Idiopathic Preterm Labor Research Articles

Women’s awareness of cardiovascular disease risk after complications of pregnancy

BackgroundCertain maternal complications of pregnancy, including hypertensive disorders of pregnancy, gestational diabetes mellitus, birth of a growth restricted infant, idiopathic preterm labour, and placental abruption, are associated with a significantly increased risk of future maternal cardiovascular disease. In Australia, it is relatively unknown how many women with a history of complicated pregnancies are aware of their future cardiovascular disease risk. AimThe aim of this study was to determine what percentage of women attending a cardiovascular disease prevention clinic in South Australia soon after a complicated pregnancy were aware of their increased risk of cardiovascular disease. MethodsThis prospective observational study included 188 women attending a postpartum prevention clinic between 7th August 2018 and 10th February 2021. These women had experienced a serious maternal complication of pregnancy approximately seven months earlier. Women completed a self-administered health awareness survey immediately prior to their first clinic appointment to assess their awareness of their increased cardiovascular risk. FindingsOver two-thirds (69.1 %) of the women were unaware of the association between pregnancy complications and cardiovascular disease, and 6.4 % of the cohort did not realise they had experienced a complicated pregnancy. Almost 10 % of the cohort did not correctly identify the complication/s they had been diagnosed with during pregnancy. ConclusionAwareness of the association between complications of pregnancy and future cardiovascular disease was low in our cohort of women who had experienced a complication of pregnancy only seven months earlier. This emphasises the need for improved education for and communication with women to assist in implementing preventative care strategies.

Changes in cAMP effector predominance are associated with increased oxytocin receptor expression in twin but not infection-associated or idiopathic preterm labour

We previously reported that at term pregnancy, a decline in myometrial protein kinase A (PKA) activity leads to an exchange protein activated by cyclic AMP (Epac1)-dependent increase in oxytocin receptor (OTR) expression, promoting the onset of labour. Here, we studied the changes in the cyclic adenosine monophosphate (cAMP) effector system present in different phenotypes of preterm labour (PTL). Myometrial biopsies obtained from women with phenotypically distinct forms of PTL and the levels of PKA and OTR were examined.Although we found similar changes in the cAMP effector pathway in all forms of PTL, only in the case of twin PTL (T-PTL) was myometrial OTR levels increased in association with these results. Although there were several changes in the mRNA levels of components of the cAMP synthetic pathway, the total myometrial cAMP levels did not change with the onset of any subtype of PTL. With regards to the expression of cAMP-responsive genes, we found that the mRNA levels of 4 of the 5 cAMP-down-regulated genes were increased in T-PTL, similar to our findings in term labour.These data signify that although changes in the cAMP effector system were common to all forms of PTL, only in T-PTL were OTR levels increased. Similarly, the mRNA levels of cAMP-repressed genes were only increased in T-PTL supporting the concept that the decline in PKA levels influences myometrial function driving the onset of T-PTL.

Efficacy of an internet-based cognitive behavioral stress management training in women with idiopathic preterm labor: A randomized controlled intervention study

ObjectiveThis randomized controlled trial aimed at evaluating the efficacy of an internet-based cognitive behavioral stress management program (IB-CBSM) for pregnant women with preterm labor (PTL) on birth outcome and stress-related psychological and biological parameters. Methods93 pregnant women with PTL (gestational age 18–32) were assigned to either the IB-CBSM (n=50) or a control group (CG) based on distraction (n=43). Participants in both groups worked through six weekly modules. Birth outcome measures included gestational age, neonatal weight and length at birth and the rate of preterm birth (PTB). Questionnaires assessed psychological wellbeing and the activity of the HPA-axis was measured with the cortisol awakening reaction (CAR), both before (T1) and after the intervention (T2). ResultsBirth outcome and psychological wellbeing did not differ between IB-CBSM and CG. However, psychological wellbeing was higher after both interventions (PSS: ηp2=0.455, STAIX1: ηp2=0.455, STAIX2: ηp2=0.936, PRAT: ηp2=0.465, EPDS: ηp2=0.856). Cortisol levels were stable and did not alter differently between groups from T1 to T2. Higher cortisol levels were associated with lower gestational age at birth, whereas no significant correlations were found between weight and length at birth. ConclusionsAlthough there were no significant differences between the two groups and birth outcome, psychological and biological parameters, both interventions (CBSM and CG) showed equivalent effects and proved to be beneficial with regard to psychosocial distress and well-being. Further research is needed to investigate CBSM and distraction interventions for pregnant women at risk for PTB together with a non-intervention control condition.

