Amniotic fluid interleukin 6 and interleukin 8 are superior predictors of fetal lung injury compared with maternal or fetal plasma cytokines or placental histopathology in a nonhuman primate model

McCartney, Stephen A.; Kapur, Raj P.; Liggitt, H. Denny; Baldessari, Audrey; Coleman, Michelle; Orvis, Austyn; Ogle, Jason; Katz, Ronit; Rajagopal, Lakshmi; Waldorf, Kristina M. Adams

doi:10.1016/j.ajog.2020.12.1214

Cited by 24 publications

(14 citation statements)

References 93 publications

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“…The parameters derived were expressed as mean ± standard error of the mean. The statistical method [15] used was the Student's t-test (two-tailed for two independent groups). For multiple group comparisons, statistical analysis was performed using the Kruskal-Wallis one-way analysis of variance.…”

Section: Discussionmentioning

confidence: 99%

“…The causes of cerebral palsy in term and preterm babies are different. Compared with other models, such as the preterm brain damage model [13,14], the infectious preterm chorioamnionitis model [15], and the LPS induced maternal systematic to fetal inflammation model [16][17][18][19][20][21][22], our mouse model was only designed to mimic increasing inflammation at term. It is critical to model asymptomatic BV-like vaginal inflammation to intrauterine inflammation following uterine contractions-like ischemic reperfusion.…”

Section: Introductionmentioning

confidence: 99%

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Amniotic LPS-Induced Apoptosis in the Fetal Brain Is Suppressed by Vaginal LPS Preconditioning but Is Promoted by Continuous Ischemic Reperfusion

Dong

Kimura

Yaegashi

2022

IJMS

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Chorioamnionitis (CAM) is an increasingly common disease affecting pregnant women which derives from bacterial vaginosis. In different clinical cases, it has been shown that CAM can cause multiple risk factors for fetal brain damage, such as infection, and intra-uterine asphyxia. However, the molecular mechanism remains unknown. In this study, we established a novel CAM mouse model by exposing pregnant mice to a combination of three risk factors: vaginal lipopolysaccharides (LPS), amniotic LPS, and ischemic reperfusion. We found amniotic LPS caused Parkinson’s disease-like fetal brain damage, in a dose and time-dependent manner. Moreover, the mechanism of this fetal brain damage is apoptosis induced by amniotic LPS but it was inhibited by being pretreated with a vaginal LPS challenge before amniotic LPS injection. In contrast, amniotic LPS with continuous ischemic reperfusion caused a higher level of apoptotic cell death than amniotic LPS alone. In particular, a potential neuroprotective biomarker phosphorylation (p)-CREB (ser133) appeared in only vaginal LPS preconditioned before amniotic LPS, whereas ischemic reperfusion triggered IKK phosphorylation after amniotic LPS. Despite the need for many future investigations, this study also discussed a developed understanding of the molecular mechanism of how these phenotypes occurred.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Amniotic LPS-Induced Apoptosis in the Fetal Brain Is Suppressed by Vaginal LPS Preconditioning but Is Promoted by Continuous Ischemic Reperfusion

Dong

Kimura

Yaegashi

2022

IJMS

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“…Further study should be done to evaluate the interaction between azithromycin concentration and amniotic fluid inflammatory markers, which have been associated with both maternal and neonatal outcomes; these markers are potential PD indicators for azithromycin therapy and/or prognostic indicators for outcome. Additionally, it is critical to evaluate how maternal azithromycin dosing impacts fetal exposure and potentially neonatal outcomes, including risk of respiratory illness, 25 , 26 , 27 in order to determine appropriate maternal azithromycin dosing.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal evaluation of azithromycin and cytokine concentrations in amniotic fluid following one‐time oral dosing in pregnancy

Boelig

Lam

Rochani

et al. 2021

Clinical Translational Sci

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“…Prostaglandins, which increase cervical softening, are also observed to increase in the amniotic fluid during GBS invasion of the chorioamniotic membranes and amniotic cavity (Boldenow et al, 2016;Coleman et al, 2021). A recent study found that higher amniotic fluid IL-6 and IL-8 concentrations are also useful predictors of fetal lung injury in a nonhuman primate model of GBS chorioamnionitis (McCartney et al, 2021). Thus, amniotic fluid cytokines and chemokines play a role in the development of adverse maternal and fetal outcomes during GBS infection.…”

Section: Gbs Trafficking Into the Amniotic Cavitymentioning

confidence: 99%

Bacterial and Host Determinants of Group B Streptococcal Vaginal Colonization and Ascending Infection in Pregnancy

Brokaw

Furuta

Dacanay

et al. 2021

Front. Cell. Infect. Microbiol.

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Group B streptococcus (GBS) is a gram-positive bacteria that asymptomatically colonizes the vaginal tract. However, during pregnancy maternal GBS colonization greatly predisposes the mother and baby to a wide range of adverse outcomes, including preterm birth (PTB), stillbirth, and neonatal infection. Although many mechanisms involved in GBS pathogenesis are partially elucidated, there is currently no approved GBS vaccine. The development of a safe and effective vaccine that can be administered during or prior to pregnancy remains a principal objective in the field, because current antibiotic-based therapeutic strategies do not eliminate all cases of invasive GBS infections. Herein, we review our understanding of GBS disease pathogenesis at the maternal-fetal interface with a focus on the bacterial virulence factors and host defenses that modulate the outcome of infection. We follow GBS along its path from an asymptomatic colonizer of the vagina to an invasive pathogen at the maternal-fetal interface, noting factors critical for vaginal colonization, ascending infection, and vertical transmission to the fetus. Finally, at each stage of infection we emphasize important host-pathogen interactions, which, if targeted therapeutically, may help to reduce the global burden of GBS.

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Amniotic fluid interleukin 6 and interleukin 8 are superior predictors of fetal lung injury compared with maternal or fetal plasma cytokines or placental histopathology in a nonhuman primate model

Cited by 24 publications

References 93 publications

Amniotic LPS-Induced Apoptosis in the Fetal Brain Is Suppressed by Vaginal LPS Preconditioning but Is Promoted by Continuous Ischemic Reperfusion

Amniotic LPS-Induced Apoptosis in the Fetal Brain Is Suppressed by Vaginal LPS Preconditioning but Is Promoted by Continuous Ischemic Reperfusion

Longitudinal evaluation of azithromycin and cytokine concentrations in amniotic fluid following one‐time oral dosing in pregnancy

Bacterial and Host Determinants of Group B Streptococcal Vaginal Colonization and Ascending Infection in Pregnancy

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