Placental Vascular Pathology Findings and Pathways to Preterm Delivery

Kelly, Rosemary; Holzman, Claudia; Senagore, Patricia K.; Wang, J.; Tian, Yuxin; Rahbar, Mohammad Hossein; Chung, Hwan

doi:10.1097/01.ogx.0000361373.44269.38

Cited by 22 publications

(31 citation statements)

References 28 publications

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“…Shallow EVT invasion and insufficient spiral artery remodeling are shared pathophysiologies of other pregnancy complications, such as intrauterine growth restriction (IUGR) 63 and pre-term labor. 64 Therefore, our findings regarding miR-218-5p may warrant further investigation into other gestational disorders. The use of miRNAs as potential plasma biomarkers has been investigated, 28,65 and the utility of miR-218-5p as both a predictive and prognostic marker in cancer has been suggested.…”

Section: Discussionmentioning

confidence: 79%

MicroRNA-218-5p Promotes Endovascular Trophoblast Differentiation and Spiral Artery Remodeling

et al. 2018

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Preeclampsia (PE) is the leading cause of maternal and neonatal morbidity and mortality. Defects in trophoblast invasion, differentiation of endovascular extravillous trophoblasts (enEVTs), and spiral artery remodeling are key factors in PE development. There are no markers clinically available to predict PE, leaving expedited delivery as the only effective therapy. Dysregulation of miRNA in clinical tissues and maternal circulation have opened a new avenue for biomarker discovery. In this study, we investigated the role of miR-218-5p in PE development. miR-218-5p was highly expressed in EVTs and significantly downregulated in PE placentas. Using first-trimester trophoblast cell lines and human placental explants, we found that miR-218-5p overexpression promoted, whereas anti-miR-218-5p suppressed, trophoblast invasion, EVT outgrowth, and enEVT differentiation. Furthermore, miR-218-5p accelerated spiral artery remodeling in a decidua-placenta co-culture. The effect of miR-218-5p was mediated by the suppression of transforming growth factor (TGF)-β2 signaling. Silencing of TGFB2 mimicked, whereas treatment with TGF-β2 partially reversed, the effects of miR-218-5p. Taken together, these findings demonstrate that miR-218-5p promotes trophoblast invasion and enEVT differentiation through a novel miR-218-5p-TGF-β2 pathway. This study elucidates the role of an miRNA in enEVT differentiation and spiral artery remodeling and suggests that downregulation of miR-218-5p contributes to PE development.

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Section: Discussionmentioning

confidence: 79%

MicroRNA-218-5p Promotes Endovascular Trophoblast Differentiation and Spiral Artery Remodeling

et al. 2018

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“…A single pathologist blinded to clinical information performed gross and microscopic evaluation of placentas. As previously described, these data were used to classify women as having histological chorioamnioitis and high vs. not high evidence of five placental vascular pathology constructs (24,25). Placental evaluations were available for 1057 of the 1309 women with lipid levels.…”

Section: Methodsmentioning

confidence: 99%

Maternal lipids at mid‐pregnancy and the risk of preterm delivery

Mudd

Holzman

Catov

et al. 2012

Acta Obstet Gynecol Scand

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Objective This study examined associations between maternal lipid levels at mid-pregnancy and preterm delivery, medically indicated or spontaneous. Design Prospective cohort study. Setting Women were recruited from 52 clinics in five Michigan, U.S.A communities (1998–2004). Population Pregnant women were enrolled at 15–27 weeks’ gestation and followed to delivery (n=3019). Methods A single blood sample was obtained at study enrollment. Blood lipids, i.e., total (TC), high-density lipoprotein (HDLc), low-density lipoprotein (LDLc) cholesterol, and triglycerides (TG), were measured on a subcohort (n=1,309). Main Outcome Measures There were 221 spontaneous, 100 medically indicated preterm deliveries and 988 term deliveries. Polytomous logistic regression models examined relations among cholesterol levels (Low: <10th %tile, Referent: 10th–<70th %tile, High: ≥70th %tile), quartiles of TG (Referent: first quartile) and delivery outcome (Referent: term). Results Odds of medically indicated preterm delivery were increased among women with low TC (adjusted odds ratio (aOR)= 2.04, 95% confidence interval (CI): 1.12,3.72), low HDLc (aOR=1.89, 95%CI: 1.04,3.42), or low LDLc (aOR=1.96, 95%CI: 1.09,3.54). Odds of spontaneous preterm delivery were increased among women with high TC (aOR=1.51, 95%CI: 1.06,2.15), high LDLc (aOR=1.42, 95%CI: 0.99,2.04) or high TG (aOR=1.90, 95%CI: 1.21,2.97 and aOR=1.72, 95%CI: 1.06,2.78 for third and fourth quartiles, respectively). Conclusions Extremely low TC, HDLc and LDLc were associated with a modest increase in risk of medically indicated preterm delivery, while high TC, LDLc and TG modestly increased risk of spontaneous preterm delivery. Further research is needed to uncover explanations for these associations and to identify optimal ranges for maternal lipids.

