The association between selected mid-trimester amniotic fluid candidate proteins and spontaneous preterm delivery

Hallingström, Maria; Cobo, Teresa; Kacerovský, Marian; Skogstrand, Kristin; Hougaard, David M.; Holst, Rose-Marie; Akouri, Randa; Bullarbo, Maria; Carlsson, Ylva; Nilsson, Staffan; Jacobsson, Bo

doi:10.1080/14767058.2018.1497604

Cited by 3 publications

(5 citation statements)

References 72 publications

(90 reference statements)

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“…However, inconsistent MIF concentrations, such as high levels in cord blood and low levels in amniotic fluid at preterm birth, have been reported previously. [12,13] In this study, the MIF in venous blood from preterm neonates was approximately 2-fold higher than that in late preterm or term neonates (P = .016; Fig. 1 and Table 4).…”

Section: Discussionmentioning

confidence: 48%

“…Differences in the postnatal day of sample collection, and types of samples might have led to the conflicting results from the previous studies. In other words, previous reports have studied MIF from cord blood and amniotic fluid in the mid-trimester, [2,4,12,13] but we studied MIF from peripheral venous blood of neonates with diverse clinical conditions in the early postnatal period. Since preterm neonates might experience more vulnerable clinical courses in the transitional period than late preterm or term neonates, unstable early clinical conditions such as RDS, PDA, or IVH might affect high MIF concentrations in preterm neonates.…”

Section: Discussionmentioning

confidence: 99%

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Difference in macrophage migration inhibitory factor between preterm and term newborns and associating clinical factors: Preliminary study

et al. 2022

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This study aimed to investigate the macrophage migration inhibitory factor (MIF) and associated clinical factors in neonates. Clinical information and blood samples were obtained from 77 neonates. Clinical details were reviewed from medical records, and MIF was measured by enzyme-linked immunosorbent assay using blood samples acquired within a week after birth. Statistical analyses were performed between plasma MIF concentration and clinical factors. Among the 77 newborn infants, 25 were born at <34 weeks of gestation (preterm), 25 at 34 to 37 weeks (late preterm), and 27 at term gestation. The mean MIF was 9849.5 ± 7187.8 pg/mL in preterm, 5718.7 ± 4596.4 in late preterm, and 5361.1 ± 3895.7 in term infants (P = .016). Among 25 preterm infants born at <34 weeks of gestation, MIF was significantly higher in infants with necrotizing enterocolitis (NEC, 19,478.6 ± 8162.4 pg/mL, n = 5) than that in infants without NEC (feeding intolerance 7173.7 ± 4203.0 pg/mL, n = 12 and others 7844.9 ± 5311.2 pg/mL, n = 8, P = .020). Elevated plasma MIF levels in the transitional period were significantly associated with preterm birth before 34 weeks of gestation and the development of NEC.

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Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Difference in macrophage migration inhibitory factor between preterm and term newborns and associating clinical factors: Preliminary study

et al. 2022

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“…Several previous studies, including two by our group [23,35], have investigated whether mid-trimester amniotic fluid proteins are associated with subsequent spontaneous PTD. The results are conflicting, as some have found associations [36][37][38][39], while others have not [23,35,[40][41][42]. In this study, none of the selected proteins were associated with spontaneous PTD.…”

Section: Discussionmentioning

confidence: 99%

“…The assay panel was designed to explore the inflammatory processes and mechanisms preceding the onset of labor, both at term and at preterm. Selection was influenced by previous studies reporting biomarkers associated with term and preterm parturition [6,22] as well as proteins previously analyzed in a sub-cohort of this project [23]. The selection of DAMPs in the panel was based on the hypothesis that these endogenous mediators trigger an inflammatory process, defined as sterile intra-amniotic inflammation [24,25], related to the onset of labor both at term [26] and preterm [27].…”

Section: Development Of the Assay Panelmentioning

confidence: 99%

Protein Concentrations of Thrombospondin-1, MIP-1β, and S100A8 Suggest the Reflection of a Pregnancy Clock in Mid-Trimester Amniotic Fluid

