Biomarkers of spontaneous preterm birth: an overview of the literature in the last four decades.
BACKGROUND
Understanding spontaneous preterm birth ([PTB] < 37 weeks) is difficult due to heterogeneities associated with multitudes of risk factors and pathophysiological pathways. Several biomarkers are routinely used clinically for predicting preterm labor; however, these factors are either nonspecific or detected too late.


OBJECTIVE
Systematic review of literature on PTB biomarkers in the last 40 years to map out the existing knowledge and gaps in understanding PTB biomarkers.


METHODS
Five electronic databases were searched for human studies on PTB biomarkers published in any language between 1965 and 2008.


METHODS
The phenotype of interest for final data extraction was exclusively spontaneous PTB with no rupture of membranes. Data extraction included (a) general characteristics of the study (clinical setting, period, and study design), (b) study/participant characteristics (inclusion and exclusion criteria, race/ethnicity, number of participants, gestational age at sampling, (c) characteristics of the biomarker (type, rationale for its selection, type of biological sample, and assay used, and (d) concentration of biomarkers in cases and controls.


METHODS
The search yielded 7255 citations and data were extracted from 217 articles which met our inclusion and exclusion criteria.


RESULTS
A total of 116 different biomarkers were reported and these were assayed 578 times in the 217 included studies. Over two thirds of the 217 studies were performed on North American or European populations. No reliable biomarkers emerged as a risk predictor of PTB.


CONCLUSIONS
Identifying similar studies on biomarkers for the prediction of PTB was a very challenging task due heterogeneities in study design, sampling issues (types, timing and processing), assay methods, and analyses. Major areas of concern identified in this review include poor phenotype definition, nonideal study designs and poor rationale for biomarker selection and assays and population stratification issues.
Department of OB & GYN, Division of Maternal- Fetal Medicine, The University of Texas Medical Branch at Galveston, TX, USA. rmenon3@emory.edu
Ramkumar
R
Menon
Maria Regina
MR
Torloni
Chiara
C
Voltolini
Michela
M
Torricelli
Mario
M
Merialdi
Ana Pilar
AP
Betrán
Mariana
M
Widmer
Tomas
T
Allen
Iulia
I
Davydova
Zulfiya
Z
Khodjaeva
Poul
P
Thorsen
Marian
M
Kacerovsky
Vojtìch
V
Tambor
Tytti
T
Massinen
Judith
J
Nace
Chander
C
Arora
D015415:Biomarkers / Q000032:analysis; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007752:Obstetric Labor, Premature; D011247:Pregnancy; D047928:Premature Birth; D011786:Quality Control; D012107:Research Design; D012307:Risk Factors; D013048:Specimen Handling / Q000379:methods
D015415:Biomarkers