Prostaglandin E and F content of the amniotic fluid in various stages of beginning labor

Levels of prostaglandin (PG) E- and F-equivalents determined radio-immunologically in amniotic fluid from women with uncomplicated pregnancies at term were related to the cervical state and the onset of regular labour. The lowest levels of both PG E- and F-equivalents with about 400 pg/ml were measured in the group with an immature cervix. An about twofold increase of both PG's appears characteristic for the cervical ripening, whereas the readiness for the initiation of regular uterine contractions is apparently indicated by further raises of PG F2 alpha. At the beginning of parturition distinct elevations can be registered for both PG's with a dominance of PG F. From their dynamics in amniotic fluid conclusions about different functions of PG's during the period preceding labour can be drawn.     

Relation between placental site and length of gestation.

Two theories related to uterine action have been brought together to see whether the site of placental implantation influences the onset of labour: (1) that uterine contractions begin asymmetrically from a "pacemaker" in one uterine horn, and (2) that progesterone from the placenta blocks myometrial contractility primarily at the site of implantation. Case records were examined of 182 patients who had placental locations performed and who had a spontaneous onset of labour. Where the placenta was implanted in the right upper quadrant of the uterus labour occurred on average four days sooner than when it was implanted in the left upper quandrant: the difference was statistically significant.     

Intrapartum Hysteroscopy

EDITORIAL COMMENT: This technique warrants consideration /evaluation especially in the patient having a trial of vaginal delivery after a previous Caesarean section (Case 2).
Summary: A new method of visualization of fetus, uterus, placenta, umbilical cord and amniotic fluid is presented. A flexible endoscope was inserted into the uterine cavity after spontaneous or artificial rupture of the membranes via the vaginal route in 85 patients. Endoscopy could be beneficial for precise determination of the nature and type of umbilical cord and placental pathology, signs of fetal dysmaturity, the presence of meconium and evaluation of the integrity of a uterine scar. Intrapartum hysteroscopy could be especially helpful for patients with no prenatal care who appear in labour with incomplete histories. The method is proven to be safe for both the mother and the neonate.     

Prostaglandins and the induction of labour

The secret of successful induction of labour lies in replicating as accurately as possible the physiological processes of spontaneous labour. As cervical ripening is a fundamental prerequisite of spontaneous labour, it is essential to ripen the cervix pharmacologically prior to induction if this has not already occurred physiologically. Prostaglandins remain the single most effective agent for this. In the presence of a favourable cervix, a small dose of PGE₂ is often enough to induce a labour very similar to spontaneous labour. This method of induction is also associated with a decrease in postpartum haemorrhage and neonatal jaundice. The timing of amniotomy is of crucial importance. If performed too early, before the cervix is ripe, it may lead to complications for both mother and fetus. If left too late we may lose the advantage of its uterine sensitising influence and its augmentatory effect. A combination of PGE₂ and a judiciously timed amniotomy for induction will avoid the need for oxytocin in the majority of cases, but it should not be forgotten that oxytocin is a safe, effective drug which may be required to carry labour through to delivery.     

Myometrial contractile strain at uteroplacental separation during parturition

OBJECTIVE: A simplified geometric model of the uterine wall during the second and third stages of labor was created to estimate the magnitude of myometrial strain associated with the initiation of placental separation. STUDY DESIGN: The uterine wall was modeled as an isovolumetric, incompressible spherical shell whose overall radius decreased and mural thickness increased on uterine muscle contraction after delivery of the fetus. Either a 3.5-MHz or a 5-MHz ultrasonography probe was used to measure the change in uterine mural thickness of 14 healthy patients from just before delivery to the time of initial separation of the placenta. The measured change in uterine wall thickness was then used to calculate its average radial and circumferential strain with a simple mathematic model. RESULTS: Placental separation occurred at radial and circumferential strains (mean +/- SD) of 450% +/- 182% and -75% +/- 11%, respectively. These strains are consistent with the known maximal contractile strains achievable by smooth muscle. CONCLUSION: Placental separation is likely associated with maximal myometrial contractile strain. Before birth the presence of the fetal and amniotic fluid volumes usually renders such contractile strains unachievable, thereby helping to guard against premature placental separation.     

