Search Results (10)

This systematic review aimed to identify the benefits and possible harms of tocolytic therapy for preterm labour management in the context of pregnant women with extremely preterm birth, multiple gestations, or growth-restricted foetuses. A comprehensive search using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO Global Index Medicus databases was conducted from 10 to 15 July 2021. We included randomized controlled trials and non-randomized studies that assessed the effects of tocolysis compared with placebo or no treatment. We found 744 reports and, finally, nine studies (three randomized controlled trials and six cohort studies) pertaining to women with <28 weeks of gestation were included. No eligible studies were identified among women with a multiple pregnancy or a growth-restricted foetus. A meta-analysis of the trial data showed that there were no clear differences in perinatal death nor for a delay in birth. Non-randomized evidence showed that tocolysis delayed birth by 7 days, though there was no clear difference for preterm birth. In summary, it remains unclear whether tocolytic therapy for inhibiting preterm labour is beneficial for these subgroups of women and their newborns. Further well-designed randomized controlled trials and observational studies are needed to address the lack of evidence regarding tocolytic agents in these populations. Full article

Preterm birth represents a great burden to the healthcare system, resulting in the consideration for the use of tocolytic therapy to provide a “better time” for delivery in order to buy time to accelerate fetal lung maturity, thereby minimizing prematurity-related morbidity and mortality. However, the benefits and potential side effects and risks of tocolytic treatment for preterm birth should be carefully balanced. Although many countries and societies provide guidelines or consensuses for the management for preterm birth, there is no standardized national guideline or consensus in Taiwan. As such, great heterogeneity is suspected in preterm labor management, contributing to the uncertainty of attitudes and practice patterns of obstetric specialists in Taiwan. This study attempts to understand the attitudes and practice patterns regarding tocolytic therapy in Taiwan. A paper-based survey was conducted at the 2020 Taiwan Society of Perinatology Conference on 8 December 2020, exploring how obstetric specialists would use tocolytics under nine different clinical scenarios, such as a short cervix, preterm labor, maintenance tocolysis, preterm premature rupture of membranes, etc. Three hundred ten specialists attended the conference, and 77 responded to the survey with a response rate of 24.8%. According to the survey, many of these specialists would prescribe tocolytics for less evidence-based indications, including 22% for abdominal tightness, 46% for a short cervix, 60% for maintenance tocolysis, and 89% for repeat tocolysis, with the preferred first line medication being ritodrine and nifedipine. We concluded that tocolysis is widely accepted and practiced in Taiwan. More research is needed to include Taiwan-specific economic and cultural factors as well as associated adverse effects and patients’ outcomes. Full article

Uterine contractions prior to 37 weeks gestation can result in preterm labor with significant risk to the infant. Current tocolytic therapies aimed at suppressing premature uterine contractions are largely ineffective and cause serious side effects. Calcium (Ca²⁺) dependent contractions of uterine smooth muscle are physiologically limited by the opening of membrane potassium (K⁺) channels. Exploiting such inherent negative feedback mechanisms may offer new strategies to delay labor and reduce risk. Positive modulation of small conductance Ca²⁺-activated K⁺ (K_Ca2.3) channels with cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA), effectively decreases uterine contractions. This study investigates whether the receptor agonist oxytocin might solicit K_Ca2.3 channel feedback that facilitates CyPPA suppression of uterine contractions. Using isometric force myography, we found that spontaneous phasic contractions of myometrial tissue from nonpregnant mice were suppressed by CyPPA and, in the presence of CyPPA, oxytocin failed to augment contractions. In tissues exposed to oxytocin, depletion of internal Ca²⁺ stores with cyclopiazonic acid (CPA) impaired CyPPA relaxation, whereas blockade of nonselective cation channels (NSCC) using gadolinium (Gd³⁺) had no significant effect. Immunofluorescence revealed close proximity of K_Ca2.3 channels and ER inositol trisphosphate receptors (IP₃Rs) within myometrial smooth muscle cells. The findings suggest internal Ca²⁺ stores play a role in K_Ca2.3-dependent feedback control of uterine contraction and offer new insights for tocolytic therapies. Full article

