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Algorithm for use of progestogen in prevention of preterm birth in clinical care both in women with and without prior spontaneous preterm birth. † If TVU CL screening is performed. ‡ 17P 250 mg intramuscularly every week from 16-20 weeks to 36 weeks. § e.g., daily 200-mg suppository or 90-mg gel from time of diagnosis of short CL to 36 weeks. 17P: 17α-hydroxyprogesterone caproate; CL: Cervical length; PTB: Preterm birth; TVU: Transvaginal ultrasound. Reproduced with permission from [75]. 

Algorithm for use of progestogen in prevention of preterm birth in clinical care both in women with and without prior spontaneous preterm birth. † If TVU CL screening is performed. ‡ 17P 250 mg intramuscularly every week from 16-20 weeks to 36 weeks. § e.g., daily 200-mg suppository or 90-mg gel from time of diagnosis of short CL to 36 weeks. 17P: 17α-hydroxyprogesterone caproate; CL: Cervical length; PTB: Preterm birth; TVU: Transvaginal ultrasound. Reproduced with permission from [75]. 

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The risk of early birth increases markedly with decreasing cervical length (CL) in both singleton and multiple pregnancies. Transvaginal ultrasound of CL can be useful in determining women that are at risk of preterm delivery and may be helpful in preventing unnecessary intervention. Appropriate technique is essential for correct results. Factors t...

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... the basis of all these observations, the American College of Obstetricians Gynecologists has cautiously opened toward equal universal cervical screen- ing in singleton gestations without prior PTB, and practitioners who decide to implement universal screening are rec- ommended to follow one of the proposed protocols [31,32,62,68,69]. Pregnant patients at risk for sPTB, because of previous PTB in their history, are strongly recom- mended to take progesterone supplements starting at 16-24 weeks [74]. In woman with prior sPTB, if the TVU CL shortens to <25 mm at <24 weeks, cerclage may be offered. The Society for Maternal Fetal Medicine also proposed similar recom- mendations, and states that in singleton gestations, without prior PTB and short CL ≤20 mm at 24 weeks, vaginal proges- terone, either 90 mg gel or a 200 mg sup- pository, is associated with a reduction in PTB and perinatal morbidity, and can be offered in these cases [75]. The algorithm proposed by the Society for Maternal-Fetal Medicine for the use of progestogens in reducing the rate of PTB is shown in Figure ...

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Background Clinically, once a woman has been identified as being at risk of spontaneous preterm birth (sPTB) due to a short cervical length, a decision regarding prophylactic treatment must be made. Three interventions have the potential to improve outcomes: cervical cerclage (stitch), vaginal progesterone and cervical pessary. Each has been shown...

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... The risk of spontaneous preterm birth is higher in women with a short cervical length [34,35] and genetic factors, uterine over-extension, infection and inflammation have all been associated with cervical shortening [36,37]. Elevated levels of pro-inflammatory mediators, such as matrix metalloproteinases-8 (MMP-8), interleukin-8 (IL-8), and heat shock protein 70 (Hsp70), in the vaginal fluid have been associated with cervical shortening [38,39]. ...
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The composition of the gut microbiota (GM) undergoes significant changes during pregnancy, influenced by metabolic status, energy homeostasis, fat storage, and hormonal and immunological modifications. Moreover, dysbiosis during pregnancy has been associated with preterm birth, which is influenced by factors such as cervical shortening, infection, inflammation, and oxidative stress. However, dysbiosis also affects the levels of lipopolysaccharide-binding protein (LBP), short-chain fatty acids (SCFAs), and free fatty acids (FFA) in other tissues and the bloodstream. In this study, we investigated the plasmatic levels of some pro-inflammatory cytokines, such as matrix metalloproteinases-8 (MMP-8), interleukin-8 (IL-8), heat shock protein 70 (Hsp70), and microbial markers in pregnant women with a short cervix (≤25 mm) compared to those with normal cervical length (>25 mm). We examined the differences in the concentration of these markers between the two groups, also assessing the impact of gestational diabetes mellitus. Understanding the relationship between GM dysbiosis, inflammatory mediators, and cervical changes during pregnancy may contribute to the identification of potential biomarkers and therapeutic targets for the prevention and management of adverse pregnancy outcomes, including preterm birth.
