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When caring for women experiencing preterm labor and birth, nurses play a significant role as bedside experts, advocates, patient educators, and key members of the maternity care team. Enhanced expertise on clinical and professional knowledge of preterm labor and birth is crucial in prevention and treatment. As preterm birth rates continue to rise, perinatal nurses as well-informed clinical experts have the opportunity to offer innovative education, holistic assessments, and communication through shared decision-making models. Educating pregnant women about early recognition of preterm labor warning signs and symptoms allows for timely diagnosis, interventions, and treatment. Informed and collaborative nursing practice improves quality of clinical care based on individualized interactions. A clinical review of preterm labor and preterm birth is presented for perinatal nurses.

Purpose: To investigate whether complement and other immune-related proteins in cervicovaginal fluid (CVF) can predict intra-amniotic infection and/or inflammation (IAI) and spontaneous preterm delivery (SPTD, < 34.0 weeks) in women with preterm labor (PTL) and to compare the predictive abilities of these biomarkers with that of amniotic fluid (AF) white blood cells (WBCs)., Methods: We designed a retrospective cohort study of 145 women with PTL at 23.0-33.6 weeks who underwent amniocentesis. AF was cultured and assayed for WBC count and interleukin-6 (IL-6). CVF samples were obtained at the time of amniocentesis. CVF was assayed for complement C3a and C5a, IGFBP-1, and MMP-9 by ELISA., Results: In the multivariate analysis, elevated CVF levels of C5a and IGFBP-1 were significantly associated with IAI and SPTD at < 34 weeks, while those of C3a were associated with IAI, but not SPTD, even after adjusting for other baseline confounders. For C3a, C5a, and IGFBP-1 in the CVF, area under the curve (AUC) values were statistically similar to that of AF WBCs for detecting IAI, whereas these CVF biomarkers had similar or higher AUC values than AF WBCs for predicting SPTD at < 34 weeks. However, univariate analysis showed no significant correlation between high CVF MMP-9 and IAI or SPTD at < 34 weeks., Conclusions: In women with PTL, the CVF levels of C3a, C5a, and IGFBP-1 may be useful as novel non-invasive predictors of IAI and SPTD at < 34 weeks. These biomarkers (especially IGFBP-1) have similar or better diagnostic performance compared to AF WBCs.

Introduction: Preterm birth is the leading cause of neonatal morbidity and mortality globally and poses a substantial economic burden. Consequently, there is a need for the identification of therapeutic targets and novel experimental drugs for the inhibition of preterm labor to improve neonatal outcomes., Areas Covered: The authors review the pathophysiology of labor and the inflammatory pathways underpinning it. The interruption of these pathways forms the basis of therapeutic targets to inhibit preterm labor. Current drugs available for the treatment of preterm labor are reviewed, followed by experimental drugs including toll-like receptor 4 (TLR-4) antagonists, cytokine suppressive anti-inflammatory drugs (CSAIDs), N-acetyl cysteine (NAC), Sulfasalazine (SSZ), tumor necrosis factor-alpha (TNF-α) antagonists, interleukin-1 receptor (IL-1) inhibitors, omega-3 polyunsaturated fatty acids and lipid metabolites, and the polyphenols., Expert Opinion: A number of new therapeutic strategies for the prevention of preterm labor are being investigated. These have the potential to improve neurodevelopmental outcomes and survival in babies born preterm, reducing the economic and healthcare costs of caring for the complex needs of these children in the immediate and long term. It is likely that over the next decade there will be a new treatment option that targets the pathological inflammatory processes involved in preterm labor.

