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

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

3. 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

4. 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.

5. 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

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

7. 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

8. 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.

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

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

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

12. Results

13. 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

14. 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%)

15. 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

16. 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

17. 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

18. 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

19. Discussion

20. 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.

21. 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

22. 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.

23. 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.

24. 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.

25. Conclusion

26. 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.

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

28. 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:
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