Prevention of spontaneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment

Romero, Roberto

doi:10.1002/uog.5174

Cited by 85 publications

(76 citation statements)

References 238 publications

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“…Extension of parturition timing but with poor neonatal outcome in LPS-treated Trp53 loxP/loxP Pgr Cre/+ females by P 4 treatment alone suggests that it can address the ovarian insufficiency of P 4 secretion but cannot overcome the adverse effects of premature decidual senescence. Indeed, there is evidence that P 4 supplementation in humans can prevent preterm delivery only in certain patient populations with specific risk factors (47)(48)(49)(50)(51).…”

Section: Figurementioning

confidence: 99%

Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions

Cha¹,

Bartos²,

Egashira³

et al. 2013

J. Clin. Invest.

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There are currently more than 15 million preterm births each year. We propose that gene-environment interaction is a major contributor to preterm birth. To address this experimentally, we generated a mouse model with uterine deletion of Trp53, which exhibits approximately 50% incidence of spontaneous preterm birth due to premature decidual senescence with increased mTORC1 activity and COX2 signaling. Here we provide evidence that this predisposition provoked preterm birth in 100% of females exposed to a mild inflammatory insult with LPS, revealing the high significance of gene-environment interactions in preterm birth. More intriguingly, preterm birth was rescued in LPS-treated Trp53-deficient mice when they were treated with a combination of rapamycin (mTORC1 inhibitor) and progesterone (P 4 ), without adverse effects on maternal or fetal health. These results provide evidence for the cooperative contributions of two sites of action (decidua and ovary) toward preterm birth. Moreover, a similar signature of decidual senescence with increased mTORC1 and COX2 signaling was observed in women undergoing preterm birth. Collectively, our findings show that superimposition of inflammation on genetic predisposition results in high incidence of preterm birth and suggest that combined treatment with low doses of rapamycin and P 4 may help reduce the incidence of preterm birth in high-risk women.

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Section: Figurementioning

confidence: 99%

Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions

Cha¹,

Bartos²,

Egashira³

et al. 2013

J. Clin. Invest.

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“…[5][6][7][8][9] Interest in the cervix has recently exploded as its critical role in preterm birth has been elucidated; the complex and overlapping pathways to sPTB dovetail into the singular process of remodeling of cervical microstructure, and therefore it is hypothesized that a comprehensive understanding of that microstructure would allow targeted study of upstream molecular mechanisms. 5,7,8 Unfortunately, we lack a basic understanding of cervical microstructure, let alone its changes during pregnancy, because its identification and quantification is not trivial. Murine and bovine models suggest two or three layers of collagen in the cervix: a wide central circumferential layer that undergoes relatively greater reorganization in pregnancy than one or two flanking longitudinal layers.…”

Section: Introductionmentioning

confidence: 99%

Nonlinear optical microscopy and ultrasound imaging of human cervical structure

et al. 2013

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Abstract. The cervix softens and shortens as its collagen microstructure rearranges in preparation for birth, but premature change may lead to premature birth. The global preterm birth rate has not decreased despite decades of research, likely because cervical microstructure is poorly understood. Our group has developed a multilevel approach to evaluating the human cervix. We are developing quantitative ultrasound (QUS) techniques for noninvasive interrogation of cervical microstructure and corroborating those results with high-resolution images of microstructure from second harmonic generation imaging (SHG) microscopy. We obtain ultrasound measurements from hysterectomy specimens, prepare the tissue for SHG, and stitch together several hundred images to create a comprehensive view of large areas of cervix. The images are analyzed for collagen orientation and alignment with curvelet transform, and registered with QUS data, facilitating multiscale analysis in which the micron-scale SHG images and millimeter-scale ultrasound data interpretation inform each other. This novel combination of modalities allows comprehensive characterization of cervical microstructure in high resolution. Through a detailed comparative study, we demonstrate that SHG imaging both corroborates the quantitative ultrasound measurements and provides further insight. Ultimately, a comprehensive understanding of specific microstructural cervical change in pregnancy should lead to novel approaches to the prevention of preterm birth.

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“…For example, numerous studies have reported that excised cone size [8,13], number of cervical excisions [8], cervical length at 22-24 weeks of gestation [20,24], and the time interval between surgery and pregnancy [25] are factors that might increase the risk of preterm delivery among women who have previously undergone LEEP. Excision treatments of the transition zone depend on the nature and the extent of the disease.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy outcome after loop electrosurgical excision procedure for cervical intraepithelial neoplasia

Frega

Sesti

Sanctis

et al. 2013

Intl J Gynecology & Obste

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. Objective: To determine pregnancy outcomes among women who underwent loop electrosurgical excision procedure (LEEP). Methods: In a case-control study in Italy, 475 pregnant women who underwent LEEP and 441 untreated pregnant women were enrolled between January 2003 and January 2007. Outcome measures were spontaneous abortion, preterm delivery, and at-term delivery rates. Continuous and discrete variables were analyzed via t, χ 2 , and Fisher exact tests. Groups were compared by analysis of variance and Tukey HSD test. Results: The spontaneous abortion rate was 14.5% and 14.1% in the LEEP and untreated groups, respectively. The preterm delivery rate was 6.4% and 5.0% in the LEEP and untreated groups, respectively. The number of women with a cervical length of less than 30 mm was higher in the LEEP group, but this did not influence preterm delivery rate (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.53-1.95). Among women with a cervical length of less than 15 mm, those treated with a wider removal of cervical tissue showed increased risk of preterm delivery (OR, 5.31; 95% CI, 1.01-28.07). Conclusion: The preterm delivery rate was not higher among women who underwent LEEP than among untreated women. Preterm delivery was associated with cone size and cervical length in the second trimester.

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Prevention of spontaneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment

Cited by 85 publications

References 238 publications

Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions

Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions

Nonlinear optical microscopy and ultrasound imaging of human cervical structure

Pregnancy outcome after loop electrosurgical excision procedure for cervical intraepithelial neoplasia

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