Prevention Of Preterm Labor Research Articles

Novel application of polypropylene sling: Transvaginal cervicoisthmic cerclage in women with high risk of preterm delivery

Study objective To describe a novel technique of transvaginal cervicoisthmic cerclage with a polypropylene sling in prevention of preterm labor in pregnant women at high risk. Design Retrospective study (Canadian Task Force classification: III). Setting University hospital (department of obstetrics and gynecology). Patients Twenty-one women showing symptoms of high risk of preterm delivery: histories of pregnancy losses in the second trimester and prior failure of MacDonald’s cerclage or absent portio vaginalis of the cervix. The median age of the patients was 32.8 years (range 22–39 years). Interventions Cerclage was performed between 12 and 16 weeks’ gestation. A polypropylene tape was placed at the cervicoisthmic junction by vaginal route. Caesarean delivery was systematically performed in all patients because the cerclage was considered to be definitive. Measurements and main results No intraoperative complications occurred. The mean operating time was 36 ± 6 minutes (range 30–45 minutes). The mean length of stay was 1.4 ± 0.5 days. Mean gestational age and birth weight at delivery were respectively 37.1 ± 1.8 weeks (CI 95%: 36.4–37.9) and 2850 ± 745 g (CI 95%: 2531–3168). The preterm birth rate was 19% (4/21). One neonatal death occurred after amniotic fluid infection at 34 weeks. Birth at less than 32 weeks occurred in one patient (4%). Conclusion Transvaginal cervicoisthmic cerclage with polypropylene sling may be considered as an effective and minimally invasive alternative to the transabdominal cervicoisthmic cerclage in women presenting with high risk of preterm delivery.

Evidence Based Management of Preterm Labour

Preterm labour remains the leading cause of neonatal mortality and morbidity. Prevention and treatment of preterm labour is important, not as an and in itself, but as a means of reducing adverse events for the child. Management of preterm labour should be individualized and tailored for each case. In this article, we review advances in prediction, prevention and management of preterm labour with regard to the levels of evidence.

TOCOX-A Randomised, Double-Blind, Placebo-Controlled Trial of Rofecoxib (a COX-2-Specific Prostaglandin Inhibitor) for Prevention of Preterm Labor in Women at High Risk

TOCOX-A Randomised, Double-Blind, Placebo-Controlled Trial of Rofecoxib (a COX-2-Specific Prostaglandin Inhibitor) for Prevention of Preterm Labor in Women at High Risk

Accouchement du prématuré

Spontaneous or induced prematurity are leading causes of perinatal morbidity and mortality. Gestational age is the more important prognosis factor. Prevention and management of preterm labour are fundamental. Improvement of morbidity and mortality can be achieved by antenatal corticosteroid therapy and delivery in a maternity hospital adapted to the gestational age. The mode of delivery of premature infants is controversial. However, natural delivery seems to be privileged in case of vertex presentation. In breech presentation or in case of chorioamnionitis, caesarean section is preferred.

Synthesis of Oxytocin Analogues with Replacement of Sulfur by Carbon Gives Potent Antagonists with Increased Stability

[Chemical reaction: See text] The neuropeptide oxytocin 1 controls mammary and uterine smooth muscle contraction. Atosiban 2, an oxytocin antagonist, is used for prevention of preterm labor and premature birth. However, the metabolic lifetimes of such peptide drugs are short because of in vivo degradation. Facile production of oxytocin analogues with varying ring sizes wherein sulfur is replaced by carbon (methylene or methine) could be achieved by standard solid-phase peptide synthesis using olefin-bearing amino acids followed by on-resin ring-closing metathesis (RCM). These were tested for agonistic and antagonistic uteronic activity using myometrial strips taken from nonpregnant female rats. Peptide 8 showed agonistic activity in vitro (EC50= 1.4 x 10(3) +/- 4.4 x 10(2) nM) as compared to 1 (EC50= 7.0 +/- 2.1 nM). Atosiban analogues 17 (pA2= 7.8 +/- 0.1) and 18 (pA2= 8.0 +/- 0.1) showed substantial activity compared to the parent oxytocin antagonist 2 (pA2= 9.9 +/- 0.3). Carba analogue 35 (pA2= 6.1 +/- 0.1) had an agonistic activity over 2 orders of magnitude less than its parent 3 (8.8 +/- 0.5). A comparison of biological stabilities of 1,6-carba analogues of both an agonist 8 and antagonist 18 versus parent peptides 1 and 2 was conducted. The half-lives of peptides 8 and 18 in rat placental tissue were shown (Table 2) to be greatly improved versus their parents oxytocin 1 and atosiban 2, respectively. These results suggest that peptides 8 and 18 and analogues thereof may be important leads into the development of a long-lasting, commercially available therapeutic for initiation of parturition and treatment of preterm labor.

