oxytocin and Premature-Birth

Breech presentation at term can cause complications during birth and increase the chance of caesarean section. Moxibustion (a type of Chinese medicine which involves burning a herb close to the skin) at the acupuncture point Bladder 67 (BL67) (Chinese name Zhiyin), located at the tip of the fifth toe, has been proposed as a way of changing breech presentation to cephalic presentation. This is an update of a review first published in 2005 and last published in 2012.. To examine the effectiveness and safety of moxibustion on changing the presentation of an unborn baby in the breech position, the need for external cephalic version (ECV), mode of birth, and perinatal morbidity and mortality.. For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (which includes trials from CENTRAL, MEDLINE, Embase, CINAHL, and conference proceedings), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) (4 November 2021). We also searched MEDLINE, CINAHL, AMED, Embase and MIDIRS (inception to 3 November 2021), and the reference lists of retrieved studies.. The inclusion criteria were published and unpublished randomised or quasi-randomised controlled trials comparing moxibustion either alone or in combination with other techniques (e.g. acupuncture or postural techniques) with a control group (no moxibustion) or other methods (e.g. acupuncture, postural techniques) in women with a singleton breech presentation.. We found moderate-certainty evidence that moxibustion plus usual care probably reduces the chance of non-cephalic presentation at birth, but uncertain evidence about the need for ECV. Moderate-certainty evidence from one study shows that moxibustion plus usual care probably reduces the use of oxytocin before or during labour. However, moxibustion plus usual care probably results in little to no difference in the rate of caesarean section, and we are uncertain about its effects on the chance of premature rupture of membranes and cord blood pH less than 7.1.  Adverse events were inadequately reported in most trials.

Topics: Breech Presentation; Cesarean Section; Female; Humans; Infant, Newborn; Moxibustion; Oxytocin; Parturition; Pregnancy; Premature Birth

The neonatal period is critical for brain development and determinant for long-term brain trajectory. Yet, this time concurs with a sensitivity and risk for numerous brain injuries following perinatal complications such as preterm birth. Brain injury in premature infants leads to a complex amalgam of primary destructive diseases and secondary maturational and trophic disturbances and, as a consequence, to long-term neurocognitive and behavioral problems. Neuroinflammation is an important common factor in these complications, which contributes to the adverse effects on brain development. Mediating this inflammatory response forms a key therapeutic target in protecting the vulnerable developing brain when complications arise. The neuropeptide oxytocin (OT) plays an important role in the perinatal period, and its importance for lactation and social bonding in early life are well-recognized. Yet, novel functions of OT for the developing brain are increasingly emerging. In particular, OT seems able to modulate glial activity in neuroinflammatory states, but the exact mechanisms underlying this connection are largely unknown. The current review provides an overview of the oxytocinergic system and its early life development across rodent and human. Moreover, we cover the most up-to-date understanding of the role of OT in neonatal brain development and the potential neuroprotective effects it holds when adverse neural events arise in association with neuroinflammation. A detailed assessment of the underlying mechanisms between OT treatment and astrocyte and microglia reactivity is given, as well as a focus on the amygdala, a brain region of crucial importance for socio-emotional behavior, particularly in infants born preterm.

Topics: Brain; Brain Injuries; Female; Humans; Infant; Infant, Newborn; Microglia; Oxytocin; Pregnancy; Premature Birth

Postpartum depression (PPD) is one of the most frequent complications of childbirth affecting ~500,000 women annually (prevalence 10% to 15%). Despite the documented adverse outcomes for mother and child, there remains a great need to develop prospective approaches to identify women at risk. This review examines some of the best-characterized molecular and clinical risk factors for PPD. We illustrate that this is a growing literature but there remains a lack of reliable molecular predictors for PPD. Current best predictors are clinical assessments for psychiatric history and adverse life events, highlighting the need for increased depression screening across the perinatal period.