Background : Preterm birth is strongly associated with increasing mortality, incidence of disability, intensity of neonatal care required, and consequent costs. We examined the clinical utility of the potential preterm birth risk factors from admitted pregnant women with symptomatic preterm labor and developed prediction models to obtain information for prolonging pregnancies. Methods: This retrospective study included pregnant women registered with the KOrean Preterm collaboratE Network (KOPEN) who had symptomatic preterm labor, between 16 and 34 gestational weeks, in a tertiary care center from March to November 2016. Demographics, obstetric and medical histories, and basic laboratory test results obtained at admission were evaluated. The preterm birth probability was assessed using a nomogram and decision tree according to birth gestational age: early preterm, before 32 weeks; late preterm, between 32 and 37 weeks; and term, after 37 weeks. Results: Of 879 registered pregnant women, 727 who gave birth at a designated institute were analyzed. The rates of early preterm, late preterm, and term births were 18.16%, 44.02%, and 37.83%, respectively. With the developed nomogram, the concordance index for early and late preterm births was 0.824 (95% CI: 0.785-0.864) and 0.717 (95% CI: 0.675-0.759) respectively. Preterm birth was significantly more likely among women with multiple pregnancy and had water leakage due to premature rupture of membrane. The prediction rate for preterm birth based on decision tree analysis was 86.9% for early preterm and 73.9% for late preterm; the most important nodes are watery leakage for early preterm birth and multiple pregnancy for late preterm birth. Conclusion: This study aims to develop an individual overall probability of preterm birth based on specific risk factors at critical gestational times of preterm birth using a range of clinical variables recorded at the initial hospital admission. Therefore, these models may be useful for clinicians and patients in clinical decision-making and for hospitalization or lifestyle coaching in an outpatient setting., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: To evaluate neonatal outcomes in preterm infants with less than 34 weeks after spontaneous labor, preterm premature rupture of membranes (PPROM) or iatrogenic delivery and to clarify whether the mechanism of labor onset is a risk factor for adverse short-term neonatal outcome. Methods: We performed a retrospective case-control study, which included 266 preterm newborns with less than 34-week gestation, between 2011 and 2015. Neonatal outcomes were compared according to the mechanism of labor onset. Our primary outcomes were neonatal death, sequelae on hospital discharge and a composite of these two variables (combined neonatal outcome). Results: Compared to spontaneous preterm labor, iatrogenic preterm newborns were at increased risk of respiratory distress syndrome (RDS) [Odds Ratio (OR) 3.05 (95%CI 1.31; 7.12)], and need of exogenous surfactant administration [OR 3.87 (95%CI 1.60; 9.35)]. PPROM was associated with higher risk of neonatal sepsis [OR 12.96 (95%CI 1.18; 142.67)]. There were no differences regarding the combined outcome for iatrogenic [OR 0.94 (95%CI 0.33; 2.71)] or PPROM [OR 1.11 (95%CI 0.35; 3.49)] groups. Conclusions: In our study, the different mechanisms of labor onset are associated with different neonatal outcomes. Iatrogenic preterm birth was associated with an increased risk of RDS and a higher need of exogenous surfactant administration than spontaneous group. The rate of neonatal sepsis was significantly higher in PPROM group along with a higher prevalence of histological chorioamnionitis.

Objective: To study the tocolytic action of nifedipine combined with sildenafil citrate (SC) and if the combination is superior to nifedipine alone in inhibiting threatened preterm labour (PTL)., Design: Prospective randomised study., Setting: An Egyptian university hospital., Population: Women with threatened PTL who received either nifedipine with SC or nifedipine alone., Methods: Patients were randomly allocated to receive either (1) nifedipine 20 mg orally (stat dose), followed by 10 mg orally every 6-8 hours at the same time as vaginal administration of SC (25 mg at 8-hourly intervals) or (2) nifedipine alone. Medications were continued for 48-72 hours., Main Outcome Measures: The percentage of women who remained undelivered during hospitalisation., Results: From January 2015 to November 2016, 239 women were randomised. The baseline characteristics of participants were similar. Nifedipine combined with SC was associated with more women remaining undelivered (81.8 versus 68.6%; P = 0.018) during hospitalisation. Regarding secondary outcomes, the addition of SC was also associated with fewer deliveries within 7 days of admission (9.1 versus 20.3%; P = 0.014), prolonged latency (29 versus 7 days; P = 0.002), fewer admissions to neonatal intensive care units (31.4 versus 44.1%; P = 0.043), fewer very preterm deliveries (from 28 to <32 weeks, 20.7 versus 38.1%; P = 0.043), and increased neonatal birthweight (1900 versus 1500 g; P = 0.018)., Conclusions: Vaginal SC combined with nifedipine is an effective option for tocolytic therapy during threatened PTL., Tweetable Abstract: Vaginal SC enhances the tocolytic effect of nifedipine., (© 2018 Royal College of Obstetricians and Gynaecologists.)

Preterm labor is an urgent medical-social and demographic issue at the present stage. A considerable number of factors affects the course of pregnancy and its outcome, their effect is realized at the level of the central nervous system through numerical metabolic interactions, where monoaminergic systems play an important role. Objective - to study the features of the sympathoadrenal system state by determining the excretion level of DOPHA, dopamine, norepinephrine and epinephrine in women's daily urine with different periods of abortion. 227 pregnant women who were admitted to the Kharkiv perinatal center have been examined, 190 of them had clinical signs of premature delivery in the gestation period of 23-36 weeks. Formation of clinical groups was carried out depending on the pregnancy term in the form of premature and timely delivery. Diagnosis of preterm labor was carried out in the presence of abdominal pain syndrome and structural changes in the cervix. Consequently, pregnancy compensatory and adaptive mechanisms are complex of neurohumoral process, which are realized through monoaminergic systems and a significant factor in its interruption is their destabilization. Reducing of sympathoadrenal system activity and reserve capacity in pregnant women may be a pathogenetic factor in the development of preterm labor. Therefore determination of the imbalance initial manifestations in the catecholamines exchange may possibly prevent the loss of pregnancy in the early stages.