... [4][5][6] Despite the increased understanding of mechanisms and determinant factors related to PTB and the implementation of various medical interventions to decrease its prevalence and negative impacts, PTB remains a growing public and clinical health concern. [7][8][9] In Ethiopia, the prevalence of PTB has ranged between 4.4% and 25.9%; however, these results may not represent the entire Ethiopian population because of differences in socio-demographic characteristics, the level of hospital, and the quality of healthcare. [10][11][12][13] The alarmingly increased rate of CD observed in recent years has paralleled the scaled-up in the prevalence of PTB. 14 Several potential risk factors were reported to be associated with PTB, including extreme maternal age, [15][16][17][18][19][20][21][22][23] grand parity, [24][25][26][27][28] previous CD history, 23,29,30 antepartum hemorrhage, 18,26,31 pregnancy-induced hypertension, 10,12,20,26,32,33 and premature rupture of the membrane. ...
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Purpose: Although the underlying causes for preterm birth are thought to be multifactorial irrespective of delivery mode, no study investigated its risk factors amongst cesarean deliveries (CD). Thus, we aimed to identify potential risk factors for the occurrence of preterm birth (PTB) among intrapartum CD. Methods: Data from 1659 singleton intrapartum CDs were retrospectively recruited using medical records and an obstetric database. Gestational age was calculated using the last menstrual period (LMP) and ultrasound report of early onset pregnancy. A multivariable logistic regression analysis was performed to identify potential risk factors associated with PTB. Odds ratios (ORs) and 95% confidence intervals (95% CI) were used. Statistical analysis was performed using SPSS version 26.0. Results: In this study, the prevalence of PTB among intrapartum CD was 6.1% (95% CI: 4.9, 7.2%). In the multivariable logistic regression model; grand parity ≥5 (adjusted odds ratio (AOR) = 2.43, 95% CI: 1.72-4.73), maternal age <20 years (AOR=2.63, 95% CI, 1.03-6.71), maternal age ≥35 years (AOR=3.83, 95% CI, 1.49-5.35), cesarean section scar ≥2 (AOR=4.86, 95% CI: 2.68-8.94), antepartum hemorrhage (AOR=4.37, 95% CI: 2.22-8.63), pregnancy-induced hypertension (AOR=2.92, 95% CI: 1.41-6.04), and premature rupture of membranes (AOR=4.56; 95% CI: 1.95-10.65) were significantly associated with PTB. Conclusion: The current study showed an association between PTB and a multitude of obstetric variables, including grand parity ≥5, CS scar ≥2, antepartum hemorrhage, pregnancy-induced hypertension, and premature rupture of the membrane. Understanding these factors could help to implement improved quality of obstetric and neonatal care to increase survival and reduce morbidity among preterm birth.
... Several studies have attempted to link vaginal microbiota to preterm birth [1,10,14,15]. The risk of spontaneous preterm birth is associated with a short cervix [16,17], and a variety of etiopathogenetic mechanisms may be involved including uterine overdistension [18] and changes in the cervico-vaginal microbiome, among others [19]. ...
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Cervical shortening is a recognised risk factor for pre-term birth. The vaginal microbiome plays an essential role in pregnancy and in maternal and foetal outcomes. We studied the vaginal microbiome in 68 women with singleton gestation and a cervical length ≤25 mm and in 29 pregnant women with a cervix >25 mm in the second or early third trimester. Illumina protocol 16S Metagenomic Sequencing Library Preparation was used to detail amplified 16SrRNA gene. Statistical analyses were performed in R environment. Firmicutes was the phylum most represented in all pregnant women. The mean relative abundance of Proteobacteria and Actinobacteriota was higher in women with a short cervix. Bacterial abundance was higher in women with a normal length cervix compared to the group of women with a short cervix. Nonetheless, a significant enrichment in bacterial taxa poorly represented in vaginal microbiome was observed in the group of women with a short cervix. Staphylococcus and Pseudomonas, taxa usually found in aerobic vaginitis, were more common in women with a short cervix compared with the control group, while Lactobacillus iners and Bifidobacterium were associated with a normal cervical length. Lactobacillus jensenii and Gardenerella vaginalis were associated with a short cervix.
... If not medically induced, approximately 25% of cases are caused by preterm rupture of membranes (pPROM); 30% of cases are caused by inflammation and infection, while 45% of cases are considered spontaneous with intact membranes 5 . Recently, cervical length (CL) shortening 6 has become a clinical marker of PTB risk 7,8 . Although still controversial, the National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit Network uses a cutoff of 25 mm to define a short cervix at 22 to 24 weeks of gestation in both low-and high-risk pregnancies 9 . ...
