Morphological and functional changes in placentas from prolonged pregnancies.

Prolonged pregnancy describes a pregnancy that progresses beyond 42 weeks' gestation (294 days). In humans, prolonged pregnancy is associated with increasing perinatal mortality, neonatal compromise and birth by Caesarean section. The underpinning reasons behind these increased risks are unknown; one potential explanation is reduced placental function due to ageing processes. This review describes the structural and functional changes seen in prolonged pregnancy in humans and in animal models. Prolonged pregnancies are associated with reduced placental growth, leading to an increase in fetal to placental weight ratio. Microscopic changes include aggregation of syncytiotrophoblast nuclei, reduced villous vascularity with a concomitant impairment of trophoblast transport processes (reduced pinocytosis); this is associated with increased evidence of oxidative stress, with downstream consequences including cellular senescence, autophagy and apoptosis; importantly many of these changes are similar to fetal growth restriction and pre-eclampsia. Thus, we argue that these observations provide evidence of ageing within the placenta, which may initially be adaptive but can become pathological leading to a reduction in placental function. This provides a biological basis for the increased risk of adverse outcomes observed in prolonged pregnancies. Greater insight into the effects and risks of placental ageing may be useful to guide clinicians on the management of prolonged pregnancies.

Stillbirth in term and late term gestations in Stockholm during a 20-year period, incidence and causes.

INTRODUCTION: The incidence of stillbirth has decreased marginally or remained stable during the past decades in high income countries. A recent report has shown Stockholm to have a lower incidence of stillbirth at term than other parts of Sweden. The risk of antepartum stillbirth increases in late term and postterm pregnancies which is one of the factors contributing to the current discussion regarding the optimal time of induction of labor due to postterm pregnancy. MATERIAL AND METHODS: This is a cohort study based on the Stockholm Stillbirth Database which contains all cases of stillbirth from 1998-2018 in Stockholm County. All cases were reviewed systematically and the cause of death was evaluated according to the Stockholm Stillbirth Classification. Stillbirths diagnosed between gestational week (GW) 37+0 and 40+6 n = 605 were compared to stillbirths diagnosed from GW 41+0 and onwards n = 157, according to the cause of stillbirth and pregnancy and maternal characteristics. The aim was to evaluate the incidence of stillbirth over time and the incidence of stillbirth diagnosed from GW 41+0. RESULTS: In Stockholm County the overall incidence of stillbirth has decreased from 4.6/1000 births during the period 1998-2004 to 3.4/1000 births during the period 2014-2018, p-value <0.001. When comparing the same time periods, the incidence of stillbirth diagnosed from GW 41+0 and onwards has decreased from 0.5/1000 births to 0.15/1000 births, p-value <0.001. Among women still pregnant at GW 41+0 the incidence of stillbirth has decreased from 1.8/ 1000 to 0.5/ 1000. When comparing stillbirths diagnosed at GW 37+0-40+6 with stillbirths diagnosed from GW 41+0 and onwards infection was a more common cause of stillbirth in the latter group. CONCLUSION: In Stockholm County there was a decreasing incidence of stillbirth overall and in stillbirths diagnosed from 41+0 weeks of gestation and onwards during the period 1998-2018. In stillbirths diagnosed from GW 41+0 and onwards infection was a more common cause of death compared to stillbirths diagnosed between GW 37+0 and 40+6.

Prostaglandin-Endoperoxide Synthase 1 Mediates the Timing of Parturition in Mice Despite Unhindered Uterine Contractility.

Cyclooxygenase (COX)-derived prostaglandins stimulate uterine contractions and prepare the cervix for parturition. Prior reports suggest Cox-1 knockout (KO) mice exhibit delayed parturition due to impaired luteolysis, yet the mechanism for late-onset delivery remains unclear. Here, we examined key factors for normal onset of parturition to determine whether any could account for the delayed parturition phenotype. Pregnant Cox-1KO mice did not display altered timing of embryo implantation or postimplantation growth. Although messenger RNAs of contraction-associated proteins (CAPs) were differentially expressed between Cox-1KO and wild-type (WT) myometrium, there were no differences in CAP agonist-induced intracellular calcium release, spontaneous or oxytocin (OT)-induced ex vivo uterine contractility, or in vivo uterine contractile pressure. Delayed parturition in Cox-1KO mice persisted despite exogenous OT treatment. Progesterone (P4) withdrawal, by ovariectomy or administration of the P4-antagonist RU486, diminished the delayed parturition phenotype of Cox-1KO mice. Because antepartum P4 levels do not decline in Cox-1KO females, P4-treated WT mice were examined for the effect of this hormone on in vivo uterine contractility and ex vivo cervical dilation. P4-treated WT mice had delayed parturition but normal uterine contractility. Cervical distensibility was decreased in Cox-1KO mice on the day of expected delivery and reduced in WT mice with long-term P4 treatment. Collectively, these findings show that delayed parturition in Cox-1KO mice is the result of impaired luteolysis and cervical dilation, despite the presence of strong uterine contractions.