Effect of placental tissue on inhibition of uterine contraction by nitric oxide donors.

OBJECTIVE: Our purpose was to test the hypothesis that placental tissue modulates the effect of nitric oxide on spontaneous uterine contractility in pregnant rats. STUDY DESIGN: Rings (approximately 4 mm) of uterus taken from rats on day 14 (midpregnancy, n = 6), day 18 (late pregnancy, n = 4), and day 22 (term, n = 4) of gestation were placed in organ chambers filled with Krebs-bicarbonate buffer bubbled with 5% carbon dioxide in air (37 degrees C, pH approximately 7.4) for isometric tension recording. In some rings a piece of placenta was left attached to the uterine wall. In the other rings the fetuses, placentas, and membranes were removed completely. Change of spontaneous contractions of the rings (percentage change of basal integral activity for 10 minutes) in response to cumulative concentrations of the nitric oxide donors diethylamine-nitric oxide and nitroglycerin (10(-6) mol/L to 10(-4) mol/L) were compared between rings with and without placenta. RESULTS: Diethylamine-nitric oxide and nitroglycerin inhibited spontaneous uterine contractions in rings from midpregnancy, in both the absence and the presence of placenta. In rings from midpregnancy, the maximal inhibition of contractions by diethylamine-nitric oxide but not by nitroglycerin was significantly (P <.05) higher in the presence (26.7% +/- 3.5% of basal activity) than in the absence (39. 6% +/- 3.3%) of placenta. Inhibition of contraction by nitric oxide donors in rings from late and term pregnancy was less than in midpregnancy, and the presence of placental tissue did not influence the responses. CONCLUSIONS: The presence of placental tissue enhances inhibition of uterine contractility by agents that spontaneously release nitric oxide, such as diethylamine-nitric oxide, but not by nitroglycerin, which requires metabolic transformation for nitric oxide to be released. Refractoriness to nitric oxide near or at term does not depend on the presence or absence of placental tissue.     

Cervical Ripening Induces Labour Through Interleukin 1β

Summary: In order to study the Interleukin 1β (IL-1β) levels in mechanical cervical ripening with Foley catheter, IL-1β levels in amniotic fluid of 12 women before and after cervical ripening were compared with those in 23 women in spontaneous active labour. IL-1β was present in 81.8% of patients after cervical ripening and in none prior to it. In women with spontaneous labour 69.6% had immunodetectable IL-1β. Women with spontaneous labour and those sampled after cervical ripening had similar IL-1β levels in the amniotic fluid. Cervical ripening with Foley catheter is associated with high levels of IL-1β and this probably induces labour.     

The Distribution of Water and Electrolytes in the Fetus, Placenta and Mother at the End of Pregnancy and After Labour at Term

Summary: A study of the composition of water and electrolytes in the fetal-placental-maternal system is presented. Fifteen patients of gestational age 38–40 weeks were investigated either before labour (elective Caesarean section (4 patients)) or after labour (11 patients). The parameters studied comprised the osmolality and electrolytes of maternal venous blood and urine, placental and cord arterial and venous blood, fetal urine, and amniotic fluid, together with the water and electrolyte content of uterine muscle, placenta and cord. The main effect of labour was a fall in the tissue electrolyte levels without a corresponding change in body fluids.     