Taking On Racial And Ethnic Disparities In Health Care: The Experience At Aetna

Among the nation's health plans, Aetna is considered the industry leader in efforts to eliminate racial and ethnic disparities in health care. This Perspective describes the work of a task force led by Aetna's chairman and CEO, charged with a number of strategic activities including cultural competency training and the identification of disparities occurring within the Aetna membership population. The cornerstone of this quality-of-care initiative is a successful and ongoing data collection enterprise. Aetna is putting the data to work in its chronic disease management, breast health, and African American Preterm Labor Prevention and Breastfeeding programs.

Tocolytic effect of a Rho-kinase inhibitor in a mouse model of lipopolysaccharide-induced preterm delivery

The small guanosine triphosphatase RhoA/Rho-kinase cascade has been implicated in uterine contraction. Our purpose was to evaluate the tocolytic effect of a Rho-kinase inhibitor, Y-27632, in lipopolysaccharide-induced preterm delivery in mice. We used an animal model of lipopolysaccharide-induced preterm delivery in C3H/HeN x B6D2F1 pregnant mice. Y-27632 was delivered continuously through an osmotic pump that was implanted into the peritoneal cavity 6 hours before lipopolysaccharide treatment. The primary outcome was the preterm delivery rate. To further study the possible involvement of this cascade in lipopolysaccharide-induced preterm delivery, we determined the effect of lipopolysaccharide and prostaglandin F2alpha on RhoA activation in mouse myometrial cells and uterine smooth muscle tissues. The rate of preterm delivery for lipopolysaccharide-treated animals was 94.4%. The administration of Y-27632 (1 or 10 mg/kg/d) significantly reduced the preterm delivery rate to 61.1% or 15.8%, respectively. The level of guanosine triphosphate-bound RhoA was increased after the addition of lipopolysaccharide or prostaglandin F2alpha. The RhoA/Rho-kinase cascade is involved in lipopolysaccharide-induced preterm delivery, which suggests that Rho-kinase could be used as a new therapeutic target for the prevention of preterm labor.

