The main aim of the study was to determine progranulin levels in amniotic and cervical fluid samples from pregnancies complicated by preterm prelabor rupture of membranes (PPROM) or preterm labor with intact membranes (PTL), with concomitant microbial invasion of the amniotic cavity and/or intra-amniotic inflammation. A total of 104 and 108 women with PPROM and PTL, respectively, were included. Paired amniotic and cervical fluid samples were obtained using transabdominal amniocentesis and Dacron polyester swabs, respectively. Progranulin levels were assessed with an enzyme-linked immunosorbent assay. Women with PPROM and PTL were divided into subgroups based on microbial invasion of the amniotic cavity and/or intra-amniotic inflammation. Differences in progranulin levels among the PPROM and PTL subgroups were found in amniotic fluid: (a) PPROM: intra-amniotic infection: 51.8 pg/mL, sterile intra-amniotic inflammation: 52.8 pg/mL, colonization: 36.4 pg/mL, and negative amniotic fluid: 35.0 pg/mL; p < 0.0001; (b) PTL: intra-amniotic infection: 75.3 pg/mL, sterile intra-amniotic inflammation: 54.0 pg/mL, and negative amniotic fluid: 39.1 pg/mL; p < 0.0001. The corresponding differences were not found in cervical fluid: (a) PPROM: p = 0.14; (b) PTL: p = 0.53. In conclusion, amniotic fluid progranulin levels increased in PPROM and PTL cases with concomitant intra-amniotic inflammation, regardless of whether microbial invasion of the amniotic cavity was present or absent.

• Keywords
• Amniotic fluid, Intra-amniotic inflammation, Invasive sampling, Microbial invasion of the amniotic cavity, Non-invasive sampling, Preterm delivery,
• MeSH
• Amniocentesis MeSH
• Cervix Uteri * metabolism   MeSH
• Chorioamnionitis metabolism   MeSH
• Adult MeSH
• Humans MeSH
• Amniotic Fluid * metabolism   MeSH
• Obstetric Labor, Premature metabolism   MeSH
• Fetal Membranes, Premature Rupture * metabolism   MeSH
• Premature Birth * metabolism   MeSH
• Progranulins * metabolism   MeSH
• Retrospective Studies MeSH
• Pregnancy MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• GRN protein, human MeSH Browser
• Progranulins * MeSH

INTRODUCTION: The aim of the study was to identify predictive values of the soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) ratio and interleukin (IL)-6, assessed with a clinically available method in a large-volume biochemistry laboratory, in maternal blood, amniotic fluid, and umbilical cord blood for the presence of the placental lesions consistent with maternal vascular malperfusion (MVM) and acute histological chorioamnionitis (HCA), respectively. METHODS: This retrospective study included 92 women with preterm labor with intact membranes (PTL) delivered within 7 days of admission with gestational ages between 22+0 and 34+6 weeks. The sFlt-1/PlGF ratio and IL-6 were assessed in stored samples of maternal serum, amniotic fluid, and umbilical cord serum using Elecsys® sFlt-1, PlGF, and IL-6 immunoassays. RESULTS: Women with MVM had a higher sFlt-1/PlGF ratio in the maternal serum, compared to those without MVM (19.9 vs. 4.6; p < 0.0001), but not in the amniotic fluid or umbilical cord blood. A cut-off value of 8 for the sFlt-1/PlGF ratio in maternal serum was identified as optimal for predicting MVM in patients with PTL. Women with HCA had higher concentrations of IL-6 in maternal serum, compared to those without HCA (11.1 pg/mL vs. 8.4 pg/mL; p = 0.03), amniotic fluid (9,216 pg/mL vs. 1,423 pg/mL; p < 0.0001), and umbilical cord blood (20.7 pg/mL vs. 10.7 pg/mL, p = 0.002). Amniotic-fluid IL-6 showed the highest predictive value. A cut-off value of IL-6 concentration in the amniotic fluid of 5,000 pg/mL was found to be optimal for predicting HCA in PTL. CONCLUSION: Maternal serum sFlt-1/PlGF and amniotic fluid IL-6 concentrations can be used for liquid biopsy to predict placental lesions in women with PTL who deliver within 7 days.

• Keywords
• Amniocentesis, Amniotic fluid, Angiogenic factors, Biomarker, Inflammation, Interleukin-6, PlGF, Preeclampsia, Pregnancy, Preterm birth, Preterm labor with intact membrane, Rapid point-of-care test, Receptor, VEGF, sFlt-1,
• MeSH
• Biomarkers blood   MeSH
• Chorioamnionitis blood   diagnosis   MeSH
• Adult MeSH
• Fetal Blood metabolism   MeSH
• Interleukin-6 * blood   MeSH
• Humans MeSH
• Placenta metabolism   MeSH
• Placenta Growth Factor * blood   MeSH
• Amniotic Fluid metabolism   MeSH
• Obstetric Labor, Premature * blood   MeSH
• Predictive Value of Tests * MeSH
• Vascular Endothelial Growth Factor Receptor-1 * blood   MeSH
• Retrospective Studies MeSH
• Pregnancy MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH
• FLT1 protein, human MeSH Browser
• IL6 protein, human MeSH Browser
• Interleukin-6 * MeSH
• PGF protein, human MeSH Browser
• Placenta Growth Factor * MeSH
• Vascular Endothelial Growth Factor Receptor-1 * MeSH