Uterine natural killer cells dysregulation in idiopathic human preterm birth: a pilot study

Objective: To compare between uterine natural killer (uNK) cells in the placental samples of preterm birth and term labor.Study design: Two-arm case–control study. This study included 60 participants divided into two groups. The first group included 30 cases of idiopathic spontaneous preterm labor and the other group included 30 women who delivered by a spontaneous term vaginal delivery and with no history of previous preterm labor.Result(s): There were no CD16− CD56bright uNK cells in either groups; CD16+ CD56dim uNK cells were present in only 1 case out of 30 term delivery placentae (3.3%), whereas they were found in 21 cases out of 30 (70%) preterm placental samples with a significant statistical difference (p < 0.0001) and OR 67.667, 95% CI (7.95–575.69). CD16+CD56dim uNK cells were found to be invading both the villi and the decidua in 11 cases (70%), whereas those cells were found invading only the villi in 10 cases (33.3%).Conclusion: CD16+CD56dim cells are expressed in both the decidua and the villi of patients with idiopathic preterm labor suggesting an association between uNK cells dysregulation and idiopathic human preterm labor.

The idiopathic preterm delivery methylation profile in umbilical cord blood DNA

BackgroundPreterm delivery is the leading cause of neonatal morbidity and mortality. Two-thirds of preterm deliveries are idiopathic. The initiating molecular mechanisms behind spontaneous preterm delivery are unclear. Umbilical cord blood DNA samples are an easy source of material to study the neonatal state at birth. DNA methylation changes can be exploited as markers to identify spontaneous preterm delivery. To identify methylation differences specific to idiopathic preterm delivery, we assessed genome-wide DNA methylation changes in 24 umbilical cord blood samples (UCB) using the 450 K Illumina methylation array. After quality control, conclusions were based on 11 term and 11 idiopathic preterm born neonates. The differentially methylated positions (DMPs) specific for preterm/term delivery, neonatal sex, use of oxytocin and mode of initiation of labor were calculated by controlling the FDR p value at 0.05.ResultsThe analysis identifies 1855 statistically significant DMPs between preterm and term deliveries of which 508 DMPs are also attributable to clinical variables other than preterm versus term delivery.1347 DMPs are unique to term vs preterm delivery, of which 196 DMPs do not relate to gestational age as such. Pathway analysis indicated enrichment of genes involved in calcium signalling, myometrial contraction and relaxation pathways. The 1151 DMPs that correlate with advancing gestational age (p < 0.05) include 161 DMPs that match with two previously reported studies on UCB methylation.Additionally, 123 neonatal sex specific DMPs, 97 DMPs specific to the induction of labour and 42 DMPs specific to the mode of initiation of labor were also identified.ConclusionThis study identifies 196 DMPs in UCB DNA of neonates which do not relate to gestational age or any other clinical variable recorded and are specific to idiopathic preterm delivery. Furthermore, 161 DMPs from our study overlap with previously reported studies of which a subset is also reported to be differentially methylated at 18 years of age. A DMP on MYL4, encoding myosin light chain 4, is a robust candidate for the identification of idiopathic preterm labour as it is identified by all 3 independent studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1915-4) contains supplementary material, which is available to authorized users.

Epigenetics of human myometrium: DNA methylation of genes encoding contraction-associated proteins in term and preterm labor.