Genetic factors in preterm birth—the future

The genetic regulation of common biological functions has redundant control mechanisms, and it is unlikely that a single marker will ever be identified that will be both highly sensitive and specific. It is more likely that combinations of gene and/or protein markers, perhaps also combined with obstetric family histories, will be required to achieve the goal of a truly sensitive and specific screening profile for spontaneous preterm labour and preterm birth. The rapidly evolving disciplines of genomics and proteomics are now beginning to be applied to the study of spontaneous preterm labour and preterm birth. These techniques are able to measure multiple markers (in the thousands) in a biological sample and, given the likely presence of biological changes that precede by weeks or even months the clinical manifestations of the disease, are ideally suited to the evaluation of spontaneous preterm labour and preterm birth. Over the next few years, these technologies will hasten a deeper understanding of the pathophysiology of spontaneous preterm labour, discover novel target molecules and diagnostic biomarkers and ultimately aid in formulating more effective interventions to prevent preterm birth. Pharmacogenomics is another rapidly evolving discipline that holds great promise for the treatment and prevention of spontaneous preterm labour and preterm birth. Because spontaneous preterm labour is a final common pathway for multiple aetiologies, there remains no reason why any single therapy will work optimally for all women. As patient-specific pharmacogenomic profiles are developed, it will be possible to develop patient-specific treatment regimens. Beyond that, it may become possible to identify those women who are, or are not, destined to labour spontaneously and give birth remote from term and to institute patient-specific preventive measures. Spontaneous preterm labour and preterm birth remains a syndrome, with a final common pathway for multiple aetiologies. As a result, no single explanation, marker or treatment is likely to be 100% sensitive, specific or successful. It is also clear, however, that there is a genetic predisposition in many cases of spontaneous preterm labour. Over the next few years, several recently developed diagnostic mechanisms, and others that have yet to evolve, will hold a greater potential than ever before to unlock the secrets of the genetic predisposition to spontaneous preterm labour and its underlying causes. An improved understanding of these mechanisms will allow clinicians to employ therapies that will be optimally effective for individual women and their unborn babies. Eventually, these advances could be applied to the presymptomatic prevention of spontaneous preterm labour. It is the intent of this manuscript to review the current status of these new technologies and disciplines and to speculate on their applications in the intermediate future.

A Review of the Role of Proinflammatory Cytokines in Labor and Noninfectious Preterm Labor

The prevention of preterm labor has the potential to reduce newborn morbidity and mortality by decreasing the incidence of preterm birth. Half of all preterm births occur in women with no known clinical risk factors. Labor onset and progress is multifactorial, and we are just beginning to understand the role of cytokines in uterine activity. The purpose of this article is to review the role of cytokines in labor and preterm labor not associated with infection and to provide implications for research and practice.

In situ inhibition of uterine activity by indomethacin: Possible relevance to preterm labor prevention after fetal surgery

Purpose This report is an analysis of the effects of local indomethacin delivery on uterine activity in vitro. Methods Isolated strips of time-dated pregnant rats’ myometrium were placed within controlled tissue baths. Spontaneous muscular activity was recorded by a force transducer connected to a polygraph at cumulative concentrations of indomethacin. Statistical analysis was by single-factor analysis of variance (ANOVA), with P values of less than .05 considered significant. Results Within a narrow concentration range, the effects of indomethacin on frequency and amplitude of myometrial contractions were nonmonotonic, with an increase in frequency at levels that began to depress amplitude. However, both amplitude and frequency were significantly depressed and eventually totally abolished at most concentrations studied ( P < .05). Conclusions Indomethacin administered in situ consistently inhibits or completely arrests overall myometrial activity. The concept of local myometrial delivery of indomethacin, possibly via slow release systems, may prove clinically useful as an adjuvant to its systemic administration in preterm labor prevention after fetal surgery, warranting further trials in vivo.

Ultrasonic measurements of the cervix and preterm labor

During the past few years a clear relationship has been established between decreased cervical length and risk of spontaneous preterm delivery. In this review, the most recent publications are described, and results are compared with those of the present authors regarding the prevention of preterm labor in both asymptomatic and symptomatic patients. Cervical assessment with ultrasound is now widely accepted and a well standardized method which can be easily performed in both high- and low-risk patients as a screening test for preterm delivery. It is the authors' belief that, for an evaluation of the cervix, all that is required is a well trained operator and a few minutes.

Functional effects of 17alpha-hydroxyprogesterone caproate (17P) on human myometrial contractility in vitro

