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Background: During pregnancy and parturition a remodeling within the extracellular matrix of the cervix and the corpus uteri occurs, which is of fundamental importance to a normal labor. The aim of this study is to identify the major proteoglycans in corpus uteri of non-pregnant subjects.Methods: From human uterine tissue proteoglycans were extracted and purified using CsCl-density gradient centrifugation, gel and ion-exchange chromatography. The proteoglycans were quantified and identified by Alcian Blue before and after ABC-digestion and by Western blotting.Results: The results showed that the corpus uteri contains a substantial amount of proteoglycans, 1.825 microg/mg wet weight. Decorin is dominating, constituting 63% of the total amount of proteoglycans. Heparan sulphate proteoglycans accounted for 20% and biglycan for 16%. Less than 1% consisted of the large proteoglycan versican.Conclusions: Further investigations must be performed to provide more information of the biological role of the proteoglycans in the uterus, especially during labor, by the presence of heparan sulphate proteoglycans and the minute presence of versican which indicate that the proteoglycan composition and organization is different to that of the cervix. [ABSTRACT FROM AUTHOR]

Abstract Preterm birth is the leading cause of neonatal mortality and perinatal morbidity. The etiology of preterm is multi-factorial and still unclear. As evidence increases for a genetic contribution to PTB, so does the need to explore genomics, transcriptomics, proteomics and metabolomics in its study. This review suggests research guidelines for the conduct of high throughput systems biology investigations into preterm birth with the expectation that this will facilitate the sharing of samples and data internationally through consortia, generating the power needed to study preterm birth using integrated "-omics" technologies. The issues to be addressed include: (1) integrated "-omics" approaches, (2) phenotyping, (3) sample collection, (4) data management-integrative databases, (5) international consortia and (6) translational feasibility. This manuscript is the product of discussions initiated by the "-Omics" Working Group at the Preterm Birth International Collaborative Meeting held at the World Health Organization, Geneva, Switzerland in April 2009.

Abstract Treatment with prostaglandin(PG)-E2 is clinically efficient for cervical priming. The aim of this study was to evaluate the impact of PG-E2 on the expression of the progesterone (PR), androgen (AR) and glucocorticoid (GR) receptors in human uterine cervix in prolonged pregnancy. The study groups were postterm nulliparous women with unripe cervices undergoing cervical priming with PG-E2 before labor induction. Responders (n = 12) who delivered vaginally were compared with non-responders (n = 10), who underwent cesarean section due to failure to progress to the active phase of labor. Controls (n = 18) with vaginal partus at a normal gestational age served as a reference group. Cervical levels of PR-A and PR- B isoforms, AR and GR, serum levels of their ligands and sex hormone-binding globulin (SHBG) were quantified. The responder group displayed lower total PR-AB and AR protein levels as compared to non-responders, and lower PR-B and AR protein levels as compared to controls. In addition, the PR mRNA level was lower in responders as compared to non-responders. The GR protein level did not differ between the groups. We conclude that successful PG-E2 priming was followed by a progesterone and androgen withdrawal at the receptor level in the uterine cervix.

Abstract Background Prolonged pregnancies are associated with increased rate of maternal and fetal complications. Post term women could be divided into at least two subgroups, one where parturition is possible to induce by prostaglandins and one where it is not. Our aim was to study parameters in cervical biopsies in women with spontaneous delivery at term (controls) and compare to those that are successfully induced post term (responders), and those that are not induced (non-responders), by local prostaglandin treatment. Methods Stromal parameters examined in this study were the accumulation of leukocytes (CD45, CD68), mRNAs and/or proteins for the extracellular matrix degrading enzymes (matrix metalloproteinase (MMP)-2, MMP-8 and MMP-9), their inhibitors (tissue inhibitor of MMP (TIMP)-1 and TIMP-2), interleukin-8 (IL-8), the platelet activating factor-receptor (PAF-R), syndecan-1 and estrogen binding receptors (estrogen receptor (ER)α, ERβ and G-coupled protein receptor (GPR) 30) as well as the proliferation marker Ki-67. Results The influx of leukocytes as assessed by CD45 was strongest in the responders, thereafter in the controls and significantly lower in the non-responders. IL-8, PAF-R and MMP-9, all predominantly expressed in leukocytes, showed significantly reduced immunostaining in the group of non-responders, while ERα and GPR30 were more abundant in the non-responders, as compared to the controls. Conclusion The impaired leukocyte influx, as reflected by the reduced number of CD45 positive cells as well as decreased immunostaining of IL-8, PAF-R and MMP-9 in the non-responders, could be one explanation of the failed ripening of the cervix in post term women. If the decreased leukocyte influx is a primary explanation to absent ripening or secondary, as a result of other factors, is yet to be established.

