S. E. Illanes

J. K. Nien

G. E. Rice

Preterm Labor: Understanding of the Mechanism Involved to Improve Prediction and Prevention

Preterm birth is defined as any delivery before 37 complete weeks of gestation. It is a universal challenge in the field of obstetrics owing to its high rate of mortality, long-term morbidity, associated human suffering and economic burden. In the United States, about 12.18&#x25; deliveries in 2009 were preterm, producing an exorbitant cost of &#x24;5.8 billion. Infection-associated premature rupture of membranes (PROM) accounts for 40&#x25; of extremely preterm births (&#x3c;28 weeks of gestation). Major research efforts are directed towards improving the understanding of the pathophysiology of preterm birth and ways to prevent or at least postpone delivery. Endothelin-1 (ET-1) is a potent vasoconstrictor that plays a significant role in infection-triggered preterm birth. Its involvement in a number of pathological mechanisms and its elevation in preterm delivered amniotic fluid samples implicate it in preterm birth. Sphingosine kinase (SphK) is a ubiquitous enzyme responsible for the production of sphingosine-1-phosphate (S1P). S1P acts as second messenger in a number of cell proliferation and survival pathways. SphK is found to play a key role in ET-1 mediated myometrial contraction. This review highlights SphK as a prospective target with great potential to prevent preterm birth.

Vibhuti Vyas

Charles R. Ashby

Sandra E. Reznik

Sphingosine Kinase: A Novel Putative Target for the Prevention of Infection-Triggered Preterm Birth

<i  >Objective</i>. The aim of this study was to assess whether cervical length measurement (CL) could predict preterm birth (PTB) in symptomatic women with a twin pregnancy. <i  >Methods</i>. We searched MEDLINE and EMBASE to identify studies investigating the accuracy of CL measurement in predicting PTB in symptomatic women with a twin pregnancy. We extracted data to construct two-by-two tables and used bivariate meta-analysis to generate point estimates of sensitivity and specificity. <i  >Results</i>. Five studies (<svg     style="vertical-align:-0.1638pt;width:58.887501px;" id="M1" height="11.375" version="1.1" viewBox="0 0 58.887501 11.375" width="58.887501"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x1D441" d="M857 650l-6 -28q-44 -4 -61.5 -16.5t-29.5 -48.5q-11 -32 -37 -166l-78 -399h-29l-351 537h-4l-56 -276q-24 -120 -24 -164q0 -35 17.5 -46t75.5 -15l-6 -28h-245l7 28q41 2 62 14t31 44q10 30 41 171l53 245q8 44 6.5 60.5t-14.5 33.5q-10 15 -27 19.5t-64 6.5l6 28h153&#xA;l350 -516h5l48 257q25 131 25 171q0 34 -17.5 45t-77.5 15l7 28h240z" /></g><g transform="matrix(.017,-0,0,-.017,19.628,11.112)"><path id="x3D" d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z" /></g><g transform="matrix(.017,-0,0,-.017,34.332,11.112)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" /></g><g transform="matrix(.017,-0,0,-.017,42.491,11.112)"><use xlink:href="#x32"/></g><g transform="matrix(.017,-0,0,-.017,50.651,11.112)"><path id="x36" d="M137 343l67 33q37 17 63 17q79 0 129.5 -53t50.5 -131q0 -92 -58 -156.5t-147 -64.5t-147 68t-58 182q0 63 17 119t43 95.5t61.5 72t69 52t67.5 31.5q62 22 128 33l6 -32q-56 -11 -108 -35q-149 -71 -184 -231zM227 337q-47 0 -95 -27q-6 -23 -6 -70q0 -93 36 -155.5&#xA;t96 -62.5q53 0 78 45.5t25 105.5q0 68 -35 116t-99 48z" /></g>

		
	
</svg>) were included. Variation in definition of PTB and cut-off points for CL was strong. One study investigated delivery within seven days, demonstrating a sensitivity of 1.0 (95&#x25; CI: 0.83&#x2013;1.0) and a specificity of 0.31 (95&#x25; CI 0.2&#x2013;0.43) for a CL cutoff at 25&#x2009;mm. Three studies reported on predicting PTB &#x3c; 37 weeks at a CL cutoff of 30&#x2009;mm, with sROC point estimates of 0.76 (95&#x25; CI: 0.66 to 0.84) and 0.37 (95&#x25; CI: 0.21 to 0.56) for sensitivity and specificity, respectively. For preterm birth &#x3c;34 weeks, no pooled estimates could be estimated since only 2 studies with large heterogeneity were identified. <i  >Conclusions</i>. There is limited evidence on the accuracy of cervical length measurement testing the prediction of preterm birth in symptomatic women with a twin pregnancy, especially on the most important outcome, that is, delivery within 7 days.

