Results of a multicenter study led by Johns Hopkins
Children's Center challenge the long-
standing practice of treating premature babies with
hydrocortisone, a steroid believed to fight
inflammation and prevent lung disease.
The researchers found that such treatment offers
little or no benefit and that low cortisol
levels are not even necessarily harmful. High cortisol
levels, on the other hand, appeared to increase
the risk of dangerous bleeding in the brain and require
that babies be monitored aggressively to ward
off life-threatening complications, according to the study
published in the October issue of Pediatrics.
Premature babies and adults with a condition known as
relative adrenal insufficiency have
abnormally low levels of the stress hormone cortisol. The
standard treatment for this condition in
newborns has been hydrocortisone therapy. The study's
findings, however, shed new light on the
clinical meaning of low cortisol levels in preemies,
showing that contrary to common belief, low blood
concentrations of this hormone do not put extremely
low-birth-weight babies (those born weighing
less than 2.2 pounds) at higher risk for retinopathy of
prematurity — a potentially blinding eye
condition — inflammation and lung disease.
Researchers also found no difference in health
outcomes between babies with low cortisol levels
who were treated with hydrocortisone and those given a
placebo. While hydrocortisone had no adverse
effects on a baby's health, it also did nothing to prevent
or reduce respiratory diseases, infections,
hemorrhages or retinopathy.
"We were intrigued and somewhat surprised, but
contrary to what we expected, low cortisol
levels do not appear to be dangerous and may actually be
the norm in premature babies," said study
lead investigator Susan Aucott, a neonatologist at Johns
Hopkins Children's Center. "What this means
is we should really think twice before rushing to treatment
with hydrocortisone in our effort to
'correct' these low levels."
While surprising, the findings are not entirely
counterintuitive, investigators say, because in
utero babies have naturally low cortisol levels. "This may
mean that, in a way, low cortisol levels are
normal, and premature babies maintain them low, as they
would have been in the womb," Aucott said.
Comparing the cortisol levels of 311 extremely
low-birth-weight preemies immediately after
birth and one week after birth, researchers found low
cortisol levels did not increase the risk for
adverse short-term outcomes or death. For example,
bronchopulmonary dysplasia occurred in 58
percent of infants with low cortisol levels, in 58 percent
of infants with midrange cortisol levels and in
62 percent of those with moderately elevated cortisol
levels. Brain hemorrhages occurred in 24
percent of infants with low cortisol levels, in 36 percent
of those with midrange cortisol levels and in
49 percent of those with mildly elevated cortisol
levels.
Babies with moderately to severely elevated cortisol
levels at birth and shortly after birth had
a higher risk for life-threatening brain bleeds, dangerous
gastrointestinal perforations and severe
retinopathy, researchers found. Researchers have yet to
pinpoint the exact mechanism leading to
these dangerous spikes in cortisol, but past studies have
suggested that severe pain may drive up
production of this stress hormone. Regardless of the
trigger, investigators say, neonatologists should
aggressively monitor infants with elevated cortisol levels
because of their vulnerability to
hemorrhages and other life-threatening complications.
Elevated cortisol concentrations, especially values
higher than 31 micrograms per deciliter of
blood at 12 to 48 hours after birth, and more than 18
micrograms per deciliter at five to seven days
after birth, appeared to make babies more prone to serious
bleeding in the brain, although
researchers caution a cause-effect relationship could not
be established from this study because
elevated cortisol concentration could be a consequence of
the hemorrhage but not necessarily a
trigger of it.
Very high cortisol levels, above 62 micrograms per
deciliter, appeared to heighten a baby's risk
for severe brain hemorrhages, gastrointestinal perforation
and death. For example, death occurred in
12 percent of infants who had low cortisol levels 48 hours
after birth and in 13 percent of infants
with midrange levels of cortisol but in nearly 30 percent
of infants with severely elevated cortisol
levels at 48 hours of birth. Gastrointestinal bleeds
occurred in 3 percent of infants with low cortisol
levels at 48 hours of birth and 9 percent of infants with
cortisol levels in the mid-range but in 24
percent of those with significantly elevated cortisol
levels.
Pamela Donahue, also of Johns Hopkins, was a
co-investigator on the study. Other participating
institutions were the universities of New Mexico,
Pennsylvania and Colorado; Tufts, Virginia
Commonwealth and Pennsylvania State universities;
Children's Hospital and Clinics at University of
Minnesota; Medical College of Wisconsin; and State
University of New York, Buffalo.