Published in Birth March 2001, Vol.28, No. 1, pp.57-59.
Preemies on Steroids: A New Iatrogenic Disaster?
At the Hot Topics in Neonatology conference last December, Dr. Barbara
Schmidt referred to the year 2000 as “Annus Terribilis” for her profession.1 Large
studies from the NICHD2 in the US and the EPICure group3 in the UK had revealed
unexpectedly grim outcome statistics for extremely low birthweight and short gestation
babies -- a 50% rate of disability serious enough to be diagnosed by two to three years of
age . Because follow up at such early ages reveals only a fraction of the impairments
diagnosed by mid to late childhood,4 the eventual toll in disability promises to be
considerably higher.3 Premature birth, it was also reported, permanently disorganizes and
reduces the size of the brain, adversely affecting cognition and behavior.5, 6 The more
premature the infant, the smaller and more abnormal the brain.5 Adult cardiovascular
disease, underdeveloped kidneys and diabetes were further linked to low birth weight. 7
It had become increasingly apparent that improved survival among extremely preterm
infants was producing greater numbers of children with permanent health impairments
and handicaps.8 Further, some of this disability was linked to iatrogenic causes,2 a result
of the continued haphazard use of poorly evaluated therapies in perinatal and neonatal
care. 9,
10
Improved survival among extremely premature infants has been credited in part
to the use of steroid drugs 11, 12 currently administered to nearly half of mothers before
extremely preterm delivery and to half of all extremely preterm infants after birth.13 In
perhaps the most disturbing revelation of the year 2000, steroids were implicated as
“neurotoxic” substances 2 that further reduce the size of the premature brain14 and
increase rates of cerebral palsy,15, 16, 1 7 cognitive deficits, 2, 15 and severe retinopathy.18,
19
Two large randomized controlled trials of postnatal steroids were halted prematurely
because of serious short term complications such as intestinal perforations, growth
retardation, periventricular leukomalalcia, hyperglycemia, hypertension, and infection. 20,
21
In addition, animal and human studies of steroids in the perinatal and neonatal period
have suggested that steroids contribute to long-term cardiovascular disease, 22, 23 immune
system disorders and autoimmune diseases such as multiple sclerosis, 24 renal
calcification, 25 abnormal lung development,26 and neurological and behavioral deficits.27,
28
Prenatal steroids -- used in single two-injection doses -- have been accepted as
safe and effective in reducing neonatal mortality and morbidity, however, many
obstetricians treat high risk pregnant women with multiple courses of steroids29 on the
theory that if a little bit is good, more is better. New research now implicates multiple
doses of prenatal steroids with impaired head growth,30 impaired brain development and
behavior problems; 31, 32 increased mortality and lung disease; 26 gastroesophageal
reflux;33 and severe retinopathy.34 A consensus statement from NIH, issued in August
2000, now discourages their use.29
Postnatal steroids became widespread in neonatal care by the 1990s having been
introduced into the nursery without properly conducted clinical trials for safety and
efficacy
10
and despite warnings from researchers (beginning in the 1970s) of serious
potential dangers.35, 36 ,37 Steroids were accepted enthusiastically because they produced
dramatic short term improvements in the respiratory status of premature infants (long
term benefits were less apparent).38 Dr. William Silverman, who has written extensively
on previous iatrogenic mishaps in neonatology, 39,40 estimates that tens of thousands of
infants have now been treated with these drugs, in what he suspects will be “one of the
worst iatrogenic disasters in modern history, exceeded only by the DES fiasco.” 41
Neonatologist Alan Jobe recently criticized his profession’s embrace of poorly
tested and potentially dangerous steroid treatment by quoting Tom Lehrer’s bitter lyrics
on the misuse of scientific technology: “Once the rockets are up, who cares where they
come down? That’s not my department says Wernher von Braun.”38
Dr. Jobe further writes: “Adverse neurodevelopmental outcomes [from the use of
steroids] no doubt result from the effects of these potent agents on the developing
nervous system and should come as no surprise.”38 Except, of course , to parents and the
public.
As the rockets began landing last year, the explosions occurred out of public and
parental sight. Disturbing studies and commentaries on steroids were presented
(quietly) in neonatal journals and conferences. However the media, for the most part,
seems to have missed this iatrogenic disaster-in-the-making. Perhaps there have simply
been no press releases from the medical journals and researchers. As neonatologist
Mildred Stahlman once remarked, “We have allowed the media to publicize our
successes widely, and have minimized our failures to the public”42
I participate in several Internet listservs for parents of premature infants. The
parents with whom I correspond uniformly report that they were never informed of the
known and suspected risks of multiple prenatal or postnatal steroids. A few parents say
they were told the drugs might “slow growth,” but complications involving the brain,
eyes and other organs and systems were never mentioned. When I give parents the
studies and commentaries referenced in this article they become angry that they were
never given this information, though much of it has been available to neonatologists for
decades. They are devastated to discover that many of the illnesses and disabilities their
children now suffer may have resulted from, or have been complicated by, the use of
steroids. In addition, high risk pregnant women report they continue to be treated with
multiple doses of antenatal steroids without being informed of the risks.
The steroid issue is being discussed by physicians on the Internet, as well. A
recent poll 43 of 259 neonatologists conducted by Dr. Richard Scott Taylor revealed that
steroids are still commonly used and that neonatologists’ practices vary widely
concerning when and how they use these drugs. Less than 10% of the respondents
reported involving parents in formal informed consent procedures for the use of steroids.
Dr. Taylor comments: “It…does not make sense to me that as physicians, we get
informed consent for standard procedures with clear risk benefit balance such as
immunizations and blood transfusions yet are not necessarily expected to get consent for
PNCS [post-natal corticosteroids] where there is no standard for use, and significant
potential for harm….But perhaps we should. “
I strongly agree! Given the current widespread use of poorly evaluated therapies
in neonatal care and the dismal outcomes (with and without steroids) I must also agree
with neonatologist Jeffrey Maisels that care for very low birthweight infants is currently
“a vast and uncontrolled experiment undertaken without informed consent and with
possibly undesirable results.”44
The time has come for parents -- who, with their children, must suffer the
outcomes -- and for the public -- who ultimately pay for this care and its consequences -to be honestly informed about the “experimental” nature of neonatal treatment for very
preterm infants and its unfortunate results. It is also time for parents and the public to
demand that steroids and, in fact, all poorly evaluated neonatal treatments be used only
in the context of formal clinical trials. Furthermore, the time has come, in the wake of
this “annus terribilis” to assert the right of parents to give, or to withhold, their fully
informed consent to the experimental, arduous, and dangerous treatment of their
extremely premature infants.9
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