Topics: beta-Endorphin; Biomarkers; C-Reactive Protein; Corticotropin-Releasing Hormone; Depression, Postpartum; Epigenesis, Genetic; Female; Genetic Predisposition to Disease; Humans; Hydrocortisone; Interleukin-6; Life Change Events; Maternal Age; Mental Disorders; Oxytocin; Pregnancy; Pregnanolone; Premature Birth; Race Factors; Risk Factors; Social Class; Thyroid Function Tests

Very Early Pregnancy (< 15 years at delivery) is suggested as a risk factor for adverse pregnancy outcome including low birth weight (LBW), preterm birth (PTB), small for gestational age (SGA) infants, stillbirth, and neonatal mortality.. To systematically review the risk of an infant being born LBW/ PTB/SGA/stillbirth or neonatal mortality among patients < 15 years of age. Search strategy: Medline, Embase, CINAHL, and bibliographies of identified articles were searched for English language studies.. Selection criteria: Studies reporting birth outcomes to mothers < 15 years of age with an appropriate control group of older gravidas. Data collection and analysis: A single reviewer collected data and assessed the quality of the studies for biases in sample selection, correct age cohorts, confounder adjustment, analytical, outcome assessments, and attrition. Main results: Forty-six studies were located with very early adolescent pregnancy. Of these, only 21 papers had the correct age group (< 15 years) with a comparison cohort. The studies found in the very early adolescent pregnancy: Increased risk of SGA; Increased risk of LBW < 2,500 gms; Increased risk of PTD < 37 weeks; Decreased risk of DM; Decreased risk of cesarean section; Decreased risk of use of pitocin/active phase length; Conflicting risks for Preeclampsia/VLBW/Episiotomy/instrumental delivery rates.. Very early adolescent pregnancies (< 15 years) do not have universally grim outcomes as normally quoted. Very early adolescent pregnancies have decreased risk of cesarean delivery, DM, and of active phase disorders. Further, many of the adverse outcomes may be ameliorated with earlier, adolescent-focused, and improved antenatal care.

Topics: Adolescent; Cesarean Section; Diabetes, Gestational; Female; Humans; Infant, Low Birth Weight; Infant, Small for Gestational Age; Obstetrical Forceps; Oxytocics; Oxytocin; Pregnancy; Pregnancy Outcome; Premature Birth

Premature birth is a significant global problem and the leading cause of newborn deaths. Tobacco smoking has been associated with premature birth for over 50 years. The mechanisms through which smoking exerts its effects on pregnancy outcomes remain unclear. In this review, we discuss rates of prematurity and smoking in pregnancy, the evidence of a causal relationship between tobacco and preterm birth, and proposed biochemical pathways through which the interaction is mediated. The suggested mechanisms include nicotine-induced vasoconstriction, carbon monoxide-induced fetal hypoxia, cadmium disruption of calcium signaling, altered steroid hormone production, disruption of prostaglandin synthesis, and changed responses to oxytocin. The relative importance of each of these pathways is yet to be ascertained. Further research is necessary to explore the mechanisms through which smoking exerts its effect on gestational length and the process of parturition. Moreover, the risks of nicotine replacement in pregnancy should be investigated further.

Topics: Animals; Cadmium; Carbon Monoxide; Female; Gestational Age; Gonadal Steroid Hormones; Humans; Maternal Exposure; Oxytocin; Pregnancy; Premature Birth; Risk Assessment; Risk Factors; Signal Transduction; Smoking; Smoking Prevention; Tobacco Smoke Pollution

Preterm birth, the leading cause of neonatal morbidity and mortality, is estimated at incidence of 12.7% of all births, which has not decreased over the last four decades despite intensive antenatal care programs aimed at high-risk groups, the widespread use of tocolytics, and a series of other preventive and therapeutic interventions. Oxytocin antagonists, namely atosiban, represent an appealing choice that seems to be effective with apparently fewer side effects than the traditional tocolytics. This article reviews the available literature on the pharmacokinetics, mode of administration, and clinical utility of oxytocin antagonists for acute and maintenance tocolysis with special emphasis on its safety profile.

Topics: Female; Hormone Antagonists; Humans; Indoles; Nifedipine; Oligopeptides; Oxytocin; Premature Birth; Pyrrolidines; Sympathomimetics; Tocolytic Agents; Vasotocin

The preterm birth rate in the United States remains at an all-time high and continues to rise. Acute tocolysis has potential to delay preterm birth for 48 h, the critical period of antenatal steroid administration, or to arrest an episode of preterm labor, thus delaying birth and improving neonatal outcomes. It is therefore paramount that medical providers remain up-to-date regarding the usefulness, indications and contraindications, and side-effects and adverse effects of all tocolytics.. Magnesium sulfate remains the most common tocolyic agent in the United States. Recent evidence comparing oral nifedipine with magnesium sulfate suggests equal efficacy with fewer maternal side-effects, thus supporting this oral medication as first-line treatment. This review will summarize the most common acute tocolytic drugs, their methods of action, and clinical data regarding their utility.. All tocolytic medications have side-effects, some of them potentially life-threatening. Decisions regarding whether to use a tocolytic and which tocolytic to use require the diagnosis of preterm labor, knowledge of the patient's gestational age, medical conditions, and cost. Once tocolysis is initiated, attention must be paid to the patient's response, side-effects, and adverse events. Larger studies are needed which incorporate, in addition to efficacy, data on safety and side-effect profiles and cost.