S. M. S. Liem

L. van de Mheen

D. J. Bekedam

M. G. van Pampus

B. C. Opmeer

A. C. Lim

B. W. J. Mol

Cervical Length Measurement for the Prediction of Preterm Birth in Symptomatic Women with a Twin Pregnancy: A Systematic Review and Meta-Analysis

<i  >Introduction</i>. Reduction of preterm birth is a major goal in obstetric care. We performed a systematic review of randomized controlled trials and cohort studies on the effectiveness of the cervical pessary to prevent preterm birth. <i  >Methods</i>. We searched the electronic databases of MEDLINE and Embase from inception until April 2012 to identify studies investigating treatment with a cervical pessary to prevent preterm birth. We constructed two-by-two tables for delivery before 28, 34, and 37 weeks of gestation and calculated relative risks (RRs) with 95&#x25; confidence intervals. <i  >Results</i>. The search revealed 103 potentially eligible abstracts of which six cohort studies and four randomized controlled trials (RCTs) investigated the effectiveness of the pessary. One RCT (<svg     style="vertical-align:-0.1638pt;width:52.5625px;" id="M1" height="11.125" version="1.1" viewBox="0 0 52.5625 11.125" width="52.5625"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,10.862)"><path id="x1D45B" d="M495 86q-46 -47 -87 -72.5t-63 -25.5q-43 0 -16 107l49 210q7 34 8 50.5t-3 21t-13 4.5q-35 0 -109.5 -72.5t-115.5 -140.5q-21 -75 -38 -159q-50 -10 -76 -21l-6 8l84 340q8 35 -4 35q-17 0 -67 -46l-15 26q44 44 85.5 70.5t64.5 26.5q35 0 10 -103l-24 -98h2&#xA;q42 56 97 103.5t96 71.5q46 26 74 26q9 0 16 -2.5t14 -11.5t9.5 -24.5t-1 -44t-13.5 -68.5q-30 -117 -47 -200q-4 -19 -3.5 -25t6.5 -6q21 0 70 48z" /></g><g transform="matrix(.017,-0,0,-.017,13.305,10.862)"><path id="x3D" d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z" /></g><g transform="matrix(.017,-0,0,-.017,28.008,10.862)"><path id="x33" d="M285 378v-2q65 -13 102 -54.5t37 -97.5q0 -57 -30.5 -104.5t-74 -75t-85.5 -42t-72 -14.5q-31 0 -59.5 11t-40.5 23q-19 18 -16 36q1 16 23 33q13 10 24 0q58 -51 124 -51q55 0 88 40t33 112q0 64 -39 96.5t-88 32.5q-29 0 -64 -11l-6 29q77 25 118 57.5t41 84.5&#xA;q0 45 -26.5 69.5t-68.5 24.5q-67 0 -120 -79l-20 20l43 63q51 56 127 56h1q66 0 107 -37t41 -95q0 -42 -31 -71q-22 -23 -68 -54z" /></g><g transform="matrix(.017,-0,0,-.017,36.168,10.862)"><path id="x38" d="M249 635q70 0 116 -43t46 -105q0 -46 -28 -80q-22 -25 -80 -64q62 -35 97 -75t35 -99q0 -81 -63 -131t-135 -50q-83 0 -137.5 45.5t-54.5 123.5q0 52 45 95q29 28 89 64q-109 62 -109 155q0 66 50.5 115t128.5 49zM238 603q-42 0 -67.5 -31t-25.5 -72q0 -50 32.5 -79.5&#xA;t98.5 -62.5q61 48 61 124q0 59 -29.5 90t-69.5 31zM248 20q46 0 76.5 33.5t30.5 89.5q0 50 -39 85.5t-110 71.5q-81 -54 -81 -137q0 -67 35.5 -105t87.5 -38z" /></g><g transform="matrix(.017,-0,0,-.017,44.327,10.862)"><path id="x30" d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105&#xA;q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" /></g>