Preterm labor with intact membranes is a major cause of spontaneous preterm birth (sPTB). To prevent sPTB a clear understanding is needed of the hormonal interactions that initiate labor. The steroid hormone progesterone acting via its nuclear progesterone receptors (PRs) in uterine cells is essential for the establishment and maintenance of pregnancy and disruption of PR signaling (i.e., functional progesterone/PR withdrawal) is key trigger for labor. The process of parturition is also associated with inflammation within the uterine tissues and it is now generally accepted that inflammatory stimuli from multiple extrinsic and intrinsic sources induce labor. Recent studies suggest inflammatory stimuli induce labor by affecting PR transcriptional activity in uterine cells to cause functional progesterone/PR withdrawal. Advances in understanding the functional interaction of inflammatory load on the pregnancy uterus and progesterone/PR signaling is opening novel areas of research and may lead to rational therapeutic strategies to effectively prevent sPTB., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To assess whether women with a history of preterm birth, independent on the presence of prelabour rupture of the membranes (PROM) and growth deviation of the newborn, are more likely to develop preeclampsia with preterm or preterm birth in a subsequent pregnancy., Methods: We conducted a population-based cohort study, based on Medical Birth Registry of Norway between 1967 and 2012, including 742,980 women with singleton pregnancies who were followed up from their 1st to 2nd pregnancy. In the analyses we included 712,511 women after excluding 30,469 women with preeclampsia in the first pregnancy., Results: After preterm birth without preeclampsia in the first pregnancy, the risk of preterm preeclampsia in the second pregnancy was 4-7 fold higher than after term birth (odds ratios 3.5; 95% confidence interval (CI) 3.0-4.0 to 6.5; 95% CI 5.1-8.2). The risk of term preeclampsia in the pregnancy following a preterm birth was 2-3 times higher than after term birth (odds ratios 1.6; 95% CI 1.5-1.8 to 2.6; 95% CI 2.0-3.4). After spontaneous non-PROM preterm birth and preterm PROM, the risk of preterm preeclampsia was 3.3-3.6 fold higher than after spontaneous term birth. Corresponding risks of term preeclampsia was 1.6-1.8 fold higher. No significant time trends were found in the effect of spontaneous preterm birth in the first pregnancy on preterm or term preeclampsia in the second pregnancy., Conclusions: The results suggest that preterm birth, regardless of the presence of PROM, and preeclampsia share pathophysiologic mechanisms. These mechanisms may cause preterm birth in one pregnancy and preeclampsia in a subsequent pregnancy in the same woman. The association was particularly evident with preterm preeclampsia.

Preterm labor (PTL) accounts for almost 11% of deliveries, and is a major cause of neonatal morbidity and mortality. T regulatory (Treg) cells may prevent fetal rejection by the maternal immune system under the influence of progesterone. Case control study was conducted to determine Treg cells, IL-10, TGF-β, and membrane progesterone receptorα (mPRα) in the maternal-fetal interface (placenta), including eight pregnant women with threatened PTL (study group) and 16 normal-delivery women (control group). Comparing study group versus control, mean gestational age of delivery differed significantly (p = 0.02), as did endothelial hyperplasia in the upper half (p = 0.035) and the lower half (p = 0.005) of the placenta. Besides, there was higher expression of mPRα and IL-10 in all layers, while Foxp3 expression occurred equally and only in the decidua. TGF-β expression was similar in both groups. Preterm group placentas showed higher endothelial hyperplasia in both upper and lower halves of the placenta.

Objective: It has been shown that noninvasive uterine electromyography (EMG) can identify true preterm labor more accurately than methods available to clinicians today. The objective of this study was to evaluate the effect of body mass index (BMI) on the accuracy of uterine EMG in predicting preterm delivery., Materials and Methods: Predictive values of uterine EMG for preterm delivery were compared in obese versus overweight/normal BMI patients. Hanley-McNeil test was used to compare receiver operator characteristics curves in these groups. Previously reported EMG cutoffs were used to determine groups with false positive/false negative and true positive/true negative EMG results. BMI in these groups was compared with Student t test (p < 0.05 significant)., Results: A total of 88 patients were included: 20 obese, 64 overweight, and four with normal BMI. EMG predicted preterm delivery within 7 days with area under the curve = 0.95 in the normal/overweight group, and with area under the curve = 1.00 in the obese group (p = 0.08). Six patients in true preterm labor (delivering within 7 days from EMG measurement) had low EMG values (false negative group). There were no false positive results. No significant differences in patient's BMI were noted between false negative group patients and preterm labor patients with high EMG values (true positive group) and nonlabor patients with low EMG values (true negative group; p = 0.32)., Conclusion: Accuracy of noninvasive uterine EMG monitoring and its predictive value for preterm delivery are not affected by obesity., (Copyright © 2016. Published by Elsevier B.V.)

