Abstract
Threatened preterm labor (TPTL) is defined as persistent premature uterine contractions between 20 and 37 weeks of gestation and is the most common condition that requires hospitalization during pregnancy. Most of these TPTL women continue their pregnancies to term while only an estimated 5% will deliver a premature baby within ten days. The aim of this work was to study differential whole blood gene expression associated with spontaneous preterm birth (sPTB) within 48 hours of hospital admission. Peripheral blood was collected at point of hospital admission from 154 women with TPTL before any medical treatment. Microarrays were utilized to investigate differential whole blood gene expression between TPTL women who did (n = 48) or did not have a sPTB (n = 106) within 48 hours of admission. Total leukocyte and neutrophil counts were significantly higher (35% and 41% respectively) in women who had sPTB than women who did not deliver within 48 hours (p<0.001). Fetal fibronectin (fFN) test was performed on 62 women. There was no difference in the urine, vaginal and placental microbiology and histopathology reports between the two groups of women. There were 469 significant differentially expressed genes (FDR<0.05); 28 differentially expressed genes were chosen for microarray validation using qRT-PCR and 20 out of 28 genes were successfully validated (p<0.05). An optimal random forest classifier model to predict sPTB was achieved using the top nine differentially expressed genes coupled with peripheral clinical blood data (sensitivity 70.8%, specificity 75.5%). These differentially expressed genes may further elucidate the underlying mechanisms of sPTB and pave the way for future systems biology studies to predict sPTB.
Highlights
Preterm birth (PTB; birth at,37 weeks of gestation) occurs in about 8–11% of pregnancies worldwide and remains the main cause of perinatal mortality and morbidity in the developed world [1]
Two hundred out of 300 samples were retrospectively selected based on delivery outcome and re-examined for eligibility adhering to our inclusion and exclusion criteria; 178 samples were confirmed for eligibility and sent to the microarray facility
No woman had bacteria vaginosis. Fetal fibronectin (fFN) test was performed on 62 patients out of 154 patients (40.3%), with 83.3% sensitivity, 66.0% specificity, 37.0% and 94.3% positive and negative predictive values (PPV and NPV) respectively
Summary
Preterm birth (PTB; birth at ,37 weeks of gestation) occurs in about 8–11% of pregnancies worldwide and remains the main cause of perinatal mortality and morbidity in the developed world [1]. Threatened preterm labor (TPTL) is defined as persistent premature uterine contractions between 20 and 37 weeks of gestation and may include other symptoms such as pelvic pressure, backache, increased vaginal discharge, menstrual-like cramps, bleeding/show and shortened cervix [8,9,10,11]. Treatment of TPTL involves administration of tocolytic agents to temporarily inhibit uterine contractions and prolong the pregnancy up to 48 hours. This 48 hour window serves to achieve both the benefits of corticosteroid administration on fetal lung maturation as well as the ability to transport the woman to a tertiary hospital with advanced neonatal facilities [12,13]
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