THE VALUE OF phIGFBP-I ASSAY (Actim® Partus) FOR PREDICTING PRETERM DELIVERY IN UNCOMPLICATED TWIN PREGNANCIES.

Authors Anna Liza Roslani Alik Riasadesa Zakaria Rozihan Ismail Department of Obstetrics & Gynaecology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia

Introduction Insulin-like growth factor binding protein-1 (IGFBP-1) is produced by the decidual cells of the endometrium during pregnancy. It is found in high concentrations in amniotic fluid. phIGFBP-1 leaks into cervical secretions when the chorion & amnion (fetal membranes) detach from each other. Thus the presence of phIGFBP-1 (levels >10mg/l) is associated with 10-fold risk of preterm labour. phIGFBP-1 : phosphorylated isoform

Introduction Phosphorylated Insulin-like growth factor binding protein-1 (phIGFBP-I) assay’s (Actim® Partus) value in predicting preterm delivery in singleton pregnancies has been well documented. Superior to Fetal fibronectin & cervical length. 2,3 There are limited studies/data on phIGFBP-I in twin pregnancies.

Objectives To determine the sensitivity, specificity, PPV and NPV of phIGFBP-1 test strip for predicting preterm delivery in twin pregnancies Within 7 days of the test Within 14 days of the test To determine if phIGFBP-1 test strip improves perinatal outcomes

Methods A cross-sectional, prospective study Single centre Women with twin pregnancy were enrolled at 28 weeks gestation

Inclusion criteria Twin pregnancy diagnosed before 28 weeks gestation Gestation confirmed by 1st trimester USG Exclusion criteria Twin to twin transfusion syndrome, Selective IUGR Fetal anomalies Preterm prelabour rupture of membranes Antepartum haemorrhage

After consent to take part in the study, randomized to study and control groups. Baseline HVS, cervical length measurement via TVS and growth USG. Vaginal infections were treated accordingly.

Study group Growth scans @ 28W, 30W, 32W & 34W. pIGFBP-1 @ 28W, 30W, 32W & 34W. If pIGFBP-1 +ve, given IM dexamethasone 12mg (2 doses 12 hours apart) and tocolysed if abdominal pain present.

All twin pregnancies with gestation confirmed by 1st trimester USG Exclusion criteria: TTTS, Selective IUGR, Single fetal demise PPROM Cervical length & HVS @ 28W Randomization Study Group Growth scans and phIGFBP@ 28W, 30W, 32W & 34W Control Group Growth scans @ 28W, 30W, 32W & 34W phIGFBP Positive IM Dexamethasone & weekly follow up. phIGFBP Negative Continue follow up every 2 weeks.

Primary outcomes Secondary outcomes Delivery within 7 days of a test Gestation at delivery Birth weights NICU admissions

Results

115 women were recruited. DEMOGRAPHICS Subjects N=61 Controls N=54 Age (years) 28 (15-42) 29 (16-42) Parity 1.48 Chorionicity Monochorionic Dichorionic 70.5% 29.5% 50.0% Average Cx length (cm) 31.84 32.17

Total tests performed 228. Average number of tests performed per subject 3.74 tests. 23 +ve tests in 14 patients 3 delivered within 7 days 9 delivered within 14 days 5 delivered >36W (35.71%)

Analysis: del <7 days Delivery < 7 days Not delivered after 7 days Positive pIGFBP 3 11 Negative pIGFBP 191 Sensitivity 50.0% Specificity 95.0% PPV 0.21 NPV 0.98 3 –ve tests delivered within 7 days (5-7days) 1 had abnormal HVS 2 had abdo pain

Analysis: del <14 days Delivery <14 days Not delivered after 14 days Positive pIGFBP 9 5 Negative pIGFBP 189 Sensitivity 64.0% Specificity 97.0% PPV 0.64 NPV 0.97

False +ve and Vaginal infection 9 false +ve test (for delivery <7 days) 7 (77.78%) had vaginal infection (HVS) 2 (22.22%) had no vaginal infection p=0.021 9 (64.29%) had abnormal HVS – 6 candida, 3 GBS, as compared to 17 (36.17%) with –ve test who had abnormal HVS

Secondary outcomes Subjects N=61 Controls N=54 Average gestation at delivery (weeks) 36.2 36.0 Preterm delivery 28 (45.9%) 28 (51.9%) Mode of delivery Vaginal CS 49.2% 50.8% 40.7% 59.3% Average birth weight (g) 2230 2278 NICU admission of at least 1 twin 27.9% 37.0% P=0.294

Discussion

Preterm delivery rate in our series was 48 Preterm delivery rate in our series was 48.7%, which is lower than generally quoted rates of 57%.4 Preterm deliveries account for the highest admission rates to NICU with high morbidity and mortality. Prediction of preterm birth is vital so that neonatal care can be planned.

Sensitivity (50.0%) was lower compared to singleton pregnancies. For delivery within 7 days of the test, Specificity (95.0%) and NPV (0.98) seem to be as good as in singleton pregnancies. 85.0% specificity and NPV of 0.941 Sensitivity (50.0%) was lower compared to singleton pregnancies. 93.8% in singleton pregnancies1

Higher false positives could be caused by the larger decidua in twin pregnancies, producing higher levels of phIGFBP-1. Higher false positives in the presence of vaginal infections.

Sensitivity and PPV of the test was improved when predicting preterm delivery within 14 days of the test. Significant levels of phIGFBP-1 in cervical secretions is reached earlier with the larger decidual area.

There were lower rates of NICU admissions in our study group compared to controls (27.9% vs 37.0%, p=0.294) This could be due to earlier administration of Dexamethasone and tocolysis. However, overall preterm delivery rates were unchanged, which reiterates that we are still unable to prevent to prevent preterm labour.

Conclusion

pIGFBP-1 test strip is useful in predicting preterm delivery in twin pregnancy. It has high sensitivity and NPV for preterm delivery within 7 days in twin pregnancies. Possible value in predicting preterm delivery as early as 14 days prior to delivery.

Declaration of Interest Actim Partus test strips were supplied by Alere International.

References 1. Lembet A, Eroglu D, Ergin T, et al. New rapid bed-side test to predict prererm delivery: phosphorylated insulin-like growth factor binding protein-1 in cervical secretions. Acta Obstet Gynecol Scand 2002;81:706-12 2. Ting H-S, Chin P-S, Yeo GSH, Kwek K. Comparison of bedside test kits for prediction of preterm delivery: Phosphorylated Insulin-like Growth Factor Binding Protein-1 (pIGFBP-1) test and fetal fibronectin test. Ann Acad Med Singapore 2007;36:399-402 3. Eroglu D, Yanik F, Oktem M, Zeyneloglu HB, Kuscu E. Prediction of preterm delivery among women with threatened preterm labor. Gynecol Obstet Invest 2007;64:109-16 4. Gardner MO, Goldenburg RL, Cliver SP, Tucker JM, Nelson KG, Copper RL. The origin and outcome of twin pregnancies. Obstetrics and Gynecology 1995;85:553-57