Endocrinology of human parturition: a review

Summary. The existing data on the hormonal factors involved in human parturition indicate that the steroid hormones, progesterone and the oestrogens, play only a facilitatory role in the initiation of labour. A definite role for fetal adrenal steroids in this process has yet to be established, and they too may serve only a facilitating function. The stimulation of the uterine muscle during labour results from an interaction of oxytocin and prostaglandin (PG) F_2α. Recent evidence suggests that oxytocin is most important for the initial phase of labour, whereas increased synthesis of PGF_2α is essential for the progression of labour. The role of PGE₂ remains unclear, but this PG may play an important role in the ripening of the cervix which in turn is essential for successful parturition. The finding of maximal oxytocin receptor concentrations in the myometrium in labour adds strong support to the notion that oxytocin is the trigger for uterine contractions. The factors which control oxytocin receptor formation are therefore important; this may be one of the processes where the steroids play a crucial role. Oxytocin is also one of the stimuli that increase uterine PG synthesis; the coupling of oxytocin receptor occupancy and PG synthetase activity in uterine tissues may be another crucial factor in the mechanism of labour. The formation of gap junctions between the myometrial cells also seems essential for the synchronization and progression of myometrial activity. We propose, therefore, that the co-ordinating of oxytocin receptor formation, PG synthesis and gap junction formation is a key to the initiation and maintenance of human labour. The fetus may fulfil such a co-ordinating role through its influence on placental oestrogen production, through mechanical distention of the uterus, and through its secretion of neurohypophysial hormones and other stimulators of PG synthesis.     

Mechanical Methods for the Induction of Labour After Previous Caesarean Section – An Updated,Evidence-based Review

There are currently no up-to-date evidence-based recommendations on the preferred method to induce labour after previous Caesarean section, especially for patients with unripe cervix, as randomised controlled studies are lacking. Intravenous oxytocin and misoprostol are contraindicated in these women because of the high risk of uterine rupture. In women with ripe cervix (Bishop Score > 6), intravenous administration of oxytocin is an effective procedure with comparable rates of uterine rupture to those with spontaneous onset of labour. Vaginal prostaglandin E ₂ (PGE ₂ ) and mechanical methods (balloon catheters, hygroscopic cervical dilators) are effective methods to induce labour in pregnant women with unripe cervix and previous Caesarean section. According to current guidelines, the administration of PGE ₂ is associated with a higher rate of uterine rupture compared to balloon catheters. Balloon catheters are therefore a suitable alternative to PGE ₂ to induce labour after previous Caesarean section, even though this is an off-label use. In addition to two meta-analyses published in 2016, 12 mostly retrospective cohort/observational studies with low to moderate levels of evidence have been published on mechanical methods of cervical ripening after previous Caesarean section. But because of the significant heterogeneity of the studies, substantial differences in study design, and insufficient numbers of pregnant women included in the studies, it is not possible to make any evidence-based recommendations based on these studies. According to a recent meta-analysis, the average rate using balloon catheters is approximately 53% and the average rate after spontaneous onset of labour is 72%. The uterine rupture rate was 0.2–0.9% for vaginal PGE ₂ and 0.56–0.94% for balloon catheters and is therefore comparable to the uterine rupture rate associated with spontaneous onset of labour. According to the product informations, hygroscopic cervical dilators (Dilapan-S) are currently the only method which is not contraindicated for cervical ripening/induction of labour in women with previous Caesarean section, although data are insufficient. Well-designed, randomised, controlled studies with sufficient case numbers comparing balloon catheters and hygroscopic cervical dilators with mechanical methods and vaginal prostaglandin E ₂ /oral misoprostol are therefore necessary to allow proper decision-making.     