Preterm birth involves the interaction of societal and environmental factors potentially modulating the length of gestation via the epigenome. An established form of epigenetic regulation is DNA methylation where promoter hypermethylation is associated with gene repression. We hypothesized we would find differences in DNA methylation in the myometrium of women with preterm labor of different phenotypes versus normal term labor. Myometrial tissue was obtained at cesarean section at term with or without labor, preterm without labor, idiopathic preterm labor, and twin gestations with labor. Genomic DNA was isolated, and samples in each group were combined and analyzed on a NimbleGen 2.1M human DNA methylation array. Differences in methylation from -8 to +3 kb of transcription start sites of 22 contraction-associated genes were determined. Cytosine methylation was not present in CpG islands of any gene but was present outside of CpG islands in shores and shelves in 19 genes. No differential methylation was found across the tissue groups for six genes (PTGES3L, PTGER2, PTGER4, PTGFRN, ESR2, and GJA1). For 13 genes, differential methylation occurred in several patterns between tissue groups. We find a correlation between hypomethylation and increased mRNA expression of PTGES/mPGES-1, indicating potential functional relevance of methylation, but no such correlation for PTGS2/COX-2, suggesting other regulatory mechanisms for PTGS2 at labor. The majority of differential DNA methylation of myometrial contraction-associated genes with different labor phenotypes occurs outside of CpG islands in gene promoters, suggesting that the entirety of DNA methylation across the genome should be considered.

5&amp;lt;i&amp;gt;β&amp;lt;/i&amp;gt;-Dihydroprogesterone and Human Preterm Labor

We previously investigated the progesterone metabolite 5β-dihydroprogesterone (5βDHP) in relation to human parturition at term, demonstrating that peripheral venous concentrations decrease in association with the onset of spontaneous labour. In this study our aim was to determine if 5βDHP concentrations were lower in women presenting in spontaneous preterm labour than in controls matched for gestational age. Blood samples were obtained from women presenting in spontaneous preterm labour (n = 20). The diagnosis was made on the presence of regular contractions and cervical effacement and dilatation of at least 3 cms. All women in the preterm labour group delivered before 37 weeks gestation. Blood samples were then obtained from controls, closely matched for gestational age with uncomplicated pregnancies. The preterm labour group was further stratified by cause into three groups, chorioamnionitis (n = 5), abruption (n = 4) and idiopathic (n = 11). Following organic solvent extraction, steroids were separated by HPLC and 5βDHP quantified by radioimmunoassay. Women in the idiopathic preterm labour group were found to have significantly lower circulating concentrations of 5βDHP than controls (p

What Prevents Eligible Patients from Receiving Progesterone Therapy to Prevent Recurrent Preterm Birth

Objective: The use of intramuscular 17-alpha-hydroxyprogesterone caproate (17-OHPC) has been shown to be beneficial for the prevention of preterm birth (PTB) in women with a prior history. Not all patients with a prior preterm birth receive 17-OHPC. The purpose of this study was to investigate potential barriers to receiving this therapy. Methods: A retrospective chart review of those patients at our institution who received the diagnosis of “previous preterm delivery” in 2010 and 2011 was performed to see whether they were offered and received 17-OHPC. Patients were considered eligible if they had a prior delivery at less than 36 weeks of gestation secondary to idiopathic preterm labor. For those patients that were deemed eligible but did not receive therapy, an explanation was sought. Results: Sixty-six charts were reviewed in detail. Forty-three patients were considered eligible to receive 17-OHPC. The remaining had medical indications for delivery including premature rupture of membranes (PROM) (15), intrauterine growth restriction (IUGR) (1), and hypertension (2). Of the 43 patients deemed eligible, 17 did not receive 17-OHPC. Of these, eight patients were not offered therapy, 2 patients declined therapy, 3 patients presented with therapy after 28 weeks (too late), and 4 received a prophylactic cerclage as their only therapy. There were no significant differences between the two groups. Conclusion: In an effort to increase 17-OHPC use among eligible patients, we must continually identify physician biases and patient barriers that prevent utilization of this intervention. In addition, patients who deliver preterm should be told the importance of presenting early in subsequent pregnancies in order to receive the full benefits of this therapy.

Genetic polymorphisms in Cytochrome P 4501B1 and susceptibility to idiopathic preterm labor in North Indian population

ObjectiveThe etiology of preterm labor (PTL) is still unknown, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We investigated the relation between PTL and polymorphisms in Cytochrome P4501B1 (CYP1B1) gene, which is involved in the metabolism of a wide range of environmental toxins and hormones. Design and methodsThree hundred (n=300) cases of PTL and equal number of subjects of full term labor (FTL), after excluding all the known risk factors for PTL were included in the study. A two step allele specific PCR was performed for polymorphic analysis of CYP1B1 gene. ResultsThe homozygous variant genotype of CYP1B1*2 (OR=2.97, 95%CI=1.08–8.08, p=0.033) and heterozygous variant of CYP1B1*3 (OR=2.57, 95%CI=1.88–3.63, p=0.001), and CYP1B1*7 (OR=2.59, 95%CI=1.85–3.62, p=0.001) were found to be significantly higher in PTL cases as compared to FTL. ConclusionsThe present study demonstrates the possible association of homozygous variant of CYP1B1*2 and heterozygous variant of CYP1B1*3 and CYP1B1*7 genes with the increased risk of PTL.