Spontaneous preterm birth is a major public health problem, with a clear genetic component. Genetic association studies have evolved substantially in recent years, moving away from the traditional candidate gene analyses to newer approaches utilizing sophisticated analysis platforms to examine sequencing data, and shifting towards functional studies including methylation analysis. It is becoming increasingly evident that careful clinical phenotyping is crucial to high quality genetic association studies regardless of the assay or platform being used. Nonetheless, genetic studies of prematurity are hampered by numerous challenges including small sample sizes, incomplete phenotying, population stratification, and multiple comparisons. As the costs of sequencing and functional analyses continue to decrease, unbiased genome-wide assays will be more widely available. Researchers have met improved success recently when critically applying clinical phenotyping knowledge to group women prior to analyzing genotyping results. Eventually, as the analytic approaches evolve, it is likely that this methodology (combining precisely clinically phenotyped subjects with genome-wide data) will provide key information regarding the pathophysiology of prematurity, and provide potential new avenues for exploring innovative therapeutic strategies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: To assess the accuracy of blind vaginal swab in diagnosis of preterm labor (PTL) and prediction of subsequent occurrence of preterm birth (PTB)., Methods: Eligible women who presented at 24-34 weeks of gestation with threatened PTL had their cervicovaginal secretions sequentially sampled for fetal fibronectin (fFN) using two types of swabbing techniques. The first swab was a blind vaginal swab collected without the aid of speculum, while the second one was a routine cervicovaginal swab. All participants were followed up until delivery., Results: fFN in both swabs was significantly higher in women who delivered before term compared with women who delivered at term. On regression analysis, r(2) = 0.735 and 0.785 for blind vaginal and cervicovaginal swabs respectively, while on receiver operating characteristic analysis the area under curve was 0.965 and 0.977, respectively, without a statistically significant difference. Using an fFN cut-off of ≥0.05 μg/dL, the sensitivity, specificity, positive predictive value and negative predictive value of blind vaginal swab to predict PTB were 53.9%, 91.9%, 70.0% and 85.0%, respectively; while those for cervicovaginal swab were 58.3%, 94.7%, 77.8% and 87.8%, respectively., Conclusions: In women presenting at 24-34 weeks of gestation with threatened PTL, blind vaginal fFN swab is as effective as cervicovaginal swab to predict PTB, but it is easier to perform and does not require doctor supervision., (© 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.)

Threatened preterm labor (TPTL) accounts for ∼30% of pregnancy-related hospital admissions. Maternal peripheral leukocytes can be used to monitor a variety of physiological processes occurring in the body. Two high-throughput mass spectrometry methodologies, SWATH and iTRAQ, were used to study differentially expressed peripheral blood leukocyte lysate proteins in symptomatic women admitted for TPTL who had a preterm birth within 48 h (n = 16) and those who did not (n = 24). The SWATH spectral library consisted of 783 proteins. SWATH methodology quantified 258 proteins (using ≥2 peptides) and 5 proteins (ALBU, ANXA6, HNRPK, HSP90A, and PDIA1) were differentially expressed (p < 0.05, Mann-Whitney U). iTRAQ workflow identified 765 proteins; 354 proteins were quantified and 14 proteins (MIF, UBIQ, HXK3, ALBU, HNRPD, ST1A2, RS15A, RAP1B, CAN1, IQGA2, ST1A1, COX5A, ADDA, and UBQL1) were significantly different between the two groups of women (p < 0.05, Mann-Whitney U). Albumin was the only common differentially expressed protein in both SWATH (28% decrease) and iTRAQ studies (45% decrease). This decrease in albumin was validated using ELISA (11% decrease, p < 0.05, Mann-Whitney U) in another 23 TPTL women. This work suggests that albumin is a broad indicator of leukocyte activation with impending preterm birth and provides new future work directions to understand the pathophysiology of TPTL.

Preterm birth is a leading cause of infant morbidity and mortality worldwide, but current interventions to prevent prematurity are largely ineffective. Preterm birth is increasingly recognized as an outcome that can result from a variety of pathological processes. Despite current research efforts, the mechanisms underlying these processes remain poorly understood and are influenced by a range of biological and environmental factors. Research with modern techniques is needed to understand the mechanisms responsible for preterm labor and birth and identify targets for diagnostic and therapeutic solutions. This review evaluates the state of reproductive science relevant to understanding the causes of preterm birth, identifies potential targets for prevention, and outlines challenges and opportunities for translating research findings into effective interventions., (Copyright © 2014, American Association for the Advancement of Science.)

The phenotype of spontaneous preterm birth (SPTB) refers to the biochemical and physical characteristics present at the time of preterm delivery. These are the result of the processes that cause this complication. The lack of understanding about the etiologies and our inability to prevent SPTB are because of the complex nature and multiple processes responsible for maintenance of pregnancy and the transition to labor. Any of these processes, when activated prematurely, may lead to SPTB. This article provides an overview of the SPTB phenotype, which may assist with future attempts to reduce in the incidence of SPTB.

