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A program of cell death and extracellular matrix degradation is activated in the amnion before the onset of labor.

Fetal membranes usually rupture during the process of labor. Premature fetal membrane rupture occurs not infrequently and is associated with significant fetal and maternal morbidity. The mechanisms of normal and pathologic fetal membrane rupture are not well understood. We have examined structural and biochemical changes in the rat amnion as labor approaches in order to characterize this process in normal pregnancy. Here we report that before the onset of active labor the amnion epithelial cells undergo apoptotic cell death which encompasses degradation of 28S ribosomal subunit RNA and associated P proteins and fragmentation of nuclear DNA. Concurrent with these cellular changes, the amnion type I collagen matrix is degraded with the accumulation of three-quarter length type I collagen fragments in extraembryonic fluid, characteristic of the cleavage of fibrillar collagen by interstitial collagenase. Western blot and immunohistochemical analyses confirmed that interstitial collagenase protein appears in association with the loss of amnion type I collagen. We conclude that amnion epithelial cells undergo a process of programmed cell death associated with orchestrated extracellular matrix degradation which begins before the onset of active labor. Thus, fetal membrane rupture is likely to be the result of biochemical changes as well as physical forces.

Amnion↗

Outpatient use of prostaglandin gel for ripening of the cervix and induction of labor.

This case series reports the experience in a family practice center with the outpatient use of prostaglandin E2 (PGE2) gel in patients with a medical or obstetric indication for induction. A retrospective medical record review of a 15-month period was completed for 45 women receiving intravaginal PGE2 gel for cervical ripening before the induction of labor. A change in Bishop score was seen following application of the first gel in 21 women (54%). Six women (13%) had labor onset 1 to 16 hours after the initial gel placement, and an additional 19 women (42%) had labor onset within 48 hours of the final gel placement. Twenty-one women (47%) gave birth without the use of oxytocin, and only 11 women (24%) required oxytocin induction of labor. No significant differences were seen in type of delivery, delivery complications, or newborn outcome between categories of labor onset (spontaneous, PGE2 gel, oxytocin). Two complications followed gel insertions, one case of uterine hyperstimulation and one case of a brief episode of fetal bradycardia. Both women were identified within the monitoring period and subsequently were delivered of healthy term infants. This case series demonstrates the usefulness and lack of adverse effects of outpatient PGE2 gel as an adjunct in labor induction.

Administration, Intravaginal↗

Fetal fibronectin in the cervical secretion predicts accurately the onset of labor at term.

OBJECTIVE: The objective of our study was to check if presence of fetal fibronectin in the cervical secretion of full term patient predicts accurately the onset of labour at term. STUDY DESIGN: 78 women in the term period were included in the study, serial samples for fetal fibronectin were assessed, each patient underwent spontaneous labour, delay between last sample and delivery were analysed. RESULTS: Patient with positive fetal fibronectin delivered within 3 +/- 1.9 days where as patient with negative fetal fibronectin delivered within 5.7 +/- 3.9 days (P = 0.01). CONCLUSION: Presence of fetal fibronectin in cervical secretions seems to be a powerful tool to predict in a short delay the onset of labour at term, it should be used in conjunction with clinical and fetal assessment data.

Adult↗

[Alterations of oxytocin and prostaglandin E1, E2, F2 alpha levels in human plasma during labor (author's transl)].

In order to investigate the role of oxytocin (OT) and prostaglandins (PGs) in the mechanism of labor onset, changes of OT and PGs levels in human plasma were evaluated before labor, soon after the labor onset, and at the time of established labor in the following three groups. Group 1 consisted of 6 cases with spontaneous labor, group 2, of 6 cases with induced labor with PGF2 alpha drip infusion, and group 3, of 5 cases with induced with PGE2 vaginal suppository. OT concentrations were measured by RIA, PGE1, PGE2, and PGF2 alpha were extracted and determined by Inagawa's method. Levels of OT in group 1 were divided into two subgroups: subgroup 1 with high OT levels (24.0-116.2 microunits/ml) and subgroup 2 with low OT levels (below 7.2 microunits/ml) throughout labor. Changes of PGs level in subgroup 1 showed no definite tendency during labor, suggesting that OT appears to play the leading role in spontaneous labor. Those in subgroup 2 showed a particular behavioral pattern during labor, suggesting an important role played by PGs for the onset of labor following rupture of the membranes. The results of groups 2 and 3 are fully discussed in terms of labor process.

