Necrotizing enterocolitis: Pathophysiology from a historical context.

Necrotizing enterocolitis (NEC) continues to afflict approximately 7% of preterm infants born weighing less than 1500g, though recent investigations have provided novel insights into the pathogenesis of this complex disease. The disease has been a major cause of morbidity and mortality in neonatal intensive care units worldwide for many years, and our current understanding reflects exceptional observations made decades ago. In this review, we will describe NEC from a historical context and summarize seminal findings that underscore the importance of enteral feeding, the gut microbiota, and intestinal inflammation in this complex pathophysiology.

Fifty years in neonatology.

Neonatology, the care and study of newborn infants, is a 'young' specialty. Over the last 50 years, there have been many advances in the way that neonatologists care for newborn infants, particularly those born preterm, leading to dramatic improvements in mortality. To illustrate these advances, we describe four eras in neonatology from the point of view of the junior hospital doctor.

The challenge of understanding cerebral white matter injury in the premature infant.

White matter injury in the premature infant leads to motor and more commonly behavioral and cognitive problems that are a tremendous burden to society. While there has been much progress in understanding unique vulnerabilities of developing oligodendrocytes over the past 30years, there remain no proven therapies for the premature infant beyond supportive care. The lack of translational progress may be partially explained by the challenge of developing relevant animal models when the etiology remains unclear, as is the case in this disorder. There has been an emphasis on hypoxia-ischemia and infection/inflammation as upstream etiologies, but less consideration of other contributory factors. This review highlights the evolution of white matter pathology in the premature infant, discusses the prevailing proposed etiologies, critically analyzes a sampling of common animal models and provides detailed support for our hypothesis that nutritional and hormonal deprivation may be additional factors playing critical and overlooked roles in white matter pathology in the premature infant.

Early neonatal special care units and their scientific achievements.

Treatment of sick neonates originated in maternity and foundling hospitals in the 19th century. Nosocomial infections and difficult logistics of wet-nursing prevented admission of neonates in most children's hospitals well into the 20th century. In this article, 31 hospitals are described, all located in large cities, in which preterm and sick neonates were treated before the Great Depression. Even though mostly initiated by private charity, these institutions performed research right from the start. Topics included warming and feeding preterm infants, collecting and distributing human milk, developing and storing breast milk substitutes, prevention of rickets and nosocomial infections, maternal and public education regarding infection control, pathoanatomic characterisation of diseases and malformations and epidemiologic studies of infant mortality. These pioneering hospitals, their founding dates, researchers and classic publications are presented in a table.

A history of our understanding of cerebral vascular development and pathogenesis of perinatal brain damage over the past 30 years.

This article reviews our studies focusing on cerebral vascular development, the pathogenesis of subependymal/intraventricular hemorrhage (SEH/IVH), periventricular leukomalacia (PVL), and pontosubicular neuron necrosis (PSN). Their pathogenesis consists of predisposing developmental and causal factors. SEH/IVH may be caused by reperfusion or overperfusion following ischemia in the subependymal germinal matrix with characteristic vasculature. The cause of PVL is multifactorial (ie, ischemia and inflammation), predisposed by the maturational status of the vasculature and oligodendroglia in the white matter. Focal PVL is ischemic necrosis, and diffuse PVL or white matter injury may include cytotoxic damage. PSN has an apoptotic character, and may be induced by ischemic and oxidative stress on specific immature neurons. Further studies on preventive and therapeutic measures are necessary in clinical, pathologic, and experimental fields. The monitoring and control methods of brain hemodynamics and cellular stability should be more developed to prevent brain damages.

What caused the epidemic of Pneumocystis pneumonia in European premature infants in the mid-20th century?

An epidemic of interstitial pneumonia principally involving premature infants occurred in Germany and nearby European countries between the 1920s and 1960s. Fatalities were due to Pneumocystis. Because the principal defenses against Pneumocystis are T cells, an acquired T-cell deficiency was postulated. A number of potential causes including malnutrition were considered. All were implausible except for a retrovirus that was benign in adults but virulent in premature infants. Furthermore, we suspect that the virus was imported into Germany from former German African colonies. Premature infants were vulnerable because of the developmental status of their T cells. Given the practices in that part of Europe at that time, the virus was most likely transmitted by contaminated blood transfusions and subsequent contamination of reusable needles and syringes used in injections. Although the epidemic ended 4 decades ago, a search for the postulated retrovirus can be conducted if tissues from affected infants are available.

The discovery of retrolental fibroplasia and the role of oxygen: a historical review, 1942-1956.

Nearly 50 years after it was thought to be conquered, retinopathy of prematurity (ROP) continues to cause vision disturbances and blindness among prematurely born infants. During the 1940s and early 1950s, researchers and caregivers first identified and struggled to eliminate this problem, which seemed to come from nowhere and was concentrated among the most advanced premature nurseries in the U.S. Research studies initially identified many potential causes, none of which could be proved conclusively. By the mid 1950s, oxygen was identified as the culprit, and its use was immediately restricted. The rate of blindness among premature infants decreased significantly. ROP was not cured, however. By the 1960s, it had reappeared. The history of ROP serves to remind us that, despite our best intentions, the care and treatment of premature newborns will always carry with it the possibility of iatrogenic disease. This caution is worth remembering as we work to expand the quality and quantity of clinical research.

Kernicterus in preterm newborns: past, present, and future.

This historical overview of kernicterus in prematurity, from the 1950s to the present, provides a unique perspective on this clinical conundrum. Three separate periods of pediatric history are detailed in relationship to our understanding of kernicterus in the preterm newborn: (1) the pre-intensive care era (1950 to 1965); (2) the low bilirubin kernicterus era (1965 to 1982); and (3) the 1980s. Each period demonstrates selected insights regarding kernicterus in prematurity, and together with recent reports suggest that premature newborns are now at extremely low risk of developing kernicterus when managed using current standards of care. However, the current conservative empiric guidelines for preventing kernicterus are questioned, and it is suggested that additional study is needed to clarify this issue in the 1990s.