Background17alpha-hydroxyprogesterone caproate (17P) administration reportedly improves outcome for women with a previous spontaneous preterm delivery. This study, using in vitro strips of human uterine smooth muscle, aimed to investigate the direct non-genomic effects of 17P on spontaneous and induced contractions in tissues obtained during pregnancy, and in the non-pregnant state.MethodsBiopsies of human myometrium were obtained at elective cesarean section, and from hysterectomy specimens, and dissected strips suspended for isometric recordings. The effects of 17P (1 nmol/L -10 micro mol/L) on spontaneous and agonist-induced (oxytocin 0.5 nmol/L for pregnant, phenylephrine 10 μmol/L for non-pregnant) contractions were measured. Integrals of contractile activity, including the mean maximal inhibition values (MMI) observed at the maximal concentration, were compared with those from simultaneously run control strips.ResultsThere was no significant direct effect exerted by 17P on pregnant or non-pregnant human myometrial contractility. The MMI ± SEM for spontaneous contractions in pregnant myometrium was 4.9% ± 7.2 (n = 6; P = 0.309) and for oxytocin-induced contractions was 2.2% ± 1.3 (n = 6; P = 0.128). For non-pregnant myometrium, the MMI ± SEM for spontaneous contractions was 8.8% ± 11.0 (n = 6; P = 0.121) and for phenylephrine induced contractions was -7.9% ± 6.5 (n = 6; P = 0.966).ConclusionsThe putative benefits of 17P for preterm labor prevention are not achieved, even partially, by a direct utero-relaxant effect. These findings outline the possibility that genomic effects of 17P, achieved over long periods of administration, are required for its reported therapeutic benefits.

Prediction of preterm labor (PTL) and premature delivery (PTD): comparison of transvaginal ultrasound (TVU) vs direct cervical length

(PTD): COMPARISON OF TRANSVAGINAL ULTRASOUND (TVU) VS DIRECT CERVICAL LENGTH MICHAEL ROSS, LARRY COUSINS, ROSALYN BAXTER-JONES, ROSE BEMIS-HEYS, LINDY YOW, HarborUCLA Medical Center, Department of Obstetrics and Gynecology, Torrance, CA Mary Birch Hospital for Women, San Diego, CA Cervilenz, Irvine, CA OBJECTIVE: Despite efforts directed at prediction and prevention of PTL, the incidence of PTD in the United States has not decreased. Cervical length (CL) measurement, via ultrasound or digital exam, has been proposed for screening and intervention of patients at risk of PTD. Although transvaginal ultrasound (TVU)more accurately predicts PTD than digital examination, TVU ismore costly and technology intensive. TheCervilenz (Cervilenz trade;, Irvine, CA) measuring device reliability quantifies vaginal CL in comparison to TVU. We sought to compare Cervilenz and TVU measurements for the detection of short CL ( < 3 cm) and prediction of PTL and PTD in a group of at-risk pregnancies. STUDY DESIGN: In consented patients (n = 52) at risk for PTD (multiple gestation) Cervilenz and TVU CL were measured by different, blinded examiners) at 12 to 34 weeks. Cervilenz right and left forniceal measurements were averaged to determine the lateral CL. All patients were treated as clinically indicated by the TVU results. Data were analyzed by T-tests. RESULTS: Among the screened patients, there was a 38% PTD. Cervilenz identified a greater proportion of short CL (11.5 vs 7.7%) as compared to TVU, with a sensitivity of 75% and specificity of 94%. Both Cervilenz and TVU detected 13% (4 of 30) of PTL patients. Cervilenz detected 15% (3 of 20) of PTD patients as compared to TVU (10%; 2 of 20). CONCLUSION:Cervilenz is an excellent screening device, detecting nearly all patients with short CL (as identified by TVU) and equal or greater ability to detect patients at risk of PTL or PTD. The relatively low percentage of PTD associated with short CL is further evidence of the multifactorial etiologies of PTD.

The prevention of preterm labour -- corticotropin releasing hormone type 1 receptors as a target for drug design and development.

The role of the corticotropin releasing hormone in the onset of labour and the subsequent medicinal chemistry implications of CRH antagonists for the prevention of premature birth, and identification of the CRH type 1 receptor as the target for this drug design, are reviewed here.