Abstract Background Cervical ripening is a prerequisite for a normal obstetrical outcome. This process, including labor, is a painful event that shares features with inflammatory reactions where peripheral nociceptive pathways are involved. The capsaicin and heat receptor TRPV1 is a key molecule in sensory nerves involved in peripheral nociception, but little is known regarding its role in the pregnant uterus. Therefore, the aim of this study was to investigate human corpus and cervix uteri during pregnancy and labor and non-pregnant controls for the presence of TRPV1. Methods We have investigated human uterine corpus and cervix biopsies at term pregnancy and parturition. Biopsies were taken from the upper edge of the hysterotomy during caesarean section at term (n = 8), in labor (n = 8) and from the corresponding area in the non-pregnant uterus after hysterectomy (n = 8). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial frozen sections were examined immunohistochemically using specific antibodies to TRPV1 and nerve markers (neurofilaments/peripherin). Results In cervix uteri, TRPV1-immunoreactive fibers were scattered throughout the stroma and around blood vessels, and appeared more frequent in the sub-epithelium. Counts of TRPV1-immunoreactive nerve fibers were not significantly different between the three groups. In contrast, few TRPV1-immunoreactive fibers were found in nerve fascicles in the non-pregnant corpus, and none in the pregnant corpus. Conclusion In this study, TRPV1 innervation in human uterus during pregnancy and labor is shown for the first time. During pregnancy and labor there was an almost complete disappearance of TRPV1 positive nerve fibers in the corpus. However, cervical innervation remained throughout pregnancy and labor. The difference in TRPV1 innervation between the corpus and the cervix is thus very marked. Our data suggest that TRPV1 may be involved in pain mechanisms associated with cervical ripening and labor. Furthermore, these data support the concept that cervix uteri may be the major site from which labor pain emanates. Our findings also support the possibility of developing alternative approaches to treat labor pain.

Abstract Background The uterus is exposed to changes such as enlargement and distension during pregnancy and labor. In these processes and in the process of cervical ripening, proprioceptive information is likely to be of great importance. Therefore, we wanted to study the possible existence of sensory nerve corpuscles in uterine corpus and cervix during pregnancy and labor. Studies on this aspect have not previously been perfomed. Methods Biopsies were taken from the upper edge of the hysterotomy during caesarean section at term (n = 8), in labor (n = 5) and from the corresponding area in the non-pregnant uterus after hysterectomy (n = 7). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial cryostat sections were prepared for immunohistochemistry using polyclonal antibodies against nerve growth factor receptor p75, protein gene product 9.5 and S-100. Results Structures with the characteristics of sensory nerve corpuscles were observed in several specimens after staining for p75, PGP 9.5 and S-100. They were observed in specimens of the non-pregnant corpus and cervix and also in specimens of the pregnant cervix before onset of labor. However, they were absent in all specimens during labor. Conclusion Sensory corpuscles have here for the first time been detected in the human corpus and cervix uteri. Studies on the importance of the corpuscles in relation to the protective reflex actions that occur in the uterus during pregnancy should be performed in the future.