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Objective: Recently, the PTB risk has been related to the objective measurement of cervical length (CL), since a CL of less than 25 mm is an accurate predictor of increased risk of PTB. Primary prevention of preterm labor is based on the early identification of symptoms and on pharmacological treatments with tocolytic drugs for inhibition of uterine contractions that are associated with a shortening of the cervix. Unfortunately, most of these drugs have important side effects. Patients and methods: This study aimed to evaluate whether the administration of a combination of oral α-lipoic acid (ALA), magnesium, vitamin B6 and vitamin D to pregnant women presenting risk factors for PTB could reduce the rate of cervical shortening at 19-22 weeks of gestational age. Results: A total of 122 women attending the first-trimester aneuploidy screening at 11-14 weeks of pregnancy and presenting risk factors for PTB were included in the study. Cervical length significantly decreased in the control group compared with the treatment group (-3.86 ± 1.97 vs. 1.50 ± 1.26; p=0.02). Although the rate of preterm birth did not significantly decrease (9.5% vs. 5.1%), admission for threatened PTB was statistically reduced in the treatment group compared with the control group (3.4% vs. 14.3%). Conclusions: Oral supplementation of ALA, magnesium, vitamin B6 and vitamin D significantly counteracted cervix shortening in pregnant women presenting risk factors for PTB.
... A genetic study of cervical length could prove highly informative, given that the length of the cervix is an easily measured, quantitative trait that is highly correlated with risk for spontaneous preterm delivery. 88 Biomechanical properties of the cervix The uterine cervix has two opposing functions during pregnancy: first, it must remain firmly closed to prevent intrauterine infection, spontaneous abortion, or preterm delivery; and second, at the onset of labour, it must open to allow successful parturition. 89 90 These changes are reflected in the histology, 91-94 biochemistry 94-97 and biomechanical properties 98-100 of the cervix. ...
... [98][99][100] Remodelling of this collagen-rich, connective tissue is a complex process which begins early in pregnancy, and culminates with softening, effacement and dilation of the cervix at parturition. [91][92][93][94][95][96][97] The length of the cervix is defined as the distance between the external os and the functional internal os, 88 and can be easily measured by transvaginal ultrasonography over the course of a pregnancy. [101][102][103] Estimates for the mean length of the cervix in the midtrimester vary between 35 and 45 mm, depending on the population, 1 2 9-11 88 104-109 with cervical lengths shorter than 25 mm before 24 weeks meeting the clinical definition of a short cervix. ...
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Introduction A short cervix (cervical length <25 mm) in the midtrimester (18–24 weeks) of pregnancy is a powerful predictor of spontaneous preterm delivery. Although the biological mechanisms of cervical change during pregnancy have been the subject of extensive investigation, little is known about whether genes influence the length of the cervix, or the extent to which genetic factors contribute to premature cervical shortening. Defining the genetic architecture of cervical length is foundational to understanding the aetiology of a short cervix and its contribution to an increased risk of spontaneous preterm delivery. Methods/analysis The proposed study is designed to characterise the genetic architecture of cervical length and its genetic relationship to gestational age at delivery in a large cohort of Black/African American women, who are at an increased risk of developing a short cervix and delivering preterm. Repeated measurements of cervical length will be modelled as a longitudinal growth curve, with parameters estimating the initial length of the cervix at the beginning of pregnancy, and its rate of change over time. Genome-wide complex trait analysis methods will be used to estimate the heritability of cervical length growth parameters and their bivariate genetic correlation with gestational age at delivery. Polygenic risk profiling will assess maternal genetic risk for developing a short cervix and subsequently delivering preterm and evaluate the role of cervical length in mediating the relationship between maternal genetic variation and gestational age at delivery. Ethics/dissemination The proposed analyses will be conducted using deidentified data from participants in an IRB-approved study of longitudinal cervical length who provided blood samples and written informed consent for their use in future genetic research. These analyses are preregistered with the Center for Open Science using the AsPredicted format and the results and genomic summary statistics will be published in a peer-reviewed journal.
... The uterine cervix acts as a physical and immune barrier against pathogens' passage into the uterine cavity during pregnancy. Premature cervical remodeling, shortening, and dilation of the cervix are known risk factors for spontaneous preterm birth (sPTB) [1][2][3][4] with the notion that the shorter the cervix, the higher the risk of sPTB [1]. In addition to congenital disorders [5], genetic syndromes ...
... In our study, microbiota analysis of vaginal fluids was performed in a selected cohort of pregnant women with cervical shortening during the second or early third trimester of pregnancy, to identify vaginal communities associated with "extreme" cervical shortening (1-10 mm), a high-risk factor for spontaneous preterm birth [1][2][3]. A cervical length shorter than 10 mm is considered abnormal (below the 5th or 10th percentile for gestational age) even at 28-32 weeks' gestation [1,20]. ...
