Quantitative fetal fibronectin to predict preterm birth in asymptomatic women at high risk.
OBJECTIVE
To evaluate the diagnostic accuracy of cervicovaginal fluid quantitative fetal fibronectin, measured by a bedside analyzer, to predict spontaneous preterm birth before 34 weeks of gestation.


METHODS
We conducted a prospective masked observational cohort study of cervicovaginal fluid quantitative fetal fibronectin concentration in asymptomatic women at high risk of spontaneous preterm birth (n=1,448; 22-27 6/7 weeks of gestation) measured using a rapid bedside analyzer. The routine qualitative result (positive-negative) was made available to clinicians at the time of testing, but the quantitative result remained blinded until after delivery.


RESULTS
Spontaneous preterm birth (less than 34 weeks of gestation) increased from 2.7%, 11.0%, 14.9%, 33.9%, and 47.6% with increasing concentration of fetal fibronectin (less than 10, 10-49, 50-199, 200-499, and 500 ng/mL or greater, respectively). A threshold of 200 ng/mL had a positive predictive value of 37.7 (95% confidence interval [CI] 26.9-49.4) with specificity 96% (95% CI 95.3-97.3). Women with a fetal fibronectin concentration of less than 10 ng/mL had a very low risk of spontaneous preterm birth at less than 34 weeks of gestation (2.7%), no higher than the background spontaneous preterm birth rate of the general hospital population (3.3%). The quantitative fetal fibronectin test predicted birth at less than 34 weeks of gestation with an area under the curve (AUC) of 0.78 (95% CI 0.73-0.84) compared with the qualitative test AUC 0.68 (95% CI 0.63-0.73). Quantitative fetal fibronectin discriminated risk of spontaneous preterm birth at less than 34 weeks of gestation among women with a short cervix (less than 25 mm); 9.5% delivered prematurely less than 10 ng/mL compared with 55.1% greater than 200 ng/mL (P<.001).


CONCLUSIONS
Alternative risk thresholds (less than 10 ng/mL and greater than 200 ng/mL) improve accuracy when using quantitative fetal fibronectin measurements to define risk of spontaneous preterm birth. This is particularly relevant for asymptomatic women with a short cervix.


METHODS
II.
Division of Women's Health, King's College London, Women's Health Academic Centre Kings Health Partners, St. Thomas' Hospital, the UCL Institute for Women's Health, the Parturition Research Group, and the Institute for Reproductive and Developmental Biology, Imperial College London, London, the University of Edinburgh MRC Centre for Reproductive Health, Queen's Medical Research Institute, Edinburgh, and West Middlesex University Hospital, Middlesex, United Kingdom; and the Division of Maternal-Fetal Medicine, Loma Linda University Medical Center, Loma Linda, California.
Danielle S
DS
Abbott
Natasha L
NL
Hezelgrave
Paul T
PT
Seed
Jane E
JE
Norman
Anna L
AL
David
Phillip R
PR
Bennett
Joanna C
JC
Girling
Manju
M
Chandirimani
Sarah J
SJ
Stock
Jenny
J
Carter
Ruth
R
Cate
James
J
Kurtzman
Rachel M
RM
Tribe
Andrew H
AH
Shennan
D000328:Adult; D019540:Area Under Curve; D058070:Asymptomatic Diseases; D002584:Cervix Uteri / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D011237:Predictive Value of Tests; D047928:Premature Birth / Q000175:diagnosis*; D011446:Prospective Studies; D014463:Ultrasonography
D005353:Fibronectins