Abstract Background Preterm birth is still the leading cause of neonatal morbidity and mortality. The level of corticotropin-releasing hormone (CRH) is known to be significantly elevated in the maternal plasma at preterm birth. Although, CRH, CRH-binding protein (CRH-BP), CRH-receptor 1 (CRH-R1) and CRH-R2 have been identified both at mRNA and protein level in human placenta, deciduas, fetal membranes, endometrium and myometrium, no corresponding information is yet available on cervix. Thus, the aim of this study was to compare the levels of the mRNA species coding for CRH, CRH-BP, CRH-R1 and CRH-R2 in human cervical tissue and myometrium at preterm and term labor and not in labor as well as in the non-pregnant state, and to localize the corresponding proteins employing immunohistochemical analysis. Methods Cervical, isthmic and fundal (from non-pregnant subjects only) biopsies were taken from 67 women. Subjects were divided in 5 groups: preterm labor (14), preterm not in labor (7), term labor (18), term not in labor (21) and non-pregnant (7). Real-time RT-PCR was employed for quantification of mRNA levels and the corresponding proteins were localized by immunohistochemical analysis. Results The levels of CRH-BP, CRH-R1 and CRH-R2 mRNA in the pregnant tissues were lower than those in non-pregnant subjects. No significant differences were observed between preterm and term groups. CRH-BP and CRH-R2 mRNA and the corresponding proteins were present at lower levels in the laboring cervix than in the non-laboring cervix, irrespective of gestational age. In most of the samples, with the exception of four myometrial biopsies the level of CRH mRNA was below the limit of detection. All of these proteins could be detected and localized in the cervix and the myometrium by immunohistochemical analysis. Conclusion Expression of CRH-BP, CRH-R1 and CRH-R2 in uterine tissues is down-regulated during pregnancy. The most pronounced down-regulation of CRH-BP and CRH-R2 occurred in laboring cervix, irrespective the length of gestation. The detection of substantial expression of the CRH and its receptor proteins, as well as receptor mRNA in the cervix suggests that the cervix may be a target for CRH action. Further studies are required to elucidate the role of CRH in cervical ripening.

Abstract Background Prolonged labour is associated with greater morbidity and mortality for mother and child. Connexin 43 is a major myometrial gap junction protein found in human myometrium. Syndecan 3 seems to prevail in the human uterus among heparan sulphate proteoglycans, showing the most significant increase during labour. The aims of the present study were to investigate syndecan 3 and connexin 43 mRNA expressions and protein distributions in human uterine tissue during normal and prolonged labour. Methods Uterine isthmic biopsies were collected from non-pregnant (n = 7), term pregnant women not in labour (n = 14), in normal labour (n = 7) and in prolonged labour (n = 7). mRNA levels of syndecan 3 and connexin 43 were determined by real time RT-PCR. The localization and expression were demonstrated by immunohistochemistry and confocal microscopy. Results In women with prolonged labour, the mRNA expressions of syndecan 3 and Connexin 43 were considerably lower than the expression level at normal labour (p < 0.05). In term-pregnant tissue, the expression of syndecan 3 and connexin 43 did not differ significantly compared to non-pregnant and normal labour. The immunoreactivity of syndecan 3 was strong at normal labour, in contrast to prolonged labour, where both a weaker expression and an irregular distribution were detected. The immunoreactivity of connexin 43 increased until term and further stronger staining occurred at normal labour. At prolonged labour, the immunoreactivity was weaker and more unevenly distributed. At labour, a co-localization of syndecan 3 and connexin 43 could be demonstrated in the smooth muscle by confocal microscopy. Conclusion The high expression of syndecan 3 and connexin 43 and their co-localization to the smooth muscle bundles during normal labour, together with the significant reduction in prolonged labour, may indicate a role for these proteins in the co-ordination of myometrial contractility.

Abstract Background Preterm birth is the primary cause of the neonatal mortality and morbidity. There will be no preterm birth without a cervical softening. Nitric oxide (NO) is shown to be a mediator of term cervical ripening. The aim of this study was to investigate mRNA expression of the three isomers of NO synthases (NOS) and to identify them by immunohistochemistry in the human cervix at preterm birth compared to term. Methods The three isomers of NOS- inducible (iNOS), endothelial (eNOS) and neuronal (bNOS) – were investigated in the human cervix. The expression of mRNA was determined using Real-Time Multiplex RT-PCR. The localisation of synthases in the cervical tissue was analysed using immunohistochemistry. Cervical biopsies were obtained from 4 groups of women without clinical signs of infection: preterm (PTL), term labour (TL), preterm not in labour (PTnotL) and term not in labour (TnotL) patients. One-Way ANOVA, Kruskal-Wallis, Student t-test or Mann-Whitney test were applied as appropriate to determine statistically significant differences among the groups. Results Patients in preterm labour had significantly (p < 0.01) higher mRNA levels of all the three NOS isomers compared to those in term labour. Women not in labour, irrespective of gestational age, thus with unripe cervices, had significantly lower eNOS mRNA levels compared to those in labour (p < 0.01). Immunoreactivity for all three NO synthases was observed in each examined sample in all groups. The bNOS staining was the most prominent. Conclusion The mRNA levels were higher in the preterm labour group compared to the women at term labour. The significant increase of the eNOS mRNA expression, from the unripe to the favourable cervical state during labour, may indicate a role of eNOS and supports the role of NO in the cervical ripening process. All the three synthases were identified by immunohistochemistry in all the groups of study.

