Growth Restriction and Systemic Immune Development in Preterm Piglets

Bæk, Ole; Sangild, Per Torp; Thymann, Thomas; Nguyen, Duc Ninh

doi:10.3389/fimmu.2019.02402

Cited by 24 publications

(29 citation statements)

References 38 publications

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“…Cord blood of FGR and NBW pigs was initially used to examine immune competence at birth by a whole blood stimulation assay with LPS. Before LPS stimulation, FGR preterm pigs showed lower baseline expressions of few genes, However, we did not measure the leucocyte levels in Exp 1, but we have previously shown that FGR piglets tend to have lower lymphocyte counts (but not neutrophil and monocyte counts) in cord blood (10). Therefore, it is possible that differences in expressions of some lymphocytes-related genes at baseline may be influenced by the leucocyte levels.…”

Section: Discussionmentioning

confidence: 89%

“…Collectively, our results suggest that preterm pigs born moderately growth restricted were immune suppressed or experienced some delay in immune maturation, which may be further exacerbated by neonatal antibiotic use. Such effects may be most pronounced in the immediate neonatal period (e.g., the first 1-2 weeks), as supported by the limited effects of moderate FGR and prematurity on blood immune parameters (10,53) and gut and brain development beyond the first 2 weeks of life (53,54). Correspondingly, a dysfunctional immune system and an increased risk of infections in preterm infants with fetal growth restriction suggest special care and medical attention in this population to avoid damaging infections in the critical neonatal period.…”

Section: Discussionmentioning

confidence: 96%

“…After stimulation, whole blood was stabilized with a mixture of lysis/binding solution concentrate and isopropanol (MagMax 96 blood RNA isolation kit, Thermofisher, Roskilde, Denmark), and stored at −80 • C until RNA extraction. RNA was extracted and prepared for quantitative polymerase chain reaction (qPCR) as described elsewhere (10). Using a LightCycler 480 system (Roche, Switzerland) and a commercial qPCR kit (QuantiTect SYBR Green PCR Kit, Qiagen, Netherlands), gene expressions were determined for a panel of 23 genes related to innate and adaptive immunity, as well as cellular metabolism.…”

Section: Whole Blood Stimulation and Neutrophil Phagocytosis Assaysmentioning

confidence: 99%

“…Some studies even suggested that this impaired immune status may persist for years after birth with SGA ( 8 , 9 ). From animal studies, low birth weight following term birth has been correlated with negative long term effects on growth as well as systemic and gut immune functions ( 10 – 13 ). The possible effects of being both premature and SGA on immune development and infection risks during the first few days of life, remain elusive.…”

Section: Introductionmentioning

confidence: 99%

“…FGR was defined as the lowest 25% birth weight percentile to include both moderately and extremely growth restricted neonates in evaluating immune status, spontaneous infections and responses to infection challenges, with or without antibiotic treatment just after preterm birth. Different from our previous longer term study on systemic immune status in FGR and NBW preterm pigs with optimal feeding to avoid clinical complications ( 10 ), we now focused on the in vitro and in vivo responses to systemic infection in the first week after preterm birth when both preterm pigs and infants are highly sensitive to infections.…”

Section: Introductionmentioning

confidence: 99%

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Impaired Neonatal Immunity and Infection Resistance Following Fetal Growth Restriction in Preterm Pigs

et al. 2020

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Background: Infants born preterm or small for gestational age (SGA, due to fetal growth restriction) both show an increased risk of neonatal infection. However, it remains unclear how the co-occurrence of preterm birth and SGA may affect neonatal immunity and infection risk. We hypothesized that fetal growth restricted (FGR) preterm newborns possess impaired immune competence and increased susceptibility to systemic infection and sepsis, relative to corresponding normal birth weight (NBW) newborns. Methods: Using preterm pigs as a model for preterm infants, gene expression in lipopolysaccharide (LPS) stimulated cord blood was compared between NBW and FGR (lowest 25% birth weight percentile) preterm pigs. Next, clinical responses to a systemic Staphylococcus epidermidis (SE) challenge were investigated in newborn FGR and NBW preterm pigs. Finally, occurrence of spontaneous infections were investigated in 9 d-old FGR and NBW preterm pigs, with or without neonatal antibiotics treatment. Results: At birth, preterm FGR piglets showed diminished ex vivo cord blood responses to LPS for genes related to both innate and adaptive immunity, and also more severe septic responses following SE infection (e.g., higher blood lactate, decreased blood pH, neutrophil and platelet counts, relative to NBW pigs). After 9 d, FGR pigs had higher incidence and severity of spontaneous infections (e.g., higher bacterial densities in the bone marrow), increased regulatory T cell numbers, reduced neutrophil phagocytosis capacity, and impaired ex vivo blood gene responses to LPS, especially when receiving neonatal antibiotics. Conclusion: FGR at preterm birth is associated with poor immune competence, impaired infection resistance, and greater sepsis susceptibility in the immediate postnatal period. Our results may explain the increased morbidity and mortality of SGA preterm infants and highlight the need for clinical vigilance for this highly sensitive subgroup of preterm neonates.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 96%

