OBJECTIVE:We observed two clusters of spontaneous pneumoperitoneums in extremely low birth weight infants during the use of a protocol for early dexamethasone prophylaxis (EDP) for bronchopulmonary dysplasia from 1996 to 1997. During surgery, focal small bowel perforation (FSBP) was found in eight of nine cases. A retrospective study was designed to identify risk factors for FSBP in these extremely low birth weight infants. METHODS:A case-controlled analysis was performed using all infants born weighing Ͻ1001 gm and admitted to the University of Washington Medical Center Neonatal Intensive Care Unit during a 13-month period. A total of 51 infants were identified and divided into groups based on treatment or not with dexamethasone and indomethacin. These cohorts were homogeneous for gestational age, birth weight, and perinatal stability. Relative risk and confidence intervals were calculated for each of the comparisons. Routine pathology was performed on all surgical specimens and additional sections were cut and stained for further study. RESULTS:Infants who received EDP had a relative risk of perforation that was 12.3 times that of untreated infants. Those treated with indomethacin had a risk that was comparable with that for infants who did not receive indomethacin. Infants who received both EDP and indomethacin tended to have higher rates of pneumoperitoneum than infants who received EDP alone but comprised a cohort too small for valid analysis. The pathology of surgical specimens revealed FSBP with segmental loss of the muscularis externa. There was no evidence of fungal or bacterial infection in any of the surgical specimens. CONCLUSION:These findings implicate EDP, but not indomethacin, as a significant risk factor for FSBP.Focal small bowel perforation (FSBP) is a sporadic problem occurring in premature infants. It is often clinically mistaken for perforation secondary to necrotizing enterocolitis (NEC). 1 Case reports of FSBP have associated this disorder with hypoxic-ischemic injury, 2,3 congenital absence of the muscularis externa, 4 -6 indomethacin, 7,8 dexamethasone, 9,10 and candidal infection. 11 Risk factors for FSBP have also been postulated to be multifactorial. 1 Unfortunately, evidencebased research on FSBP is scant.In late 1996 and mid 1997, two clusters of FSBP occurred in extremely low birth weight (ELBW) infants at the University of Washington Medical Center (UWMC) neonatal intensive care unit (NICU). These clusters coincided with the onset of a standardized protocol for early dexamethasone prophylaxis (EDP) in premature infants at risk for bronchopulmonary dysplasia. During the first month, four infants who received EDP required urgent surgery for pneumoperitoneum and were found to have FSBP. The EDP protocol was suspended pending review of the cases and literature.Review of the literature failed to find any reports of FSBP occurring in clusters. Review of all neonatal surgical cases in the previous 6 months revealed two more infants with FSBP who also weighed Ͻ1001 gm. Indomethacin proph...
When making decisions about whether or not to limit care for a patient, caregivers were more likely to rely on the perceived benefit to the patient than preadmission quality of life.
To the Editor:We are a group of scholars and leaders in bioethics and pediatrics with extensive experience in ethical and regulatory issues in pediatrics and human subjects research. We urge the Office for Human Research Protections (OHRP) to withdraw its notification to the institutions involved in the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) that they failed to meet regulatory informed-consent requirements, in particular regarding reasonably foreseeable risks of enrollment in the study. We believe that this conclusion was a substantive error and will have adverse implications for future research.SUPPORT was undertaken, in part, because neonatologists lacked reliable scientific evidence regarding the blood oxygen-saturation levels that were the safest and most effective for extremely premature babies. The infants included in the study were randomly assigned to oxygen-saturation targets that were consistent with standard clinical care at the participating institutions. The conclusion of the OHRP that the study's experimental evaluation of these otherwise routinely used oxygen-saturation levels exposed subjects to additional risk (above the risks of routine clinical treatment) is not supported by the evidence.Furthermore, the conclusion of the OHRP that the SUPPORT investigators violated federal regulations in failing to include specific information elements regarding risks of the study interventions in the parental permission documents is without substantive merit and overreaches. Although we acknowledge that the permission forms could have been improved, we disagree that the random assignment of infants to a high oxygensaturation level or a low oxygen-saturation level imposed additional risks that the investigators failed to disclose. There is nothing to indicate that the institutional bodies responsible for reviewing SUPPORT failed to exercise appropriate care and judgment regarding all the factors required by the "Common Rule" in approving the study. The OHRP should not sanction research institutions simply because it disagrees with their assessment of the risks of research but should do so only if it finds that an institution has failed to meet the terms of its federal-wide assurance, such as in the manner in which its institutional review board is constituted or operates.In the absence of a formal mechanism for appeal, we urge the OHRP to regard this expression of disagreement by signatories representing leaders in research ethics and pediatrics as an appropriate basis for it to reconsider this decision. Allowing the decision to stand would be unfair to the investigators and institutions involved in SUPPORT. It would also set a precedent that would impede ongoing and future patient-centered outcomes studies. Such studies are crucial for advancing medical practice, reducing risks, improving outcomes, and enhancing cost-effectiveness, particularly in the field of pediatrics.The consent process for clinical research can no doubt be improved. The recent scrutiny of SUPPORT highl...
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