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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:BackgroundSickle cell disease in pregnancy is associated with high maternal and fetal mortality. However, studies reporting pregnancy, fetal, and neonatal outcomes in women with sickle cell disease are extremely limited.ObjectivesThe objectives of the study are to determine whether women with sickle cell disease have a greater risk of adverse pregnancy, fetal, and neonatal outcomes than women without sickle cell disease and identify the predictors of adverse pregnancy, fetal, and neonatal outcomes in women with sickle cell disease.DesignA retrospective pair-matched case-control study was conducted to compare 171 pregnant women with sickle cell disease to 171 pregnant women without sickle cell disease in Muscat, Sultanate of Oman.MethodsAll pregnant Omani women with sickle cell disease who delivered between January 2015 and August 2021 at Sultan Qaboos University Hospital and Royal Hospital, who were either primipara or multipara and who had a gestational age of 24-42 weeks, were included as patients, whereas women who had no sickle cell disease or any comorbidity during pregnancy, who delivered within the same timeframe and at the same hospitals, were recruited as controls. The data were retrieved from electronic medical records and delivery registry books between January 2015 and August 2021.ResultsWomen with sickle cell disease who had severe anemia had increased odds of (χ2 = 58.56, p < 0.001) having adverse pregnancy outcomes. Women with sickle cell disease had 21.97% higher odds of delivering a baby with intrauterine growth retardation (χ2 = 17.80, unadjusted odds ratio = 2.91-166.13, p < 0.001). Newborns born to women with sickle cell disease had 3.93% greater odds of being admitted to the neonatal intensive care unit (χ2 = 16.80, unadjusted odds ratio = 1.97-7.84, p < 0.001). In addition, the children born to women with sickle cell disease had 10.90% higher odds of being born with low birth weight (χ2 = 56.92, unadjusted odds ratio = 5.36-22.16, p < 0.001). Hemoglobin level (odds ratio = 0.17, p < 0.001, 95% confidence interval = 0.10-3.0), past medical history (odds ratio = 7.95, p < 0.001, 95% confidence interval = 2.39-26.43), past surgical history (odds ratio = 17.69, p < 0.001, 95% confidence interval = 3.41-91.76), and preterm delivery (odds ratio = 9.48, p = 0.005, 95% confidence interval = 1.95-46.23) were identified as predictors of adverse pregnancy, fetal, and neonatal outcomes in women with sickle cell disease.ConclusionAs pregnant women with sickle cell disease are at increased risk for pregnancy, fetal, and neonatal adverse outcomes; improved antenatal surveillance and management may improve the outcomes.

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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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