PMID- 22752762
OWN - NLM
STAT- MEDLINE
DCOM- 20121123
LR  - 20221017
IS  - 1619-3997 (Electronic)
IS  - 0300-5577 (Print)
IS  - 0300-5577 (Linking)
VI  - 40
IP  - 4
DP  - 2012 Jun
TI  - Midtrimester amniotic fluid concentrations of interleukin-6 and 
      interferon-gamma-inducible protein-10: evidence for heterogeneity of 
      intra-amniotic inflammation and associations with spontaneous early (<32 weeks) 
      and late (>32 weeks) preterm delivery.
PG  - 329-43
LID - /j/jpme.2012.40.issue-4/jpm-2012-0034/jpm-2012-0034.xml [pii]
LID - 10.1515/jpm-2012-0034 [doi]
AB  - INTRODUCTION: Intra-amniotic inflammation is traditionally defined as an 
      elevation of amniotic fluid interleukin (IL)-6. Previous case control studies 
      have suggested an association between an elevated midtrimester amniotic fluid 
      IL-6 and preterm delivery, although such an association has been recently 
      challenged. Intra-amniotic inflammation can also be defined by an elevation of 
      the T-cell chemokine, Interferon-gamma-inducible protein (IP)-10. An elevation in 
      amniotic fluid IP-10 has been associated with chronic chorioamnionitis, a lesion 
      frequently found in late spontaneous preterm birth and fetal death. In contrast, 
      an elevation in amniotic fluid IL-6 is typically associated with acute 
      chorioamnionitis and funisitis. This study was conducted to examine the 
      relationship between an elevation in amniotic fluid IL-6 in the midtrimester and 
      preterm delivery at or before 32 weeks of gestation, and the amniotic fluid 
      concentration of IP-10 and preterm delivery after 32 weeks of gestation. 
      MATERIALS AND METHODS: This cohort study included 847 consecutive women 
      undergoing genetic midtrimester amniocentesis; in 796 cases, amniotic fluid and 
      pregnancy outcome was available for study after exclusion of abnormal karyotype 
      and/or fetal congenital anomalies. Spontaneous preterm delivery was defined as 
      early (</=32 weeks) or late (after 32 completed weeks of pregnancy). The amniotic 
      fluid and maternal blood concentrations of IL-6 and IP-10 were measured by 
      specific immunoassays. RESULTS: 1) The prevalence of preterm delivery was 8.3% 
      (66/796), while those of early and late spontaneous preterm delivery were 1.5% 
      (n=12), and 4.5% (n=36), respectively; 2) patients who had a spontaneous preterm 
      delivery after 32 weeks of gestation had a higher median amniotic fluid IP-10 
      concentration than those who delivered at term [median 713 pg/mL, inter-quartile 
      range (IQR) 509-1427 pg/mL vs. median 589 pg/mL, IQR 402-953 pg/mL; P=0.006] and 
      an elevation of amniotic fluid IP-10 concentration above 502 pg/mL (derived from 
      an ROC curve) was associated with late spontaneous preterm delivery [odds ratio 
      3.9 (95% CI 1.6-9.9)]; 3) patients who had a spontaneous preterm delivery </=32 
      weeks of gestation had a higher median amniotic fluid IL-6 concentration than 
      those who delivered at term [median 2052 pg/mL, IQR 435-3015 pg/mL vs. median 414 
      pg/mL, IQR 209-930 pg/mL; P=0.006], and an elevated amniotic fluid IL-6 
      concentration above 1740 pg/mL (derived from an ROC curve) was associated with 
      early spontaneous preterm delivery [odds ratio 9.5 (95% CI 2.9-31.1)]; 4) 
      subclinical intra-amniotic inflammation, defined as an elevation of IL-6 (>/=2.9 
      ng/mL) or IP-10 (>/=2.2 ng/mL) concentration above the 95th percentile of patients 
      who had uncomplicated term delivery (n=652 for IL-6 and n=633 for IP-10), was 
      observed in 6.3% (50/796) and 5.8% (45/770) of cases, respectively. Although each 
      type of inflammation is a risk factor for spontaneous preterm delivery, many 
      patients had a term delivery without complication; 5) the amniotic fluid in the 
      midtrimester did not contain microorganisms detectable with cultivation 
      techniques. CONCLUSIONS: INTRA-amniotic inflammation is heterogeneous. Some 
      patients have elevated amniotic fluid concentrations of IL-6, and are at risk for 
      spontaneous preterm delivery before 32 weeks of gestation, while others have an 
      elevated IP-10 (a chemotactic T-cell chemokine) and such patients are at risk for 
      spontaneous preterm delivery after 32 weeks of gestation. A fraction of patients 
      have subclinical intra-amniotic inflammation and deliver at term. The clinical 
      significance of this condition remains to be determined.
FAU - Gervasi, Maria-Teresa
AU  - Gervasi MT
AD  - Ob/Gyn Unit, Department for Health of Mothers and Children, Azienda Ospedaliera, 
      Padua, Italy.
FAU - Romero, Roberto
AU  - Romero R
FAU - Bracalente, Gabriella
AU  - Bracalente G
FAU - Erez, Offer
AU  - Erez O
FAU - Dong, Zhong
AU  - Dong Z
FAU - Hassan, Sonia S
AU  - Hassan SS
FAU - Yeo, Lami
AU  - Yeo L
FAU - Yoon, Bo Hyun
AU  - Yoon BH
FAU - Chaiworapongsa, Tinnakorn
AU  - Chaiworapongsa T
LA  - eng
GR  - ZIA HD002400-18/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PL  - Germany
TA  - J Perinat Med
JT  - Journal of perinatal medicine
JID - 0361031
RN  - 0 (CXCL10 protein, human)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Interleukin-6)
SB  - IM
MH  - Adult
MH  - Amniotic Fluid/*chemistry
MH  - Chemokine CXCL10/*analysis
MH  - Chorioamnionitis/metabolism
MH  - Female
MH  - *Gestational Age
MH  - Humans
MH  - Interleukin-6/*analysis
MH  - Pregnancy
MH  - Premature Birth/diagnosis/epidemiology/*metabolism
PMC - PMC3498502
MID - NIHMS419042
EDAT- 2012/07/04 06:00
MHDA- 2012/12/10 06:00
PMCR- 2013/06/01
CRDT- 2012/07/04 06:00
PHST- 2012/02/21 00:00 [received]
PHST- 2012/03/19 00:00 [accepted]
PHST- 2012/07/04 06:00 [entrez]
PHST- 2012/07/04 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2013/06/01 00:00 [pmc-release]
AID - /j/jpme.2012.40.issue-4/jpm-2012-0034/jpm-2012-0034.xml [pii]
AID - 10.1515/jpm-2012-0034 [doi]
PST - ppublish
SO  - J Perinat Med. 2012 Jun;40(4):329-43. doi: 10.1515/jpm-2012-0034.