Topics: Acute Disease; Administration, Oral; Calcium Channel Blockers; Clinical Trials as Topic; Female; Humans; Magnesium Sulfate; Nifedipine; Obstetric Labor, Premature; Obstetrics; Oxytocin; Pregnancy; Premature Birth; Prostaglandin Antagonists; Tocolysis; Treatment Outcome

With the growing frequency of preterm birth, increased effort has been made to elucidate the physiology of normal and aberrant parturition. As with many developmental processes, the study of genetically altered mice has led to an increased understanding of mechanisms controlling the maintenance and resolution of pregnancy. Studies in genetically altered mice have implicated critical roles for both prostaglandin synthesis and degradation in luteolysis and the progression of labor. The importance of local modulation of progesterone activity to cervical ripening has also been demonstrated. Although a decline in levels of serum progesterone is a part of normal labor initiation in mice but not humans, murine labor without progesterone withdrawal has been reported in some cases. These findings emphasize the importance of other components of the parturition cascade that are shared in mice and humans and highlights the importance of an increased understanding of the physiology of mouse parturition.

Topics: 20-Hydroxysteroid Dehydrogenases; Animals; Cervical Ripening; Circadian Rhythm; Connexin 43; Female; Humans; Hydroxyprostaglandin Dehydrogenases; Luteolysis; Mice; Mice, Transgenic; Oxytocin; Parturition; Potassium Channels, Calcium-Activated; Pregnancy; Pregnancy, Animal; Premature Birth; Progesterone; Prostaglandins; Pulmonary Surfactant-Associated Protein A; Uterine Contraction

Evaluation of hormone profiles in late pregnancy is one of the major determinants of fetoplacental compromise in equine clinical practice. Use of hormone therapies is subjective and reflects, to a large extent, our lack of understanding about the endocrine relations between the mare, placenta, and fetus. This article describes the normal endocrine events in late gestation, the abnormal hormone patterns associated with fetoplacental dysfunction, and the hormone interventions that are currently used or could be used to improve pregnancy outcome.

Topics: Animals; Estrogens; Female; Fetus; Glucocorticoids; Hormones; Horses; Hydrocortisone; Oxytocin; Parturition; Placenta; Pregnancy; Pregnancy Complications; Pregnancy, Animal; Premature Birth; Progesterone; Progestins; Prostaglandin Antagonists; Prostaglandins; Relaxin

Various single nucleotide polymorphisms (SNPs) in the oxytocin receptor (OXTR) gene have been associated with behavioral traits, autism spectrum disorder (ASD) and other diseases. The non-synonymous SNP rs4686302 results in the OXTR variant A218T and has been linked to core characteristics of ASD, trait empathy and preterm birth. However, the molecular and intracellular mechanisms underlying those associations are still elusive. Here, we uncovered the molecular and intracellular consequences of this mutation that may affect the psychological or behavioral outcome of oxytocin (OXT)-treatment regimens in clinical studies, and provide a mechanistic explanation for an altered receptor function. We created two monoclonal HEK293 cell lines, stably expressing either the wild-type or A218T OXTR. We detected an increased OXTR protein stability, accompanied by a shift in Ca

Topics: Autism Spectrum Disorder; Female; HEK293 Cells; Humans; Infant, Newborn; Oxytocin; Pregnancy; Premature Birth; Receptors, Oxytocin; Structure-Activity Relationship