Female↗

Expression of the gap junction protein connexin-43 is increased in the human myometrium toward term and with the onset of labor.

OBJECTIVES: Our aim was to determine the temporal pattern of expression of transcripts encoding the myometrial gap junction protein connexin-43 in the human myometrium during late pregnancy and with the onset of labor. We also correlated these data with levels of total connexin-43 protein and the appearance of gap junctions within the myometrial cell membrane. STUDY DESIGN: Myometrial tissue was collected during cesarean section from 27 women between 37 and 41 weeks of gestation not in labor and from 7 women between 39 and 41 weeks during active labor. The levels of connexin-43 messenger ribonucleic acid and protein were estimated by Northern and Western analysis, respectively. The appearance of gap junctions between myometrial cells was assessed by immunofluorescence of histologic sections of myometrium from these women. RESULTS: Levels of connexin-43 messenger ribonucleic acid in myometrial tissue collected from women not in labor increased (p < 0.01) between 37 and 40 weeks' gestation with a further significant increase occurring during labor (p < 0.05). The level of connexin-43 protein decreased (p < 0.05) during late pregnancy and was not increased during labor although gap junctions (which were not present during pregnancy) did appear in the myometrial cell membrane during labor. CONCLUSIONS: These data suggest that the mechanisms responsible for the increased myometrial cell-cell communication necessary for the development of effective labor contractions likely involves regulation at the level of both messenger ribonucleic acid and gap junction formation in the cell membrane.

Animals↗

Intercourse doesn't hasten onset of labor.

Sexual intercourse at term pregnancy is not associated with earlier delivery. In this cohort, the mean gestational age at delivery was actually a few days older. We can throw out the common belief that intercourse hastens the onset of labor and delivery.

Comment↗

Metabolism of oxytocin in human decidua, chorion, and placenta.

Oxytocin (OT) synthesized within human decidua may influence the timing of human parturition. Metabolism of OT within intrauterine tissues may regulate local concentrations. We hypothesized that a decrease in OT metabolism may contribute to an increase in local tissue concentrations around the time of parturition. Thus, we compared OT degradation in human decidua with that in chorion and placenta obtained before or after labor onset at term. We measured kinetic parameters for OT metabolism and determined pathways of degradation. Both cytosol and microsomal fractions contained aminopeptidase and postproline endopeptidase activities. Metabolism in the microsomal fractions was predominantly by an aminopeptidase enzyme that cleaves the ring structure of OT and removes amino acid residues from the N-terminal end. Metabolism in the cytosol fractions was predominantly via postproline endopeptidase activity, which cleaves the C-terminal Leu8-Gly9NH2. The resultant OT-(1-7) also is a substrate for aminopeptidase activity. The apparent maximum velocities of OT metabolism in the cytosol subcellular fractions of decidua (0.87 +/- 0.30 nmol/mg protein.min) and chorion (1.04 +/- 0.47) were significantly (P < or = 0.05) higher than those in corresponding microsomal fractions (0.17 +/- 0.05 and 0.29 +/- 0.10, respectively). Placental cytosols (1.08 +/- 0.34) were similar to decidua and chorion, but the microsomal fractions had significantly greater activity (0.82 +/- 0.22). The Km values for all tissues were in the range of 8-20 mumol/L. There were no significant changes in the kinetic parameters for OT metabolism around the time of labor onset. We conclude that human decidua and chorion as well as placenta actively metabolize OT, but changes in metabolism do not occur around parturition. If increasing decidual concentrations of OT play a role in the timing of human labor onset, mechanisms that increase production or secretion are of primary importance.

