Cervicovaginal vascular endothelial growth factor (VEGF) and risk of preterm birth (PTB)

Objective - During pregnancy, the human cervix undergoes angiogenic transformations. VEGF is expressed in cervical stroma and is proposed to play key roles in the process of cervical ripening and dilation. This study was conducted to evaluate whether cervical secretion of VEGF can be of clinical value in predicting impending PTB.

Study Design - In an observational prospective cohort study, we analyzed cervical fluid samples from 103 pregnant women (GA: median [IQR]: 28 [25-31] wks) who presented for either a routine prenatal visit (n=61) or for evaluation of threatened preterm labor (n=42). Cervical secretions were collected under a standard protocol which was followed in all cases. Cervical length (CL) was assessed by transvaginal ultrasound using well-established criteria. Dilation was evaluated by digital exam performed only after collection of the biological samples. VEGF levels were immunoassayed by investigators unaware of the clinical outcome. Main exclusion criteria were ruptured membranes, active labor, vaginal bleeding, vaginal exam or intercourse within 24h. Results were analyzed with and without normalization for total protein.

Results - 1) Clinical characteristics of the cohort are presented in Table;2) VEGF was detectable in all specimens, with no correlation between its levels, CL, twins or GA at collection; 3) There was an inverse correlation between VEGF and cervical dilation (R=-0.646, P=0.003); 4) Women with cervical dilation =1 cm had lower VEGF compared to those with a closed cervix (P=0.003); 5) Women who experienced PTB within 14 days (n=11) had lower VEGF (P=0.003); 6) A free VEGF level of =600 pg/mL had a sensitivity, specificity, +LR and -LR of 70%, 95%, 13.5 and 0.3, respectively in predicting PTB within 14 days.

Conclusions - Low VEGF levels in the cervicovaginal secretions of pregnant women are associated with an increased risk of PTB within 2 weeks of collection. Active engagement of VEGF in the process of cervical ripening and dilatation and/or increased affinity of extracellular matrix components for VEGF may provide explanation for our findings.