Cognitive Impairment at Age 5 Years in Very Preterm Infants Born Following Premature Rupture of Membranes

To evaluate the relationship between preterm premature rupture of membranes (PPROM) and cognitive impairment in 5-year-old children born very preterm. The Etude Epidémiologique sur les Petits Ages Gestationnels Study is a population-based cohort of children followed up from birth to age 5 years recruited in 9 French regions in 1997. We analyzed data from singletons born between 24 and 32 weeks gestation categorized into 4 groups according to etiology of prematurity: infants born after PPROM, after idiopathic preterm labor, in a vascular context (Vasc), and to women with other complications (Other). Cognitive development at age 5 years was assessed using the Mental Processing Composite score of the Kaufman-Assessment Battery for Children. Among the 1051 children followed up to age 5 years, the mean Mental Processing Composite score was 93.6 ± 19.7, and 13.3% of the children (140 of 1051) had cognitive impairment. After adjustment for potential confounders, the risk of cognitive impairment among infants in the PPROM group was not significantly different than that in the idiopathic preterm labor group (OR, 1.09; 95% CI, 0.62-1.92) and the Other group (OR, 1.36; 95% CI, 0.75-2.47), but was lower than that in the Vasc group (OR, 1.86; 95% CI, 1.16-2.97). In the PPROM group, the risk of cognitive impairment was greater when the latency period (ie, time from rupture to delivery) was <3 days (OR, 2.32; 95% CI, 1.07-5.02). Preterm infants born after PPROM are not at increased risk for cognitive impairment in childhood, but the time between PPROM and birth may influence that risk.

Identification of Chemokines Associated with the Recruitment of Decidual Leukocytes in Human Labour: Potential Novel Targets for Preterm Labour

Current therapies for preterm labour (PTL) focus on arresting myometrial contractions but are largely ineffective, thus alternative therapeutic targets need to be identified. Leukocytes infiltrate the uterus around the time of labour, and are in particularly abundant in decidua (maternal-fetal interface). Moreover, decidual inflammation precedes labour in rat pregnancies and thus may contribute to initiation of labour. We hypothesized that chemokines mediate decidual leukocyte trafficking during preterm labour (PTL) and term labour (TL), thus representing potential targets for preventing PTL. Women were recruited into 4 groups: TL, term not in labour (TNL), idiopathic PTL and PTL with infection (PTLI). Choriodecidual RNA was subjected to a pathway-specific PCR array for chemokines. Differential expression of 12 candidate chemokines was validated by real time RT-PCR and Bioplex assay, with immunohistochemistry to confirm cellular origin. 25 chemokines were upregulated in choriodecidua from TL compared to TNL. A similar pattern was detected in PTL, however a distinct profile was observed in PTLI consistent with differences in leukocyte infiltration. Upregulation of CCL2, CCL4, CCL5, CXCL8 and CXCL10 mRNA and protein was confirmed in TL, with CCL8 upregulated in PTL. Significant correlations were detected between these chemokines and decidual leukocyte abundance previously assessed by immunohistochemical and image analysis. Chemokines were primarily expressed by decidual stromal cells. In addition, CXCL8 and CCL5 were significantly elevated in maternal plasma during labour, suggesting chemokines contribute to peripheral inflammatory events during labour. Differences in chemokine expression patterns between TL and idiopathic PTL may be attributable to suppression of chemokine expression by betamethasone administered to women in PTL; this was supported by in vitro evidence of chemokine downregulation by clinically relevant concentrations of the steroid. The current study provides compelling evidence that chemokines regulate decidual leukocyte recruitment during labour. The 6 chemokines identified represent potential novel therapeutic targets to block PTL.