Aminopeptidases↗

Expectations, perceptions, and management of labor in nulliparas prior to hospitalization.

This ethnographic qualitative study was designed to explore the phenomenon of prehospitalization labor from the perspective of nulliparous women. Twenty-three women were interviewed in the early postpartum period using a semistructured interview guide. The participants recounted their experiences with labor onset recognition and management before being admitted to the hospital for birthing. Qualitative analyses included verbatim transcription of audiotaped interviews, line-by-line coding, and categorization of data into codes and categories. Interpretive analyses were validated with a collaborative research team and the participants themselves. The central theme that emerged from this study was confronting the relative incongruence between expectations and actual experiences. Supporting categories included: expectations about the labor experience, identifying labor onset, managing the physical and emotional responses to labor, supportive resources, and decision making about hospital admission. Early labor experiences in nulliparas offer insight into the contributions of both expectations and environment to adaptation in labor. Midwives and perinatal nurses are in a unique position to design interventions that support and reinforce laboring women's activities outside of the hospital setting.

Attitude to Health↗

Evidence for 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene C4(LTC4) in the onset of labor.

UNLABELLED: Arachidonic acid is metabolized by cyclooxygenase leading to prostaglandins (PG), and by lipoxygenases leading to hydroxyeicosatetraenoic acids (HETE) and leukotrienes (LT). PGs are potent uterine constrictors. 5-HETE and LTC4 also stimulate uterine contractions, but their role in labor is not known. To estimate the activities of these pathways before parturition and their relationship to uterine contractility, amniotic fluid (AF) concentrations of 5-HETE, LTC4 and PGF2 alpha were determined in 5 chronically catheterized rhesus monkeys. Uterine contractility was continually assessed by changes in AF pressure. RESULTS: AF concentrations at the time of intrauterine surgery were 4.4 +/- 0.8 ng/ml for 5-HETE and 2.5 +/- 0.7 ng/ml for LTC4. PGF2 alpha levels were nondetectable. Indomethacin infusion into the mother, although effective in suppressing PGF2 alpha levels, did not prevent the onset of premature labor and vaginal delivery in 2 animals. PGF2 alpha did not increase in 1 monkey with term labor. Approximately 1 week before delivery, 5-HETE and LTC4 concentrations increased sharply in all animals in association with a nocturnal pattern of labor contractions. Peak AF concentrations during labor were 5-HETE: 40 +/- 8 ng/ml, LTC4: 20 +/- 4 ng/ml, and PGF2 alpha: 5.4 +/- 2.1 ng/ml. COMMENT: LTC4 and 5-HETE stimulate uterine contractility in vitro, and probably act in concert with PGF and PGE to stimulate uterine contractions during parturition. HETEs may also act as a signal to recruit white blood cells to the uterus and to activate them, there to augment PG and LT production and act as a first line of defense against any infection that might enter the uterus from the vagina during or after delivery. CONCLUSIONS: 1) 5-HETE and LTC4, but not PGF2 alpha, are associated with uterine contractility after preterm intrauterine surgery. Surprisingly, AF PGF2 alpha levels were nondetectable for 1 to 2 weeks after surgery. 2) 5-HETE and LTC4 are present in higher concentrations than PGF2 alpha in AF. 3) 5-HETE, LTC4 and PGF2 alpha all increase with the onset of labor. AF concentrations of 5-HETE and LTC4 are significantly higher than PGF2 alpha before and during term and preterm labor. 4) Labor can occur with suppressed PGF2 alpha levels, but with increasing 5-HETE and LTC4 levels. 5) These data suggest that 5-HETE and LTC4 are important components of the parturitional process, and they challenge the dogma that PGs are the universal mediators of labor.

Amniotic Fluid↗

Rupture of uterus in a primigravida prior to onset of labor.

Spontaneous rupture of the uterus in a primigravida is very rare. Furthermore, uterine rupture in a primigravida prior to the onset of active labor is extremely uncommon, with very few reported cases. We present a case of antepartum uterine rupture in a 20-year-old primigravida in whom the clinical features resembled those of abruptio placentae.