Objective: The objective of the study was to estimate the relationship between midtrimester cervical length (CL) and maternal serum markers of systemic inflammation, activation of the maternal-fetal hypothalamic-pituitary axis, and alterations in thrombosis-hemostasis., Study Design: This is a secondary analysis of a prospective cohort study designed to predict preterm birth in the general obstetric population. Women had serial CL ultrasounds and assessment of maternal serum corticotrophin-releasing hormone, C-reactive protein, and thrombin-antithrombin III complexes between 20 and 33 weeks' gestation and were followed up until delivery., Results: Shortening of CL was associated with the rate of rise in corticotrophin-releasing hormone (r(2) = 0.34, P = .014) and C-reactive protein (r(2) = 0.44, P = .001) for women with CL less than 25 mm but not for the cohort overall. There was no association of change in CL with change in thrombin-antithrombin III concentration., Conclusion: Among women with a midtrimester sonographically short cervix, changes in serum markers suggest that a shortening CL may be associated with systemic inflammation and activation of the maternal-fetal hypothalamic-pituitary axis but not systemic thrombosis-hemostasis., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Threatened preterm labor (TPTL) is defined as persistent premature uterine contractions between 20 and 37 weeks of gestation and is the most common condition that requires hospitalization during pregnancy. Most of these TPTL women continue their pregnancies to term while only an estimated 5% will deliver a premature baby within ten days. The aim of this work was to study differential whole blood gene expression associated with spontaneous preterm birth (sPTB) within 48 hours of hospital admission. Peripheral blood was collected at point of hospital admission from 154 women with TPTL before any medical treatment. Microarrays were utilized to investigate differential whole blood gene expression between TPTL women who did (n = 48) or did not have a sPTB (n = 106) within 48 hours of admission. Total leukocyte and neutrophil counts were significantly higher (35% and 41% respectively) in women who had sPTB than women who did not deliver within 48 hours (p<0.001). Fetal fibronectin (fFN) test was performed on 62 women. There was no difference in the urine, vaginal and placental microbiology and histopathology reports between the two groups of women. There were 469 significant differentially expressed genes (FDR<0.05); 28 differentially expressed genes were chosen for microarray validation using qRT-PCR and 20 out of 28 genes were successfully validated (p<0.05). An optimal random forest classifier model to predict sPTB was achieved using the top nine differentially expressed genes coupled with peripheral clinical blood data (sensitivity 70.8%, specificity 75.5%). These differentially expressed genes may further elucidate the underlying mechanisms of sPTB and pave the way for future systems biology studies to predict sPTB.

Background: Premature birth is defined as birth of before 37 completed weeks' gestation. Not all pregnant women showing symptoms of preterm labour will go on to deliver before 37 weeks' gestation. Hence, addition of fetal fibronectin (fFN) testing to the diagnostic workup of women with suspected preterm labour may help to identify those women who do not require active management, and thus avoid unnecessary interventions, hospitalisations and associated costs., Objective: To assess the clinical effectiveness and cost-effectiveness of rapid fFN testing in predicting preterm birth (PTB) in symptomatic women., Data Sources: Bibliographic databases (including EMBASE, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials) were searched from 2000 to September/November 2011. Trial registers were also searched., Review Methods: Systematic review methods followed published guidance; we assessed clinical effectiveness and updated a previous systematic review of test accuracy. Risk of bias was assessed using the Cochrane tool (randomised controlled trials; RCTs) and a modification of QUADAS-2 (diagnostic test accuracy studies; DTAs). Summary risk ratios or weighted mean difference were calculated using random-effects models. Summary sensitivity and specificity used a bivariate summary receiver operating characteristic model. Heterogeneity was investigated using subgroup and sensitivity analyses. Health economic analysis focused on cost consequences. The time horizon was hospital admission for observation. A main structural assumption was that, compared with usual care, fFN testing doesn't increase adverse events or negative pregnancy outcomes., Results: Five RCTs and 15 new DTAs were identified. No RCT reported significant effects of fFN testing on maternal or neonatal outcomes. One study reported a subgroup analysis of women with negative fFN test observed > 6 hours, which showed a reduction in length of hospital stay where results were known to clinicians. Combining data from new studies and the previous systematic review, the pooled estimates of sensitivity and specificity were: 76.7% and 82.7% for delivery within 7-10 days of testing; 69.1% and 84.4% for delivery < 34 weeks' gestation; and 60.8% and 82.3% for delivery < 37 weeks' gestation. Estimates were similar across all subgroups sensitivity analyses. The base-case cost analysis resulted in a cost saving of £23.87 for fFN testing compared with usual care. The fFN testing was cost-neutral at an approximate cost of £45. Probabilistic sensitivity analysis gave an incremental cost (saving) of -£25.59 (97.5% confidence interval -£304.96 to £240.06), indicating substantial uncertainty. Sensitivity analyses indicated that admission rate had the largest impact on results., Conclusions: Fetal fibronectin testing has moderate accuracy for predicting PTB. The main potential role is likely to be reducing health-care resource usage by identifying women not requiring intervention. Evidence from RCTs suggests that fFN does not increase adverse outcomes and may reduce resource use. The base-case analysis showed a modest cost difference in favour of fFN testing, which is largely dependent on whether or not fFN testing reduces hospital admission. Currently, there are no high-quality studies and the existing trials were generally underpowered. Hence, there is a need for high-quality adequately powered trials using appropriate study designs to confirm the findings presented., Study Registration: PROSPERO 2011:CRD42011001468. Available from www.crd.york.ac.uk/PROSPERO/display&#95;record.asp?ID=CRD42011001468., Funding: The National Institute for Health Research Health Technology Assessment programme.