To examine the association between intrapartum synthetic oxytocin and child behavioral and emotional problems and to assess if maternal depressive or anxious symptoms or mother-to-infant bonding play a mediating role in this association.. Prospective cohort study.. Population-based Pregnancy Anxiety and Depression Study.. Pregnant women in their first trimester of pregnancy visiting a total of 109 primary and nine secondary obstetric care centers in the Netherlands between 2010 and 2014 were invited to participate. Follow-up measures used for the present study were collected from May 2010 to January 2019. Women with multiple gestations and with a preterm birth were excluded.. Intrapartum synthetic oxytocin exposure status was based on medical birth records and was defined as its administration (Yes/No), either for labour induction or augmentation. Child behavioral and emotional problems were measured with the Child Behavior Checklist at up to 60 months postpartum. Maternal depressive symptoms, anxiety and mother-to infant bonding were measured with the Edinburgh Postnatal Depression Scale, State Trait Anxiety Inventory and the Mother-to-Infant Bonding Scale from 6 months postpartum. We used multivariable linear regression models to estimate standardized beta coefficients and unique variance explained.. 1,528 women responded. In total 607 women received intrapartum synthetic oxytocin. Intrapartum synthetic oxytocin administration was not associated with child behavioral and emotional problems, mother-to-infant bonding nor with postnatal anxiety. Intrapartum synthetic oxytocin was however significantly but weakly associated with more postnatal depressive symptoms (β=0.17, 95%CI of 0.03 to 0.30) explaining 0.6% of unique variance. Maternal postnatal depressive symptoms, postnatal anxiety symptoms and suboptimal mother-to-infant bonding were positively associated with child behavioral and emotional problems.. We found no evidence that intrapartum synthetic oxytocin is associated with child behavioral and emotional problems, mother-to-infant bonding, or with postnatal anxiety symptoms. Because there was no association between intrapartum synthetic oxytocin and behavioral and emotional problems in children no mediation analysis was carried out. However, intrapartum synthetic oxytocin was positively but weakly associated with postnatal depressive symptoms. The clinical relevance of this finding is negligible in the general population, but unknown in a population with a high risk of depression.

Topics: Anxiety; Child; Depression; Depression, Postpartum; Female; Humans; Infant; Infant, Newborn; Mother-Child Relations; Mothers; Oxytocin; Pregnancy; Premature Birth; Prospective Studies

To identify the ideal gestational age at delivery for preterm premature rupture of membranes and modalities of birth.. To identify studies, research was conducted using Pub-Med, Embase and Cochrane databases.. Prolonged latency duration after pPROM does not worsen neonatal prognosis (NP3). Therefore, it is recommended not to deliver before 34 weeks of gestation for patient with uncomplicated preterm rupture of membranes (pPROM) (Grade C). After 34 weeks of gestation, expectant management for pPROM is not associated with neonatal sepsis (NP1) but is associated to intra-uterine infection (NP2). Early delivery is associated with higher risk of respiratory distress syndrome (NP2), higher risk of cesarean section (NP2) and longer duration of NICU hospitalization (NP2). Before 37 weeks of gestation, expectant management is recommended for uncomplicated pPROM (Grade A), even if vaginal group B streptococcus is positive, as long as antibiotics are used at the time of membranes rupture (Professional consensus). Elective cesarean section is reserved for usual obstetrical indications. Oxytocin and prostaglandins are reasonable options for inducing labor (Professional consensus). Data are too scarce to establish recommendation regarding intra-cervical balloons in case of pPROM (Professional consensus).. Expectant management is recommended for uncomplicated pPROM before 37 weeks of gestation.

Topics: Anti-Bacterial Agents; Cesarean Section; Delivery, Obstetric; Female; Fetal Membranes, Premature Rupture; France; Gestational Age; Humans; Infant, Newborn; Infections; Labor, Induced; Oxytocin; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Prognosis; Prostaglandins; Uterine Diseases

