Validating the ratio of insulin like growth factor binding protein 4 to
sex hormone binding globulin as a prognostic predictor of preterm birth
in Viet Nam: a case-cohort study
Abstract
Objective To validate a serum biomarker developed in the
USA for preterm birth (PTB) risk stratification in Viet Nam.
Design Case-cohort study Setting Tu Du
Hospital, Ho Chi Minh City, Viet Nam Population Women
with a viable singleton pregnancy (n=5000). Methods
Maternal serum was collected between 19 +0-22
+6 weeks’ gestation and participants followed to
neonatal discharge. Relative insulin-like growth factor binding protein
4 (IGFBP4) and sex hormone binding globulin (SHBG) abundances were
measured by mass spectrometry and their ratio compared between PTB cases
and term controls. Discrimination (area under the receiver operating
characteristic curve, AUC) and calibration for PTB <37 and
<34 weeks were tested, with model tuning using clinical
factors. Main outcomes measures All PTBs (any birth ≤37
weeks’ gestation) and spontaneous PTBs (birth ≤37 weeks’ gestation with
clinical signs of initiation of parturition). Results
Complete data were available for 4984 (99.7%), cohort PTB rate=6.7%;
n=335. We observed an inverse association between IGFBP4/SHBG ratio and
gestational age at birth (p=0.017); AUC 0.60 (95% CI, 0.53-0.68).
Including previous PTB (multiparous women) or prior miscarriage
(primiparous women) improved performance (AUC 0.65 and 0.70,
respectively, for PTB <37 and <34 weeks’ gestation).
Optimal performance (AUC 0.74) was between 19-20 weeks’ gestation, for
BMI >21kg/m 2 and age 20-35 years.
Conclusions We have validated a novel serum biomarker
for PTB risk stratification in a very different setting to the original
study. Further research is required to determine appropriate ratio
thresholds based on the prevalence of risk factors and the availability
of resources and preventative therapies.