Combination of cervical interleukin-6 and-8, phosphorylated insulin-like growth factor-binding protein-1 and transvaginal cervical ultrasonography inassessment of the risk of preterm birth

Objective To determine the value of combinations of cervical interleukin-6 (IL-6), cervical interleukin-8 (IL-8), the phosphorylated isoform of insuli n-like growth-factor binding protein-1 (IGFBP-1), and cervical ultrasonogra phy in the prediction of preterm birth. Design Prospective follow up. Setting Oulu University Hospital maternity clinic from February 1997 to Jul y 1998. Population Women with singleton pregnancies (n = 77), referred from outpati ent clinics at 22-32 weeks of,gestation with symptoms (uterine contractions ) or signs (cervical change) of threatened preterm birth. Symptomless women (n = 78) matched for gestational age, parity and maternal age at recruitme nt were studied as a reference group. Methods A urine sample for bacterial culture was collected, and cervical sw ab samples for assays of interleukin-6 and -8 and phoshorylated IGFBP-1 wer e taken before digital cervical examination. A Pap smear for analysis of ba cterial vaginosis and samples for analysis of chlamydia and streptococci we re also obtained. Cervical measurements were made by transvaginal ultrasono graphy. The same sampling and cervical measurement were repeated twice at t wo-week intervals. The cutoff values of the markers were determined by rece iver-operating characteristic curve analysis. Main outcome measure Preterm birth (< 37 weeks). Results The preterm. birth (< 37 weeks) rate for women in the study group w as 16% (12/77). The cervical interleukin-6 cutoff value (61 ng/L) at first visit had a sensitivity of 73% and a specificity of 61% in predicting prete rm birth, with a positive likelihood ratio (LR +) of 1.9 (95% CI 1.2-3.0). An ultrasonographically measured cervical index value of > 0.36 at recruitm ent predicted preterm birth in 25% (5/20) of the study Cr cup compared with 9% (5/54); LR + 2.2 (95% CI 1.03-4.7). Cervical phosphorylated IGFBP-1 > 6 .4 Lg/L [LR + 1.8 (95% CI 0.7-2.9)], interleukin-8 > 3739 ng/L [LR + 1.4 (9 5% CI 0.9-2.4)], and ultrasonograpic cervical length < 29.3 min [LR + 2.7 ( 95% CI 0.8-9.7)] increased the risk of preterm birth. According to the logi stic regression model, a combination of IL-6, and IL-8 and cervical index i ncreased the specificity to 97%, but the sensitivity fell to 30% in detecti ng preterm birth. There was a significantly increased incidence of puerpera l infections if phosphorylated IGFBP-1 concentrations were elevated (> 21.0 mug/L), 36% (4/11) compared with 4.6% (3/65), LR + 6.7 (95% CI 2.7-17), th e sensitivity being 67% (4/6) and the specificity 90% (63/70). Elevated pho sphorylated IGFBP-1 concentrations (> 21.6 Lg/L) were also associated with an increased risk of neonatal infections; LR + 8.0 (95% CI 3.5-18). Conclusions An increase in cervical IL-6 concentration and the ultrasonogra phically measured cervical index appear to be associated with preterm birth . A combination of these markers with measurement of cervical IL-8 appears to be the best predictor of preterm. birth. Neither the sensitivity nor spe cificity of the tests used in this study are good enough to predict preterm birth for clinical decision making. Cervical phosphorylated IGFBP-1 seems to be a marker of puerperal and neonatal infectious morbidity in cases of t hreatened preterm delivery, suggesting early tissue degradation at the chor iodecidual interface.