Hydroxyprogesterone delivers on prevention of recurrent preterm labour

Hydroxyprogesterone delivers on prevention of recurrent preterm labour

Socio‐economic and psychosocial factors in the management and prevention of preterm labour

Socio-economic factors associated with preterm labour include social class, (usually assessed by earnings and education), working conditions (professional status, ergonomic environment, working hours), physical and travelling activities, daily life activities, lifestyle, family status and psychosocial state as related to past and current pregnancy history together with current stress factors. A review of the association of these factors with preterm birth will be reported with an emphasis of the biological plausibility linking mostly emotional, and at a lesser degree, physical and psychological stress to the occurrence of preterm labour. A case control study, carried out in Quebec City among 101 women in preterm labour and 202 matched pregnancies for parity and gestational age, identified 7 risk factors in an explanatory multivariate model among 117 variables: Body mass index (BMI) <20 (OR; 95% CI: 3.96; 2.61-7.09), previous preterm labour (OR; 95% CI: 3.61; 1.12-11.65) previous low birth weight (OR; 95% CI: 2.24; 1.05-7.71), standing at work >2 hours (OR; 95% CI: 3.90; 1.53-9.91), Abruptio placentae (OR; 95% CI: 5.88; 1.20-28.76), urinary tract infection (UTI) (OR; 95% CI: 4.4.3; 1.47-13.34), and stress score >5 (OR; 95% CI: 2.56; 1.20-5.54). The most stressful events were related to family illness, mortality, disruption, violence or financial distress. Some risk factors cannot be modified (previous preterm labour, low birth weight and UTI), while preventive efforts should be directed towards attaining BMI >20 before conception, modifying working conditions during current pregnancy and appropriate management of acute emotional stress.

Socio-economic and psychosocial factors in the management and prevention of preterm labour

Socio-economic factors associated with preterm labour include social class, (usually assessed by earnings and education), working conditions (professional status, ergonomic environment, working hours), physical and travelling activities, daily life activities, lifestyle, family status and psychosocial state as related to past and current pregnancy history together with current stress factors. A review of the association of these factors with preterm birth will be reported with an emphasis of the biological plausibility linking mostly emotional, and at a lesser degree, physical and psychological stress to the occurrence of preterm labour. A case control study, carried out in Quebec City among 101 women in preterm labour and 202 matched pregnancies for parity and gestational age, identified 7 risk factors in an explanatory multivariate model among 117 variables: Body mass index (BMI) <20 (OR; 95% CI: 3.96; 2.61–7.09), previous preterm labour (OR; 95% CI: 3.61; 1.12–11.65) previous low birth weight (OR; 95% CI: 2.24; 1.05–7.71), standing at work >2 hours (OR; 95% CI: 3.90; 1.53–9.91), Abruptio placentae (OR; 95% CI: 5.88; 1.20–28.76), urinary tract infection (UTI) (OR; 95% CI: 4.4.3; 1.47–13.34), and stress score >5 (OR; 95% CI: 2.56; 1.20–5.54). The most stressful events were related to family illness, mortality, disruption, violence or financial distress. Some risk factors cannot be modified (previous preterm labour, low birth weight and UTI), while preventive efforts should be directed towards attaining BMI >20 before conception, modifying working conditions during current pregnancy and appropriate management of acute emotional stress.

Infection in the prediction and antibiotics in the prevention of spontaneous preterm labour and preterm birth

The association between infection and spontaneous preterm labour is now well established and thought to be responsible for preterm birth in up to 40% of cases. Preterm labour that is due to infection is refractory to the use of tocolytic agents. So the knowledge that infection may be the cause is unhelpful once a woman is admitted in spontaneous preterm labour, since by that time there may be irreversible changes in the uterine cervix, which renders futile those attempts to inhibit the process. It would be much more logical to use the association between infection and spontaneous preterm labour to identify a group of women at risk and to intervene using antibiotic prophylaxis. It is important to record, that the earlier in gestation at which abnormal genital tract colonisation is detected, the greater is the risk of an adverse outcome. For example, abnormal genital tract flora at 26–32 weeks gestation is associated with preterm birth with an odds ratio (OR) of 1.4 to 2, whereas abnormal genital tract flora at 7–16 weeks gestation carries an OR of 5 to 7.5. Intervention studies have used different antibiotics in different dosage regimes by different routes of administration to patients of differing risks at different gestational ages. Not surprisingly this has led to differing results. If intervention is to be successful, the antibiotics chosen should be active against bacterial vaginosis or bacterial vaginosis-related organisms and should be used early in pregnancy in those women with the greatest degree of abnormal genital tract flora. While there is logic in using intravaginal antibiotics to deliver a heavy antibiotic load to the vagina where heavy abnormal colonisation exists, there is also logic in considering systemic antibiotics to eradicate those organisms, which have already gained access to the decidua. It may be that the greatest chance of benefit would exist if both routes of administration were combined. Yet no study has evaluated the combination of both intravaginal and systemic antibiotics to eradicate abnormal genital tract flora for the prevention of preterm birth.

