Independent Panel Discourages Routine Use of Treatment Regimen for Premature infants

BETHESDA, Md., Oct. 29, 2010--Premature infants often suffer from respiratory problems due to their underdeveloped lungs. Over the past decade, many of these infants have been treated with inhaled nitric oxide-a treatment designed to ease breathing by widening blood vessels in the lungs. This week, an independent panel convened by the National Institutes of Health determined that the scientific data taken as a whole do not support the use of inhaled nitric oxide in the routine clinical care of premature infants born before the 34th week of pregnancy. Additional studies are needed to ascertain the short and long-term benefits and risks of this treatment.

"In recent years, continuing advances in obstetrics and neonatal intensive care have increased survival of preterm infants," said Dr. F. Sessions Cole, conference panel chairperson and director of the Division of Newborn Medicine at Washington University School of Medicine, St. Louis. "However, these babies remain at substantial risk for medical problems that can create lifelong challenges. We need safe and effective treatments, but the current evidence does not point to inhaled nitric oxide as providing a clear benefit to most of these children."

Premature infants, in general, face increased risk for adverse outcomes including death, lung disease, and neurodevelopmental problems such as cerebral palsy, blindness, and learning disabilities. In 1999, the U.S. Food and Drug Administration approved inhaled nitric oxide therapy to treat one of these risks-pulmonary hypertension, or high blood pressure in the blood vessels supplying the lungs-in term and near-term infants. Since that time, some hospitals have extended the use of nitric oxide on an off-label basis for younger babies, less than 34 weeks gestation, in the hope of promising results.

The consensus development panel examined combined evidence from 14 randomized controlled trials of nitric oxide in premature infants = 34 weeks gestation and concluded that as a whole, the studies did not show a favorable impact on survival or lung function.

The panel concluded that long-term follow-up studies would be necessary to determine the balance of treatment risks and benefits, but also acknowledged difficulties in conducting this research. "Inhaled nitric oxide affects multiple organ systems, and developing premature infants are especially vulnerable to adverse treatment effects, long after they leave the neonatal intensive care unit. If further trials are pursued, children must be followed at least through school age," Dr Cole explained. "Unfortunately, this research is not only logistically challenging but in many cases very expensive."

The panel pointed to remaining uncertainties regarding the respective roles of dosing, timing, and delivery method of inhaled nitric oxide that should be addressed to optimize benefits and reduce treatment risks. The panel recommended that future trials examine the relative contributions of different treatment regimens and use larger sample sizes to assess safety and efficacy among different subgroups of premature infants.

Although inhaled nitric oxide is approved for term and near-term infants with pulmonary hypertension, the panel concluded that this treatment should be considered only for certain premature infant subgroups, and only when other clinical options have been exhausted. The panel suggested that clinicians provide families with accurate and understandable information about inhaled nitric oxide, and foster partnership and shared decision-making when considering its use.

An updated version of the panel's draft consensus statement, which incorporates public comments, will be posted later today at .

The panel will hold a press telebriefing to discuss their findings today at 2 p.m. eastern time. To participate, call 888-428-7458 (inside the United States) or 201-604-5177 (International) and reference the NIH Consensus Development Conference. Audio playback will be available shortly after conclusion of the telebriefing and can be accessed by calling 888-632-8973 (US) or 201-499-0429 (International) and entering replay code 30780312.

The conference was sponsored by the NIH Office of Medical Applications of Research and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, along with other NIH and U.S. Department of Health and Human Services components. This conference was conducted under the NIH Consensus Development Program, which convenes conferences to assess the available scientific evidence and develop objective statements on controversial medical issues.

The 16-member consensus development panel included experts in the fields of biostatistics; child psychology; clinical trials; ethics; family-centered care; neonatology; neurodevelopmental follow-up; nursing; pediatric epidemiology, neurobehavior, neurological surgery, neurology, and pulmonology; pediatrics; perinatology; and research methodology. A complete listing of the panel members and their institutional affiliations is included in the draft conference statement. Additional materials, including panel biographies, photos, and other related resources, are available at . Interviews with panel members can be arranged by contacting Elizabeth Neilson at 301-496-4999 or .

The conference was webcast live and will be archived shortly. Links to the archived webcast will be available at .

Individuals interested in obtaining information about resources for premature infants may wish to contact the Eunice Kennedy Shriver National Institute of Child Health and Human Development Information Resource Center at 800-370-2943 or via email at .

In addition to the material presented at the conference by speakers and the comments of conference participants presented during discussion periods, the panel considered pertinent research from the published literature and the results of a systematic review of the literature. The systematic review was prepared through the Agency for Healthcare Research and Quality Evidence-based Practice Centers (EPC) program by The Johns Hopkins University Evidence-based Practice Center. The EPCs develop evidence reports and technology assessments based on rigorous, comprehensive syntheses and analyses of the scientific literature, emphasizing explicit and detailed documentation of methods, rationale, and assumptions. The evidence report on inhaled nitric oxide in preterm infants is available at .

The panel's statement is an independent report and is not a policy statement of the NIH or the Federal Government. The NIH Consensus Development Program was established in 1977 as a mechanism to judge controversial topics in medicine and public health in an unbiased, impartial manner. NIH has conducted 123 consensus development conferences and 34 state-of-the-science (formerly "technology assessment") conferences, addressing a wide range of issues. A backgrounder on the NIH Consensus Development Program process is available at .

The Office of the Director, the central office at NIH, is responsible for setting policy for NIH, which includes 27 Institutes and Centers. This involves planning, managing, and coordinating the programs and activities of all NIH components. The Office of the Director also includes program offices that are responsible for stimulating specific areas of research throughout NIH. Additional information is available at .

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
 

Posted: October 2010

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