Adult↗

Increases of plasma eosinophil major basic protein levels late in pregnancy predict onset of labor.

Major basic protein (MBP), the core of the eosinophil granule, is a potent toxin for parasites and mammalian cells; it also causes histamine release from mast cells and basophils. Plasma levels of MBP are increased in all pregnant women, and MBP has been localized by immunofluorescence to placental X cells and placental-site giant cells. Analyses of plasma MBP levels during pregnancy showed a striking correlation between increases late in the third trimester and spontaneous onset of labor. In one case with premature labor, the plasma MBP level also was increased coincidentally with labor. In contrast, in cases of prolonged gestation in which labor was induced, there were no late increases in MBP levels. Also, uterine contraction during spontaneous labor or oxytocin-induced labor did not cause elevations of plasma MBP. Measurement of plasma MBP levels in pregnancy may be useful for the prediction of labor and for the development of new means of intervention for premature labor and prolonged gestation.

Blood Proteins↗

Neonatal clinical outcome after elective cesarean section before the onset of labor at the 37th and 38th week of gestation.

BACKGROUND: Although elective cesarean sections are often performed after the 37th week of gestation without any complicating factor that may influence the timing of delivery,there is a possibility that infants born in the 37th week of gestation,especially early in the 37th week of gestation, do not obtain a satisfactory clinical outcome due to premature birth. METHODS: The authors analyzed the clinical course during the neonatal period in 96 infants born in the 37th (n = 81)and 38th (n = 15) week of gestation by an elective cesarean section. Subjects were retrospectively divided into two groups: infants born in the first half of the 37th week of gestation (37+0-37+3)(n = 48), and infants born from the latter half of the 37th week of gestation (37+4-37+6)through the 38th week of gestation (n = 48). Twin pregnancies, pregnancy with placenta previa, and pregnancy of women who had a diversity of medical complications were excluded from the present study, because of the possibility that these conditions may have affected the infants' status. The incidence of infants who showed clinical symptoms during the neonatal period and who needed medical care was compared between the two groups. RESULTS: Of the 96 subjects, 25 infants(26.0%) had significant clinical symptoms. The incidence of breathing difficulty was significantly higher in the infant group born in the first half of the 37th week of gestation than in the latter group. CONCLUSIONS: An elective cesarean section before the onset of labor early in the 37th week of gestation should not be routinely undertaken.

Cesarean Section↗

[Prognostic significance of risk factors in pregnancy. II. Risk status at onset of labor].

A group of 383 women with pregnancy risks were screened at the onset of labour. 70% of the EPH-Gestosis, 56% of the urinary tract infections and cervical incompetence, 48% of the anaemias, 38,6% of the premature labour, 11% of the hypotension and 4% of the antepartal haemorrhages were found still to be present at the onset of labour. In those women with EPH-Gestosis at the onset of labour, the risk of cesarean section was markedly higher. When the risks premature contractions and cervical incompetence were recorded, the resulting birth weights were lower and the necessity for intensive paediatric care higher than normal. EPH-Gestosis and urinary tract infections which were still present at the onset of labour were of a longer duration. If the risks premature contractions and cervical incompetence were present at the onset of labour one could imply a shorter period of gestation.

Anemia↗

Fetal lung maturity. I. Mode of onset of premature labor. Influence of premature rupture of the membranes.

In a prospective study of 133 spontaneous premature deliveries the relation between premature rupture of the membranes (PRM) and development of respiratory distress syndrome (RDS) in newborn infants is examined. PRM is associated with a significantly decreased incidence of RDS in newborn infants (P less than 0.002). This relation is valid at a gestational age of 28 weeks or more and a birthweight greater than 1000 g. Total respiratory morbidity in newborn infants (transient tachypnea + RDS) is also significantly decreased when labor is associated with PRM (P less than 0.005). Assessment of the influences of sex of the infant, fetal asphyxia, and delivery by cesarian section shows that PRM bears a stronger relation than each of these individual factors to a decreased incidence of RDS. Duration of the latent period has no influence on protection from RDS, and it is suggested that fetal lung maturity occurs before the membranes rupture.