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The vaginal microbiota plays a critical role in pregnancy. Bacteria from Lactobacillus spp. are thought to maintain immune homeostasis and modulate the inflammatory responses against pathogens implicated in cervical shortening, one of the risk factors for spontaneous preterm birth. We studied vaginal microbiota in 46 pregnant women of predominantly Caucasian ethnicity diagnosed with short cervix (<25 mm), and identified microbial communities associated with extreme cervical shortening (≤10 mm). Vaginal microbiota was defined by 16S rRNA gene sequencing and clustered into community state types (CSTs), based on dominance or depletion of Lactobacillus spp. No correlation between CSTs distribution and maternal age or gestational age was revealed. CST-IV, dominated by aerobic and anaerobic bacteria different than Lactobacilli, was associated with extreme cervical shortening (odds ratio (OR) = 15.0, 95% confidence interval (CI) = 1.56-14.21; p = 0.019). CST-III (L. iners-dominated) was also associated with extreme cervical shortening (OR = 6.4, 95% CI = 1.32-31.03; p = 0.02). Gestational diabetes mellitus (GDM) was diagnosed in 10/46 women. Bacterial richness was significantly higher in women experiencing this metabolic disorder, but no association with cervical shortening was revealed by statistical analysis. Our study confirms that Lactobacillus-depleted microbiota is significantly associated with an extremely short cervix in women of predominantly Caucasian ethnicity, and also suggests an association between L. iners-dominated microbiota (CST III) and cervical shortening.
... Among those evaluated till date, fetal fibronectin in cervicovaginal fluid and cervical length has been most strongly and consistently associated with subsequent spontaneous preterm birth. [16][17][18][25][26][27][28] Anai et al was the first to measure hCG levels in vaginal fluid. Their original study suggested that quantitative measurement of hCG from vaginal fluid may serve as a useful marker of premature rupture of fetal membranes secretions. ...
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Background: The World Health Organization (WHO) factsheet revealed that 15 million babies are born too early every year and almost 1 million children die each year due to complications of preterm birth. The objective of this study was to determine whether cervicovaginal β-hCG level can be used as predictor of preterm delivery in asymptomatic high-risk pregnant women at 24-34 weeks gestation age.Methods: This was prospective observational study. Total 134 asymptomatic pregnant women were taken for study who had at least one risk factor for preterm delivery at 24-34 weeks gestation age. Cervicovaginal secretion was collected and β-hCG level was measured by chemiluminescent immunoassay.Results: Out of 134 cases, 42.5% had preterm delivery and 57.5% had term delivery. Mean cervicovaginal β-hCG level (mIU/ml) in preterm delivery group was 39.38±19.66 and term delivery group was 21.86±11.18. Cervicovaginal β-hCG level was significantly higher in preterm group compare to term group demonstrating significant association of raised β-hCG with preterm group (p value <0.001). ROC curve analysis was done to find out best cut off value of cervicovaginal β-hCG for prediction of preterm delivery and optimal cut off value was 36.45 mIU/ml. The optimal cut off value for cervicovaginal β-hCG (36.45 mIU/ml) gave sensitivity 71.9%, specificity 81.8%, positive predictive value 74.5%, negative predictive value 79.7% and diagnostic accuracy of 77.6% for prediction of preterm delivery.Conclusions: Cervicovaginal β-hCG can be used as sensitive and specific biomarker of prediction of preterm delivery in asymptomatic high-risk women.
... The procedure was performed after emptying the bladder. After obtaining three measurements, the shortest measurement in millimeters was reported [10]. Exclusion criteria were: multiple gestation, fetal anomalies, cervical dilatation 3 cm, premature rupture of membranes, and presence of cervical cerclage or pessary. ...
Article
Objective: To evaluate the diagnostic accuracy of cervicovaginal fetal fibronectin (fFN) in predicting preterm delivery (PTD) in symptomatic and asymptomatic women with cervical length (CL) ≤ 20 mm. Methods: A retrospective cohort study on pregnant singleton women admitted for CL ≤ 20 mm, with or without uterine contractions, between 22 and 34 weeks. For each group, symptomatic and asymptomatic, the following outcomes were evaluated: PTD before 37 and 34 weeks, delivery within 48 h, 7, 14 and 21 days after fibronectin sampling. Results: 128 women admitted for CL ≤ 20 mm were identified. Of these, 43 had uterine contractions, while 85 were asymptomatic. A positive fFN test was detected in 33% of symptomatic patients and it was significantly associated with PTD < 37 and 34 weeks and within 48 hours, 7, 14 and 21 days from admission (p < 0.05). After logistic regression analysis, fFN remained an independent predictor for all outcomes. In the asymptomatic group fFN test was positive only in 6% of patients, and a positive result was not significantly associated with any of the outcomes. Conclusions: In women with contractions and CL ≤ 20 mm, fFN is an effective marker of PTD. Sensitivity and specificity rates for PTD within 7-14 days are higher than those reported in studies including women with CL > 20 mm. In asymptomatic women, fFN appeared not as effective in predicting PTD.