[Factors predicting unsuccessful labor induction with dinoprostone in post-term pregnancy with unfavorable cervix]. / Facteurs prédictifs d'échec d'entrée en travail par dinoprostone en cas de grossesse prolongée et de conditions locales défavorables.

OBJECTIVE: To identify predictive factors for unsuccessful induction of labor within 24hours after dinoprostone insertion in post-term pregnancy with unfavorable cervix. MATERIAL AND METHODS: We retrospectively reviewed 325 singleton pregnancies with a diagnosis of post-term pregnancy and unfavorable cervix (Bishop score<6) during the period January 2012-Decembre 2012. Patients were classified into 2 groups: successful labor, defined as cervical ripening, within 24hours after dinoprostone insertion (Group R; n=248; 76.3 %) or failure group (Group E; n=77; 23.7 %). Antepartum and perpartum characteristics of women were compared. RESULTS: Nulliparity (74.0 versus 56.0 %; OR=2.23; 95 % CI: 1.27-4.00; P=0.005), gestational age ≤41 SA+4 (53.2 versus 33.9 %; OR=2.22; 95 % CI: 1.32-3.74; P=0.003) and history of dilatation and curettage (27.3 versus 10.5 %; OR=3.19; 95 % CI: 1.66-6.11; P=0.0005) were significantly associated with unsuccessful induction of labor. Bishop score was significantly higher in Group R (3.6 versus 1.9; P=0.001). Also, consistency (74.0 versus 44.4 %; OR=3.57; 95 % CI: 2.04-6.40; P<10(-5)) and absence of dilatation of the cervix (59.7 versus 23.0 %; OR=4.97; 95 % CI: 2.89-8.56; P<10(-6)) were identified as significant predictive factors for unsuccessful induction of labor. CONCLUSION: Nulliparity, gestational age ≤41 SA+4, history of dilatation and curettage and Bishop score, in particular consistency and dilatation, are correlated with failure of cervical ripening in post-term pregnancy with unfavorable cervix.

Poor spontaneous and oxytocin-stimulated contractility in human myometrium from postdates pregnancies.

Prolongation of pregnancy i.e. going more than 10 days over the estimated due date, complicates up to 10% of all pregnancies and is associated with increased risk to both mother and fetus. Despite the obvious need for contractions of the uterus to end pregnancy, there have been no studies directly examining the role of uterine smooth muscle, myometrium, in the aetiology of prolonged pregnancy. This study tested the hypothesis that the intrinsic contractile characteristics of myometrium taken from women with prolonged pregnancy (>41 weeks and 3 days) was reduced compared to those delivering at term (39-41 weeks). We recruited women undergoing Caesarean Section (CS) delivery either pre-labour (n = 27) or in labour (n = 66) at term or postdates. The contractile ability of the postdates myometrium, whether spontaneous or elicited by oxytocin or high-K solution, was significantly reduced compared to term myometrium. These differences remained when adjusted for parity and other maternal characteristics. The findings remained significant when expressed per cross sectional area. Histological examination revealed no differences between the two groups. The contractile differences were however related to intracellular Ca transients suggesting an effect of [Ca] on reduced force production in the postdates group. In summary, myometrium from prolonged pregnancies contracts poorly in vitro even when stimulated with oxytocin and in active labour. Responses to high K(+) and measurements of Ca suggest that alterations in excitation contraction coupling, rather than any histological changes of the myometrium, may underlie the differences between term and postdates myometrium. We show that postdates pregnancy is associated with poor myometrial activity and suggest that this may contribute to increased myometrial quiescence and hence, prolonged gestation.