Widely prescribed in the years 1970-1980 to prolong gestation, progesterone has regained interest after the publication of randomized trials since 10 years. In women at increased risk of preterm birth with a history of preterm delivery or late miscarriage, the use of progesterone, especially intramuscularly may reduce the incidence of spontaneous preterm birth. In contrast, in cases of preterm labor or twin pregnancies, progesterone efficacy to reduce preterm birth has not been demonstrated. In women with asymptomatic midtrimester sonographic short cervix, randomized studies show conflicting results and new studies are necessary before its widespread utilisation., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Rates of preterm birth vary between different populations and ethnic groups. Epidemiologic studies have suggested that the incidence of preterm birth is also higher in pregnancies carrying a male fetus; the male:female difference is greater in earlier preterm pregnancy. Placental or chorion trophoblast cells from pregnancies with a male fetus produced more pro-inflammatory TNFα in response to LPS stimulation and less anti-inflammatory IL-10 and granulocyte colony stimulating factor (G-CSF) than cells from pregnancies with a female fetus, more prostaglandin synthase (PTGS-2) and less prostaglandin dehydrogenase (PGDH). These results suggest that in the presence of a male fetus the trophoblast has the potential to generate a more pro-inflammatory environment. Maturation of the fetal hypothalamic-pituitary-adrenal axis and expression of placental genes, particularly 11β hydroxysteroid dehydrogenase-2 are also expressed in a sex dependent manner, consistent with the sex-biasing influences on gene networks. Sex differences in these activities may affect clinical outcomes of pre- and post-dates pregnancies and fetal/newborn wellbeing. These factors need consideration in studies of placental function and in the development of personalized strategies for the diagnosis of preterm labor and postnatal health., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To investigate the association between two genetic variations in the Interleukin-1 beta (IL1B) gene and preterm birth., Study Design: In this case-control study we tested the allelic distribution of two of its common polymorphisms (IL1B +3953C>T [rs1143634], IL1B -511C>T [rs16944]) in one hundred women with preterm birth and one hundred healthy women with at least one uncomplicated full term pregnancy and no history of preterm birth., Results: A significant association was found between the presence of the IL1B +3953C>T polymorphism and preterm birth (p=0.049, OR 0.6 [0.3-1.0]). No significant association was found between the IL1B -511C>T polymorphism and preterm birth (p=0.471, OR 1.3 [0.7-2.3])., Conclusion: Our findings suggest that the IL1B +3953C>T polymorphism is associated with a risk reduction for preterm birth in Caucasian women, possibly by altering the inflammatory response during pregnancy., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: Women who experience preterm birth (PTB) are at increased risk of cardiovascular morbidity and mortality in the subsequent decades. Individuals with cardiovascular disorders have increased central aortic systolic blood pressure (SBP(Ao)) and arterial stiffness, assessed by pulse wave velocity (PWV) and augmentation index (AIx). The aim of this screening study was to evaluate SBP(Ao), PWV and AIx at 11-13 weeks' gestation in women who delivered preterm., Methods: This was a prospective study in singleton pregnancies at 11 + 0 to 13 + 6 weeks' gestation. Maternal history and characteristics were recorded, and PWV, AIx and SBP(Ao) were measured. We compared these parameters in women who had spontaneous (n = 244) or iatrogenic (n = 110) PTB before 37 weeks' gestation and before 34 weeks with those in women who had term delivery (n = 7489)., Results: Compared with women who had term delivery, women who had iatrogenic PTB had significantly higher AIx (1.08 (interquartile range (IQR), 0.91-1.27) multiples of the median (MoM), vs. 1.00 (IQR, 0.86-1.16) MoM) and SBP(Ao) (1.06 (IQR, 0.98-1.15) MoM vs. 1.00 (IQR, 0.93-1.07) MoM). However, there was no significant difference in AIx, PWV or SBP(Ao) between those who had spontaneous PTB and those who had term delivery. These findings were similar for those who had PTB at < 34 and < 37 weeks' gestation., Conclusion: Women who had iatrogenic PTB, but not those who had spontaneous PTB, have increased SBP(Ao) and arterial stiffness that is apparent from as early as the first trimester of pregnancy., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Moderate and late preterm births account for the majority of preterm babies. The common perception that birth at 32-36 weeks' gestation carries few risks is now being challenged, as these babies have increased risk of neonatal mortality and morbidity. However, spontaneous labour at this gestation frequently has no specific, easily identifiable precursor, although preterm birth per se has a number of epidemiological and clinical associations. Prediction and prevention of preterm birth is currently largely aimed at identifying women at high risk such as those with previous preterm birth, and targeting intervention at this group. Both cervical length assessment and fibronectin testing permit some modification of the likelihood of preterm birth in this group. Progesterone treatment for the prevention of preterm birth is currently being researched widely, and appears a potentially promising strategy. Babies born at 32-36 weeks' gestation need careful monitoring in labour, with modification of intervention in labour due to their prematurity., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Aims: Preterm birth is the most common cause of neonatal morbidity and mortality. Neonatal morbidity and mortality are known to decrease significantly after 34 weeks in preterm births following preterm labor, and after 32 weeks in preterm births following preterm rupture of the membranes. However, these outcomes may not apply to Korean preterm neonates. This study analyzed the morbidity of preterm neonates based on gestational age to determine the optimal gestational age of delivery following preterm labor., Materials and Methods: We retrospectively analyzed the medical records of preterm neonates and their mothers who delivered at Seoul St. Mary's Hospital between January 1995 and December 2007., Results: Among 1234 preterm neonates, 1008 were singletons and 226 were multiple births. In both singleton and multifetal pregnancies, the maternal characteristics did not differ based on gestational age. The 1- and 5-min Apgar scores were significantly lower than at 35 weeks in singleton births, and at 33 weeks in multiple births. Major complications, such as intraventricular hemorrhage and the use of a respirator, decreased significantly after 35 weeks in singleton births, and after 33 weeks in multiple births., Conclusions: The optimal gestational age for decreasing the morbidity of major complications in preterm neonates was 1 week later than the American College of Obstetricians and Gynecologists recommendations. For Korean mothers with preterm labor, delivery needs to be delayed until 35 weeks in singletons, 33 weeks in twins, and 32 weeks in singletons with preterm rupture of the membranes., (© 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.)