et al. 2020

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The development of immunoassays enables more sophisticated studies of the associations between protein concentrations and pregnancy outcomes, allowing early biomarker identification that can improve neonatal outcomes. The aim of this study was to explore associations between selected mid-trimester amniotic fluid proteins and (1) overall gestational duration and (2) spontaneous preterm delivery. A prospective cohort study, including women undergoing mid-trimester transabdominal genetic amniocentesis, was performed in Gothenburg, Sweden, 2008–2016 (n = 1072). A panel of 27 proteins related to inflammation was analyzed using Meso-Scale multiplex technology. Concentrations were adjusted for gestational age at sampling, experimental factors, year of sampling, and covariates (maternal age at sampling, parity (nulliparous/multiparous), smoking at first prenatal visit, and in vitro fertilization). Cox regression analysis of the entire cohort was performed to explore possible associations between protein concentrations and gestational duration. This was followed by Cox regression analysis censored at 259 days or longer, to investigate whether associations were detectable in women with spontaneous preterm delivery (n = 47). Finally, linear regression models were performed to analyze associations between protein concentrations and gestational duration in women with spontaneous onset of labor at term (n = 784). HMG-1, IGFBP-1, IL-18, MIP-1α, MIP-1β, S100A8, and thrombospondin-1 were significantly associated with gestational duration at term, but not preterm. Increased concentrations of thrombospondin-1, MIP-1β, and S100A8, respectively, were significantly associated with decreased gestational duration after the Holm-Bonferroni correction in women with spontaneous onset of labor at term. This adds to the concept of a pregnancy clock, where our findings suggest that such a clock is also reflected in the amniotic fluid at early mid-trimester, but further research is needed to confirm this.

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“…Immediately after withdrawal, samples were stored at 4-8 C for 4 ± 1.9 h (mean ± SD) before centrifugation for 20 min at 12,000 g, 4 C. Supernatants and pellets were thereafter separated, aliquoted, frozen and stored at À80 C awaiting analysis. Parts of the larger prospective pregnancy cohort study have previously been used for a few different subset analyses [13][14][15].…”

Section: Collection and Processing Of Samplesmentioning

confidence: 99%

Metabolomic profiles of mid-trimester amniotic fluid are not associated with subsequent spontaneous preterm delivery or gestational duration at delivery

Hallingström

Barman

Savolainen

et al. 2020

The Journal of Maternal-Fetal & Neonatal Medicine

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Introduction: Spontaneous preterm delivery (<37 gestational weeks) has a multifactorial etiology with still incompletely identified pathways. Amniotic fluid is a biofluid with great potential for insights into the feto-maternal milieu. It is rich in metabolites, and metabolic consequences of inflammation is yet researched only to a limited extent. Metabolomic profiling provides opportunities to identify potential biomarkers of inflammatory conditioned pregnancy complications such as spontaneous preterm delivery. Objective: The aim of this study was to perform metabolomic profiling of amniotic fluid from uncomplicated singleton pregnancies in the mid-trimester to identify potential biomarkers associated with spontaneous preterm delivery and gestational duration at delivery. A secondary aim was to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers of spontaneous preterm delivery in asymptomatic women. Method: A nested case-control study was performed within a larger cohort study of asymptomatic pregnant women undergoing mid-trimester genetic amniocentesis at 14-19 gestational weeks in Gothenburg, Sweden. Medical records were used to obtain clinical data and delivery outcome variables. Amniotic fluid samples from women with a subsequent spontaneous preterm delivery (n ¼ 37) were matched with amniotic fluid samples from women with a subsequent spontaneous delivery at term (n ¼ 37). Amniotic fluid samples underwent untargeted metabolomic analyses using liquid chromatography-mass spectrometry. Multivariate random forest analyses were used for data processing. A secondary targeted analysis was performed, aiming to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers in women with a subsequent spontaneous preterm delivery. Results: Multivariate analysis did not distinguish the samples from women with a subsequent spontaneous preterm delivery from those with a subsequent term delivery. Neither was the metabolic profile associated with gestational duration at delivery. Potential metabolic biomarker candidates were identified from four publications by two different research groups relating midtrimester amniotic fluid metabolomes to spontaneous PTD, of which fifteen markers were included in the secondary analysis. None of these were replicated. Conclusions: Metabolomic profiles of early mid-trimester amniotic fluid were not associated with spontaneous preterm delivery or gestational duration at delivery in this cohort.

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The association between selected mid-trimester amniotic fluid candidate proteins and spontaneous preterm delivery

Cited by 3 publications

References 72 publications

Difference in macrophage migration inhibitory factor between preterm and term newborns and associating clinical factors: Preliminary study

Difference in macrophage migration inhibitory factor between preterm and term newborns and associating clinical factors: Preliminary study

Protein Concentrations of Thrombospondin-1, MIP-1β, and S100A8 Suggest the Reflection of a Pregnancy Clock in Mid-Trimester Amniotic Fluid

Metabolomic profiles of mid-trimester amniotic fluid are not associated with subsequent spontaneous preterm delivery or gestational duration at delivery

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