Informed consent and SUPPORT.

In the summer of 1963, the nation watched in sadness as Patrick Bouvier Kennedy, the youngest child of President John F. Kennedy and First Lady Jacqueline Bouvier Kennedy, was born prematurely and then died of lung disease 2 days later at Children’s Hospital in Boston. Even now, it is common knowledge that children born prematurely are at high risk for death. So it is easy to imagine the stress when, in 2005, your new baby decides to come into the world after only 6 months of gestation, long before your pregnancy has reached term. You know that extremely premature babies like yours may not survive, but you are reassured that you are giving birth at an academic medical center with a sophisticated nursery for premature newborns and with physicians who have extensive experience with very preterm infants. Decades of study and refining practice have resulted in major improvements in the care of premature infants; now most babies weighing a kilogram or more, and many weighing less than this, survive. This progress has come through careful research in multiple aspects of neonatal care, but many questions remain regarding practice that will maximize survival and minimize the long-term sequelae resulting from surviving severe prematurity. Without research studies, your neonatologist would simply be guessing about what is best rather than knowing what is best for your child. The physicians in the nursery ask you to allow your very premature baby to participate in a research study, called the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT), part of which is focused on the amount of supplemental oxygen they will give to your baby. They orally explain the study to you and ask you to sign an informed-consent document; it is six pages of single-spaced typescript. Premature babies often require supplemental oxygen; what was not known in 2005 was exactly how much oxygen to give. The doctors knew that maintaining very high oxygen levels in the blood might cause retinopathy of prematurity (ROP), or abnormal growth of blood vessels in the eyes, which can damage the retinas and impair vision. The informed-consent form notes the higher risk of ROP that is associated with prolonged exposure to supplemental oxygen but states that “the benefit of higher versus lower levels of oxygenation in infants, especially for premature infants, is not known” and also notes that “the use of lower saturation ranges may result in a lower incidence of severe ROP.” Clinical practice at the time (and that recommended in the 2002 and 2007 guidelines of the American Academy of Pediatrics,1,2 on whose guidelines committee one of us served) was to target values for the partial pressure of arterial oxygen anywhere between 50 and 80 mm Hg, consistent with oxygen saturations measured by pulse oximetry between 85% and 95%. Among the clinical questions addressed by SUPPORT was whether targeting the upper or lower end of this range might result in better outcomes for very preterm infants. The study was conceived in 2003, initiated in 2005, and completed in 2009. Trials addressing the same clinical question were initiated in 2006 in the United Kingdom, Australia, and New Zealand (Benefits of Oxygen Saturation Targeting [BOOST II]), indicating the importance of the question.3 For a baby not enrolled in any of these trials, the specific range of oxygen saturation targeted within these broader guidelines was left to the discretion of the