​Intestinal injury in preemies: Potential preventive strategies on the horizon

Isabelle De Plaen, MD (right), ​with pediatric surgeon Catherine Hunter, MD, in the NICU.

Babies who are born very pre-term are at risk of developing serious and potentially life-threatening conditions that only rarely occur in full-term infants. Among these is necrotizing enterocolitis (NEC), the most common and serious intestinal disease in preemies. Indeed, NEC affects approximately 7 to 10 percent of very low birth weight infants (infants weighting less than 3.3 pounds). In NEC, the intestinal tissues die off, leading to passage of bacterial products through the dying intestinal wall into the bloodstream, which causes the baby to go into shock. 

When NEC strikes, babies are very sick and cannot eat for an extended period of time. Commonly, dead intestinal tissues need to be surgically removed. When it is extensive, it results in the inability of babies with NEC to digest food normally and the need to receive long-term intravenous nutrition. Although the condition can resolve, some babies succumb to the disease. Those who survive may suffer from significant long-term effects. There is currently no cure for NEC, and the therapeutic options are limited. 

Isabelle De Plaen, MD, has been studying NEC for her entire career. As a neonatologist, she has cared for babies with NEC and their families. “These parents,” she says, “feel helpless to make things better for their newborns. Our goal is to prevent NEC from ever happening.” 

Her laboratory has recently shown evidence that insufficient intestinal microvasculature may be critical in developing NEC. She has hypothesized that maintaining low levels of oxygen in utero is essential for proper development of the tiny blood vessels feeding the intestinal tissue. However, premature birth slows down the growth of these incompletely formed intestinal blood vessels, increasing the susceptibility of the intestine to NEC.

In a new study published on October 25, 2017 in Pediatric Research, the De Plaen laboratory tested a novel agent called DMOG, which increases the stability of the signaling molecule called hypoxia inducible factor-1 (HIF-1) triggered by low oxygen levels. They found that mice treated with DMOG produce higher levels of VEGF, a key vascular growth-promoting factor, in their intestines. Furthermore, DMOG treated mice maintain intestinal blood vessel growth and are protected against intestinal injury when exposed to an experimental NEC model. 

“Several factors may affect the growth of the intestinal tiny blood vessels in the developing fetus,” says De Plaen. “It is critical for us to continue these studies in order to find ways to best stimulate molecular pathways that promote intestinal vascular development. We want to prevent conditions that would interfere with vascular development, so intestinal tiny vessel development is maintained in premature infants and NEC does not happen.”

Isabelle De Plaen, MD, is an attending physician in the Division of Neonatology (Neonatal Intensive Care Unit) at Lurie Children’s, Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine, and a member of the Center for Intestinal and Liver Inflammation Research​ at Stanley Manne Children’s Research Institute.