Inflammation in the womb may explain why some babies are more prone to sepsis after birth

October 9, 2018, Elsevier
Analyses of chorioamnion, lungs, gut, and plasma samples. (A-C) Images from hematoxylin and eosin staining in the chorioamnion, scale bars represent 100 μm. (D-E, G-H) Myeloperioxidase (MPO) staining in lungs and gut, scale bars represent 200 μm. (F) Lung CXCL8 levels. (I-K) Incidence of severe diarrhea and physical activities in postnatal control and LPS-exposed pigs. (L) Plasma interleukin (IL)-1β levels in the two treatment groups. CON, control pigs; LPS, intra-amniotic lipopolysaccharide exposed pigs. *P < 0.05, **P < 0.01, and ***P < 0.001. Credit: American Journal of Pathology

Each year 15 million infants are born preterm and face high risks of short- and long-term complications, including sepsis, severe inflammation of the gut, and neurodevelopmental disorders. A new report in the American Journal of Pathology demonstrates a link between prenatal inflammation and postnatal immune status and organ function in preterm pigs, suggesting that early intervention (eg, antibiotics or anti-inflammatory drugs) may be warranted for infants born preterm with signs of inflammation of fetal membranes.

"Our study may urge clinicians to be more aware of the population of preterm infants with chorioamnionitis ( of the fetal membrane) as they have higher risks of systemic inflammation and neonatal sepsis," explained lead investigator Per T. Sangild, DVSc, DMSc, Ph.D., of the Section of Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark, and the Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.

"The data imply the importance of the integrity of barriers between epithelial tissues (eg, gut, lungs, and skin) and the circulation. Those barriers are more fragile in preterm neonates, and they can facilitate translocation of bacteria and inflammatory molecules, leading to systemic inflammation and internal organ disorders."

To induce prenatal inflammation, the bacterial endotoxin lipopolysaccharide (LPS) was injected into the amniotic sacs of prenatal pigs. LPS and control groups were analyzed at birth, three days after birth, and five days after birth (formula feeding).

At birth, prenatal LPS induced mild histologic chorioamnionitis and strong fetal lung and gut innate immune responses with elevated inflammatory cytokines and neutrophil/macrophage infiltration. "We believe the epithelial responses were likely derived from direct exposure to intra-amniotic LPS or LPS-induced cytokines," noted Dr. Sangild.

Five days later, the gut and subsided; however, the pigs exposed to LPS prenatally gradually developed systemic inflammation, with high levels of blood leukocyte subsets (eg, neutrophils, lymphocytes) and plasma cytokines (eg, IL-1β), similar to symptoms found in septic infants. Among those who survived, the pigs in the control group were on their feet and walked for the first time before the LPS-exposed animals. High levels of bacteria were also found in the spleen in the LPS-exposed pigs, indicating increased systemic infection or decreased capacity to clear translocated bacteria. The in utero death rate was higher in the LPS-exposed fetuses compared to the control group, as was the incidence of severe diarrhea. Interestingly, intra-amniotic LPS did not increase the incidence of formula-induced necrotizing enterocolitis (NEC) on Day 5. This is important as it has been suspected that at birth might also predispose to later NEC in the gut of ; however, this hypothesis was not supported by this study.

"These data suggest that the postnatal systemic effects of short-term prenatal LPS were indirectly initiated from the preceding local inflammation of in the fetal period, and the effects were gradually amplified systemically during the first few days after preterm birth," commented Dr. Sangild.

The results of this study highlight the importance of early diagnosis of prenatal inflammation to facilitate nutritional, medical, or pharmaceutical interventions that attenuate the detrimental postnatal responses to prenatal inflammation. The problem still remains that a pregnant woman with intra-amniotic inflammation may be asymptomatic and, therefore, unaware she has an infection that could harm her baby.

Explore further: Study finds human milk components in amniotic fluid

More information: "Prenatal Intra-Amniotic Endotoxin Induces Fetal Gut and Lung Immune Responses and Postnatal Systemic Inflammation in Preterm Pigs," American Journal of Pathology (2018). DOI: 10.1016/j.ajpath.2018.07.020

Related Stories

Study finds human milk components in amniotic fluid

October 2, 2018
Human milk oligosaccharides (HMOs) are complex carbohydrates that are highly abundant and unique to human milk. Accumulating evidence indicates that exposure to HMOs in the postnatal period has both immediate and long-term ...

Pregnant sheep considered in pre-term birth study

November 7, 2014
Scientists are a step closer to understanding how bacterial infections in pregnant women lead to pre-term births—the main cause of neonatal death and disease in Australia.

Study shows how fetal infections may cause adult heart disease

January 23, 2018
Recent studies have shown that infants born prematurely have a higher risk of developing heart disease later in life. Now, a study led by researchers at the University of Washington School of Medicine in Seattle shows that, ...

Study describes potential clinical test and treatment for preterm birth

March 9, 2017
Scientists identified a molecular driver of inflammation that may finally answer a key question about what causes mild systemic prenatal infections to trigger preterm birth.

Presence of intra-amniotic debris a risk for early preterm birth in first pregnancy

February 11, 2013
In a study to be presented on February 14 at the Society for Maternal-Fetal Medicine's annual meeting, The Pregnancy Meeting, in San Francisco, California, researchers will report findings suggesting an increased risk of ...

Recommended for you

Study shows changes in histone methylation patterns in nutritionally stunted children

November 13, 2018
An international team of researchers has found changes in histone methylation patterns in nutritionally stunted children. In their paper published in Proceedings of the National Academy of Sciences, the group describes their ...

Your 6-month-old isn't sleeping through the night? Relax

November 12, 2018
(HealthDay)—If your 6-month-old still wakes up at 2 a.m., a new study suggests you don't lose any additional sleep worrying about it.

New exercise guidelines: Move more, sit less, start younger

November 12, 2018
Move more, sit less and get kids active as young as age 3, say new federal guidelines that stress that any amount and any type of exercise helps health.

Some activity fine for kids recovering from concussions, docs say

November 12, 2018
(HealthDay)—Children and teens who suffer a sports-related concussion should reduce, but not eliminate, physical and mental activity in the days after their injury, an American Academy of Pediatrics report says.

Breast milk and babies' saliva shape oral microbiome

November 8, 2018
Newborn breastfed babies' saliva combines with breastmilk to release antibacterial compounds that help to shape the bacterial communities (microbiota) in babies' mouths, biomedical scientists have found.

Preschool children show awake responses to naptime nonsense words

November 7, 2018
Of all of our senses, hearing is the only one that has long been suspected as being "on" all the time—even in our sleep. Sounds that occur during the night have a way of registering in the brain. Now a group of scientists ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.