Abstract Background Human cervical ripening is an inflammatory process. In labour at term the mRNA-levels and protein concentrations for interleukin-6 (IL-6) and IL-8 in cervix significantly increase. The aim of this study was to investigate if there are differences in the inflammatory process of preterm and term cervical ripening. Methods Cervical biopsies from 50 singleton pregnant women without clinical signs of infection were allocated to four groups: preterm labour, term labour, preterm not in labour and term not in labour. The protein levels of IL-8, IL-6, monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal t cells expressed and secreted (RANTES) and tumour necrosis factor-alpha (TNF-alpha) were quantified in tissue homogenates by ELISA or Immulite. The mRNA expression of IL-8, MCP-1 and RANTES was studied using RT-PCR. White blood cell count (WBC) and C-reactive protein (CRP) in the blood were determined. For determination of statistically significant differences between study groups Mann-Whitney U test or Kruskal-Wallis test were applied. Results Protein concentrations of IL-8, IL-6, and MCP-1 were significantly increased during labour compared to non-labouring groups, whereas no changes were observed for RANTES and TNF-alpha. The mRNA levels of representative cytokines such as IL-8 and MCP-1 increased significantly during labour whereas RANTES mRNA expression remained unchanged. WBC and CRP were significantly higher in the labouring groups as compared to groups not in labour. For neither of the analysed cytokines, WBC or CRP levels were there any changes between preterm and term respective groups. Conclusion Our findings indicate that non-infected preterm cervical ripening is an inflammatory process, just as cervical ripening at term, with cytokines as important mediators.

Abstract Background Cervical ripening is an inflammatory reaction. The glucocorticoid receptor (GR) mediates glucocorticoid anti-inflammatory reactions, whereas nuclear factor (NF)kappaB is a key pro-inflammatory transcription factor. Prostaglandins as well as platelet activating factor (PAF) are inflammatory mediators. Inducible nitric oxide synthase (iNOS) regulates the level of nitric oxide (NO) in response to various inflammatory stimuli. We hypothesize that a changed biological response to glucocorticoids could be a mechanism regulating the inflammatory events resulting in cervical ripening. Methods We monitored GR and NFkappaB, prostaglandin synthases cyclooxygenase (COX)-1 and -2, iNOS, as well as the PAF-receptor (PAF-R) in the uterine cervix from term pregnant women (with unripe cervices) before the onset of labor (TP), immediately after parturition (PP), as compared to non-pregnant (NP), using immunohistochemistry and RT-PCR. Results The GR protein was detected by immunohistochemistry in the nuclei of stroma and squamous epithelium (SQ). Stromal GR staining was increased in TP as compared to the NP group and decreased again after parturition. GR staining in SQ was decreased after parturition as compared to term. NFkappaB was present in SQ and glandular epithelium (GE), stroma and vascular endothelium. Increased nuclear NFkappaB staining was observed postpartum as compared to term pregnancy in stroma and GE. Stromal immunostaining for COX-1 as well as COX-2 was increased in the TP and PP groups as compared to the NP, and GE displayed an intensely increased COX-2 immunostaining at term and postpartum. Stromal PAF-R immunostaining was highest at term, while it was greatly increased in GE postpartum. No difference in the immunostaining for iNOS was found between the groups. RT-PCR showed a predominance of GRalpha to GRbeta mRNA in cervical tissue. The COX-2 mRNA level was increased in the PP group as compared to the TP group. Conclusions There is a decrease in GR levels in human cervix at parturition. Concomitantly there is an increase of factors such as NFkappaB, PAF-R, COX-1 and COX-2, suggesting that they may participate in the sequence of events leading to the final cervical ripening.

