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

Abstract 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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Amniotic fluid “sludge”; prevalence and clinical significance of it in asymptomatic patients at high risk for spontaneous preterm delivery

The Journal of Maternal-Fetal & Neonatal Medicine ◽

10.1080/14767058.2016.1277700 ◽

2017 ◽

Vol 31 (2) ◽

pp. 135-140 ◽

Cited By ~ 6

Author(s):

Ilknur Adanir ◽

Ozgur Ozyuncu ◽

Ayse Filiz Gokmen Karasu ◽

Lutfu S. Onderoglu

Keyword(s):

High Risk ◽

Amniotic Fluid ◽

Preterm Delivery ◽

Clinical Significance ◽

Spontaneous Preterm Delivery ◽

Asymptomatic Patients

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OC07.02: Clinical significance of the presence of amniotic fluid 'sludge' in asymptomatic patients at low and high risk for spontaneous preterm delivery

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.13504 ◽

2014 ◽

Vol 44 (S1) ◽

pp. 16-16

Author(s):

A.R. Hatanaka ◽

R. Mattar ◽

T. Kawanami ◽

M.S. França ◽

L.C. Rolo ◽

...

Keyword(s):

High Risk ◽

Amniotic Fluid ◽

Preterm Delivery ◽

Clinical Significance ◽

Spontaneous Preterm Delivery ◽

Asymptomatic Patients

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Associations between second-trimester amniotic fluid levels of ADAMTS4, ADAMTS5, IL-6, and TNF-α and spontaneous preterm delivery in singleton pregnancies

Journal of Perinatal Medicine ◽

10.1515/jpm-2018-0297 ◽

2019 ◽

Vol 47 (3) ◽

pp. 304-310 ◽

Cited By ~ 5

Author(s):

Rauf Melekoglu ◽

Ercan Yilmaz ◽

Osman Ciftci ◽

Yusuf Taner Kafadar ◽

Ebru Celik

Keyword(s):

Preterm Birth ◽

Amniotic Fluid ◽

Pregnant Women ◽

Preterm Delivery ◽

Control Group ◽

Second Trimester ◽

Spontaneous Preterm Delivery ◽

Tnf Α ◽

Factor Α ◽

Fluid Levels

Abstract Background We investigated the roles of inflammatory cytokines and the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family in the etiopathogenesis of spontaneous preterm delivery by comparing the ADAMTS4, ADAMTS5, interleukin (IL)-6, and tumor necrosis factor-α (TNF-α) levels in second-trimester amniotic fluid between pregnant women with preterm birth and term controls. Methods All pregnant women who underwent second-trimester amniocentesis for genetic analysis between January 1, 2016, and January 1, 2018, were enrolled in this study. From this cohort, 22 patients who subsequently experienced spontaneous preterm delivery before 34 weeks of pregnancy formed the study group, and 22 age- and body mass index (BMI)-matched patients without preterm birth constituted the control group. Results No significant differences were observed between the preterm birth and control groups in terms of age, BMI, obstetric history of preterm delivery, gestational age at amniocentesis, or indication for amniocentesis. The mean amniotic fluid levels of ADAMTS4 and ADAMTS5 were significantly increased in the preterm birth group compared to the control group (248.3±22.6 and 182.4±19.8 pg/mL, P=0.012; and 198.6±21.6 and 159.1±21.7 pg/mL, P=0.035, respectively). Significantly increased IL-6 and TNF-α levels were also detected in the amniotic fluid of women who experienced spontaneous preterm delivery, relative to controls (142.1±16.2 and 95.8±16.4 pg/mL, P<0.001; and 139.4±12.5 and 89.6±11.2 pg/mL, P<0.001, respectively). Conclusion The results of this study imply that increased mid-trimester amniotic fluid levels of ADAMTS4, ADAMTS5, IL-6, and TNF-α play an important role in the pathophysiology of spontaneous preterm delivery.

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Steroid Hormone Levels in Recipient Amniotic Fluid in Twin–Twin Transfusion Syndrome and Their Association with Preterm Delivery

American Journal of Perinatology ◽

10.1055/s-0039-1700862 ◽

2019 ◽

Vol 37 (06) ◽

pp. 562-569

Author(s):

Mallory Hoffman ◽

Lovepreet K. Mann ◽

Jong H. Won ◽

Eric P. Bergh ◽

Roopali Donepudi ◽

...

Keyword(s):

Amniotic Fluid ◽

Preterm Delivery ◽

Case Series ◽

Fetal Surgery ◽

Protein Levels ◽

Spontaneous Preterm Delivery ◽

Cortisol Levels ◽

Early Preterm Birth ◽

Estradiol Levels

Abstract Objective Preterm delivery following fetoscopic laser surgery (FLS) of twin–twin transfusion syndrome (TTTS) is associated with severe perinatal morbidity and mortality. The role of steroid hormones in amniotic fluid (AF) after FLS remains unknown. Study Design A prospective cohort study of consecutive case series of FLS for TTTS was performed from April 2012 to February 2017. Cases were divided into early (≤27 weeks) spontaneous preterm delivery (ED) and late delivery (LD; ≥34 weeks) following FLS and compared. AF supernatants were assessed for protein, estradiol, progesterone and cortisol levels (using the ELISA kit), and normalized to total protein levels to adjust for dilution. Results A total of 294 consecutive cases of FLS for TTTS in monochorionic–diamniotic twins were performed during the study period. AF was available in 44 ED patients and 50 LD patients. On logistic regression, ED was associated with higher normalized progesterone levels (odds ratio [OR]: 1.25; 95% confidence interval [CI]: 1.12–1.41), lower normalized cortisol (OR: 0.78; 95% CI: 0.64–0.96), and higher estradiol levels (OR: 1.3; 95% CI: 1.03–1.63). Conclusion Elevated AF normalized progesterone and estradiol, and lower normalized cortisol levels were associated with ED. This novel finding requires further exploration to establish the molecular mechanism operational in pregnancies complicated by TTTS to potentially prevent early preterm birth after fetal surgery.

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