Background: Preeclampsia and preterm labor often underlie preterm birth, and are associated with maternal inflammation. In preterm infants, respiratory distress syndrome (RDS) and mechanical ventilation are associated with systemic inflammation., Objective: We aimed to study whether early-onset preeclampsia or preterm labor modulate the systemic inflammation affecting preterm infants with RDS., Methods: We recruited mechanically ventilated infants with gestational ages <32 weeks; 11 infants were born after early-onset preeclampsia and 25 after preterm labor. Blood was drawn during postnatal days 1-7, and the mean values of days 1-2, 3-4 and 5-6 were used. Phagocyte CD11b expression was analyzed with flow cytometry, and plasma C-reactive protein (CRP) concentrations with immunoturbidimetry., Results: As compared with infants born after preterm labor, infants born after early-onset preeclampsia had higher CD11b expression on days 1-6 on both neutrophils and monocytes. In addition, infants born after early-onset preeclampsia had higher CRP concentrations on days 2-6 (all p < 0.05)., Conclusions: As compared with infants born after preterm labor to mothers without preeclampsia, infants born after early-onset preeclampsia presented with a stronger postnatal systemic inflammatory reaction. Antenatal exposure to preeclampsia may induce fetal leukocyte priming and regulation of inflammation, and thereby modify postnatal inflammatory reactions and morbidity., (Copyright © 2011 S. Karger AG, Basel.)

Preterm birth is the defining challenge to modern perinatal medicine. It is now clear that preterm birth is not caused by one pathologic process but many, some not identified. Prevention of preterm birth is possible if perinatal medicine, science, and society give the necessary priority to this most urgent problem of maternal, fetal, and neonatal patients.

The diagnosis of preterm labor (PTL) is challenging, especially in women whose cervical dilatation is <2 cm and who are <80% effaced. In symptomatic women, with threatened PTL in both singletons and twins, transvaginal ultrasound cervical length (CL) identifies a high-risk group that is more likely to be in true PTL, more likely to deliver sooner, and more likely to deliver preterm. The addition of fetal fibronectin improves the predictive accuracy in women whose CL is <30 mm but >15 mm. Transvaginal ultrasound CL can also be performed in the presence of ruptured membranes and predicts latency. Although additional data are needed, the evidence so far suggests that the use of transvaginal ultrasound CL and fetal fibronectin can be used to better identify and manage women with PTL likely to have an imminent preterm delivery, and to avoid interventions in women who would not.

We sought to determine the risk of preterm (< 32 weeks) delivery as it relates to cervical dilatation at presentation of an initial preterm labor admission episode. We retrospectively reviewed the records of all patients presenting with preterm contractions at 22 to 32 weeks' gestation. Multiple regression was used to analyze the relationship between the interval from initial preterm labor admission episode to delivery and cervical dilatation at presentation. Logistic regression analysis was used to identify variables associated with preterm birth. Mean gestational age on admission for preterm labor episode was 28.1 +/- 2.9 weeks. With a cervical dilatation of 0 to 1 cm, 6% of the women delivered within 48 hours, 20% delivered at < 32 weeks, and 38% delivered at < 35 weeks. With cervical dilatation of 6 to 10 cm, 89% delivered in < 24 hours, 11% between 24 and 48 hours, 94% delivered at < 32 weeks, and 100% delivered at < 35 weeks. Time from admission for initial preterm labor episode to delivery was inversely associated with cervical dilatation. Variables associated with preterm birth at < 32 weeks' gestation were cervical dilatation ( P < 0.0001), gestational age ( P < 0.0001), and effacement ( P < 0.0001) at presentation. In women who experience preterm contractions, cervical dilatation on admission is inversely related to interval to delivery. However, women with cervical dilatation of 0 to 1 cm are still at significant risk for preterm delivery: 19/94 (20%) at < 32 weeks' gestation and 40/104 (38%) at < 35 weeks' gestation.

