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

Abstract

Objective To determine the value of combinations of cervical interleukin-6 (IL-6), cervical interleukin-8 (IL-8), the phosphorylated isoform of insulin-like growth-factor binding protein-1 (IGFBP-1), and cervical ultrasonography in the prediction of preterm birth. Design Prospective follow up.Setting Oulu University Hospital maternity clinic from February 1997 to July 1998. Population Women with singleton pregnancies (n 77), referred from outpatient 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 recruitment were studied as a reference group.Methods A urine sample for bacterial culture was collected, and cervical swab samples for assays of interleukin-6 and -8 and phoshorylated IGFBP-1 were taken before digital cervical examination. A Pap smear for analysis of bacterial vaginosis and samples for analysis of chlamydia and streptococci were also obtained. Cervical measurements were made by transvaginal ultrasonography. The same sampling and cervical measurement were repeated twice at two-week intervals. The cutoff values of the markers were determined by receiveroperating characteristic curve analysis.Main outcome measure Preterm birth (,37 weeks). ResultsThe preterm birth (,37 weeks) rate for women in the study group was 16% (12/77). The cervical interleukin-6 cutoff value (61 ng/L) at ®rst visit had a sensitivity of 73% and a speci®city of 61% in predicting preterm birth, with a positive likelihood ratio (LR 1 ) of 1.9 (95% CI 1.2±3.0). An ultrasonographically measured cervical index value of . 0.36 at recruitment predicted preterm birth in 25% (5/20) of the study group compared with 9% (5/54); LR 1 2.2 (95% CI 1.03±4.7). Cervical phosphorylated IGFBP-1 . 6.4mg/L [LR 1 1.8 (95% CI 0.7±2.9)], interleukin-8 . 3739 ng/L [LR 1 1.4 (95% CI 0.9±2.4)], and ultrasonograpic cervical length , 29.3 mm [LR 1 2.7 (95% CI 0.8±9.7)] increased the risk of preterm birth. According to the logistic regression model, a combination of IL-6, and IL-8 and cervical index increased the speci®city to 97%, but the sensitivity fell to 30% in detecting preterm birth. There was a signi®cantly increased incidence of puerperal infections if phosphorylated IGFBP-1 concentrations were elevated (. 21.0 mg/L), 36% (4/11) compared with 4.6% (3/65), LR 1 6.7 (95% CI 2.7±17), the sensitivity being 67% (4/6) and the speci®city 90% (63/70). Elevated phosphorylated IGFBP-1 concentrations (. 21.6mg/L) were also associated with an increased risk of neonatal infections; LR 1 8.0 (95% CI 3.5±18).Conclusions An increase in cervical IL-6 concentration and the ultrasonographically 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 speci®city of the tests used in this study are good enough to predict preterm birth for clinical decision making. C...

Zinc Supplementation during Pregnancy Protects against Lipopolysaccharide-Induced Fetal Growth Restriction and Demise through Its Anti-inflammatory Effect

“…We found that zinc supplementation during pregnancy significantly attenuated LPS-induced upregulation of TNF-a and IL-1b in placenta. Increasing evidence demonstrates that IL-6 and IL-8 are associated with preterm delivery (36,37). An earlier report showed that treatment of murine decidual explants with LPS resulted in significant increases in IL-6 (38).…”

Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling

“…231 For symptomatic women, one study reported spontaneous preterm birth within 24 hours, 240 five studies within 48 hours 120,223,225,237,239 and four studies reported birth within 5-7 days of testing, 226,236,238,241 while the remainder reported birth before 35-37 weeks' gestation. 90,103,218,224,[227][228][229][230]233,235 Accuracy of IL-6 in asymptomatic women For (Figure 43). For predicting spontaneous preterm birth before 37 weeks' gestation, a single amniotic fluid IL-6 measurement had an LR+ of 1.91 (95% CI 0.99-3.67) and LR-of 0.95 (95% CI 0.90-1.00) ( Figure 43).…”

“…103 There were 12 studies evaluating the amniotic level of IL-6, two in asymptomatic women 220,222 and ten in symptomatic women, 120,218,[223][224][225][226][227][228][229][230] as a predictor for spontaneous preterm birth. There were ten studies evaluating cervical IL-6, three in asymptomatic women 103,221,231 and seven in symptomatic women 90,103,[232][233][234][235][236] as a predictor of spontaneous preterm birth in women. One study evaluated serial testing of cervical IL-6 in asymptomatic women.…”

“…103,221,227 All studies in both asymptomatic and symptomatic women provided adequate test description. However, out of 20 studies on symptomatic women, most were lacking in reporting of consecutive enrolment with only three studies reporting consecutive enrolment 103,227,233 and blinding of test results, where only eight studies reported it. 90,103,120,224 ,225,227,237,238 The methodological quality of the primary studies included is summarised in Figure 42.…”

Elevated levels of decidual insulin‐like growth factor binding protein‐1 in cervical fluid in early and mid‐pregnancy are associated with an increased risk of spontaneous preterm delivery

“…4 Many chorion/decidual products have been evaluated as markers for PTD. [4][5][6][7][8][9][10] In most studies, the performance of potential marker molecules has been evaluated among women with uterine contractions or preterm labour during the late-second trimester or third trimester.…”