AUTHOR=Bæk Ole , Sangild Per Torp , Thymann Thomas , Nguyen Duc Ninh 

TITLE=Growth Restriction and Systemic Immune Development in Preterm Piglets

JOURNAL=Frontiers in Immunology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02402

DOI=10.3389/fimmu.2019.02402

ISSN=1664-3224

ABSTRACT=Background: Many preterm infants are born with growth restriction (GR) following maternal or fetal complications before birth. Such infants may continue to grow slowly after birth, regardless of birth weight (BW), due to morbidities related to their immature organs. Severe GR increases the susceptibility to infections, but it is not clear if this is a consequence of impaired systemic immunity or other factors, such as prolonged hospital stay or poor mucosal barrier function. Using preterm pigs as models for preterm infants, we hypothesized that moderate GR, exerting limited clinical effects, does not influence systemic immune development. Methods: Preterm pigs were delivered by caesarean section and fed bovine milk diets until 19 d. Piglets with fetal growth restriction (F-GR, the lowest 25% of BW, n=27, excluding those with BW < 350 g) and postnatal growth restriction (P-GR, the lowest 25% of postnatal growth rate, n=24) were compared with their corresponding controls (F-CON, n=92, and  P-CON, n=85, respectively). Organ weights were determined and blood collected for assessment of clinical status (blood chemistry and hematology). For a subgroup (n=58), in depth analysis of neutrophil function, T cell counts, plasma cytokine levels and leucocyte gene expression were performed. Results: For F-GR pigs, adrenal gland weight was increased and bone mineral content decreased at 19 d. Total leucocyte levels were lower at birth and interleukin-10 levels increased at d 8-10.  In P-GR pigs, total leucocyte, neutrophil, monocyte and eosinophil counts along with helper T cell fractions were elevated at 8-19 d of age, while the fraction of neutrophils with phagocytic capacity was reduced. Diarrhea and all remaining organ weight, blood chemistry and immune variables were not affected by F-GR or P-GR. Conclusion: Moderate GR before and after preterm birth has limited impacts on systemic immune development in preterm pigs, despite marginal effects on immune cell populations, adrenocortical function and body composition. Similar trends may occur in preterm infants with moderate fetal and postnatal growth restriction.