[Correlations between placental morphological and functional parameters and neonatal status after normal full-term, prolonged pregnancy, and truly protracted pregnancy].

To solve the problem of differentiating protracted pregnancy, a special morphometric study was undertaken to examine three placental groups: 1) after normal full-term pregnancy (n = 35); 2) after prolonged pregnancy (n = 40); 3) after truly protracted pregnancy with partial or complete Clifford's syndrome (n = 30). A semiquantitative score (14 most important placental indicators), placenta and birth weights, Apgar scores, the infant's weight and height at the end of the first year of life were used so as to estimate the mild, moderate, and severe degree at 0.5, 1.5, and 3 points, respectively. One hundred and twenty-six possible pairs of structural and functional parameters were made up in all the groups. Pearson's correlation coefficient (r > 0.4) was applied to graphically display the pairs. Normal full-term pregnancy was characterized by few positive correlations mainly between the terminal villi and weight-height indices without associations with the Apgar scale. Prolonged pregnancy with the multiple placental tissue structural parameters along with organometric indices being involved was intermediate. The total scores permitted grades 1 and 2 chronic placental insufficiency (CPI) to be diagnosed in 27.5 and 2.5%, respectively. The severest form was truly protracted pregnancy that was distinguished by the maximum positive and negative correlations between all the parameters and the highest rate of diagnosis of CPI of grades 1 (45%) and 2 (15%). The findings strongly suggest that it is essential to identify prolonged and truly protracted pregnancy as important risk factors, by following up the infants for a year.

Body mass index, Bishop score, and sonographic measurement of the cervical length as predictors of successful labor induction in twin gestations.

AIMS: To evaluate the predictive value of body mass index (BMI), Bishop score, and sonographic measurement of cervical length for predicting successful labor induction (defined as an ability to achieve the active phase of labor corresponding to a cervical dilatation of > or =4 cm within 12 h of initiating oxytocin) in near-term twin gestations. METHODS: This prospective, observational study enrolled 72 consecutive women with twin gestations at >36.0 weeks' gestation who were scheduled for induction of labor. Transvaginal ultrasound for measurement of the cervical length was performed and the Bishop score was determined by digital examination. The BMI was calculated based on the weight and height at the time of induction. RESULTS: Labor induction was successful in 63% (45/72) of women. The mean BMI was significantly lower in women who had successfully induced labor, but no significant differences existed with respect to the mean cervical length, median Bishop score, proportion of parous and nulliparous women, and the mean total birth weight of the twin pairs between the two patient groups. Multiple logistic regression demonstrated that only BMI provided a significant contribution in predicting successful labor induction. CONCLUSIONS: BMI independently predicted the success of labor induction in twin gestations but the sonographic measurement of the cervical length and Bishop score had poor predictive values for successful induction.

Cervical length and maternal factors in expectantly managed prolonged pregnancy: prediction of onset of labor and mode of delivery.

OBJECTIVE: To examine the value of combining cervical length and maternal characteristics in a prolonged-pregnancy clinic in the prediction of the probability of firstly, spontaneous onset of labor within the subsequent 10 days and secondly, the need for Cesarean section. METHODS: This was a prospective study of women with singleton pregnancies attending an ultrasound-based prolonged-pregnancy clinic at 40 + 4 to 41 + 6 weeks of gestation. The policy was to delay induction of labor by 7-10 days unless there was evidence of a specific medical or obstetric indication or the mother wanted earlier delivery. The measurement of cervical length was not given to the obstetrician, midwife or patient. Regression analysis was used to determine which of the following factors had a significant contribution in predicting induction of labor: maternal age, body mass index (BMI), ethnic origin, parity and cervical length. Regression analysis was also used to determine which of the factors amongst the maternal characteristics, onset of labor and cervical length provided significant prediction of Cesarean section. RESULTS: We examined 2316 pregnancies but we excluded from further analysis 452 (19.5%) cases because iatrogenic delivery was carried out within the subsequent 6 days, including 427 cases of induction of labor (340 at the request of the mother and 87 for medical indications) and 25 cases of Cesarean section. In the remaining 1864 cases there was spontaneous onset of labor and delivery within 10 days in 1536 (82.4%) and induction of labor in 7-10 days in 328 (17.6%). The rate of Cesarean section was 15.2% (233 of 1536) in those with spontaneous onset of labor and 36.0% (118 of 328) in those whose labor was induced. Regression analysis demonstrated that in the prediction of induction of labor there were significant contributions from cervical length, BMI, parity and gestational age, and in the prediction of Cesarean section there were significant contributions from onset of labor, cervical length, BMI, parity and ethnicity. CONCLUSION: Ultrasonographic measurement of cervical length at 41 weeks together with maternal factors can define the patient-specific probability of spontaneous onset of labor in the subsequent week and the risk of Cesarean section.

