Setting Of Preterm Labor Research Articles

Identifying causes and associated factors of stillbirths using autopsy of the fetus and placenta.

The study aimed to evaluate the causes of death and associated factors in cases of stillbirth, using post-mortem examination and applying a rigorous, evidence-based holistic approach. Our retrospective observational study included cases of autopsy following stillbirth that occurred at our tertiary medical center during a period of 8 years. Detailed up-to-date criteria that incorporate clinical reports, medical history, prenatal imaging, and histopathological findings were used to evaluate the cause of death and associated factors. After applying our proposed methodology, 138 cases of stillbirth were classified into eight categories based on the causes of death. A definitive cause of death was observed in 100 (72%) cases, while 38 (28%) cases were considered unexplained. The leading cause of death was placental lesions (n = 39, 28%) with maternal vascular malperfusion (MVM) lesions being the most common (54%). Ascending infection was the second most common cause of fetal death (n = 24, 17%) and was often seen in the setting of preterm labor and cervical insufficiency. The largest category of cause of death was attributed to placental pathology. Using rigorous detailed up-to-date criteria that incorporate pathological and clinical factors may help in objectively classifying the cause of death.

FIGO good practice recommendations for preterm labor and preterm prelabor rupture of membranes: Prep-for-Labor triage to minimize risks and maximize favorable outcomes.

Preterm labor occurs in around 10% of pregnancies worldwide. Once diagnosed, significant efforts must be made to reduce the likelihood of morbidity and mortality associated with preterm birth. In high-resource settings, access to hospitals with a neonatal intensive care unit (NICU) is readily available, whereas access to NICU care is limited in low- and middle-income countries (LMICs) and many rural settings. Use of FIGO's Prep-for-Labor triage method rapidly identifies low- and high-risk patients with preterm labor to enable clinicians to decide whether the patient can be managed on site or if transfer to a level II-IV facility is needed. The management steps described in this paper aim to minimize the morbidity and mortality associated with preterm labor and in the setting of preterm labor with preterm premature rupture of membranes (PPROM). The methods for accurate diagnosis of PPROM and chorioamnionitis are described. When the risk of preterm birth is high, antenatal corticosteroids should be administered for lung maturation combined with limited tocolysis for 48 hours to permit the corticosteroid course to be completed. Magnesium sulfate is also administered for fetal neuroprotection. Implementation of FIGO's Prep-for-Labor triage method in an LMIC setting will help improve maternal and neonatal outcomes.

503 Rescue antenatal corticosteroids in early onset preeclampsia

Early onset preeclampsia (PE) is associated with increased maternal and neonatal morbidity, often warranting prompt delivery following diagnosis. Those who remain pregnant for ≥7-14 days after course of antenatal corticosteroids (ANCS) while still under 34 weeks gestation may be candidates for rescue ANCS course. Data suggests neonatal respiratory benefit from a single additional course of ANCS in the setting of preterm labor. We aimed to explore whether the same benefit is observed in expectant management of early onset PE. Retrospective chart review of pregnancies diagnosed with early onset PE, defined as PE with severe features that developed < 34 weeks of gestation, that delivered at a single tertiary care center between 2011-2020. Women were excluded if they had an incomplete course of ANCS (single dose), fetal demise or fetal anomaly. Our primary outcome was a composite of neonatal outcomes, including respiratory distress syndrome (RDS), intubation within 24 hours of life, and any oxygen supplementation. Results were adjusted for gestational age at delivery and infant sex. Of 261 patients identified, 234 patients completed at least one course of ANCS and 27 (11.5%) received at least one dose of rescue ANCS. Maternal age, gestational age at delivery, nulliparity, ethnicity/race, and history of pregestational diabetes, indication for delivery, birthweight and infant sex were similar between groups. (Table 1) The time interval from initial ANCS course to rescue dose was a median of 17 days [IQR 13-25]. There was no difference in the composite of adverse neonatal outcomes, including supplemental oxygen. (Table 2) Administration of rescue ANCS in expectantly managed pregnancies complicated by early onset PE did not improve neonatal outcomes. Larger studies are necessary to confirm these findings.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Tips & Tricks: Minimally Invasive Removal of Transabdominal Cerclage