Section: Whole Blood Stimulation and Neutrophil Phagocytosis Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impaired Neonatal Immunity and Infection Resistance Following Fetal Growth Restriction in Preterm Pigs

et al. 2020

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Ultra‐High Temperature Treatment of Liquid Infant Formula, Systemic Immunity, and Kidney Development in Preterm Neonates

Sun,

Akıllıoğlu,

Zhong

et al. 2023

Molecular Nutrition Food Res

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ScopeReady‐to‐feed liquid infant formulas (IFs) are increasingly being used for newborn preterm infants when human milk is unavailable. However, sterilization of liquid IFs by ultra‐high temperature (UHT) introduces Maillard reaction products (MRPs) that may negatively affect systemic immune and kidney development.Methods and resultsUHT‐treated IF without and with prolonged storage (SUHT) are tested against pasteurized IF (PAST) in newborn preterm pigs as a model for preterm infants. After 5 days, blood leukocytes, markers of systemic immunity and inflammation, kidney structure and function are evaluated. No consistent differences between UHT and PAST pigs are observed. However, SUHT increases plasma TNFα and IL‐6 and reduces neutrophils and in vitro response to LPS. In SUHT pigs, the immature kidneys show minor upregulation of gene expressions related to inflammation (RAGE, MPO, MMP9) and oxidative stress (CAT, GLO1), together with glomerular mesangial expansion and cell injury. The increased inflammatory status in SUHT pigs appears unrelated to systemic levels of MRPs.ConclusionSUHT feeding may impair systemic immunity and affect kidney development in preterm newborns. The systemic effects may be induced by local gut inflammatory effects of MRPs. Optimal processing and length of storage are critical for UHT‐treated liquid IFs for preterm infants.

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Nomogram for predicting fulminant necrotizing enterocolitis

Zhang

et al. 2023

Pediatr Surg Int

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Background Fulminant necrotizing enterocolitis (FNEC) is the most serious subtype of NEC and has a high mortality rate and a high incidence of sequelae. Onset prediction can help in the establishment of a customized treatment strategy. This study aimed to develop and evaluate a predictive nomogram for FNEC. Methods We conducted a retrospective observation to study the clinical data of neonates diagnosed with NEC (Bell stage ≥ IIB). Neonates were divided into the FNEC and NEC groups. A multivariate logistic regression model was used to construct the nomogram model. The performance of the nomogram was assessed using area under the curve, calibration analysis, and decision curve analysis. Results A total of 206 neonate cases were included, among which 40 (19.4%) fulfilled the definition of FNEC. The identified predictors were assisted ventilation after NEC onset; shock at NEC onset; feeding volumes before NEC onset; neutrophil counts on the day of NEC onset; and neutrophil, lymphocyte, and monocyte counts on day 1 after NEC onset. The nomogram exhibited good discrimination, with an area under the receiver operating characteristic curve of 0.884 (95% CI 0.825–0.943). The predictive model was well calibrated. Decision curve analysis confirmed the clinical usefulness of this nomogram. Conclusion A nomogram with a potentially effective application was developed to facilitate the individualized prediction of FNEC, with the hope of providing further direction for the early diagnosis of FNEC and timing of intervention.

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Growth Restriction and Systemic Immune Development in Preterm Piglets

Cited by 24 publications

References 38 publications

Impaired Neonatal Immunity and Infection Resistance Following Fetal Growth Restriction in Preterm Pigs

Impaired Neonatal Immunity and Infection Resistance Following Fetal Growth Restriction in Preterm Pigs

Ultra‐High Temperature Treatment of Liquid Infant Formula, Systemic Immunity, and Kidney Development in Preterm Neonates

Nomogram for predicting fulminant necrotizing enterocolitis

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