Inhibition of gingipains prevents Porphyromonas gingivalis-induced preterm birth and fetal death in pregnant mice

Background: Preterm birth (PTB), or birth that occurs before 37 weeks of gestation, accounts for the majority of perinatal morbidity and mortality. As of 2016, PTB has an occurrence rate of 9.6% in the United States and accounts for up to 18 percent of births worldwide. Inflammation has been identified as the most common cause of PTB, but effective pharmacotherapy has yet to be developed to prevent inflammation driven PTB. Our group has discovered that N,N-dimethylacetamide (DMA), a readily available solvent commonly used as a pharmaceutical excipient, rescues lipopolysaccharide (LPS)-induced timed pregnant mice from PTB. Methods: We have used in vivo, ex vivo and in vitro approaches to investigate this compound further. Results: Interestingly, we found that DMA suppresses cytokine secretion by inhibiting nuclear factor-kappa B (NF-κB). In ongoing work in this exciting line of investigation, we are currently investigating structural analogs of DMA, some of them novel, to optimize this approach focused on the inflammation associated with PTB. Conclusion: Successful development of pharmacotherapy for the prevention of PTB rests upon the pursuit of multiple strategies to solve this important clinical challenge.

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Fertility Treatments and the Risk of Preterm Birth Among Women with Subfertility: A Linked-Data Retrospective Cohort Study

10.21203/rs.3.rs-206714/v1 ◽

2021 ◽

Author(s):

Jessica N Sanders ◽

Sara E Simonsen ◽

Christina A Porucznik ◽

Ahmad O Hammoud ◽

Ken Smith ◽

...

Keyword(s):

Cohort Study ◽

Preterm Birth ◽

In Vitro Fertilization ◽

Retrospective Cohort ◽

Fetal Death ◽

Perinatal Outcomes ◽

Birth Certificates ◽

Vitro Fertilization ◽

Fertility Treatments

Abstract Background: In vitro fertilization (IVF) births contribute to a considerable proportion of preterm birth (PTB) each year. However, there is no formal surveillance of adverse perinatal outcomes for less invasive fertility treatments. The study objective was to determine the effect of fertility treatment (in vitro fertilization, intrauterine insemination, usually with ovulation drugs (IUI), or ovulation drugs alone) on preterm birth, compared to no treatment in subfertile women.Methods: The Fertility Experiences Study (FES) is a retrospective cohort study conducted at the University of Utah between April 2010 and September 2012. Women with a history of primary subfertility self-reported treatment data via survey and interviews. Participant data were linked to birth certificates and fetal death records to asses for perinatal outcomes, particularly preterm birth.Results: A total 487 birth certificates and 3 fetal death records were linked as first births for study participants who completed questionnaires. Among linked births, 19% had a PTB. After adjustment for maternal age, paternal age, maternal education, annual income, religious affiliation, female or male fertility diagnosis, and duration of subfertility, the odds ratios and 95% confidence intervals (CI) for PTB were 2.17 (CI: 0.99, 4.75) for births conceived using ovulation drugs, 3.17 (CI: 1.4, 7.19) for neonates conceived using IUI and 4.24 (CI: 2.05, 8.77) for neonates conceived by IVF, compared to women with subfertility who used no treatment during the month of conception. A reported diagnosis of female factor infertility increased the adjusted odds of having a PTB 2.99 (CI: 1.5, 5.97). Duration of pregnancy attempt was not independently associated with PTB. In restricting analyses to singleton gestation, odds ratios remained elevated but were not significant for any type of treatment.Conclusion: IVF, IUI, and ovulation drugs were all associated with a higher incidence of preterm birth and low birth weight, predominantly related to multiple gestation births.

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Galectin-3 Plays an Important Role in Preterm Birth Caused by Dental Infection of Porphyromonas gingivalis

Scientific Reports ◽

10.1038/s41598-018-21072-y ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 9

Author(s):

Mutsumi Miyauchi ◽

Min Ao ◽

Hisako Furusho ◽

Chanbora Chea ◽

Atsuhiro Nagasaki ◽

...

Keyword(s):

Preterm Birth ◽

Porphyromonas Gingivalis ◽

Dental Infection ◽

Galectin 3

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Fetal death and preterm birth associated with maternal influenza vaccination: systematic review

BJOG An International Journal of Obstetrics & Gynaecology ◽

10.1111/1471-0528.12977 ◽

2014 ◽

Vol 122 (1) ◽

pp. 17-26 ◽

Cited By ~ 68

Author(s):

DB Fell ◽

RW Platt ◽

A Lanes ◽

K Wilson ◽

JS Kaufman ◽

...

Keyword(s):

Systematic Review ◽

Preterm Birth ◽

Influenza Vaccination ◽

Fetal Death ◽

Maternal Influenza

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Porphyromonas gingivalis, a cause of preterm birth in mice, induces an inflammatory response in human amnion mesenchymal cells but not epithelial cells

Placenta ◽

10.1016/j.placenta.2020.07.016 ◽

2020 ◽

Vol 99 ◽

pp. 21-26

Author(s):

Haruhisa Konishi ◽

Satoshi Urabe ◽

Yuko Teraoka ◽

Yoshito Morishita ◽

Iemasa Koh ◽

...

Keyword(s):

Preterm Birth ◽

Epithelial Cells ◽

Inflammatory Response ◽

Porphyromonas Gingivalis ◽

Mesenchymal Cells ◽

Human Amnion

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Dental infection of porphyromonas gingivalis induces preterm birth

Placenta ◽

10.1016/j.placenta.2014.08.083 ◽

2014 ◽

Vol 35 (10) ◽

pp. A22

Author(s):

Mutsumi Miyauchi ◽

Hisako Furusho ◽

Atsuhiro Nagasaki ◽

Satoshi Urabe ◽

Haruhisa Konishi ◽

...

Keyword(s):

Preterm Birth ◽

Porphyromonas Gingivalis ◽

Dental Infection

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Prospective risk of intrauterine death of monochorionic twins: update

Journal of Perinatal Medicine ◽

10.1515/jpm-2015-0319 ◽

2016 ◽

Vol 44 (8) ◽

Cited By ~ 3

Author(s):

Teresinha Simões ◽

Alexandra Queirós ◽

Ana Teresa Marujo ◽

Sandra Valdoleiros ◽

Patricia Silva ◽

...

Keyword(s):

Preterm Birth ◽

Fetal Death ◽

Intrauterine Death ◽

Monochorionic Twins ◽

Death Rates ◽

Gestational Period ◽

Period Data ◽

Prospective Risk ◽

Twin Pregnancies ◽

Over Time

AbstractObjective:To calculate an updated prospective risk of fetal death in monochorionic-biamniotic (MCBA) twins.Study design:We evaluated 520 MCBA twin pregnancies that had intensive prenatal surveillance and delivered in a single Portuguese referral center. The prospective risk of fetal death was calculated as the total number of deaths at the beginning of the gestational period divided by the number of continuing pregnancies at or beyond that period. Data were compared to the 2006 previous report.Results:Nearly 80% of the neonates weighed <2500 g, including 13.5% who weighed <1500 g. Half were born at <36 weeks, including 13.8% who were born at <32 weeks. The data indicate an increased IUFD rate over time – 16 fetal deaths per pregnancy (3.1%) and 22 IUFDs per fetus (2.1%). The rate of IUFD after 32–33 weeks, however, was halved (1/187 pregnancies and 1/365 fetuses, 0.5 and 0.3%, respectively).Conclusion:Intensive prenatal surveillance might decrease the unexpected fetal death rates after 33 week’s gestation and our data do not support elective preterm birth for uncomplicated MCBA twins.

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