Infection in the prediction and antibiotics in the prevention of spontaneous preterm labour and preterm birth

The association between infection and spontaneous preterm labour is now well established and thought to be responsible for preterm birth in up to 40% of cases. Preterm labour that is due to infection is refractory to the use of tocolytic agents. So the knowledge that infection may be the cause is unhelpful once a woman is admitted in spontaneous preterm labour, since by that time there may be irreversible changes in the uterine cervix, which renders futile those attempts to inhibit the process. It would be much more logical to use the association between infection and spontaneous preterm labour to identify a group of women at risk and to intervene using antibiotic prophylaxis. It is important to record, that the earlier in gestation at which abnormal genital tract colonisation is detected, the greater is the risk of an adverse outcome. For example, abnormal genital tract flora at 26–32 weeks gestation is associated with preterm birth with an odds ratio (OR) of 1.4 to 2, whereas abnormal genital tract flora at 7–16 weeks gestation carries an OR of 5 to 7.5. Intervention studies have used different antibiotics in different dosage regimes by different routes of administration to patients of differing risks at different gestational ages. Not surprisingly this has led to differing results. If intervention is to be successful, the antibiotics chosen should be active against bacterial vaginosis or bacterial vaginosis‐related organisms and should be used early in pregnancy in those women with the greatest degree of abnormal genital tract flora. While there is logic in using intravaginal antibiotics to deliver a heavy antibiotic load to the vagina where heavy abnormal colonisation exists, there is also logic in considering systemic antibiotics to eradicate those organisms, which have already gained access to the decidua. It may be that the greatest chance of benefit would exist if both routes of administration were combined. Yet no study has evaluated the combination of both intravaginal and systemic antibiotics to eradicate abnormal genital tract flora for the prevention of preterm birth.

Clostridium botulinum toxin inhibits myometrial activity in vitro: Possible application on the prevention of preterm labor after fetal surgery

Background/Purpose: The current study aimed to analyze the effects of Clostridium botulinum toxin (Botox) on pregnant myometrium activity in vitro. Methods: Strips of myometrium were obtained from pregnant Wistar rats on gestational day 13 through 15 and placed under controlled conditions within tissue baths containing DeJalon solution. Muscular activity, including amplitude and frequency of contractions, was recorded by a force transducer connected to a polygraph. After stable baseline values were recorded, different concentrations of Botox were added to the tissue baths. Myometrial activity data points for each drug concentration were entered as mean percentual variations of the baseline. A total of 26 uterine samples from 13 animals were studied. Statistical analysis was by single-factor analysis of variance (ANOVA) with P <.05 considered significant. Results: Except for a narrow concentration range, when the effects were nonmonotonic, both amplitude and frequency of myometrial contractions were significantly depressed (P <.05) and eventually totally abolished at most concentrations studied, albeit in a potentially biphasic pattern. Those effects could be reversed by a complete washout of the tissue bath. Conclusions: Within appropriate concentrations, Botox consistently inhibits or completely arrests myometrial activity in potentially reversible fashion. This agent may prove valuable in premature labor prevention after fetal surgery. J Pediatr Surg 38:511-513. Copyright 2003, Elsevier Science (USA). All rights reserved.