		
	
</svg>) demonstrated a lower delivery rate prior to 34 weeks (RR 0.24; 95&#x25; CI 0.13&#x2013;0.43) in the pessary group, while another RCT (<svg     style="vertical-align:-0.1638pt;width:52.5625px;" id="M2" height="11.125" version="1.1" viewBox="0 0 52.5625 11.125" width="52.5625"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,10.862)"><use xlink:href="#x1D45B"/></g><g transform="matrix(.017,-0,0,-.017,13.305,10.862)"><use xlink:href="#x3D"/></g><g transform="matrix(.017,-0,0,-.017,28.008,10.862)"><path id="x31" d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z" /></g><g transform="matrix(.017,-0,0,-.017,36.168,10.862)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,44.327,10.862)"><use xlink:href="#x38"/></g>

		
	
</svg>) showed no positive effect of pessary for delivery before 34 weeks (RR 1.73; 95&#x25; CI 0.43&#x2013;6.88). Two older quasi randomized studies and cohort studies indicated potential effect of the pessary. <i  >Conclusions</i>. Available randomized and nonrandomized studies indicate potential effectiveness of a cervical pessary in the prevention of preterm birth. More randomized clinical trials are needed before this device can be used in clinical practice. 




Sophie M. S. Liem

Mari&#xeb;lle G. van Pampus

Ben Willem J. Mol

Dick J. Bekedam

Cervical Pessaries for the Prevention of Preterm Birth: A Systematic Review

The aim of this paper is to provide a thorough summary of published studies that have assessed the efficacy of adjunctive therapies used in addition to cervical cerclage as a preventive measure for preterm birth. We limited our paper to patients treated with cerclage plus an additional prophylactic therapy compared to a reference group of women with cerclage alone. The specific adjunctive therapies included in this systematic review are progesterone, reinforcing or second cerclage placement, tocolytics, antibiotics, bedrest, and pessary. We searched PubMed and Cochrane databases without date criteria with restriction to English language and human studies and performed additional bibliographic review of selected articles and identified 305 total studies for review. Of those, only 12 studies compared the use of an adjunctive therapy with cerclage to a reference group of cerclage alone. None of the 12 were prospective randomized clinical trials. No comparative studies were identified addressing the issues of antibiotics, bedrest, or pessary as adjunctive treatments to cerclage. None of the 12 studies included in this paper demonstrated a clear benefit of any adjunctive therapy used in addition to cerclage over and above cerclage used alone; however, few studies with small numbers limited the strength of the conclusions.

Emily A. DeFranco

Amy Miyoshi Valent

Tondra Newman

Jodi Regan

Jessica Smith

Louis J. Muglia

Adjunctive Therapies to Cerclage for the Prevention of Preterm Birth: A Systematic Review

Human fetal membranes play an important role in term and preterm labor and are responsive to steroids. We examined the expression of steroid receptor coactivators in fetal membranes obtained prior to and following labor at term. Proteins were localized by immunohistochemistry, Western analysis was carried out in nuclear extracts, and mRNA levels were determined by real-time RT-PCR. SRC-1, SRC-2, p300, and PCAF proteins were present in all nuclear extracts. The amnion nuclei expressed higher levels of SRC-1, p300, and PCAF than nuclei from the chorion-decidua, whereas the reverse was true for SRC-2. Chorion-decidua from patients before labor expressed higher levels of SRC-1 than those from patients after labor. Also, the PCAF level was higher in the amnion obtained before labor than the same tissue obtained after labor. In contrast to the protein expression, mRNA levels of SRC-1 and p300 were higher in the chorion-decidua compared to the amnion, whereas there was no difference in levels of SRC-2 and PCAF mRNAs between these two tissues. These data underline that the regulation of the expression of the coactivators in these tissues occurs during labor and is complex and tissue specific.

Che-Wei Ryan Ou

Meihua Sun

Weronika Sadej

William Gibb

Expression of Nuclear Receptor Coactivators in the Human Fetal Membranes at Term before and after Labor

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<p><em>Obstetrics and Gynecology International</em> publishes articles related to obstetrics, maternal-fetal medicine, gynecologic oncology, uro-gynecology, reproductive medicine, infertility, reproductive endocrinology, and sexual medicine.</p>


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S. Illanes

J. Nien

G. Rice