Premature cervical remodeling resulting in spontaneous preterm birth may begin with premature failure or relaxation at the internal os (termed "funneling"). To date, we do not understand why the internal os fails or why funneling occurs in some cases of premature cervical remodeling. Although the human cervix is thought to be mostly collagen with minimal cellular content, cervical smooth muscle cells are present in the cervix and can cause cervical tissue contractility.. To understand why the internal os relaxes or why funneling occurs in some cases of premature cervical remodeling, we sought to evaluate cervical smooth muscle cell content and distribution throughout human cervix and correlate if cervical smooth muscle organization influences regional cervical tissue contractility.. Using institutional review board-approved protocols, nonpregnant women <50 years old undergoing hysterectomy for benign indications were consented. Cervical tissue from the internal and external os were immunostained for smooth muscle cell markers (α-smooth muscle actin, smooth muscle protein 22 calponin) and contraction-associated proteins (connexin 43, cyclooxygenase-2, oxytocin receptor). To evaluate cervical smooth muscle cell morphology throughout the entire cervix, whole cervical slices were obtained from the internal os, midcervix, and external os and immunostained with smooth muscle actin. To correlate tissue structure with function, whole slices from the internal and external os were stimulated to contract with 1 μmol/L of oxytocin in organ baths. In separate samples, we tested if the cervix responds to a common tocolytic, nifedipine. Cervical slices from the internal os were treated with oxytocin alone or oxytocin + increasing doses of nifedipine to generate a dose response and half maximal inhibitory concentration. Student t test was used where appropriate.. Cervical tissue was collected from 41 women. Immunohistochemistry showed cervical smooth muscle cells at the internal and external os expressed mature smooth muscle cell markers and contraction-associated proteins. The cervix exhibited a gradient of cervical smooth muscle cells. The area of the internal os contained 50-60% cervical smooth muscle cells that were circumferentially organized in the periphery of the stroma, which may resemble a sphincter-like pattern. The external os contained approximately 10% cervical smooth muscle cells that were randomly scattered in the tissue. In organ bath studies, oxytocin stimulated the internal os to contract with more than double the force of the external os (1341 ± 693 vs 523 ± 536 integrated grams × seconds, respectively, P = .009). Nifedipine significantly decreased cervical tissue muscle force compared to timed vehicle control (oxytocin alone) at doses of 10(-5) mol/L (vehicle 47% ± 15% vs oxytocin + nifedipine 24% ± 16%, P = .007), 10(-4) mol/L (vehicle 46% ± 16% vs oxytocin + nifedipine -4% ± 20%, P = .003), and 10(-3) mol/L (vehicle 42% ± 14% vs oxytocin + nifedipine -15% ± 18%, P = .0006). The half maximal inhibitory concentration for nifedipine was 1.35 × 10(-5) mol/L.. Our findings suggest a new paradigm for cervical tissue morphology-one that includes the possibility of a specialized sphincter at the internal os. This new paradigm introduces novel avenues to further investigate potential mechanisms of normal and premature cervical remodeling.

Topics: Adult; Cervix Uteri; Dose-Response Relationship, Drug; Female; Humans; Immunohistochemistry; Middle Aged; Myocytes, Smooth Muscle; Nifedipine; Oxytocics; Oxytocin; Premature Birth; Tocolytic Agents; Uterine Contraction

Preterm birth (PTB) is a complex disorder associated with significant neonatal mortality and morbidity and long-term adverse health consequences. Multiple lines of evidence suggest that genetic factors play an important role in its etiology. This study was designed to identify genetic variation associated with PTB in oxytocin pathway genes whose role in parturition is well known.. To identify common genetic variants predisposing to PTB, we genotyped 16 single nucleotide polymorphisms (SNPs) in the oxytocin (OXT), oxytocin receptor (OXTR), and leucyl/cystinyl aminopeptidase (LNPEP) genes in 651 case infants from the U.S. and one or both of their parents. In addition, we examined the role of rare genetic variation in susceptibility to PTB by conducting direct sequence analysis of OXTR in 1394 cases and 1112 controls from the U.S., Argentina, Denmark, and Finland. This study was further extended to maternal triads (maternal grandparents-mother of a case infant, N=309). We also performed in vitro analysis of selected rare OXTR missense variants to evaluate their functional importance.. Maternal genetic effect analysis of the SNP genotype data revealed four SNPs in LNPEP that show significant association with prematurity. In our case-control sequence analysis, we detected fourteen coding variants in exon 3 of OXTR, all but four of which were found in cases only. Of the fourteen variants, three were previously unreported novel rare variants. When the sequence data from the maternal triads were analyzed using the transmission disequilibrium test, two common missense SNPs (rs4686302 and rs237902) in OXTR showed suggestive association for three gestational age subgroups. In vitro functional assays showed a significant difference in ligand binding between wild-type and two mutant receptors.. Our study suggests an association between maternal common polymorphisms in LNPEP and susceptibility to PTB. Maternal OXTR missense SNPs rs4686302 and rs237902 may have gestational age-dependent effects on prematurity. Most of the OXTR rare variants identified do not appear to significantly contribute to the risk of PTB, but those shown to affect receptor function in our in vitro study warrant further investigation. Future studies with larger sample sizes are needed to confirm the findings of this study.

Topics: Alleles; Animals; Argentina; Case-Control Studies; Chlorocebus aethiops; COS Cells; Cystinyl Aminopeptidase; Denmark; Female; Finland; Genetic Association Studies; Genetic Predisposition to Disease; Genomic Structural Variation; Gestational Age; Haplotypes; Humans; Inheritance Patterns; Inositol Phosphates; Mutation, Missense; Oxytocin; Polymorphism, Single Nucleotide; Pregnancy; Premature Birth; Protein Binding; Receptors, Oxytocin; Risk Factors