Birth Weight↗

Onset of spontaneous labor and changes in E2 and progesterone levels--possible interrelation.

Unlike the findings in animal studies, in which a decline in progesterone levels is clearly associated with the onset of labor, investigation of progesterone levels among human parturients has resulted in controversy. This study was designed to address the issue and evaluate labor-onset related changes of estradiol-progesterone (E2-P) concentration in fetal scalp serum, umbilical vein serum and in the peripheral maternal serum. Seven women in spontaneous labor, were compared to 7 women in whom labor was induced. Our results reveal a significant decrease in the maternal serum P concentration when spontaneous labor is taking place (120.6 +/- 24.5 mg/ml verus 177.3 +/- 61.4 mg/ml, p < 0.05). Significant change in the ratio of the fetal scalp to the maternal serum E2/P ratio in women at spontaneous labor versus induced labor is also shown. We could not demonstrate any changes in the E2 levels in relation to labor. We conclude that the onset of labor in human pregnancy is most probably preceded by local changes in the levels of P and ratio of P to E2. These changes may play an important regulatory role in onset of labor.

Adult↗

Chronic stimulation of uterine prostaglandin synthesis during cervical ripening before the onset of labor.

Concentrations of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were measured in plasma of six carefully selected primigravid women with an unripe cervix at term before and at various intervals after extra-amniotic insertion of a Foley catheter with or without methylhydroxyethylcellulose (Tylose) gel. The procedure caused an acute elevation of PGFM levels within 5 min (P less than 0.025), which was maintained for at least 6 hours in the absence of uterine activation at 179 +/- 32% of the initial values (P less than 0.01). Extra-amniotic administration of Tylose gel caused an increase in PGFM levels which was both higher and more prolonged (greater than 12 hours) than insertion of a Foley catheter alone. The observations indicate that cervical ripening without concomitant uterine activation is associated with an increase in PGFM levels. They also demonstrate that prolonged activation of (intra) uterine prostaglandin synthesis may occur several hours before the onset of labor-like uterine activity. A chance finding further suggests that spontaneous rupture of the membranes too may be preceeded by an increase in (intra) uterine prostaglandin synthesis. In their totality these observations lend strong support to the proposition that an increase in (intra) uterine prostaglandin production is a prerequisite to rather than a consequence of the initiation of labor.

Amnion↗

Estrogen stimulates oxytocin gene expression in human chorio-decidua.

We have recently shown that oxytocin (OT) is synthesized within human amnion, chorion, and decidua during late gestation. The levels of OT messenger ribonucleic acid (mRNA) increased around the time of parturition, suggesting that locally produced OT may play a role in this poorly understood process. In this report, we present results from investigations into the effects of estrogen and progesterone on the synthesis of OT by human chorio-decidua. Using an in vitro incubation system, estradiol at physiological concentrations more than doubled the concentration of OT mRNA. This was reflected by an increase in the amount of OT peptide secreted into the medium. The increase in OT mRNA was antagonized by tamoxifen, suggesting that the effects were estrogen receptor mediated. Progesterone had no effect on OT mRNA synthesis. Using ribonuclease protection assays, mRNAs for estrogen receptor (ER) and progesterone receptor (PR) were detected in all tissues examined. The highest levels were found in decidua, with lower amounts in chorion and very small amounts in amnion and placenta. This is the same relative tissue distribution that we previously demonstrated for OT mRNA. A single transcript was present for ER, and two transcripts were protected for PR. The concentrations of ER mRNA in chorio-decidua were 3-fold higher in tissues obtained after spontaneous labor onset than in tissues obtained from cesarean section at a similar gestational age but before labor onset. Levels of PR did not change significantly. We conclude that synthesis of OT in human chorio-decidua may be regulated in part by estrogen, and that regulation of ER levels may be an important factor modulating this effect. These data support the hypothesis of a paracrine network within human fetal membranes and decidua that may participate in regulating the timing of human birth.

Chorion↗