Video Objective To present surgical tips and tricks for the minimally invasive removal of transabdominal cerclage and surgical technique during transabdominal cerclage placement that facilitates easier removal. Setting Three patients are presented that underwent uncomplicated robotic transabdominal cerclage placements in pregnancy. The first patient subsequently had a laparotomy for cerclage removal due to second trimester preterm labor at an outside hospital. This case prompted this tips and tricks surgical video to educate surgeons regarding minimally invasive removal of transabdominal cerclage. The second patient underwent an uncomplicated laparoscopic removal of transabdominal cerclage in the setting of preterm labor at 18 weeks. The third case had a term cesarean delivery although her cerclage was not removed at that time. She underwent a robotic transabdominal cerclage removal without complication. Apart from the laparotomy, all placement and removal procedures were performed at an academic medical center by one primary surgeon. Interventions In this surgical video, we present surgical tips and tricks for placement and removal of transabdominal cerclage in a minimally invasive fashion using conventional laparoscopic and robotic approaches. Tips described in this video include the “needleless” approach with creation of an avascular tunnel for cerclage placement as well as considerations for anterior versus posterior knot placement. Regarding cerclage removal, we present techniques such as undermining the cerclage tape anteriorly and posteriorly as well as blunt dissection in the previously created avascular tunnel to facilitate removal. Additionally, we present tricks for improved visualization and to delineate anatomic borders around a gravid uterus during these cases. Conclusion The removal of transabdominal cerclage is often performed at time of cesarean delivery. However, in cases of intrapartum and postpartum removal, a minimally invasive approach is effective utilizing these surgical tips and tricks.

Case 3: Respiratory Distress and Tachycardia in a Preterm Neonate

A 31-week-gestation male infant is delivered vaginally in the setting of preterm labor and chorioamnionitis. The pregnancy was remarkable for late prenatal care, but no other complications. Maternal antenatal testing results were normal and the mother denied any significant medical history. The infant is initially stunned, but quickly recovers, with Apgar scores of 1 and 7 at 1 and 5 minutes, respectively. His size is appropriate for gestational age and his vital signs in the intensive care nursery include a temperature of 98.8°F (36.5°C), pulse of 172 beats/min, right lower extremity blood pressure of 76/34 mm Hg, respiratory rate of 62 breaths/min, and oxygen saturation of 98% on nasal continuous positive airway pressure support at 5 cm H2O and 21% fraction of inspired oxygen. On examination, the infant’s anterior fontanelle is soft, flat, and approximately 1 fingertip in size. His lungs are clear despite a mildly increased respiratory effort, including grunting and subcostal retractions. He has normal first and second heart sounds, a gallop rhythm, and no murmurs, and his liver is palpable 4 cm below the right costal margin. On investigation, chest radiography demonstrates an enlarged cardiac silhouette (Fig 1), and echocardiography shows findings consistent with restrictive cardiomyopathy, normal systolic function, but impaired diastolic function (Fig 2). Given this rare finding, pediatric cardiology is consulted, which recommends conducting a comprehensive cardiomyopathy genetic testing panel. During his first week after delivery, the infant develops frequent ventricular ectopic beats …

Timing of Histologic Progression from Chorio-Deciduitis to Chorio-Deciduo-Amnionitis in the Setting of Preterm Labor and Preterm Premature Rupture of Membranes with Sterile Amniotic Fluid.