... Intra-amniotic sludge in isolation has no increased risk of PTB, but in conjunction with a shortened cervical length as seen in Figure 1, results in a higher risk of PTB than a short cervix alone. 15 Detachment of fetal membranes from the decidua at the level of the internal os as seen in Figure 2 is also associated with an increased risk for PTB. 15 There have been nomograms constructed which demonstrate expected cervical length throughout pregnancy. [16][17][18] At 20 weeks gestation the 50th percentile for cervical length in singleton pregnancies has been shown to be 42 mm. ...
... 15 Detachment of fetal membranes from the decidua at the level of the internal os as seen in Figure 2 is also associated with an increased risk for PTB. 15 There have been nomograms constructed which demonstrate expected cervical length throughout pregnancy. [16][17][18] At 20 weeks gestation the 50th percentile for cervical length in singleton pregnancies has been shown to be 42 mm. ...
... 23 A suture or tape is placed around the cervix in an attempt to prevent dilatation resulting in subsequent PTB. 4 It has been found that cerclage can significantly reduce PTB rates in high-risk women (prior PTB) who present with a shortened TVU cervical length prior to 24 weeks gestation. 15 However, cerclage is associated with increased rates of vaginal bleeding, discharge and fever, and also a significant increase in caesarean section deliveries. 4 In cases of twin pregnancy, cerclage has been associated with a higher incidence of PTB and is contraindicated. ...
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Introduction The incidence of preterm birth has continued to rise in most countries in the world during the last decade. There are many clinical risk factors that increase the risk of preterm birth. It has been shown that a sonographically shortened cervical length is a strong indicator of subsequent preterm birth in pregnancy. Background It has been established that women at an increased risk of preterm birth should have the cervical length recorded using a transvaginal approach. The sensitivity of a shortened cervical length to predict preterm birth is higher in women with a previous preterm birth, with reduced sensitivity in low risk women. The maternal cervix may be assessed using transabdominal, transperineal and transvaginal ultrasound approaches. This article discusses the available research into the use of these differing techniques and current guidelines for measuring maternal cervical length. Summary Measuring the maternal cervical length has become an important part of the mid trimester morphology examination. The appropriate technique to screen the cervical length in women at low risk of preterm birth is still debatable throughout the wider obstetric and ultrasound communities.
... The length of cervix was measured by the physician using the appropriate technique. [10] This consists of the insertion of a clean transvaginal probe covered by a condom in the anterior fornix of the vagina after the woman has emptied her bladder. When a sagittal long-axis view of the entire endocervical canal is obtained, the image is enlarged until the cervix occupies at least two-thirds of the screen and both the external and internal os are seen. ...
... [16] Ultrasound measurement of cervical length is in fact the most accurate method. [10,17] We found no correlation between the length of the cervix at admission and time interval to delivery. This finding suggests that in women with an already dilated cervix, the ultrasound examination of the cervix for the prediction of PTD is unlikely to add information of clinical value, as confirmed by one previous study. ...
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Background: Early recognition of the signs and symptoms of preterm labor (PTL) is important in order to establish treatment. Our aim was to determine the relation between cervical dilatation and time interval from admission to delivery in women with preterm labor. Materials and methods: A retrospective cohort study was conducted on 83 singleton gestations admitted for preterm labor between 24 weeks and 34 weeks, who subsequently delivered preterm. Women were categorized into three groups of cervical dilatation (0-2 cm, 3-6 cm, >6 cm) and the time interval from admission to delivery was compared. Cox regression analysis was performed to assess the association between cervical dilatation and time interval from admission to delivery. The other variables examined were gestational age (GA) at admission and length of the cervix, when performed. Results: The time interval from admission to delivery was significantly shorter in women with higher dilatation of the cervix (p < 0.02) and in those admitted at a more advanced gestational age (p < 0.05). Forty-eight percent of women with cervical dilatation 0-2 cm delivered in the first 48 h compared to 85% of the women with a dilatation of 3-6 cm. No significant association was found between the length of the cervix and the time interval to delivery. Conclusion: Dilatation of the cervix and gestational age at admission are associated with the time interval to delivery in women with preterm labor. The assessment of the length of the cervix is unlikely to add clinical information in women with an already dilated cervix.