Elevated second-trimester amniotic fluid interleukin-6 levels
predict preterm delivery
Katharine D. Wenstrom, MD, William W. Andrews, PhD, MD, John C. Hauth, MD, Robert L.
Goldenberg, MD, Mary B. DuBard, MA, and Suzanne P. Cliver, BA
OBJECTIVE: Our purpose was to determine whether early second-trimester amniotic fluid interleukin-6 lev-
els predict delivery before 34 weeks’ gestation.
STUDY DESIGN: We used stored second-trimester amniotic fluid samples obtained from women undergoing
genetic amniocentesis from 1988 to 1996. Interleukin-6 levels were measured by enzyme-linked immunosor-
bent assay in samples from every case known to result in delivery from 20 to 34 weeks’ gestation (
and 290 matched controls delivering at ≥37 weeks. Fetal aneuploidies, anomalies, and all cases delivering
within 30 days of the amniocentesis (which were thought to be possibly procedure related) were excluded.
RESULTS: Interleukin-6 levels were higher in cases than controls (1.9 ± 5.2 vs 1.0 ± 2.4 ng/ml,
Cases were grouped according to whether the preterm delivery was indicated or spontaneous: The mean in-
terleukin-6 levels were significantly higher than controls in the spontaneous group (1.6 ± 3.2 vs 0.8 ± 1.2
= 0.01) but not in the indicated group (1.4 ± 4.0 vs 0.8 ± 1.2 ng/ml,
= 0.12). In all samples the in-
terleukin-6 level was negatively correlated with the gestational age at delivery (
CONCLUSION: Elevated early second-trimester amniotic fluid interleukin-6 levels are associated with
preterm delivery, confirming that in some women this indicator of very early intrauterine inflammation pre-
dicts birth before 34 weeks’ gestation. (Am J Obstet Gynecol 1998;178:546-50.)
Key words: Interleukin-6, preterm delivery, amniotic fluid
Antenatal upper genital tract infection is known to be
strongly associated with preterm labor and delivery.
Because such infection is often subclinical, intractable
preterm labor may be the first indication of a pathologic
process. Tocolysis may then be contraindicated by infec-
tion or may fail because of underlying inflammation. The
earliest preterm births (i.e., <30 weeks’ gestation) are
most likely to be infection related
; these extremely pre-
mature or very-low-birth-weight infants have the highest
morbidity and mortality.
It is theorized that inflammation of the chorioamnion
stimulates prostaglandin production and ultimately leads
to cervical ripening and uterine contractions.
it is not known when such inflammation typically begins
or how long it smolders subclinically before producing
symptoms of preterm labor. The accepted standard crite-
rion for diagnosis of chorioamnion infection is
chorioamnion culture or histologic examination.
Unfortunately, these modalities are unavailable in an on-
going pregnancy. Amniotic fluid cultures have been used
to diagnose intrauterine infection, but they accurately re-
flect chorioamnion colonization in only 50% of cases.
However, several studies have shown that levels of an am-
niotic fluid cytokine, interleukin-6 (IL-6), correlate well
with chorioamnion colonization.
Amniotic fluid IL-6
levels are thus an excellent marker of intrauterine in-
flammation that can be evaluated prenatally.
We hypothesized that women destined to deliver
preterm have subacute chorioamnion inflammation be-
ginning very early in pregnancy, and that such inflamma-
tion can be identified by measuring early second
trimester amniotic fluid IL-6 levels. We used our bank of
stored amniotic fluid and our pregnancy outcomes com-
puter database to test this hypothesis.
Material and methods
With institutional review board approval, we accessed
our pregnancy outcomes computerized database and
linked bank of second-trimester amniotic fluid samples
obtained aseptically from all women undergoing genetic
amniocentesis from 1988 to 1996 (n = 12,610). Although
this was a select patient population, the incidence of
preterm delivery in this group (18.9%) was not different
from the incidence in our general patient population
(21.1%). All fluid was obtained by an experienced opera-
From the Center for Obstetric Research, Division of Maternal-Fetal
Medicine, Department of Obstetrics and Gynecology, The University of
Alabama at Birmingham.
Received for publication June 16, 1997; revised August 6, 1997; ac-
cepted September 22, 1997.
Reprint requests: Katharine D. Wenstrom, MD, The University of
Alabama at Birmingham, Department of Obstetrics and Gynecology,
618 South 20th St., UAB Station, Birmingham, AL 35233-7333.
Copyright © 1998 by Mosby, Inc.
0002-9378/98 $5.00 + 0 6/1/86441