Spontaneous preterm delivery presents one of the most complex challenges in obstetrics and is a leading cause of perinatal morbidity and mortality. Although it is a common endpoint for multiple pathological processes, the mechanisms governing the etiological complexity of spontaneous preterm birth and the placental responses are poorly understood. This study examined placental tissues collected between May 2019 and May 2022 from a well-defined cohort of women who experienced spontaneous preterm birth (n = 72) and healthy full-term deliveries (n = 30). Placental metabolomic profiling of polar metabolites was performed using Ultra-High Performance Liquid Chromatography/Mass Spectrometry (UHPLC/MS) analysis. The resulting data were analyzed using multi- and univariate statistical methods followed by unsupervised clustering. A comprehensive metabolomic evaluation of the placenta revealed that spontaneous preterm birth was associated with significant changes in the levels of 34 polar metabolites involved in intracellular energy metabolism and biochemical activity, including amino acids, purine metabolites, and small organic acids. We found that neither the preterm delivery phenotype nor the inflammatory response explain the reported differential placental metabolome. However, unsupervised clustering revealed two molecular subtypes of placentas from spontaneous preterm pregnancies exhibiting differential enrichment of clinical parameters. We also identified differences between early and late preterm samples, suggesting distinct placental functions in early spontaneous preterm delivery. Altogether, we present evidence that spontaneous preterm birth is associated with significant changes in the level of placental polar metabolites. Dysregulation of the placental metabolome may underpin important (patho)physiological mechanisms involved in preterm birth etiology and long-term neonatal outcomes.

• Keywords
• inflammation, metabolism, metabolomics, placenta, preterm birth,
• Publication type
• Journal Article MeSH

OBJECTIVE: To assess the association between newborn birth weight and the presence of intra-amniotic infection, presence of sterile intra-amniotic inflammation, and absence of intra-amniotic inflammation in pregnancies with preterm labor with intact membranes. METHODS: A total of 69 pregnancies with preterm labor with intact membranes between gestational ages 22 + 0 and 34 + 6 weeks who delivered within seven days of admission were included in this retrospective cohort study. Transabdominal amniocentesis to determine the presence of microorganisms and/or their nucleic acids in amniotic fluid (through culturing and molecular biology methods) and intra-amniotic inflammation (according to amniotic fluid interleukin-6 concentrations) were performed as part of standard clinical management. The participants were further divided into three subgroups: intra-amniotic infection (presence of microorganisms and/or nucleic acids along with intra-amniotic inflammation), sterile intra-amniotic inflammation (intra-amniotic inflammation alone), and without intra-amniotic inflammation. Birth weights of newborns were expressed as percentiles derived from the INTERGROWTH-21st standards for (i) estimated fetal weight and (ii) newborn birth weight. RESULTS: No difference in birth weights, expressed as percentiles derived from the standard for estimated fetal weight, was found among the women with intra-amniotic infection, with sterile intra-amniotic inflammation, and without intra-amniotic inflammation (with infection, median 29; with sterile inflammation, median 54; without inflammation, median 53; p = 0.06). Differences among the subgroups were identified in the birth weight rates, expressed as percentiles derived from the standard for estimated fetal weight, which were less than the 10th percentile (with infection: 20%, with inflammation: 13%, without inflammation: 0%; p = 0.04) and 25th percentile (with infection: 47%, with inflammation: 31%, without inflammation: 9%; p = 0.01). No differences among the subgroups were observed when percentiles of birth weight were derived from the birth weight standard. CONCLUSIONS: The presence of intra-amniotic inflammatory complications in pregnancies with preterm labor with intact membranes prior to the gestational age of 35 weeks was associated with a higher rate of newborns with birth weight less than the 10th and 25th percentile, when percentiles of birth weight were derived from the standard for estimated fetal weight.

• Keywords
• amniocentesis, amniotic fluid, estimated fetal weight, fetal growth, intergrowth, intra-amniotic inflammation, microbial invasion of the amniotic cavity, preterm birth,
• Publication type
• Journal Article MeSH

To determine the main clinical characteristics of preterm prelabor rupture of membranes (PPROM) complicated by colonization of the amniotic cavity (microbial invasion of the amniotic cavity without intra-amniotic inflammation). A total of 302 women with PPROM were included. Transabdominal amniocentesis was performed and amniotic fluid was assessed. Based of microbial invasion of the amniotic cavity and intra-amniotic inflammation (interleukin-6 ≥ 3000 pg/mL), the women were divided into following groups: intra-amniotic infection, sterile intra-amniotic inflammation, colonization of the amniotic cavity, and negative amniotic fluid. Colonization was found in 11% (32/302) of the women. The most common bacteria identified in the amniotic fluid were Ureaplasma spp. with a lower burden than those with intra-amniotic infection (p = 0.03). The intensity of intra-amniotic inflammatory response measured by interleukin-6 was higher in women with colonization than in those with negative amniotic fluid (medians: 961 pg/mL vs. 616 pg/mL; p = 0.04). Women with colonization had higher rates of acute inflammatory placental lesions than those with negative amniotic fluid. In PPROM, colonization, caused mainly by microorganisms from the lower genital tract, might represent an early stage of microbial invasion of the amniotic cavity with a weak intra-amniotic inflammatory response.

• MeSH
• Chorioamnionitis * microbiology   MeSH
• Interleukin-6 MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Placenta MeSH
• Amniotic Fluid microbiology   MeSH
• Fetal Membranes, Premature Rupture MeSH
• Retrospective Studies MeSH
• Pregnancy MeSH
• Inflammation complications   MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Interleukin-6 MeSH