Factors predicting labour onset in patients treated with prostaglandin E2 for cervical ripening

The aim of this study is the evaluation of predictive factors in the onset of labour after pre-induction cervical ripening with prostaglandins. We enrolled 112 consecutive singleton term pregnancies (37–42.3 weeks) with unfavourable cervix and intact membranes, requiring induction of labour because prolonged pregnancy (59%) or maternal/fetal complications (41%). Treatment consisted of the cervical application (once or twice, 12 h apart) of prostaglandin E₂ gel (Upjohn, Italy). Uterine activity was monitored by external cardio-tocography before and during the next 2 h. Two patients showed uterine hyperstimulation and acute fetal distress requiring caesarean section. Sixty percent of patients went to labour and delivered without further stimulations. In this group the rate of caesarean section (9.1%) was lower than in patients failing to onset labour (68.2%). According to the logistic regression three factors positively predicted the onset of labour: first-hour uterine contractility, basal uterine activity and gestational age. The first-hour contractility in particular, represents the myometrial sensitivity to prostaglandin E₂ and may become a practical marker of spontaneous onset of labour in patients undergoing cervical ripening.     

Role of cytokines and other inflammatory mediators

In spite of impressive advances in biochemistry and molecular biology, it has not yet been possible to fit the individual biochemical components of cervical ripening and dilatation to a uniform clinical moiety or to uncover any regulatory mechanisms. The production of interleukin-8 by activated fibroblasts and macrophages plays a key role in cervical ripening, since this cytokine induces chemotaxis, activation, and degranulation of neutrophilic granulocytes with the consequent release of various proteases, including collagenase. In addition, the extravasation of neutrophilic granulocytes is mediated—as in the early stage of an acute inflammatory reaction—by a brief increase in adhesiveness of vascular endothelium. This is known to be modulated by the cytokine-induced increase in the expression of endothelial adhesion molecules. Furthermore, an increase in pro-inflammatory cytokine and proteinase concentrations in preterm delivery seems to occur at earlier stages of cervical dilatation than in term delivery. It is also well known that in patients with chorioamnionitis, the levels of pro-inflammatory cytokines are elevated in amniotic fluid, maternal serum, cervical secretion, placenta, and other compartments of the placento-maternal unit, and are associated with preterm uterine contractions. We have demonstrated for the first time that cytokine concentrations in the lower uterine segment in patients with chorioamnionitis are strongly elevated. We conclude from our data that increased concentrations of pro-inflammatory cytokines may also play a pivotal role in cervical softening and dilatation during chorioamniotic infection. Our data agree with the hypothesis of Liggins who stated nearly 20 years ago that cervical ripening may be an inflammatory reaction, which leads to increased prostaglandin synthesis, preterm labour and finally to preterm delivery.     

Pregnancy in a patient with Raynaud's disease.

We report a patient who, at the time of her third pregnancy at the age of 35, had had Raynaud's disease for 18 years. Her first pregnancy (during which she took Marcumar, an anticoagulant) ended in a miscarriage at three months gestation. The second pregnancy ended in fetal death due to placental insufficiency. The third pregnancy was also complicated by placental insufficiency which became evident during the second trimester. The patient was observed carefully and allowed to continue to 37 weeks gestation when a Caesarean section was done for late fetal heart rate decelerations during early labour of spontaneous onset. The baby had a low birth weight but developed normally. The placenta showed certain abnormalities which are described.     

Factors implicated in the initiation of human parturition in term and preterm labor: a review

Abstract

After accommodating the pregnancy for an average of 40 weeks, the uterus expels the fetus, the placenta and the membranes through the birth canal in a process named parturition. The absolute sequence of events that trigger and sustain human parturition are not yet fully clarified. Evidence suggests that spontaneous preterm and term labor seem to share a common inflammatory pathway. However, there are several other factors being involved in the initiation of human parturition. Placental corticotropin releasing hormone production seems to serve as a placental clock that might be set to ring earlier or later determining the duration of pregnancy and timing of labor. Estrogens do not cause contractions but their properties seem to capacitate uterus to coordinate and enhance contractions. Cytokines, prostaglandins, nitric oxide and steroids seem also to induce ripening by mediating remodeling of the extracellular matrix and collagen. Infection and microbe invasion resulting in chorioamnionitis also represents a common cause of early preterm labour. This review provides an overview of all these factors considered to be implicated in the initiation of human parturition.     