The Clinical and Molecular Relations Between Idiopathic Preterm Labor and Maternal Congenital Heart Defects

Preterm labor (PTL) is an important cause of preterm delivery. The trigger initiating the process toward overt labor and parturition is poorly understood and the molecular basis remains an enigma. It recently emerged that the overall occurrence of PTL in pregnant women with congenital heart disease (CHD) is increased. In this review, we present data on pregnancy in women with CHD and the opportunities this provides for research on the initiating mechanisms of inappropriately premature contractions. This may provide means for early detection of women at high risk of PTL in the general population, with models using cervical length, novel biomarkers, and maternal factors. We discuss human embryonic development of the heart and the uterus and the molecular pathways shared by the cardio- and uteromyocytes. We propose 2 hypotheses for the co-occurrence of maternal CHD and PTL; one based on a shared genetic origin and the other on a shared epigenetic origin.

Expression of inflammatory cytokines in placentas from pregnancies complicated with preeclampsia and HELLP syndrome

Objective: To investigate the expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in villous trophoblast, syncytial knots and decidua placentas from pregnancies complicated with preeclampsia (PE), Hemolysis, Elevated Liver enzymes and Low Platelet count (HELLP) syndrome and gestational age-matched controls.Methods: Study group included 35 placentas from pregnancies complicated with PE and 35 placentas from pregnancies with HELLP syndrome. Control group included 35 placentas from idiopathic preterm labor. Placentas were matched according to the gestational age. Expression of TNF-α, IL-6 and IL-10 was determined by immunohistochemistry and semi-quantitative HSCORE method in villous trophoblast, syncytial knots and decidua. Non-parametric statistics were used for analyses.Results: There was no difference in the expression of TNF-α, IL-6 and IL-10 in all the studied placental segments between PE, HELLP and gestational age-matched control group. TNF-α (F = 32, 41, p < 0.001), IL-6 (F = 58, 53, p < 0.001) and IL-10 (F = 17, 62, p < 0.001) expression was significantly different in different placental cell types, the highest expression of cytokines was in decidua.Conclusion: There was no difference in cytokine expression in villous trophoblast, syncytial knots and decidua among the studied placental groups. The expression of cytokines was highest in decidua in all the studied placental groups.

Preserved Ex Vivo Inflammatory Status in Decidual Cells from Women with Preterm Labor and Subclinical Intrauterine Infection

ObjectiveTo compare the inflammatory response preserved ex vivo by decidual cells isolated from women who experienced preterm labor with and without subclinical intrauterine infection.MethodsFetal membranes were obtained after cesarean section from 35 women who delivered before 37 weeks of gestation following spontaneous preterm labor, with no clinical evidence of intrauterine infection. Decidua was microbiologically tested and cultured. Concentrations of anti-inflammatory cytokines (IL-2, IL-4, IL-10), pro-inflammatory cytokines (IL-6, IL-8, IL-1β and TNF-α), and matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9) were measured in the supernatants using Bio-Plex, and prostaglandin E2 (PGE2) was measured by enzyme immunoassay.ResultsSubclinical infection was confirmed in 10 women (28.5%). Microorganisms isolated were Ureaplasma urealyticum (4), group B streptococci (3), Gardnerella vaginalis (1), and Escherichia coli (2). We found a significant increase of pro-inflammatory cytokines and a significant decrease of anti-inflammatory cytokines in supernatants from decidual cells obtained from women with preterm labor and subclinical intrauterine infection compared to women without infection. Secretion of MMP-1, MMP-8, MMP-9 and PGE2 was significantly higher in infected women. Secretion of IL-8 by decidual cells from infected women persisted upon repeated in vitro culture passages.ConclusionsAlmost 30% of idiopathic preterm labor cases were associated with subclinical intrauterine infection, and decidual cells isolated from these cases preserved an ex vivo inflammatory status after in vivo bacterial exposure.