Postpartum depression (PPD) is associated with negative physical and mental health outcomes for the mother and infant. Women often experience elevated symptoms of PPD, and the incidence of PPD has increased in recent years. There were lack of studies to investigate the effects of medications during pregnancy. Herein, we focused on the most common obstetric medical therapies used in labor and determined whether the medical therapies cause mental stress in pregnant women. This 14-year retrospective population-based nationwide study was based on the National Health Insurance Research Database. Univariate and multivariate logistic regression analyses were used to evaluate unadjusted and adjusted odds ratios and 95% confidence intervals for each tocolytic and uterotonic treatments during pregnancy and common medical illnesses. In comparing the effects of tocolytic and uterotonic medications on maternal PPD, tocolysis with the injection form of ritodrine resulted in a significantly higher risk of PPD based on multivariate analysis. This study supports existing research demonstrating an association between tocolysis with ritodrine and PPD. Ritodrine treatment for preterm labor was a significant risk factor for PPD, especially the injection form. This information provides obstetricians and health policy providers to pay attention to maternal mental health outcomes among high-risk pregnant women. Full article

This prospective cross-sectional case-control study investigated the postpartal gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases in the peripheral white blood cells of women with anamnesis of preterm prelabor rupture of membranes (n = 58), spontaneous preterm birth (n = 55), and term delivery (n = 89) by a quantitative reverse transcription polymerase chain reaction. After pregnancies complicated by preterm prelabor rupture of membranes or spontaneous preterm birth, mothers showed diverse expression profiles for 25 out of 29 tested microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-499a-5p, and miR-574-3p). The earliest gestational ages at delivery and the lowest birth weights of newborns were associated with the highest postpartal levels of the previously mentioned microRNAs in maternal peripheral white blood cells. Administration of tocolytic drugs in order to prolong pregnancy, used in order to administer and complete a full course of antenatal corticosteroids, was associated with alterations in postpartal microRNA expression profiles to a lesser extent than in women with imminent delivery, where there was insufficient time for administration of tocolytics and antenatal corticosteroids. Overall, mothers who did not receive tocolytic therapy (miR-24-3p and miR-146a-5p) and mothers who did not receive corticosteroid therapy (miR-1-3p, miR-100-5p, and miR-143-3p) had increased or showed a trend toward increased postpartal microRNA expression when compared with mothers given tocolytic and corticosteroid therapy. In addition, mothers with serum C-reactive protein levels above 20 mg/L, who experienced preterm labour, showed a trend toward increased postpartal expression profiles of miR-143-3p and miR-199a-5p when compared with mothers with normal serum C-reactive protein levels. On the other hand, the occurrence of maternal leukocytosis, the presence of intra-amniotic inflammation (higher levels of interleukin 6 in the amniotic fluid), and the administration of antibiotics at the time of preterm delivery had no impact on postpartal microRNA expression profiles in mothers with a history of preterm delivery. Likewise, the condition of the newborns at the moment of birth, determined by Apgar scores at 5 and 10 min and the pH of cord arterial blood, had no influence on the postpartal expression profiles of mothers with a history of preterm delivery. These findings may contribute to explaining the increased cardiovascular risk in mothers with anamnesis of preterm delivery, and the greater increase of maternal cardiovascular risk with the decrease of gestational age at delivery. Women with preterm delivery in their anamnesis represent a high-risk group with special needs on a long-term basis, with a need to apply preventive and therapeutic interventions as early as possible. Full article

Preterm birth is the leading cause of death in newborns and the survivors are prone to health complications. Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy. The current methods used in clinical practice to diagnose preterm labor, the Bishop score or cervical length, have high negative predictive values but not positive ones. In this work we analyzed the performance of computationally efficient classification algorithms, based on electrohysterographic recordings (EHG), such as random forest (RF), extreme learning machine (ELM) and K-nearest neighbors (KNN) for imminent labor (<7 days) prediction in women with TPL, using the 50th or 10th–90th percentiles of temporal, spectral and nonlinear EHG parameters with and without obstetric data inputs. Two criteria were assessed for the classifier design: F1-score and sensitivity. RF_{F1_2} and ELM_{F1_2} provided the highest F1-score values in the validation dataset, (88.17 ± 8.34% and 90.2 ± 4.43%) with the 50th percentile of EHG and obstetric inputs. ELM_{F1_2} outperformed RF_{F1_2} in sensitivity, being similar to those of ELM_Sens (sensitivity optimization). The 10th–90th percentiles did not provide a significant improvement over the 50th percentile. KNN performance was highly sensitive to the input dataset, with a high generalization capability. Full article