Background: Slow progression of labor is a common obstetrical problem with multiple associated complications. Tafoxiparin is a depolymerized form of heparin with a molecular structure that eliminates the anticoagulant effects of heparin. We report on 2 phase II clinical studies of tafoxiparin in primiparas. Study 1 was an exploratory, first-in-pregnant-women study and study 2 was a dose-finding study., Objective: Study 1 was performed to explore the effects on labor time of subcutaneous administration of tafoxiparin before onset of labor. Study 2 was performed to test the hypothesis that intravenous treatment with tafoxiparin reduces the risk for prolonged labor after spontaneous labor onset in situations requiring oxytocin stimulation because of dystocia., Study Design: Both studies were randomized, double-blind, and placebo-controlled. Participants were healthy, nulliparous females aged 18 to 45 years with a normal singleton pregnancy and gestational age confirmed by ultrasound. The primary endpoints were time from onset of established labor (cervical dilation of 4 cm) until delivery (study 1) and time from start of study treatment infusion until delivery (study 2). In study 1, patients at 38 to 40 weeks of gestation received 60 mg tafoxiparin or placebo daily as 0.4 mL subcutaneous injections until labor onset (maximum 28 days). In study 2, patients experiencing slow progression of labor, a prolonged latent phase, or labor arrest received a placebo or 1 of 3 short-term tafoxiparin regimens (initial bolus 7, 21, or 35 mg followed by continuous infusion at 5, 15, or 25 mg/hour until delivery; maximum duration, 36 hours) in conjunction with oxytocin., Results: The number of participants randomized in study 1 was 263, and 361 were randomized in study 2. There were no statistically significant differences in the primary endpoints between those receiving tafoxiparin and those receiving the placebo in both studies. However, in study 1, the risk for having a labor time exceeding 12 hours was significantly reduced by tafoxiparin (tafoxiparin 6/114 [5%] vs placebo 18/101 [18%]; P=.0045). Post hoc analyses showed that women who underwent labor induction had a median (range) labor time of 4.44 (1.2-8.5) hours with tafoxiparin and 7.03 (1.5-14.3) hours with the placebo (P=.0041) and that co-administration of tafoxiparin potentiates the effect of oxytocin and facilitates a shorter labor time among women with a labor time exceeding 6 to 8 hours (P=.016). Among women induced into labor, tafoxiparin had a positive effect on cervical ripening in 11 of 13 cases (85%) compared with 3 of 13 participants (23%) who received the placebo (P=.004). For women requiring oxytocin because of slow progression of labor, the corresponding results were 34 of 51 participants (66%) vs 16 of 40 participants (40%) (P=.004). In study 2, tafoxiparin had no positive effects on the secondary endpoints when compared with the placebo. Except for injection-site reactions in study 1, adverse events were no more common for tafoxiparin than for the placebo among either mothers or infants. There were few serious or treatment-related adverse events., Conclusion: Subcutaneous treatment with tafoxiparin before labor onset (study 1) may be effective in reducing the labor time among women undergoing labor induction and among those requiring oxytocin for slow progression of labor. Moreover, tafoxiparin may have a positive effect on cervical ripening. Short-term, intravenous treatment with tafoxiparin as an adjunct to oxytocin in patients with labor arrest (study 2) did not affect labor time or other endpoints. Both studies suggest that tafoxiparin has a favorable safety profile in mothers and their infants., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Inflammation is a hallmark in the human cervix remodelling. A possible candidate inducing the inflammatory driven ripening of the cervix is the matrix component heparan sulphate, which has been shown to be elevated in late pregnancy in the cervix and uterus. Heparin and a glycol-split low molecular weight heparin (gsHep) with low anticoagulant potency has been shown to enhance myometrial contraction and interleukin (IL)-8 production by cervical fibroblasts. The aim of this study was to investigate the mechanism by which heparin promotes cervical inflammation. Wild-type, Toll-like receptor 4 (TLR4), Myeloid differentiation primary response gene 88 (MyD88) and Interferon regulatory factor 3 (IRF3)-deficient mice were treated by deposition of gsHep into the vaginas of nonpregnant mice. To identify which cells that responded to the heparin fragments, a rhodamine fluorescent construct of gsHep was used, which initially did bind to the epithelial cells and were at later time points located in the sub-mucosa. The heparin fragments induced a strong local inflammatory response in wild-type mice shown by a rapid infiltration of neutrophils and to a lesser extent macrophages into the epithelium and the underlying extracellular matrix of the cervix. Further, a marked migration into the cervical and vaginal lumen was seen by both neutrophils and macrophages. The induced mucosal inflammation was strongly reduced in TLR4- and IRF3-deficient