Prediction of spontaneous preterm delivery in women with preterm labor: analysis of multiple proteins in amniotic and cervical fluids.
OBJECTIVE
To analyze whether specific proteins in amniotic and cervical fluids, alone or in combination with risk factors, can identify women in preterm labor with intact membranes who will deliver spontaneously within 7 days of sampling.


METHODS
In a cohort of 89 women in preterm labor, amniotic and cervical fluids were collected between 22 and 33 weeks of gestation. Twenty-seven proteins were analyzed simultaneously using multiplex technology. Individual levels of each protein were compared and calculations performed to find associations among different proteins, background variables, and spontaneous preterm delivery within 7 days of sampling. The area under the curve (AUC) was calculated using receiver operating characteristic curve analysis, and prediction models were created based on stepwise logistic regression.


RESULTS
We found two multivariable models that predicted spontaneous preterm delivery better than any single variable. One combined multivariable prediction model was based on amniotic macrophage inflammatory protein-1beta, cervical interferon-gamma, and monocyte chemotactic protein-1. This model predicted outcome with 91% sensitivity, 84% specificity, 78% positive predictive value, and 94% negative predictive value, with a likelihood ratio of 5.6 and AUC of 0.91. An alternative, noninvasive model based on cervical length, cervical interferon-gamma, interleukin-6, and monocyte chemotactic protein-1 predicted delivery within 7 days with 85% sensitivity, 82% specificity, 74% positive predictive value, and 90% negative predictive value, with a likelihood ratio of 4.7 and AUC of 0.91.


CONCLUSIONS
A combination of proteins from amniotic fluid and cervical fluid or cervical length can help determine which women will deliver preterm.


METHODS
II.
Holst
Rose-Marie
RM
From the Perinatal Center, Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Sahlgrenska University Hospital/East, Göteborg, Sweden; the Imperial College, Institute of Reproductive and Developmental Biology, Queen Charlotte's & Chelsea Hospital, Hammersmith Campus, London, United Kingdom; the Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark; NANEA at the Department of Epidemiology, Aarhus University, Aarhus, Denmark; the Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia; and the Department of Obstetrics and Gynecology, Rikshospitalet, Oslo, Norway.
Hagberg
Henrik
H
Wennerholm
Ulla-Britt
UB
Skogstrand
Kristin
K
Thorsen
Poul
P
Jacobsson
Bo
B
D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry*; D001826:Body Fluids / Q000737:chemistry; D002584:Cervix Uteri; D018932:Chemokine CCL2 / Q000032:analysis; D054407:Chemokine CCL4 / Q000032:analysis; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D007752:Obstetric Labor, Premature; D011237:Predictive Value of Tests; D011247:Pregnancy; D047928:Premature Birth; D011506:Proteins / Q000032:analysis*; D012680:Sensitivity and Specificity
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D011506:Proteins; D007371:Interferon-gamma