Macrophages Infiltrate the Human and Rat Decidua During Term and Preterm Labor: Evidence That Decidual Inflammation Precedes Labor1

Preterm delivery is the leading cause of perinatal mortality and morbidity. Current tocolytics target myometrial contractions, a late step in the labor cascade. Identifying earlier events in parturition may lead to more effective therapeutic strategies. We hypothesized that inflammatory events in decidua (the maternal-fetal interface), characterized by leucocyte infiltration, are an early event during term and preterm labor (PTL). Leucocyte abundance in decidua of human pregnancies was quantified following term labor and PTL (idiopathic and infection associated), in conjunction with investigation of temporal inflammatory events in rat uterus during the perilabor period and in PTL induced by mifepristone. In human decidua, macrophage numbers were 4-fold higher in term labor (P < 0.01) and 2.5-fold higher in non-infection-associated PTL (P < 0.05) than in term nonlaboring samples. Neutrophil abundance was unchanged with labor but elevated in PTL with infection (5- to 53-fold increase; P < 0.01). T and NK cells were more abundant in idiopathic PTL than TL (P < 0.05). In rat, decidual macrophage infiltration increased 4.5-fold 12 h prior to labor and remained elevated during labor and early postpartum (P < 0.01). Decidual infiltration preceded that of the myometrium and was 4-fold higher (P < 0.01). In rat PTL, decidual macrophage numbers were also elevated (P < 0.01) and exceeded those of the myometrium (P < 0.05). These studies show for the first time that leucocytes infiltrate decidua during labor at term and preterm, supporting a role for leucocyte-derived inflammatory mediators in decidual activation. In the rat, this occurred prior to labor, suggesting it is an early event during parturition and thus a potential target for intervention.

Maintenance Therapy by Vaginal Progesterone after Threatened Idiopathic Preterm Labor: A Randomized Placebo-Controlled Double-blind Trial

Background Patients with arrested preterm labor (PTL) are at increased risk for recurrence of preterm birth (PTB). Maintenance tocolysis after arrest of acute PTL is of questionable value. The objective of this study was to evaluate the efficacy of 200 mg vaginal progesterone in order to prevent PTB in women with episodes of threatened PTL. Materials and methods This is a randomized double blind clinical trial study.Women with singleton pregnancies between 28-36 weeks of gestation, who were hospitalized for PTL were included. A total of 173 pregnant patients were randomly allocated to receive 200 mg vaginal progesterone suppositories (n=86) or placebo (n=87) daily until the 36th gestational week. The two groups were compared relative to demographic characteristics, incidence of PTB before 34 and 37 weeks, and maternal and neonatal complications. Data were analyzed by chi-square and Fisher’s exact tests. Results Mean latency until delivery in the cases was longer than the control group (23.88 ± 18.01 vs. 16.67 ± 12.9; p=0.004).Treatment with progesterone was not associated with a reduction in the rate of PTB before 34 weeks [cases: 9 (10.8%) vs. controls: 8 (10%)] and 37 weeks [cases: 45 (54.2%) vs. controls: 33 (41.2%)]. Log rank analysis revealed a significant difference for mean time to delivery between the two groups (p=0.028). There were no significant differences for neonatal and maternal complications in the two groups. Conclusion Prophylactic administration of 200 mg vaginal progesterone suppositories after successful tocolysis in patients with threatened idiopathic PTL is associated with a longer latency to delivery, but failed to reduce the rate of PTB (Registeration Number: IRCT138706051096N1).

Exploring pregnancy following a pre-term birth or pregnancy loss

This is the first of two papers. The first paper outlines the literature review that informed the pilot study; the second describes the qualitative pilot study: stress, immunity and preterm birth pilot study (SIPP). The review examined qualitative research to understand the area of investigation and determine whether this corresponded with the findings of the pilot study. The SIPP study used semi-structured interviews exploring women's answers to a life events questionnaire as part of a larger quantitative prospective observational study, the stress, immunity and preterm birth (SIP) study. The SIP study examined the association between maternal stress, maternal immune response and pregnancy outcome in women with a history of recurrent idiopathic preterm labour. The review evolved into three broad themes: the impact of perinatal loss on a subsequent pregnancy; the preterm labour experience; and disenfranchised grief.

Expression and regulation of prostaglandin receptors in the human placenta and fetal membranes at term and preterm