BackgroundHistologic chorio-deciduitis and chorio-deciduo-amnionitis (amnionitis) in extra-placental membranes are known to represent the early and advanced stages of ascending intra-uterine infection. However, there are no data in humans about the time required for chorio-deciduitis to develop and for chorio-deciduitis without amnionitis to progress to chorio-deciduitis with amnionitis, and the effect of prolongation of pregnancy on the development of chorio-deciduitis and amnionitis in patients with preterm labor and intact membranes (PTL) and preterm premature rupture of membranes (preterm-PROM). We examined these issues in this study.MethodsThe study population consisted of 289 women who delivered preterm (133 cases with PTL, and 156 cases with preterm-PROM) and who had sterile amniotic fluid (AF) defined as a negative AF culture and the absence of inflammation as evidenced by a matrix metalloproteinase-8 (MMP-8) level <23 ng/ml. We examined the association between amniocentesis-to-delivery interval and inflammatory status in the extra-placental membranes (i.e., inflammation-free extra-placental membranes, choroi-deciduitis only, and chorio-deciduitis with amnionitis) in patients with PTL and preterm-PROM.ResultsAmniocentesis-to-delivery interval was longer in cases of chorio-deciduitis with amnionitis than in cases of chorio-deciduitis only in both PTL (median [interquartile-range (IQR)]; 645.4 [319.5] vs. 113.9 [526.9] hours; P = 0.005) and preterm-PROM (131.3 [135.4] vs. 95.2 [140.5] hours; P<0.05). Amniocentesis-to-delivery interval was an independent predictor of the development of both chorio-deciduitis and amnionitis after correction for confounding variables such as gestational age at delivery in the setting of PTL, but not preterm-PROM.ConclusionsThese data confirm for the first time that, in cases of both PTL and preterm-PROM with sterile AF, more time is required to develop chorio-deciduitis with amnionitis than chorio-deciduitis alone in extra-placental membranes. Moreover, prolongation of pregnancy is an independent predictor of the development of both chorio-deciduitis and amnionitis in cases of PTL with sterile AF.

Compartmentalization of acute phase reactants Interleukin-6, C-Reactive Protein and Procalcitonin as biomarkers of intra-amniotic infection and chorioamnionitis

BackgroundThe arsenal of maternal and amniotic fluid (AF) immune response to local or systemic infection includes among others the acute-phase reactants IL-6, C-Reactive Protein (CRP) and Procalcitonin (PCT). If these molecules can be used as non-invasive biomarkers of intra-amniotic infection (IAI) in the subclinical phase of the disease remains incompletely known. MethodsWe used time-matched maternal serum, urine and AF from 100 pregnant women who had an amniocentesis to rule out IAI in the setting of preterm labor, PPROM or systemic inflammatory response (SIR: pyelonephritis, appendicitis, pneumonia) to infection. Cord blood was analyzed in a subgroup of cases. We used sensitive immunoassays to quantify the levels of inflammatory markers in the maternal blood, urine and AF compartment. Microbiological testing and placental pathology was used to establish infection and histological chorioamnionitis. ResultsPCT was not a useful biomarker of IAI in any of the studied compartments. Maternal blood IL-6 and CRP levels were elevated in women with subclinical IAI. Compared to clinically manifest chorioamnionitis group, women with SIR have higher maternal blood IL-6 levels rendering some marginal diagnostic benefit for this condition. Urine was not a useful biological sample for assessment of IAI using either of these three inflammatory biomarkers. ConclusionsIn women with subclinical IAI, the large overlapping confidence intervals and different cut-offs for the maternal blood levels of IL-6, CRP and PCT likely make interpretation of their absolute values difficult for clinical decision-making.

286: Effect of magnesium sulfate and betamethasone on inflammation and glial differentiation in a preterm labor murine model

Prematurity is associated with fetal neuroinflammation and subsequent neurologic injury. The impact of magnesium sulfate (MgSO4) and betamethasone (BMTZ), commonly employed therapies in the setting of preterm labor, on prematurity-related neurologic morbidity remains incompletely understood. The objective of this study was to identify effects of MgSO4 and BMTZ on markers of inflammation and glial development in offspring of a murine model of preterm birth and perinatal brain injury.

Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes.