Increased uterine stretch appears to increase the risk of preterm labour, but the mechanism is unknown. The aim of this study was to identify factors that mediate the effect of stretch on human myometrium.Myometrial explants, prepared from biopsies obtained at elective caesarean delivery, were either studied acutely, or were maintained in prolonged culture (up to 65 h) under tension with either a 0.6 g or a 2.4 g mass, and compared using in vitro contractility, whole genome array, and qRT-PCR. Tissue held at tonic stretch with the 2.4 g mass for either 24 or 65 h showed increased potassium chloride (KCl)-induced and oxytocin-induced contractility compared with that held with the 0.6 g mass. Gene array identified 62 differentially expressed transcripts after 65 h exposure to increased stretch. Two probes for gastrin-releasing peptide (GRP), a known stimulatory agonist of smooth muscle, were among the top five up-regulated by stretch (3.4-fold and 2.0-fold). Up-regulation of GRP mRNA by stretch was confirmed in a separate series of 10 samples using quantitative RT-PCR (qRT-PCR) (2.8-fold, P =0.01). GRP stimulated contractions acutely when added to freshly obtained myometrial strips in 2 out of 9 cases, but Western blot demonstrated expression of the GRP receptor in 9 out of a further 9 cases. Prolonged incubation of stretched explants in the GRP antagonists PD-176252 or RC-3095 (65 and 24 h, respectively) significantly reduced KCl- and oxytocin-induced contractility.Tonic stretch of human myometrium increases contractility and stimulates the expression of a known smooth muscle stimulatory agonist, GRP. Incubation of myometrium with GRP receptor antagonists attenuates the effect of stretch. GRP may be a target for novel therapies to reduce the risk of preterm birth in multiple pregnancy.

Topics: Biopsy; Blotting, Western; Bombesin; Female; Gastrin-Releasing Peptide; Gene Expression Profiling; Hormone Antagonists; Humans; Immunohistochemistry; Indoles; Mechanotransduction, Cellular; Myometrium; Oligonucleotide Array Sequence Analysis; Oxytocics; Oxytocin; Peptide Fragments; Potassium Chloride; Pregnancy; Premature Birth; Receptors, Bombesin; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Tissue Culture Techniques; Up-Regulation; Uterine Contraction

To identify factors related to retained placenta in the context of contemporary obstetric practice.. This was a case-control study comparing 408 cases of retained placenta and an equivalent number of control individuals. Epidemiological and delivery-related variables were registered in computerized prenatal and in-hospital medical records. Univariable and multivariable logistic regressions were used for estimation of risk ratios and statistical significance.. Independent risk factors for retained placenta were: previous retained placenta (odds ratio [OR] 12.61, 95% confidence interval [CI] 3.61-44.08); preterm delivery (OR 3.28, 95% CI 1.60-6.70); oxytocin use for 195-415 minutes (OR 2.00, 95% CI 1.20-3.34); oxytocin use more than 415 minutes (OR 6.55, 95% CI 3.42-12.54, number needed to harm 2.3); preeclampsia (OR 2.85, 95% CI 1.20-6.78); two or more previous miscarriages (OR 2.62, 95% CI 1.31-5.20); and one or more previous abortion (OR 1.58, 95% CI 1.09-2.28). Parity of two or more had a seemingly protective effect (OR 0.40, 95% CI 0.24-0.70), as did smoking at the start of pregnancy (OR 0.28, 95% CI 0.09-0.88). Retained placenta was significantly associated with an increased risk of postpartum hemorrhage. The OR related to blood loss exceeding 500 mL, 1,000 mL, and 2,000 mL and the need for blood transfusion was 33.07 (95% CI 20.57-53.16), 43.44 (95% CI 26.57-71.02), 111.24 (95% CI 27.26-454.00), and 37.48 (95% CI 13.63-103.03), respectively. Diabetes was numerically overrepresented in the case group, but the power of the study to detect a significant difference in risk outcome was insufficient.. Identifying risk factors for retained placenta is important in the assessment of women after delivery. The increased risk associated with duration of oxytocin use is of interest, considering its widespread use.. II.