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“…(1/70)). (56) Regarding preterm delivery, previous studies have demonstrated that a subset of pregnant women with spontaneous preterm birth has placental lesions associated with uteroplacental ischemia (97)(98)(99)(100)(101)(102) and abnormal uterine artery Doppler. (103,104) Such findings are frequently observed in women with preeclampsia.…”

Section: Resultsmentioning

confidence: 99%

Does low-dose aspirin initiated before 11 weeks’ gestation reduce the rate of preeclampsia?

Chaemsaithong

Cuenca-Gomez

Plana

et al. 2020

American Journal of Obstetrics and Gynecology

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Condensation: Aspirin given at <11 weeks' gestation in high risk women does not reduce the risk of preeclampsia and gestational hypertension but may reduce the risk of preterm delivery. Short title: Early aspirin administration and preeclampsia PROSPERO registration number: CRD42019125006 AJOG at a Glance: Why was this study conducted? • To perform a systematic review and meta-analysis to evaluate the effect of lowdose aspirin initiated at <11 weeks' gestation on the risk of preeclampsia, gestational hypertension, or any hypertensive disorder of pregnancy. Secondary outcomes included preterm delivery at <37 weeks' gestation and fetal growth restriction. Key findings • The administration of low-dose aspirin at <11 weeks' gestation in women with a history of recurrent pregnancy loss, women who had undergone in vitro fertilization or women with thrombophilia or antiphospholipid syndrome was associated with a non-significant decrease in the risk of preeclampsia, gestational hypertension, and any hypertensive disorder of pregnancy. • Early low-dose aspirin reduced the risk of preterm delivery but had no impact on the risk of fetal growth restriction. • Except for preterm delivery and any hypertensive disorder of pregnancy, sensitivity analysis demonstrated similar observations; confirming the robustness of our analysis. What does this add to what is known? • Administration of low-dose aspirin at <11 weeks' gestation to high risk women does not reduce the risk of preeclampsia, gestational hypertension, any hypertensive disorder of pregnancy and fetal growth restriction but might reduce the risk of preterm delivery at <37 weeks of gestation. ABSTRACT OBJECTIVE DATA: Pre-conception or early administration of low-dose aspirin might improve endometrial growth, placental vascularization and organogenesis. Most studies have evaluated the potential benefit of pre-conception or early administration of low-dose aspirin in women with a history of recurrent pregnancy loss, women who have undergone in vitro fertilization or women with thrombophilia or antiphospholipid syndrome. These women are at an increased risk of placenta-associated complications of pregnancy, including preeclampsia, preterm delivery and fetal growth restriction. STUDY: We performed a systematic review and meta-analysis to evaluate the effect of low-dose aspirin initiated at <11 weeks' gestation on the risk of preeclampsia, gestational hypertension, or any hypertensive disorder of pregnancy. Secondary outcomes included preterm delivery at <37 weeks' gestation and fetal growth restriction. STUDY APPRAISAL AND SYNTHESIS METHODS: We searched in MEDLINE via PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.Gov and the World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) from 1985 to November 2018. Entry criteria were randomized controlled trials evaluating the effect of aspirin administered at <11 weeks' gestation in preventing preeclampsia and/or hypertensive disorders in pregnancy or improvi...

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Placental Vascular Pathology Findings and Pathways to Preterm Delivery

Cited by 22 publications

References 28 publications

MicroRNA-218-5p Promotes Endovascular Trophoblast Differentiation and Spiral Artery Remodeling

MicroRNA-218-5p Promotes Endovascular Trophoblast Differentiation and Spiral Artery Remodeling

Maternal lipids at mid‐pregnancy and the risk of preterm delivery

Does low-dose aspirin initiated before 11 weeks’ gestation reduce the rate of preeclampsia?

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