Inflammation and infection play a major role in preterm birth. The purpose of this study was to (i) determine the prevalence and clinical significance of sterile intra-amniotic inflammation and (ii) examine the relationship between amniotic fluid (AF) concentrations of high mobility group box-1 (HMGB1) and the interval from amniocentesis to delivery in patients with sterile intra-amniotic inflammation. AF samples obtained from 135 women with preterm labor and intact membranes were analyzed using cultivation techniques as well as broad-range PCR and mass spectrometry (PCR/ESI-MS). Sterile intra-amniotic inflammation was defined when patients with negative AF cultures and without evidence of microbial footprints had intra-amniotic inflammation (AF interleukin-6 ≥ 2.6 ng/mL). (i) The frequency of sterile intra-amniotic inflammation was significantly greater than that of microbial-associated intra-amniotic inflammation [26% (35/135) versus 11% (15/135); (P = 0.005)], (ii) patients with sterile intra-amniotic inflammation delivered at comparable gestational ages had similar rates of acute placental inflammation and adverse neonatal outcomes as patients with microbial-associated intra-amniotic inflammation, and (iii) patients with sterile intra-amniotic inflammation and high AF concentrations of HMGB1 (≥8.55 ng/mL) delivered earlier than those with low AF concentrations of HMGB1 (P = 0.02). (i) Sterile intra-amniotic inflammation is more frequent than microbial-associated intra-amniotic inflammation, and (ii) we propose that danger signals participate in sterile intra-amniotic inflammation in the setting of preterm labor.

Pregnancy Outcomes in Patients With Prior Uterine Rupture or Dehiscence

To report obstetric outcomes in a series of women with prior uterine rupture or prior uterine dehiscence managed with a standardized protocol. Series of patients delivered by a single maternal-fetal medicine practice from 2005 to 2013 with a history of uterine rupture or uterine dehiscence. Uterine rupture was defined as a clinically apparent, complete scar separation in labor or before labor. Uterine dehiscence was defined as an incomplete and clinically occult uterine scar separation with intact serosa. Patients with prior uterine rupture were delivered at approximately 36-37 weeks of gestation or earlier in the setting of preterm labor. Patients with prior uterine dehiscence were delivered at 37-39 weeks of gestation based on obstetric history, clinical findings, and ultrasonographic findings. Patients with prior uterine rupture or uterine dehiscence were followed with serial ultrasound scans to assess fetal growth and lower uterine segment integrity. Outcomes measured were severe morbidities (uterine rupture, hysterectomy, transfusion, cystotomy, bowel injury, mechanical ventilation, intensive care unit admission, thrombosis, reoperation, maternal death, perinatal death). Fourteen women (20 pregnancies) had prior uterine rupture and 30 women (40 pregnancies) had prior uterine dehiscence. In these 60 pregnancies, there was 0% severe morbidity noted (95% confidence interval [CI] 0.0-6.0%). Overall, 6.7% of patients had a uterine dehiscence seen at the time of delivery (95% CI 2.6-15.9%). Among women with prior uterine rupture, the rate was 5.0% (95% CI 0.9-23.6%), whereas among women with prior uterine dehiscence, the rate was 7.5% (95% CI 2.6-19.9%). Patients with prior uterine rupture or uterine dehiscence can have excellent outcomes in subsequent pregnancies if managed in a standardized manner, including cesarean delivery before the onset of labor or immediately at the onset of spontaneous preterm labor.