Topics: Abortion, Induced; Abortion, Spontaneous; Adolescent; Adult; Case-Control Studies; Dystocia; Female; Humans; Oxytocin; Placenta, Retained; Pregnancy; Premature Birth; Sweden; Young Adult

Endogenous uterine agonists can activate numerous signaling pathways to effect increased force. Our objective was to assess expression of key constituents of these pathways, in alliance with contractile function, through late gestation and during term and preterm labor.. Using myography, we measured the response to 3 agonists compared with depolarization alone (K(+), 124 mEq/L) and calculated agonist/depolarization ratio. We measured gene expression using quantitative reverse transcription-polymerase chain reaction.. Contractile responsiveness to depolarization alone, oxytocin, or endothelin-1 increased during pregnancy compared with nonpregnant animals. The agonist/depolarization ratio did not change during uterine activation or parturition. Inhibition of rhoA-associated kinase decreased responses to oxytocin in all tissues, but significantly more during uterine activation. Expression of rhoA and rhoA-associated kinase was increased significantly in active labor at term or preterm.. The rhoA/rhoA-associated kinase pathway is a key regulator of uterine activation during labor and may be a useful target for the prevention of spontaneous preterm birth.

Topics: Animals; Endothelin-1; Female; Models, Animal; Myography; Oxytocin; Parturition; Potassium; Pregnancy; Premature Birth; Rats; Reverse Transcriptase Polymerase Chain Reaction; rho-Associated Kinases; rhoA GTP-Binding Protein; Uterine Contraction

Organized uterine contractions, including those necessary for parturition, are dependent on calcium entry through voltage-gated calcium channels in myometrial smooth muscle cells. Recent evidence suggests that small-conductance Ca(2+)-activated potassium channels (K(Ca)2), specifically isoforms K(Ca)2.2 and 2.3, may control these contractions through negative feedback regulation of Ca(2+) entry. We tested whether selective pharmacologic activation of K(Ca)2.2/2.3 channels might depress uterine contractions, providing a new strategy for preterm labor intervention. Western blot analysis and immunofluorescence microscopy revealed expression of both K(Ca)2.2 and K(Ca)2.3 in the myometrium of nonpregnant (NP) and pregnant (gestation day 10 and 16; D10 and D16, respectively) mice. Spontaneous phasic contractions of isolated NP, D10, and D16 uterine strips were all suppressed by the K(Ca)2.2/2.3-selective activator CyPPA in a concentration-dependent manner. This effect was antagonized by the selective K(Ca)2 inhibitor apamin. Whereas CyPPA sensitivity was reduced in D10 and D16 versus NP strips (pIC(50) 5.33 ± 0.09, 4.64 ± 0.03, 4.72 ± 0.10, respectively), all contractions were abolished between 30 and 60 μM. Blunted contractions were associated with CyPPA depression of spontaneous Ca(2+) events in myometrial smooth muscle bundles. Augmentation of uterine contractions with oxytocin or prostaglandin F(2α) did not reduce CyPPA sensitivity or efficacy. Finally, in an RU486-induced preterm labor model, CyPPA significantly delayed time to delivery by 3.4 h and caused a 2.5-fold increase in pup retention. These data indicate that pharmacologic stimulation of myometrial K(Ca)2.2/2.3 channels effectively suppresses Ca(2+)-mediated uterine contractions and delays preterm birth in mice, supporting the potential utility of this approach in tocolytic therapies.

Topics: Abortifacient Agents; Animals; Apamin; Calcium; Dinoprost; Female; Mice; Mice, Inbred C57BL; Mifepristone; Myometrium; Obstetric Labor, Premature; Oxytocin; Potassium Channels, Calcium-Activated; Pregnancy; Premature Birth; Pyrazoles; Pyrimidines; Uterine Contraction

Topics: 17-alpha-Hydroxyprogesterone; Castor Oil; Female; Humans; Oxytocin; Pregnancy; Pregnancy Trimester, Third; Premature Birth; Randomized Controlled Trials as Topic; Recurrence; Risk Assessment; Risk Factors; Uterine Contraction

The present study was designed to compare milk production and hormone responses (prolactin [PRL], oxytocin [OT]) and to determine associations of hormone levels with milk production in mothers of preterm (PT) and term (TM) infants during the first 6 weeks postpartum. Mothers of PT infants (n = 95) were all pump dependent; mothers of TM infants (n = 98) were all feeding their infant at breast. Mothers of nonnursing PT infants produced less milk over time compared to mothers of TM infants. A higher proportion of PT mothers had lower basal PRL levels compared with TM mothers. PRL and frequency of breast stimulation combined positively influenced milk production in PT mothers. OT levels were higher in PT versus TM mothers, but OT was not related to milk production. Further study is warranted regarding interventions to enhance milk production, particularly in pump-dependent mothers of PT infants.