mice. In conclusion, our findings suggest that a TLR4/IRF3-mediated innate immune response in the cervical mucosa is induced by gsHep. This low anticoagulant heparin version, a novel TLR4 agonist, could contribute to human cervical ripening during the initiation of labour., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In a previous study we found a significant correlation between dystocia and hyponatraemia that developed during labour. The present study examined a possible causal relationship. In vitro studies often use area under the curve (AUC) determined by frequency and force of contractions as a measure of myometrial contractility. However, a phase portrait plot of isometric contraction, obtained by plotting the first derivate of contraction against force of contraction, could indicate that bi-or multiphasic contractions might be less effective compared to the smooth contractions., Material and Methods: Myometrial biopsies were obtained from 17 women undergoing elective caesarean section at term. Each biopsy was divided into 8 strips and mounted isometrically in a force transducer. Seven biopsies were used in the first part of the study when half of the strips were immersed in the hyponatraemic study solution S containing Na+ 120 mmol/L and observed for 1 hour, followed by 1 hour in normonatraemic control solution C containing Na+ 136 mmol/L, then again in S for 1 hour, and finally 1 hour in C. The other half of the strips were studied in reverse order, C-S-C-S. The remaining ten biopsies were included in the second part of the study. Response to increasing doses of oxytocin (OT) in solutions S and C was studied. In the first part of the study we calculated AUC, and created phase portrait plots of two different contractions from the same strip, one smooth and one biphasic. In both parts of the study we registered frequency and force of contractions, and described appearance of the contractions., Results: First part of the study: Mean (median) contractions per hour in C: 8.7 (7.6), in S 14,3 (13). Mean (SD) difference between groups 5.6 (4.2), p = 0.018. Force of contractions in C: 11.8 (10.2) mN, in S: 10.8 (9.2) mN, p = 0.09, AUC increased in S; p = 0.018. Bi-/multiphasic contractions increased from 8% in C to 18% in S, p = 0.001. All changes were reversible in C. Second part of the study: Frequency after OT 1.65 x 10-9 M in C:3.4 (2.9), in S: 3.8 (3.2), difference between groups: p = 0.48. After OT 1.65 x 10-7 M in C: 7.8 (8.9), increase from previous OT administration: p = 0.09, in S: 8.7 (9.0), p = 0.04, difference between groups, p = 0.32. Only at the highest dose of OT dose was there an increase in force of contraction in S, p = 0.05, difference between groups, p = 0.33. Initial response to OT was more frequently bi/multiphasic in S, reaching significance at the highest dose of OT(1.65 x 10-7 M), p = 0.015. when almost all contractions were bi/multiphasic., Conclusion: Hyponatraemia reversibly increased frequency of contractions and appearance of bi-or multiphasic contractions, that could reduce myometrial contractility. This could explain the correlation of hyponatraemia and instrumental delivery previously observed. Contractions in the hyponatraemic solution more frequently showed initial multiphasic contractions when OT was added in increasing doses. Longer lasting labours carry the risk both of hyponatraemia and OT administration, and their negative interaction could be significant. Further studies should address this possibility., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Anti-secretory factor is a protein that regulates secretory and inflammatory processes and preterm birth is associated with inflammation. Therefore, our hypothesis was that anti-secretory factor might play a role in immune reactivity and homeostasis during pregnancy., Material and Methods: Following spontaneous onset of labor and preterm or term delivery, placenta biopsies were collected. The levels of anti-secretory factor and markers of inflammation (CD68, CD163) and vascularization (CD34, smooth muscle actin) were analyzed by immunohistochemistry., Results: The 61 placental biopsies included 31 preterm (<37 weeks of gestation) and 30 term (37-41 weeks) samples. The preterm placentas exhibited lower levels of anti-secretory factor (p = 0.008) and larger numbers of CD68-positive cells (p < 0.001) compared to term. Preterm placentas had blood vessel of smaller diameter (p = 0.036) indicative of immaturity. The level of interleukin-6 in cord blood was higher after very preterm than term birth, suggesting a fetal inflammatory response. The placenta level of anti-secretory factor was positively correlated to the length of gestation (p = 0.025) and negatively correlated to the levels of the inflammatory markers CD68 (p = 0.015) and CD163 (p = 0.028)., Conclusions: Preterm delivery is associated with low levels of anti-secretory factor in placenta. Inflammation, a potential trigger of preterm birth, is more pronounced in the preterm placenta and inversely related to the placental level of anti-secretory factor, suggesting both a link and a potential target for intervention., (© 2017 Nordic Federation of Societies of Obstetrics and Gynecology.)