Preemies on Steroids: A New Iatrogenic Disaster? by Helen Harrison
Published in Birth March 2001, Vol.28, No. 1, pp.57-59.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, 28Prenatal 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." 41Neonatologist 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"42I 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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