Prostaglandins (PGs) play an important role in parturition in many species, including humans. The present study examined the distribution of PG receptor subtypes (EP1-4 and FP) in intrauterine tissues at term and preterm birth. Placentas and fetal membranes were collected from patients at term in labour (n = 12) or not in labour (n = 12). Preterm tissue was collected from three different groups of patients: (1) idiopathic preterm labour (PTL) without chorioamnionitis or betamethasone (BM) treatment (n = 9), (2) idiopathic PTL that received BM with no chorioamnionitis (PTL-BM; n = 9) and (3) pregnancies that were complicated with chorioamnionitis and had no BM (PTL-CHA; n = 6). EP1-4 and FP receptors were localised and levels of expression were determined by western blot analysis. All EP receptors and FP were localised to the amnion, placenta and choriodecidua. Moreover, isolated amnion mesenchymal, amnion epithelial, chorion trophoblast and syncytiotrophoblast cells in primary culture also expressed PG receptors. A significant increase was observed in EP1, EP3 and FP expression in placenta, chorion and amnion with labour. Maternal betamethasone treatment increased EP1, EP3 and FP receptor protein expression and chorioamnionitis decreased expression in all the receptor subtypes. These changes in PG receptors in the fetal membranes are consistent with the development of a feed-forwards cascade mediated through PG action that may contribute to the birth process.

The Prevalence of Chronic Deciduitis in Cases of Preterm Labor without Clinical Chorioamnionitis

Preterm labor is a major cause of perinatal mortality and morbidity, and in approximately 30% of cases a clinical cause is not identified. Acute chorioamnionitis is found histologically in a significant percentage of placentas from preterm deliveries, and the mother is often asymptomatic. Although such subclinical acute chorioamnionitis is known to play a role in preterm labor, this study explores the hypothesis that chronic deciduitis with plasma cells is seen more frequently in cases of preterm labor than in control placentas. Thirty-nine singleton placentas from patients with idiopathic preterm labor were examined microscopically and compared in a blinded fashion with 39 gestational age-matched control placentas. Cases of clinical acute chorioamnionitis and known chronic maternal diseases were excluded. Thirty-nine control singleton placentas were obtained from patients undergoing induction of labor for fetal structural abnormalities, excluding aneuploidy. The presence or absence of acute chorioamnionitis, acute fetal inflammatory response, chronic deciduitis, chronic villitis, infarction, and decidual vasculopathy was noted. Immunohistochemical staining was undertaken to further define leukocyte subtypes. Forty-one percent of cases and 15% of controls showed chronic deciduitis (P = 0.022). Forty-six percent of cases and 18% of controls showed histologic acute chorioamnionitis (P = 0.015). There were 8 cases demonstrating acute fetal inflammatory response but only 1 control (P = 0.029). Little difference was seen in the distribution of lymphocyte subsets between cases and control placentas. Our findings suggest that chronic deciduitis plays a role in the etiology of some cases of preterm labor.

Obstetric antecedents for preterm delivery

To investigate the obstetric antecedents for preterm delivery (PTD) in an Irish urban obstetric population, and to evaluate the incidence and outcome of such deliveries. A retrospective observational study of all preterm deliveries at the Rotunda Hospital, Dublin during the six-year period 1997-2002. The findings for early preterm deliveries (EPTD) (24+0-31+6 weeks' gestation), and late preterm deliveries (LPTD) (32+0-36+6 weeks' gestation) were analyzed separately. There were 38,795 deliveries after 24 weeks' gestation or >500 g birth weight, of which 2839 (7.3%) were preterm. Of all preterm deliveries, 626 (22.1%) were EPTD and 2213 (77.9%) were LPTD, resulting in an EPTD rate of 1.6% and an LPTD rate of 5.7%. Spontaneous unexplained preterm delivery accounted for 1221 (43.0%) of preterm deliveries (PTD), and of these 213 (34%) cases were EPTD and 1008 (45.5%) LPTD. The other most frequently observed obstetric causative factors, in order of importance, were multiple gestation (676; 23.8% of PTD), hypertensive disorders of pregnancy (243; 8.6%), antepartum hemorrhage (194; 6.8%), stillbirth (105; 3.7%), intrauterine growth restriction (53; 1.9%) and preterm prelabor rupture of membranes+/-chorioamnionitis (32; 1.1%). There were 75 early neonatal deaths among infants born prematurely, plus 105 stillbirths, resulting in a perinatal mortality rate of 63 per 1000 for PTD (n=180), which on subsequent analysis was 158 per 1000 for EPTD (n=99) and 37 per 1000 for LPTD (n=81). These data outline the obstetric factors linked to preterm delivery within a recent Irish urban obstetric population. Spontaneous idiopathic preterm labor was the principle causative factor in 43% of all preterm deliveries, and represents the proportion of women for whom future therapeutic intervention may be of benefit.