Topics: Adult; Analysis of Variance; Breast Feeding; Case-Control Studies; Clinical Nursing Research; Female; Gestational Age; Humans; Lactation Disorders; Mammary Glands, Human; Oxytocin; Physical Stimulation; Pituitary Gland; Premature Birth; Prolactin; Prospective Studies; Regression Analysis; Sucking Behavior; Suction

The hormonal system for induction of term and preterm labour is not fully understood. Therefore, we investigated myometrial gene expressions for neurohypophyseal hormones and their receptors, prostaglandin F(2alpha) and ovarian steroid receptors in women delivered by Caesarean section. Myometrial tissue for real time PCR was collected from 39 women delivered at term before and after the onset of labour and preterm. Women delivered electively at term had significantly higher oxytocin receptor mRNA expressions (2.52 +/- 0.37 oxytocin receptor/actin; median +/- SEM) than those delivered with ongoing labour at term (1.01 +/- 0.34; p = 0.015) and those at preterm (1.08 +/- 0.25; p = 0.004). Sub-analyses revealed that the difference at term pregnancies solely was related to patients receiving oxytocin during labour (p = 0.007). These patients had higher oxytocin peptide mRNA levels than those without labour at term (p = 0.009). PGF(2alpha) receptor mRNA concentrations were 27.80 +/- 3.55, 11.46 +/- 2.87 and 19.54 +/- 5.52 PGF receptor/actin, respectively, for the groups. Women without labour at term had higher concentration than those with labour (p = 0.005). Our results suggest that oxytocin, its receptor and the PGF(2alpha) receptor are involved in the regulation of labour through a paracrine mechanism.

Topics: Adult; Algorithms; Cesarean Section; Elective Surgical Procedures; Female; Gene Expression Regulation; Humans; Labor, Obstetric; Myometrium; Osmolar Concentration; Oxytocin; Paracrine Communication; Pregnancy; Premature Birth; Receptors, Oxytocin; Receptors, Prostaglandin; RNA, Messenger; Term Birth

The nonapeptide oxytocin (OT) is used in medicine to help begin and/or continue childbirth. Its analogs can be also used to control bleeding following fetus delivery. The main function of oxytocin is to stimulate contraction of uterus smooth muscle and the smooth muscle of mammary glands, thus regulating lactation. This paper describes theoretical simulations of the distribution of the torsional angles chi1 in the non-standard methylated phenylalanine residues of three oxytocin analogs: [(Phe)(2)o-Me]OT, [(Phe)(2)m-Me]OT, [(Phe)(2)p-Me]OT. The conformations of the oxytocin analogs were studied both in vacuum and in solution. We found some correlations between the biological activity of the considered peptides and the side-chain conformations of amino-acid residues 2 and 8.

Topics: Biochemistry; Chemistry, Pharmaceutical; Female; Humans; Models, Chemical; Molecular Conformation; Oxytocics; Oxytocin; Phenylalanine; Pregnancy; Premature Birth; Solvents; Stereoisomerism

A synthetic oxytocin analogue, barusiban, was shown to potently inhibit oxytocin-induced activity of myometrium from term pregnant women. The responsiveness to vasopressin was not influenced by the compound.. To test the effect of barusiban and a reference compound, atosiban, on oxytocin-induced activity of myometrium from women at preterm pregnancy in comparison to myometrium from women at term.. Fifteen preterm (30-36 gestational weeks) and 12 term pregnant women (38-41 weeks) who underwent cesarean delivery donated myometrial tissue for the study. Concentration-response curves following oxytocin administration to isolated myometrial strips were recorded in control experiments, in the presence of barusiban at concentrations of 2.5, 25, and 250 nM, and of atosiban at concentrations of 25, 250, and 750 nM. Effective concentration 50% (EC50) and pA2 values were calculated.. Both antagonists in higher concentrations increased the EC50 values to oxytocin. The median pA2 value for preterm myometrium with barusiban was 9.76 and with atosiban 7.86. For term myometrium the corresponding pA2 results were 9.89 and 7.81, respectively. None of these pA2 values differed to any statistically significant degree.. The selective oxytocin antagonist, barusiban, concentration-dependently inhibits oxytocin-induced myometrial contractions of both preterm and term myometrium at least as potently as atosiban. It remains to be determined if the selectivity of barusiban for the oxytocin receptor confers an advantage over atosiban as a tocolytic in preterm labor.

Topics: Adult; Dose-Response Relationship, Drug; Female; Humans; In Vitro Techniques; Myometrium; Oxytocin; Pregnancy; Premature Birth; Uterine Contraction; Vasotocin

Topics: Abortion, Induced; Abortion, Spontaneous; Abortion, Therapeutic; Female; Humans; Obstetric Labor, Premature; Oxytocin; Pregnancy; Premature Birth