Infection, antibiotics, and preterm delivery

The relationship between genital tract infection and preterm delivery has been established on the basis of biochemical, microbiological, and clinical evidence. In theory, pathogenic bacteria may ascend from the lower reproductive tract into the uterus, and the resulting inflammation leads to preterm labor, rupture of the membranes, and birth. A growing body of evidence suggests that preterm labor and/rupture of the membranes are triggered by micro-organisms in the genital tract and by the host response to these organisms, ie, elaboration of cytokines and proteolytic enzymes. Epidemiologic and in vitro studies do not prove a cause-and-effect relationship between infection and preterm birth. However, the preponderance of evidence indicates that treatment of asymptomatic bacteriuria and symptomatic lower genital tract infections such as bacterial vaginosis (BV), trichomoniasis, gonorrhea, and chlamydia will lower the risk of preterm delivery. Based on current evidence, pregnant women who note an abnormal vaginal discharge should be tested for BV, trichomonas, gonorrhea, and chlamydia. Those who test positive should be treated appropriately. A 3- to 7-day course of antibiotic treatment for asymptomatic bacteriuria during pregnancy is clinically indicated to reduce the risk of pyelonephritis and preterm delivery. Routine screening for chlamydia and gonorrhea should be performed for women at high risk of acquiring sexually transmitted diseases. The practice of routine screening for BV in asymptomatic women who are at low risk for preterm delivery cannot be supported based on evidence from the literature. Routine screening for asymptomatic bacteriuria during pregnancy is cost-effective, particularly in high-prevalence populations. The results of antibiotic trials for the treatment of preterm labor have been inconsistent. In the absence of reasonable evidence that antimicrobial therapy leads to significant prolongation of pregnancy in the setting of preterm labor, antibiotics should be used only for protecting the neonate from group B streptococci sepsis. They should not be used for the purpose of prolonging pregnancy. Multiple investigations have shown that, in patients with preterm premature rupture of the membranes, prophylactic antibiotics are of value in prolonging the latent period between rupture of the membranes and onset of labor and in reducing the incidence of maternal and neonatal infection. The most extensively tested effective antibiotic regimen for prophylaxis involves erythromycin alone or in combination with ampicilln. Controversy still exists regarding the appropriate length and route of antibiotic prophylaxis.

Oxytocin signaling in human myometrium is impaired by prolonged exposure to interleukin-1.

Intra-amniotic infection leads to preterm labor and is associated with the local release of inflammatory cytokines by fetal membranes, resulting in the production of uterotonic prostaglandins. Oxytocin, however, also plays a key role in the initiation of labor. Short-term exposure of myometrium to interleukin (IL)-1 enhances oxytocin signaling and contractility. With intrauterine infection, however, myometrium is exposed to inflammatory cytokines for prolonged periods. The present study was conducted to demonstrate that myometrial oxytocin signaling is significantly impaired following prolonged exposure to IL-1. Myometrial cells were treated with IL-1 for 24 h. Oxytocin-stimulated inositol trisphosphate (IP(3)) production was measured in tritiated myoinositol-loaded myometrial cells. Arachidonic acid (AA) release was measured in tritiated AA-loaded myometrial cells. Increases in intracellular calcium were measure with fluo-3. Prostaglandin (PG) F(2alpha) and 6-keto-PGF(1alpha) were measured by ELISA assay. Prolonged exposure of myometrial cells to IL-1 resulted in a significant reduction in oxytocin-mediated signaling as measured by IP(3) production and AA release, as well as a decrease in intracellular calcium. Prolonged exposure of myometrial cells to IL-1, however, resulted in enhanced PG release. Oxytocin may not contribute significantly to the labor-inducing action of IL-1 in the setting of preterm labor with prolonged infection.

Regulation of Uterine Contraction: Mechanisms in Preterm Labor

Preterm labor (PTL) is defined as uterine irritability accompanied by cervical dilation and/or effecement that occurs before 37 weeks gestation. In most cases, PTL becomes preterm delivery (PTD), accounting for 8% to 10% of births in the United States. Fetuses born before 37 weeks' gestation are at risk for a multitude of health and developmental problems. Most perinatal morbidity and mortality in the United States are caused by PTL. It is a costly problem, in both monetary and human terms. Although some risk factors have been identified, they by no means identify, in advance, every case of PTL and PTD. Despite the understandable emphasis on attempts to find and test risk factors that predict PTL, the ultimate benefit--preventing PTD--will come only from an understanding of the physiologic mechanisms of parturition and how to halt those processes when they occur too early. This article reviews current approaches to preventing PTD, describes the biology of myometrial contraction, and discusses recent progress from several laboratories including the authors' that may shed light on approaches to inhibit uterine contractility in the setting of PTL.