Objective: To determine whether a correlation exists between increased uterine electrical activity and cervical length (CL) in the midtrimester of pregnancy., Method: In this case-control study, 312 asymptomatic nulliparous women underwent both uterine electromyographic assessment and ultrasound CL measurement between the 16th and 23rd weeks of a singleton pregnancy. The outcome measure was the difference in ultrasound CL measurement between the women found to have uterine action potentials on electromyography and those who did not., Results: Action potentials were detected in 66 (21.1%) of the 312 women; and compared with the remainder of the study population, cervical length was significantly shorter in these women (35.7+/-8.9 mm vs 38.8+/-7.9 mm; P<0.01 by the Mann-Whitney test)., Conclusion: Ultrasound CL measurement in the midtrimester was significantly shorter in women with increased uterine electrical activity.

Background: Preterm birth is the major cause of perinatal mortality and morbidity in the developed world., Objective: The aim of this study was to establish the importance of preterm birth and the huge healthcare costs involved and review the pathophysiology of preterm labor and the use of antepartum glucocorticoids, which are the main reason why tocolytics are used to prevent or delay preterm birth. The study also reviewed the range of tocolytics available, their mode of action and the evidence for their efficacy and fetomaternal safety., Methods: An extensive review of the literature using well-recognized and accepted scientific search engines was employed., Results/conclusions: The perfect tocolytic does not exist. The evidence to support the use of magnesium sulfate as a tocolytic is poor. The use of beta-agonists is decreasing worldwide as clinicians move to nifedipine or atosiban, which are as effective but much safer. Although nifedipine is cheaper than atosiban and can be administered orally, the evidence to support atosiban is much superior to that of nifedipine and there have been recent safety concerns over nifedipine.

Objective: The purpose of this study was to determine whether preterm birth of twins is associated with an increased risk of preterm birth in a subsequent singleton pregnancy., Study Design: All patients who delivered a twin gestation and a subsequent singleton pregnancy at Northwestern Memorial Hospital during a 10-year period were identified. We used a cohort study design, comparing the outcomes of the singleton pregnancies in women with preterm twin deliveries to those pregnancies with term twin deliveries., Results: One hundred sixty-seven women delivered twins followed by a singleton pregnancy. Women whose twin delivery was preterm (n = 99) were more likely than those who had delivered a term twin pregnancy (n = 68) to deliver a subsequent preterm singleton pregnancy (13.1% vs 2.9%; odds ratio, 5.0; 95% CI, 1.1, 22.9)., Conclusion: Preterm birth of twins is associated with an increased risk of preterm delivery in a subsequent singleton pregnancy.

Objective: To investigate whether corticotropin-releasing hormone (CRH) and corticotropin (ACTH) plasma concentrations in women diagnosed with preterm labor are of potential clinical value in the assessment of the risk of preterm birth., Method: Plasma samples of 79 women diagnosed with preterm labor were used in this study. Samples were divided into three groups based on the week of gestation (24th-28th, 29th-32nd, 33rd-37th). CRH and ACTH values were determined by ELISA., Result: Mean maternal peripheral plasma values of CRH and ACTH were significantly higher (p<0.001) in women who were initially diagnosed with preterm labor and finally delivered a preterm birth, compared to women with the same diagnosis but with term birth., Conclusion: CRH and ACTH serum levels in women diagnosed with preterm labor could be used as predictors for the timing of parturition.

Preterm birth (defined as delivery prior to 37 weeks' gestation) complicates 5-10% of all births. It is a major cause of perinatal mortality and morbidity. Approximately 20% of all preterm births are iatrogenic resulting from obstetric intervention for maternal and/or fetal indications. Of the remainder, 2/3 are spontaneous preterm labor with or without preterm premature rupture of the membranes (pPROM). Preterm labor is a syndrome rather than a diagnosis since the etiologies are varied. Risk factors include, among others, pPROM, cervical insufficiency, pathologic uterine distention (polyhydramnios, multiple gestation), uterine anomalies, intrauterine infection/inflammation, and social factors (stress, smoking, heavy work). The final common pathway appears to be activation of the inflammatory cascade. Bacterial colonization and/or inflammation of the choriodecidual interface induces production of pro-inflammatory cytokines that, in turn, lead to neutrophil activation and the synthesis and release of uterotonins such as prostaglandins (which cause uterine contractions) and metalloproteinases (that weaken fetal membranes and remodel cervical collagen). This monograph reviews the role of cytokines in the pathophysiology of preterm labor and delivery.