Related Experiment Video
Updated: May 31, 2026
A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Persistence after birth of systemic inflammation associated with umbilical cord inflammation
Alan Leviton1, Jonathan L Hecht, Elizabeth N Allred
1Department of Neurology, Children's Hospital Boston and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. alan.leviton@childrens.harvard.edu
Insights
Umbilical cord inflammation in premature infants can lead to persistent postnatal inflammation. Elevated levels of key inflammation-related proteins were observed on day 7, suggesting a sustained inflammatory response.
Area of Science:
- Neonatal immunology
- Perinatal medicine
- Inflammatory biomarkers
Background:
- Intrauterine inflammation is linked to elevated neonatal blood inflammatory proteins.
- The persistence of postnatal inflammation following intrauterine inflammation is not well-understood.
- Umbilical cord inflammation (funisitis) is a marker of intrauterine inflammation.
Purpose of the Study:
- To investigate the persistence of elevated inflammation-related proteins in the blood of preterm infants with umbilical cord inflammation.
- To evaluate the association between umbilical cord inflammation and postnatal blood protein concentrations at day 7.
- To determine if adjusted factors influence the relationship between funisitis and sustained inflammation.
Main Methods:
- Analysis of 834 preterm infants (born < 28 weeks gestation).
- Assessment of umbilical cord inflammation grades (1-5).
- Measurement of nine inflammation-related proteins (e.g., CRP, MPO, IL1β, IL8, TNFα, ICAM3, MMP9) at birth, day 1, and every two weeks postnatally.
Main Results:
- 12% and 17% of infants had moderate (grade 1-2) and severe (grade 3-5) funisitis, respectively.
- Seven of nine proteins showed elevated concentrations on day 7 in infants with funisitis.
- Elevated odds ratios for MPO, IL1β, TNFα, IL8, ICAM3, and MMP9 persisted after adjusting for gestational age, growth restriction, and postnatal exposures.
Conclusions:
- Umbilical cord inflammation is associated with sustained elevated levels of specific inflammation-related proteins on postnatal day 7.
- This persistence suggests a reinforcement loop contributing to sustained systemic inflammation in preterm infants.
- Findings highlight the long-term inflammatory impact of intrauterine inflammation.
Abstract:
Intrauterine inflammation is followed by elevated concentrations of inflammation-related proteins in the newborn's blood. Many of these proteins have short half-lives. The persistence of this postnatal inflammation has not previously been investigated. In a sample of 834 infants born before the 28th week of gestation, 12% (103) had grade 1 or 2, and 17% (142) had grade 3, 4, or 5 umbilical cord inflammation. Concentrations of nine proteins previously shown to be associated with umbilical cord inflammation at birth were measured on the first postnatal day and at two weekly intervals after birth. We evaluated the hypothesis that children who had umbilical cord inflammation were no more likely than others to have elevated concentrations of inflammation-related proteins in postnatal blood. The concentrations of seven of the nine proteins [C-reactive protein (CRP), myeloperoxidase (MPO), IL1β, IL8, TNFα, intercellular adhesion molecule-1 (ICAM3), and matrix metalloproteinase (MMP9)] showed a tendency to be elevated on day 7 among infants with funisitis. Adjusting for gestational age, growth restriction, and three postnatal exposures (ventilation on day 7, presumed and definite early bacteremia, and Bell stage III necrotizing endocolitis) did not diminish the elevated odds ratios of concentrations in the top quartile (for gestational age and day the specimen was obtained) of MPO, IL1β, TNFα, IL8, ICAM3, and MMP9. The persistence of a relationship between umbilical cord inflammation and elevated blood concentrations of inflammation-related proteins on postnatal day 7 suggests the existence of phenomena that contribute to a reinforcement loop and thereby sustained systemic inflammation.
Related Concept Videos
01:12Chronic Inflammation: Introduction
01:25Inflammatory Bowel Disease III: Crohn's Disease
01:20Inflammatory Bowel Disease II: Ulcerative Colitis
01:22Development of Immunocompetence
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by transmural...
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...