Protein Concentrations of Thrombospondin-1, MIP-1β, and S100A8 Suggest the Reflection of a Pregnancy Clock in Mid-Trimester Amniotic Fluid
Artikel i vetenskaplig tidskrift, 2020

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.

Gestational duration


Amniotic fluid




Felicia Viklund


Sahlgrenska universitetssjukhuset

Maria Hallingström

Göteborgs universitet

Sahlgrenska universitetssjukhuset

M. Kacerovsky

Fakultní nemocnice Hradec Králové

T. Cobo

CIBER Enfermedades Raras

Universitat de Barcelona

Kristin Skogstrand

Statens Serum Institut

David M. Hougaard

Statens Serum Institut

Karin Sävman

Göteborgs universitet

Sahlgrenska universitetssjukhuset

Ylva Carlsson

Göteborgs universitet

Sahlgrenska universitetssjukhuset

Panos Tsiartas

Sahlgrenska universitetssjukhuset

Göteborgs universitet

Julius Juodakis

Victoria University of Wellington

Sahlgrenska universitetssjukhuset

Staffan Nilsson

Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik

Göteborgs universitet

Bo Jacobsson

Norwegian Institute of Public Health

Göteborgs universitet

Sahlgrenska universitetssjukhuset

Reproductive Sciences

1933-7191 (ISSN)

Vol. 27 12 2146-2157


Miljömedicin och yrkesmedicin

Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi

Reproduktionsmedicin och gynekologi



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