LAUSR

Important advances in neonatology have included efforts to reduce major morbidities impacting on the developmental lung, brain, eye, gastrointestinal, and immunological systems. These major morbidities include bronchopulmonary dysplasia, sonographic gray and white matter injury, retinopathy of prematurity (ROP), necrotizing enterocolitis, and postnatal sepsis. More than two decades ago, Schmidt and colleagues demonstrated in a pharmacological trial to reduce intraventricular hemorrhage in very preterm infants that severe ROP, bronchopulmonary dysplasia, and severe sonographic abnormalities of intraventricular hemorrhage grade III/IV, cystic periventricular leukomalacia, or ventriculomegaly substantially increased neurodevelopmental disabilities at age 24 months. Specifically, they found that if extremely preterm infants had all three of these morbidities then the risk for death or neurodevelopmental disability at 24 months was 88%. Subsequently, Canadian, Australian, and European investigators found that counts of these morbidities also impacted on 5and 11-year disability outcomes. The long-term follow-up of infants in the randomized controlled trial (RCT) CRYO-ROP cohort at 5.5 years found that as severity of ROP increased, prevalence of motor, manipulative, self-care, and communicative disabilities increased. Major advances in neonatology have occurred since these two pioneering studies. A key question has remained about the relationship of grades of ROP not requiring laser surgery for retinal ablation or use of bevacizumab to limit proliferative vascular angiogenesis. It is in this respect that the paper by Brumbaugh and colleagues as part of the NICHD Neonatal Research Network is important. The investigators undertook a secondary analysis of a large extremely preterm cohort initially participating in a RCT of myoinositol to reduce type 1 ROP. Among 638 infants (mean gestational age of 26 weeks; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) reached a study endpoint. Death or type 1 ROP occurred more often in the myo-inositol group compared to the placebo group (29 vs 21%, respectively; adjusted relative risk, 1.41 [95% confidence interval, 1.08–1.83], P = .01). A follow-up study of 2-year neurodevelopmental outcomes found that the treatment group did not affect the risk of death or survival with moderate or severe neurodevelopmental impairments, including Gross Motor Function Classification System >2 cerebral palsy, cognitive disability (SS <70), or sensory neural hearing loss requiring amplification or cochlear implantation. At follow-up, 95% of toddlers were sitting without support, 90% were walking independently, and 2.6% were walking but required an orthotic or rollator. The current study undertakes an analysis of the impact of severity of ROP on a broader range of motor, cognitive, communicative, and social–emotional skills at age 2 years.