Dataset Information

Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4.

ABSTRACT: Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Inflammation is causally linked to preterm birth; therefore, finding an intervention that dampens maternal and fetal inflammatory responses may provide a new strategy to prevent adverse pregnancy and neonatal outcomes. Using animal models of systemic maternal inflammation [intraperitoneal injection of lipopolysaccharide (LPS)] and fetal inflammation (intra-amniotic administration of LPS), we found that (1) systemic inflammation induced adverse pregnancy and neonatal outcomes by causing a severe maternal cytokine storm and a mild fetal cytokine response; (2) fetal inflammation induced adverse pregnancy and neonatal outcomes by causing a mild maternal cytokine response and a severe fetal cytokine storm; (3) exendin-4 (Ex4) treatment of dams with systemic inflammation or fetal inflammation improved adverse pregnancy outcomes by modestly reducing the rate of preterm birth; (4) Ex4 treatment of dams with systemic, but not local, inflammation considerably improved neonatal outcomes, and such neonates continued to thrive; (5) systemic inflammation facilitated the diffusion of Ex4 through the uterus and the maternal-fetal interface; (6) neonates born to Ex4-treated dams with systemic inflammation displayed a similar cytokine profile to healthy control neonates; and (7) treatment with Ex4 had immunomodulatory effects by inducing an M2 macrophage polarization and increasing anti-inflammatory neutrophils, as well as suppressing the expansion of CD8+ regulatory T cells, in neonates born to dams with systemic inflammation. Collectively, these results provide evidence that dampening maternal systemic inflammation through novel interventions, such as Ex4, can improve the quality of life for neonates born to women with this clinical condition.

SUBMITTER: Garcia-Flores V

PROVIDER: S-EPMC6015905 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4.

Garcia-Flores Valeria V Romero Roberto R Miller Derek D Xu Yi Y Done Bogdan B Veerapaneni Chharitha C Leng Yaozhu Y Arenas-Hernandez Marcia M Khan Nabila N Panaitescu Bogdan B Hassan Sonia S SS Alvarez-Salas Luis Marat LM Gomez-Lopez Nardhy N

Frontiers in immunology 20180618

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Inflammation is causally linked to preterm birth; therefore, finding an intervention that dampens maternal and fetal inflammatory responses may provide a new strategy to prevent adverse pregnancy and neonatal outcomes. Using animal models of systemic maternal inflammation [intraperitoneal injection of lipopolysaccharide (LPS)] and fetal inflammation (intra-amniotic administration of LPS), we found that (1) systemic ...[more]

PMID: 29967606

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Project description:BackgroundThe current study aimed to estimate the prevalence of alcohol use identified as a risk factor during pregnancies by the antenatal care providers, resulting in live births in British Columbia (BC) and to examine associations between alcohol use, adverse neonatal outcomes, and pregnancy complications.MethodsThis population-based cross-sectional study utilized linked obstetrical and neonatal records within the BC Perinatal Data Registry (BCPDR), for deliveries that were discharged between January 1, 2015 and March 31, 2018. The main outcome measures were alcohol use identified as a risk factor during pregnancy, associated maternal characteristics, pregnancy complications, and adverse neonatal outcomes. Estimates for the period and fiscal year prevalence were calculated. Chi-square tests were used to compare adverse neonatal outcomes and pregnancy complications by alcohol use during pregnancy identified as a risk factor. Logistic regression was used to examine the association between alcohol use identified as a risk factor during pregnancy and adverse neonatal outcomes and pregnancy complications, after adjusting for identified risk factors.ResultsA total of 144,779 linked records within the BCPDR were examined. The period prevalence of alcohol use during pregnancy identified as a risk factor was estimated to be 1.1% and yearly prevalence was 1.1, 1.1, 1.3 and 0.9% from the 2014/2015 to 2017/2018 fiscal years, respectively. Alcohol use identified as a risk factor was associated with younger maternal age, fewer antenatal visits, being primiparous, a history of mental illness, substance use and smoking. Neonates with alcohol use during pregnancy identified as a risk factor had greater odds of being diagnosed with: "low birth weight (1000-2499g)" (ICD-10: P07.1; aOR?=?1.25; 95% CI: 1.01, 1.53), "other respiration distress of newborn" (ICD-10: P22.8; aOR?=?2.57; 95% CI: 1.52, 4.07), "neonatal difficulty in breastfeeding" (ICD-10: P92.5; aOR?=?1.97; 95% CI: 1.27, 2.92) and "feeding problems, unspecified" (ICD-10: P92.9; aOR?=?2.06; 95% CI: 1.31, 3.09).ConclusionsThe prevalence of alcohol use during pregnancy identified as a risk factor was comparable to previous estimates within the BCPDR. Identified prenatal alcohol exposure was associated with notable differences in maternal and neonatal characteristics and adverse neonatal outcomes. More consistent, thorough screening and prevention efforts targeting alcohol use in pregnancy are urgently needed in Canada.

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Dataset Information

Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4.

Publications

Inflammation-Induced Adverse Pregnancy and Neonatal Outcomes Can Be Improved by the Immunomodulatory Peptide Exendin-4.

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