steroids to pre-term newborns with low oxygen levels whose mothers did not receive steroids. The reasoning seemed logical, but the long-term results have proved disturbing.

 “Giving steroids to the mother before the baby is born not only improves the lung function but also decreases neonatal intraventricular hemorrhage rates, which in turn decreases neurodevelopmental disorders in premature babies, including cerebral palsy,” explains Meena Garg, M.D., neonatologist at Mattel Children’s Hospital at UCLA. “But when corticosteroid reatment is given in the neonatal period, following a pre-term birth, the benefits seen with decreased severity of respiratory distress and decreased rate of chronic lung disease were associated with an increased risk of neurodevelopmental impairment, including cerebral palsy. This is the reverse of the prenatal steroid use and was unanticipated until the follow-up studies emerged in the literature three years ago.”

In 2002, published papers began looking at the long-term outcomes in school-age children who had been treated with corticosteroids as premature infants. “This raised the question of whether steroids given to babies cause more problems in terms of cerebral palsy and impaired neurological development,” Dr. Garg explains.

As a result, the American Academy of Pediatrics has discouraged the routine use of corticosteroids in the treatment of chronic lung disease in low-weight infants. “The long-term follow up of babies treated with steroids showed a substantial increase in cerebral palsy and developmental problems. One of the studies actually said that for every seven babies born weighing less than 1,000 grams and treated with steroids, you end up with one extra baby with cerebral palsy,” Dr. Garg points out.

 “That was in 2002, and if you look at the current data, approximately 25percent of very small babies are still being treated with steroids,” she adds. “At UCLA, we don’t routinely use steroids in pre-term babies. For the last three years it has been an absolute no-no in our unit to treat babies less than 1,000 grams with corticosteroids.”

The data about early as well as longterm neurological effects of steroid use are expanding. According to Dr. Garg, neuroimaging studies at UCLA and other centers have shown decreased head circumference and impaired gray matter growth in babies treated with steroids, in addition to the adverse effect on overall growth “Although we know that brain imaging does not define brain function, there is definitely a problem with brain development in these babies,” she notes.

Without steroids, small pre-term babies may remain on ventilators longer. Steroids decrease the number of days babies are on oxygen or on a ventilator. “There is an early gain but in the long term you don’t have any gain in pulmonary function,” Dr. Garg explains. “The babies still need to stay in the neonatal intensive care unit just as long because all the other systems need to mature.” Either giving or not giving steroids to these babies does not affect survival, she says.

Two recent studies from England, published in Pediatrics, contradict the data from 2002. Those studies looked at teens 13 to 17 years old and found no long-term difference in neurological outcome, cerebral palsy and school performance in 195 children treated with and without steroids as neonates. “We don’t think these studies lessen or take away our concerns about adverse neurological outcomes after steroid use since we are seeing all these changes on magnetic resonance imaging (MRI) studies that are suggestive of neurological insult.

Most of the reports of babies treated with steroids in the U.S. are still pointing toward these complications,” Dr. Garg says. Most academic medical centers in the United States are not using steroids in this population, but Dr. Garg says UCLA continues to receive some babies who have already been treated with long-term steroids and come with complications, such as hypertension, hemorrhaging or perforations in the gastrointestinal tract, high blood pressure, high glucose, and cardiomyopathy. These babies need to be weaned from the medications, which can take weeks.

When babies are very sick and very premature and on high ventilator settings, what is the best treatment option? When a critically ill child is caught in the balance of life and death, he use of steroids as a life-saving measure at the risk of compromising neurodevelopmental outcome poses a dilemma for the caring physician.

Emerging research in animal models is showing that timing and dosage of corticosteroids are very important. The general consensus, Dr. Garg notes, is that giving steroids to a very immature baby in the first seven to 10 days of life is more harmful than if used later. “We now avoid the use of steroids entirely with some exceptions, keeping in mind that the cumulative dose is important in terms of the effects on brain and body,” she says.

Most of the studies on corticosteroids in pre-term babies have used dexamethasone. An alternative—hydrocortisone—is being tried in some studies to see if it causes less neurological impairment. However, the randomized control trial to prove efficacy of hydrocortisone was stopped early due to increased incidence of gastrointestinal perforations in the treated group. The follow-up studies after use of hydrocortisone are relatively few, with only two- to threeyear outcomes so far. “However, this is another option if physicians face a dilemma with a critically ill baby. Hydrocortisone seems for the time being to be affecting the brain less but still helping the lung,” she says.

Dr. Garg would like to see collaboration among medical centers treating this population to study the effects of timing and dosage of steroid administration. She observes, “We need to get together with other centers to conduct trials on consistency and timing of dosage, and tracking long-term outcomes and brain imaging to see if dosing schedules are predictive of brain function in the long run.”





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