Mid-pregnancy maternal plasma levels of interleukin 2, 6, and 12, tumor necrosis factor-alpha, interferon-gamma, and granulocyte-macrophage colony-stimulating factor and spontaneous preterm delivery.
BACKGROUND
Few studies have investigated the relationship between inflammation and spontaneous preterm delivery (sPTD) in women before preterm labour. The authors examine whether mid-pregnancy plasma cytokine levels are associated with sPTD, and whether associations vary by maternal age, body mass index, prior preterm delivery, or gravidity.


METHODS
This case-control study was nested within the Danish National Birth Cohort, a cohort of women with 101,042 pregnancies from 1997 to 2002. Included in this study are 61 women delivering at 24-29 weeks, 278 delivering at 30-33 weeks, 334 delivering at 34-36 weeks, and 1,125 delivering at > or =37 weeks. Maternal plasma interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF) at 25 weeks' gestation were measured using multiplex flow cytometry.


RESULTS
For IL-2, TNF-alpha, and GM-CSF, the proportion of women with levels >75th or >90th percentile did not differ by gestational age at delivery. IFN-gamma >90th percentile was associated with an increased risk of delivering at 30-33 weeks (crude odds ratio (cOR): 1.56; 95% confidence interval (CI): 1.07-2.30), while IFN-gamma >75th percentile and IL-6 >75th percentile were associated with an increased risk of delivering at 34-36 weeks (cOR: 1.32; 95% CI: 1.01-1.73); estimates changed little after adjusting for confounders. There was no effect-measure modification by maternal factors.


CONCLUSIONS
Elevated mid-pregnancy plasma IL-2, TNF-alpha, and GM-CSF did not appear to be associated with an increased risk of sPTD, while elevated IFN-gamma and IL-6 levels were weakly associated with moderate and late sPTD. The value of using mid-pregnancy cytokines in predicting spontaneous preterm delivery appears limited.
Curry
Allison E
AE
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA. ahead@sph.emory.edu
Vogel
Ida
I
Drews
Carolyn
C
Schendel
Diana
D
Skogstrand
Kristin
K
Flanders
W Dana
WD
Hougaard
David
D
Olsen
Jørn
J
Thorsen
Poul
P
D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005434:Flow Cytometry; D005865:Gestational Age; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007371:Interferon-gamma / Q000097:blood*; D018664:Interleukin-12 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D007752:Obstetric Labor, Premature / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D016017:Odds Ratio; D010298:Parity; D011237:Predictive Value of Tests; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood*; D011263:Pregnancy Trimester, Third / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor