Prediction of spontaneous preterm delivery in women presenting with premature labor: a comparison of placenta alpha microglobulin-1, phosphorylated insulin-like growth factor binding protein-1, and cervical length

Background Placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 have been studied in patients at risk for preterm birth with signs and symptoms of preterm labor. However, a direct comparison between these 2 biomarkers, alone or in combination with cervical length measurement with an adequate sample size, has been lacking to date. Objective The purpose of this study was to compare the placental alpha microglobulin-1 test and the phosphorylated insulin-like growth factor-binding protein-1 test alone and in combination with cervical length measurement for the prediction of imminent spontaneous preterm birth of testing in pregnant women with symptoms of preterm labor in a tertiary care setting. Study Design Four hundred three patients with intact amniotic membranes and cervical dilation ≤3 cm, without recent intercourse or cerclage, between gestational weeks of 20+0 and 36+6 were recruited prospectively from 3 international centers. Placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 tests were conducted before cervical length measurement via transvaginal ultrasound scanning. Caregivers were blinded to the biomarker test results. Medically indicated deliveries within 14 days of testing were excluded. Standard performance statistics with 95% confidence intervals were calculated and compared based on pairwise estimates from a generalized model. Results Of 403 subjects who were enrolled in the study cohort, 94% (383/403 women) met the inclusion criteria. Median gestational age and cervical length at presentation were 30+5 weeks and 27 mm, respectively; 6.8% women (26/383 women) had spontaneous birth ≤7 days from testing. The placental alpha microglobulin-1 test was positive in 7.8% of the women (30/383 women); the phosphorylated insulin-like growth factor-binding protein-1 test was positive in 29.5% women (113/383 women). Positive predictive value for placental alpha microglobulin-1, phosphorylated insulin-like growth factor-binding protein-1, and cervical length <25 mm for the prediction of spontaneous preterm birth in the overall cohort was 60.0% (18/30 women), 18.6% (21/113 women), 11.8% (18/152 women), respectively. The negative predictive value was 97.7% (345/353 women), 98.2% (265/270 women), 96.5% (223/231 women), respectively. The prevalence of spontaneous preterm birth in this group was 6.8% (26/383 women). The positive likelihood ratios were 20.6, 3.1, and 1.8, respectively. The negative likelihood ratio were 0.3, 0.3, and 0.5, respectively. Positive predictive values for placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 tests in patients with cervical length shortening of 15–30 mm for the prediction of spontaneous preterm birth were 60.9% (14/23 women) and 28.1% (16/57 women), respectively. The negative predictive values were 97.1% (168/173 women) and 97.8% (136/139 women), respectively. The prevalence of spontaneous preterm birth in the 15–30 mm cohort was 9.7% (19/196 women). The positive likelihood ratios were 14.5 and 3.6, respectively. The negative likelihood ratios were 0.3 and 0.2, respectively. Conclusion Placental alpha microglobulin-1 is significantly more specific than phosphorylated insulin-like growth factor-binding protein-1 for the prediction of spontaneous preterm birth ≤7 days (P<.0001), whereas both tests have comparable sensitivity. In patients with cervical length 15–30 mm, although placental alpha microglobulin-1 has a significantly higher positive predictive value and specificity compared with phosphorylated insulin-like growth factor-binding protein-1 for the prediction of spontaneous preterm birth at ≤7 days (P<.01), both tests have a comparable sensitivity and negative predictive value. In conclusion, placental alpha microglobulin-1 is a better predictor of imminent spontaneous preterm birth when compared with phosphorylated insulin-like growth factor-binding protein-1 alone or in combination with cervical length measurement. In patients with shortening of cervical length of 15–30 mm, the placental alpha microglobulin-1 test is a significantly better predictor of imminent spontaneous preterm birth within 7 days of testing than is phosphorylated insulin-like growth factor-binding protein-1. Placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 have been studied in patients at risk for preterm birth with signs and symptoms of preterm labor. However, a direct comparison between these 2 biomarkers, alone or in combination with cervical length measurement with an adequate sample size, has been lacking to date. The purpose of this study was to compare the placental alpha microglobulin-1 test and the phosphorylated insulin-like growth factor-binding protein-1 test alone and in combination with cervical length measurement for the prediction of imminent spontaneous preterm birth of testing in pregnant women with symptoms of preterm labor in a tertiary care setting. Four hundred three patients with intact amniotic membranes and cervical dilation ≤3 cm, without recent intercourse or cerclage, between gestational weeks of 20+0 and 36+6 were recruited prospectively from 3 international centers. Placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 tests were conducted before cervical length measurement via transvaginal ultrasound scanning. Caregivers were blinded to the biomarker test results. Medically indicated deliveries within 14 days of testing were excluded. Standard performance statistics with 95% confidence intervals were calculated and compared based on pairwise estimates from a generalized model. Of 403 subjects who were enrolled in the study cohort, 94% (383/403 women) met the inclusion criteria. Median gestational age and cervical length at presentation were 30+5 weeks and 27 mm, respectively; 6.8% women (26/383 women) had spontaneous birth ≤7 days from testing. The placental alpha microglobulin-1 test was positive in 7.8% of the women (30/383 women); the phosphorylated insulin-like growth factor-binding protein-1 test was positive in 29.5% women (113/383 women). Positive predictive value for placental alpha microglobulin-1, phosphorylated insulin-like growth factor-binding protein-1, and cervical length <25 mm for the prediction of spontaneous preterm birth in the overall cohort was 60.0% (18/30 women), 18.6% (21/113 women), 11.8% (18/152 women), respectively. The negative predictive value was 97.7% (345/353 women), 98.2% (265/270 women), 96.5% (223/231 women), respectively. The prevalence of spontaneous preterm birth in this group was 6.8% (26/383 women). The positive likelihood ratios were 20.6, 3.1, and 1.8, respectively. The negative likelihood ratio were 0.3, 0.3, and 0.5, respectively. Positive predictive values for placental alpha microglobulin-1 and phosphorylated insulin-like growth factor-binding protein-1 tests in patients with cervical length shortening of 15–30 mm for the prediction of spontaneous preterm birth were 60.9% (14/23 women) and 28.1% (16/57 women), respectively. The negative predictive values were 97.1% (168/173 women) and 97.8% (136/139 women), respectively. The prevalence of spontaneous preterm birth in the 15–30 mm cohort was 9.7% (19/196 women). The positive likelihood ratios were 14.5 and 3.6, respectively. The negative likelihood ratios were 0.3 and 0.2, respectively. Placental alpha microglobulin-1 is significantly more specific than phosphorylated insulin-like growth factor-binding protein-1 for the prediction of spontaneous preterm birth ≤7 days (P<.0001), whereas both tests have comparable sensitivity. In patients with cervical length 15–30 mm, although placental alpha microglobulin-1 has a significantly higher positive predictive value and specificity compared with phosphorylated insulin-like growth factor-binding protein-1 for the prediction of spontaneous preterm birth at ≤7 days (P<.01), both tests have a comparable sensitivity and negative predictive value. In conclusion, placental alpha microglobulin-1 is a better predictor of imminent spontaneous preterm birth when compared with phosphorylated insulin-like growth factor-binding protein-1 alone or in combination with cervical length measurement. In patients with shortening of cervical length of 15–30 mm, the placental alpha microglobulin-1 test is a significantly better predictor of imminent spontaneous preterm birth within 7 days of testing than is phosphorylated insulin-like growth factor-binding protein-1.