Circulating levels of cytokines during pregnancy: thrombopoietin is elevated in miscarriage.
OBJECTIVE
To evaluate the hypothesis that cytokine levels are associated with miscarriage risk using serum samples collected before report of miscarriage.


METHODS
A nested case-control study.


METHODS
Biospecimens from the multisite Collaborative Perinatal Project, University of Florida, laboratory assessment of interleukin (IL)-1 receptor antagonist, IL-1beta, IL-4, IL-6, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, thrombopoietin (TPO), and granulocyte colony-stimulating factor (G-CSF).


METHODS
Cases of miscarriage (n = 439) were matched to controls (n = 373) by gestational age at sample collection.


METHODS
None.


METHODS
Miscarriage.


RESULTS
Increased risk of miscarriage was associated with elevated TPO (adjusted odds ratio [OR] 1.16, 95% confidence interval [CI] 1.00-1.36) and decreased G-CSF (adjusted OR 0.78, 95% CI 0.64-0.95). When analysis was restricted to samples collected more than 35 days before miscarriage, the effect of G-CSF was not observed (adjusted OR 0.96, 95% CI 0.72-1.28), whereas increased risk related to higher TPO remained.


CONCLUSIONS
Circulating levels of TPO may be associated with increased risk of miscarriage.
Whitcomb
Brian W
BW
Epidemiology Branch, Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, National Insttutes of Health, Bethesda, Maryland 20852, USA.
Schisterman
Enrique F
EF
Klebanoff
Mark A
MA
Baumgarten
Mona
M
Luo
Xiaoping
X
Chegini
Nasser
N
D000022:Abortion, Spontaneous / Q000097:blood*; D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D007378:Interleukins / Q000097:blood; D008423:Maternal Age; D011247:Pregnancy / Q000502:physiology*; D012016:Reference Values; D012959:Socioeconomic Factors; D013926:Thrombopoietin / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D013926:Thrombopoietin
N Engl J Med. 1999 Nov 25;341(22):1639-44
10572151
Hum Reprod. 2006 Oct;21(10):2555-63
16891626
Hum Reprod. 2000 Mar;15(3):713-8
10686225
J Reprod Fertil Suppl. 2000;55:91-7
10889838
J Reprod Immunol. 2000 Jul;47(2):87-103
10924744
Hum Reprod. 2000 Sep;15(9):2011-7
10967006
Obstet Gynecol. 2001 Feb;97(2):229-34
11165587
BJOG. 2001 Aug;108(8):777-83
11510699
Eur J Obstet Gynecol Reprod Biol. 2001 Sep;98(1):66-71
11516802
Am J Epidemiol. 2002 Jan 15;155(2):176-84
11790682
Med Sci Monit. 2002 Aug;8(8):CR607-10
12165750
Hum Reprod. 2002 Sep;17(9):2439-44
12202438
Am J Reprod Immunol. 2002 Oct;48(4):245-51
12516635
Ann Epidemiol. 2003 May;13(5):303-11
12821268
Eur J Obstet Gynecol Reprod Biol. 2003 Nov 10;111(1):43-9
14557010
Int Arch Allergy Immunol. 2004 Jun;134(2):93-119
15153791
Hokkaido Igaku Zasshi. 2004 May;79(3):237-41
15188632
Eur J Obstet Gynecol Reprod Biol. 2004 Jul 15;115(1):51-4
15223165
Ann Immunol (Paris). 1984 Nov-Dec;135D(3):309-12
6241446
Eur J Obstet Gynecol Reprod Biol. 1985 Dec;20(6):381-4
3910493
Am J Epidemiol. 1987 Sep;126(3):546-53
3618585
N Engl J Med. 1988 Jul 28;319(4):189-94
3393170
N Engl J Med. 1988 Dec 22;319(25):1617-23
3200277
J Exp Med. 1989 Dec 1;170(6):2081-95
2531194
Am J Epidemiol. 1991 Jan 15;133(2):144-53
1985444
Arch Gynecol Obstet. 1991;249(2):73-8
1953054
Hum Reprod. 1991 Oct;6(9):1332-7
1752937
Immunol Today. 1993 Jul;14(7):353-6
8363725
J Immunol. 1993 Nov 1;151(9):4562-73
8409418
Am J Epidemiol. 1995 Mar 1;141(5):417-27
7879786
Placenta. 1994 Dec;15(8):819-35
7886023
J Soc Gynecol Investig. 1996 Sep-Oct;3(5):259-61
8796838
Hum Reprod Update. 1996 Mar-Apr;2(2):118-36
9079408
Science. 1997 Sep 12;277(5332):1669-72
9287221
Am J Obstet Gynecol. 1998 Jul;179(1):100-4
9704772
Nat Med. 1998 Sep;4(9):1020-4
9734394
Arch Gynecol Obstet. 2004 Dec;270(4):227-9
15449074
Int J Gynaecol Obstet. 2005 Jan;88(1):44-8
15617704
Clin Obstet Gynecol. 2005 Jun;48(2):372-86
15805796
J Mol Med (Berl). 2005 Apr;83(4):316-20
15647951
Eur J Obstet Gynecol Reprod Biol. 2005 Oct 1;122(2):136-43
15893871
Hum Reprod Update. 2005 Nov-Dec;11(6):613-30
16006437
Cell Cycle. 2005 Dec;4(12):1729-31
16258288
Fertil Steril. 2000 Jan;73(1):136-42
10632428