Retained placenta and associated risk factors.

In a retrospective study, the factors that might influence the retention of placenta such as age, parity, antenatal abnormalities, labour onset and duration, history of uterine surgery and previous retained placenta, were studied in 146 patients with retained placenta. Three hundred women who were delivered vaginally without retained placenta were similarly evaluated under the same conditions. The results showed (in descending order of significance), history of retained placenta, previous uterine surgery, preterm delivery, age above 35 years, placental weight less than 601 g, pethidine use in labour, labour induction and parity of more than five to be associated with retained placenta. The existence of some or all these risk factors in a pregnant woman should alert the obstetrician about the possibility of retained placenta in labour.     

Surgical uterine devascularization for placenta accreta: immediate and long-term follow-up

BACKGROUND: To report immediate and long-term outcome in patients with surgical uterine devascularization for placenta accreta. METHODS: Six patients with placenta accreta were treated conservatively during a cesarean section by a bilateral uterine and ovarian surgical devascularization procedure. Menstrual flow, imaging monitoring and further pregnancy were retrospectively reported. RESULTS: Blood transfusion was necessary in five cases and a hysterectomy was performed in one patient with placenta previa accreta. All patients resumed menstruation without oral contraception but one of them reported temporary clinical symptoms of estrogen insufficiency. A chronic placental retention occurred in three patients with incomplete placenta removal. One patient with both bilateral uterine and ovarian arterial ligations had a subsequent pregnancy complicated by a recurrent placenta accreta that was subsequently treated conservatively. CONCLUSIONS: Surgical uterine devascularization for placenta accreta may be useful for uterine conservation. However, reproductive capacity may be altered by placental chronic retention and further pregnancies may be complicated by recurrent placenta accreta.     

Antepartum fetal assessment in hypertensive pregnancies.

Antepartum fetal assessment in hypertensive pregnancies helps to prevent perinatal morbidity and mortality. The pathophysiology of chronic maternal hypertension often leads to placental insufficiency and fetal growth retardation. Current testing schemes include serial ultrasonographic assessment of fetal growth, placental morphology, and amniotic fluid volume; fetal heart rate testing using either non-stress or contraction stress methods; multiple parameter biophysical profile; and Doppler flow velocimetry of fetal umbilical and maternal uterine arteries. The values of individual and combined testing approaches are evaluated and an integrated scheme for fetal management, illustrated by case examples, is presented.     

Group B streptococcus infection, not birth asphyxia

This case illustrates 2 main points. Firstly, fetal infection can mimic exactly both the immediate and delayed signs of perinatal asphyxia. Secondly, the placenta may hold the key to the diagnosis of sepsis which may be made difficult in the neonate by labour ward practices such as the use of intrapartum and immediate newborn antibiotics. We strongly support the recommendation that newborn blood and fetal membrane cultures should always be obtained in babies with a diagnosis of 'intrapartum asphyxia and fetal distress' (1). To this we would add the recommendation that placental histology be performed in these circumstances.     

Dynamics of cervical remodeling during pregnancy and parturition: mechanisms and current concepts

The cervix serves as a protective barrier from invading microorganisms and as a structural barrier to delivery of the fetus. Among all biological processes, the phenomenal connective tissue remodeling that occurs in the cervix during and after parturition is unparalleled in scope and magnitude. The process of connective tissue remodeling in the cervix during pregnancy occurs in four stages: softening, ripening, dilation, and repair. Although overlapping in time, each stage is uniquely regulated. Results from studies using serial measurements of cervical length indicate that cervical ripening precedes myometrial contractions of labor by several weeks, suggesting that parturition in women is a process of long duration and that uterine contractions of labor are late events in the parturition process. A clear understanding of the biologic mechanisms that regulate cervical remodeling during pregnancy is needed to influence the preterm birth rate and to develop strategies to prevent preterm dilation of the cervix.