Comportamiento del embarazo prolongado en el año 2003 / The behaviour of the postterm pregnacy in 2003

Se realizó un estudio observacional descriptivo para conocer algunas variables clínicas epidemiológicas relacionadas con el embarazo prolongado en el Hospital General Docente de Morón en el año 2003. El universo del trabajo fueron 171 gestantes a las que se les diagnosticó embarazo prolongado en este período. Del total de 2171 nacimientos que ocurrieron en nuestro hospital el 8 por ciento fueron posteriores a las 42 semanas. De los 171 embarazos prolongados 122 iniciaron espontáneamente el trabajo de parto, se indicaron 45 inducciones y 4 cesáreas electivas, 121 partos fueron eutócicos y se realizaron 40 cesáreas. Solo 11 nacidos presentaron morbilidad postnatal y 3 depresión al nacimiento.

An observational, descriptive study has been done in order to know some epidemiological and clinical variable related to the postterm preganacy in the General Hospital of Morón in 2003. There were analize 171 pregnants that had a postterm pregnacy during this period. From 2171 births that took place in our hospital, 8 percent were after 42 weeks. From 171 postterm pregnacies 122 began espontaneously the birth labour, there were indicated 45 inductions and 4 elective caesarean delivery, 121 births were normal and there were 40 caesarean delivery. Only 11 babies presented postnatal morbidity and 3 postnatal depression.

Alterations of N-glycan branching and expression of sialic acid on amniotic fluid alpha-1-acid glycoprotein derived from second and third trimesters of normal and prolonged pregnancies.

BACKGROUND: Alterations in the AGP glycoform pattern are not only disease related, but also can occur during physiological processes such as pregnancy. In this paper, possible changes in human amniotic fluid AGP glycan branching and in the type of sialic acid glycosidic attachment to glycans were analyzed with regard to different stages of human pregnancy. METHODS: Crossed-affinity immunoelectrophoresis with concanavalin A was used to study AGP branching and lectin-ELISA with two agglutinins from Maackia amurensis and Sambucus nigra was applied to differentiate alpha2,3 and alpha2,6 type sialic acid attachments. RESULTS: Despite almost unchanged levels of total amniotic fluid AGP during pregnancy, alterations in N-glycan branching and in the expression of sialic acid linkage on AGP were found to be associated with different stages of normal pregnancy. Amniotic fluid AGP glycans derived from third trimester compared with those from the second trimester had a higher percentage of tri- and tetra-antennary sialylated N-glycans. In the second trimester, sialic acid alpha2,6 linkage occurred twice as frequently as alpha2,3 linkage, while during the third trimester alpha2,3 linkage increased and both types of linkage appeared in equal proportion. CONCLUSIONS: Branched and alpha2,3-sialylated AGP glycoforms in amniotic fluid could contribute to natural innate fetomaternal defense.

Appearance of the levator ani muscle in pregnancy as assessed by 3-D MRI.

OBJECTIVE: The purpose of this study was to describe levator ani (LA) anatomy in postterm nulliparas using 3-dimensional (3-D) magnetic resonance (MR). STUDY DESIGN: Nulliparas (n = 84) with uncomplicated, postterm pregnancies underwent an MR (4 mm slices, 0 gap) of the uterus and pelvis. LA volume and morphometry were assessed using 3-D post-processing software. RESULTS: LA insertion into the symphysis was visible in 93%, and the iliococcygeus muscle assumed a convex shape (arch) in the 92% of the 84 women. The LA shape was characterized as "U" in 53% and "V" in 47%. Mean LA volume was 13.5 (3.7) cm3. There was a positive association between LA volume and higher fetal station (P = .02) and increasing BMI (P < .001). However, no relationship between LA volume and station was found after adjusting for BMI. CONCLUSION: BMI was correlated with LA volume in postterm nulliparas. LA insertion into the symphysis and the iliococcygeus arch were well-preserved overall and morphometry was variable.