Background: Infections are the main cause of death in preterm infants. Causative agents often descend from the intestinal flora of the infected neonate, indicating insufficient protection by the mucosal barrier. Breast milk (BM) contains different subsets of immune cells. We recently showed that BM contains significant numbers of myeloid-derived suppressor cells (MDSC)—immune cells that actively suppress pro-inflammatory immune responses—and hypothesized that the transfer of BM-MDSC may modulate the mucosal immunity of the newborn. Methods: Percentages of MDSC in the BM from mothers of 86 preterm infants between 23 + 0 and 36 + 6 weeks of gestation during their first five postnatal weeks were analyzed by flow cytometry and correlated with maternal and infant characteristics. Results: Percentages of BM-MDSC positively correlated with gestational age and postnatal age. The expression of activation markers on BM-MDSC did not change with gestational age, but it decreased with postnatal age. Mothers who received antepartum tocolytics had lower percentages of BM-MDSC, and infant’s sex strongly influenced percentages of BM-MDSC. Conclusion: Our results point toward a role of BM-MDSC for immune regulation in the neonatal gut, making them a potential target of immune-based therapies shortly after birth. Full article

Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy and entails high costs for health systems. Currently, no reliable labor proximity prediction techniques are available for clinical use. Regular checks by uterine electrohysterogram (EHG) for predicting preterm labor have been widely studied. The aim of the present study was to assess the feasibility of predicting labor with a 7- and 14-day time horizon in TPL women, who may be under tocolytic treatment, using EHG and/or obstetric data. Based on 140 EHG recordings, artificial neural networks were used to develop prediction models. Non-linear EHG parameters were found to be more reliable than linear for differentiating labor in under and over 7/14 days. Using EHG and obstetric data, the <7- and <14-day labor prediction models achieved an AUC in the test group of 87.1 ± 4.3% and 76.2 ± 5.8%, respectively. These results suggest that EHG can be reliable for predicting imminent labor in TPL women, regardless of the tocolytic therapy stage. This paves the way for the development of diagnostic tools to help obstetricians make better decisions on treatments, hospital stays and admitting TPL women, and can therefore reduce costs and improve maternal and fetal wellbeing. Full article

Deregulation in uterine contractility can cause common pathological disorders of the female reproductive system, including preterm labor, infertility, inappropriate implantation, and irregular menstrual cycle. A better understanding of human myometrium contractility is essential to designing and testing interventions for these important clinical problems. Robust studies on the physiology of human uterine contractions require in vitro models, utilizing a human source. Importantly, uterine contractility is a three-dimensionally (3D)-coordinated phenomenon and should be studied in a 3D environment. Here, we propose and assess for the first time a 3D in vitro model for the evaluation of human uterine contractility. Magnetic 3D bioprinting is applied to pattern human myometrium cells into rings, which are then monitored for contractility over time and as a function of various clinically relevant agents. Commercially available and patient-derived myometrium cells were magnetically bioprinted into rings in 384-well formats for throughput uterine contractility analysis. The bioprinted uterine rings from various cell origins and patients show different patterns of contractility and respond differently to clinically relevant uterine contractility inhibitors, indomethacin and nifedipine. We believe that the novel system will serve as a useful tool to evaluate the physiology of human parturition while enabling high-throughput testing of multiple agents and conditions. Full article

Dihydropyridine Ca²⁺ channel blockers (CCBs) are widely accepted in the treatment of premature labour. Their mechanism of action in tocolysis involves the blockade of L-type Ca²⁺ channels, influenced by the Ca²⁺-activated K⁺ channels, beta-adrenergic receptors (β-ARs) and sexual hormones. In clinical practice, most experience has been gained with the use of nifedipine, whose efficacy is superior or comparable to those of β-agonists and oxytocin antagonists. Additionally, it has a favourable adverse effect profile as compared with the majority of other tocolytics. The most frequent and well-tolerated side-effects of CCBs are tachycardia, headache and hypotension. In tocolytic therapy efforts are currently being made to find combinations of tocolytic agents that yield better therapeutic action. The available human and animal studies suggest that the combination of CCBs with β-AR agonists is beneficial, although such combinations can pose risk of pulmonary oedema in multiple pregnancies and maternal cardiovascular diseases. Preclinical data indicate the potential benefit of combinations of CCBs and oxytocin antagonists. However, the combinations of CCBs with progesterone or cyclooxygenase inhibitors may decrease their efficacy. The CCBs are likely to remain one of the most important groups of drugs for the rapid inhibition of premature uterine contractions. Their significance may be magnified by further clinical studies on their combined use for tocolysis. Full article