Fetal growth restriction (FGR) reflects placental dysfunction and incurs a 10+ fold increased risk of stillbirth. Current practice (fundal height with selective ultrasound) only identifies 14.5-22% of babies <3rd centile (1-2). We previously reported low maternal circulating serine peptidase inhibitor Kunitz type-1 (SPINT1) as associated with low birthweight (3). Here, we developed a novel, point-of-care test (POCT) for SPINT1, and measured circulating levels at 36 weeks’ gestation to examine its performance as a screening test for FGR.
To develop the SPINT1 POCT, we utilized lanthanide-doped up-conversion nanoparticles (UCNP) bioconjugated with our SPINT1 detector antibody (UCNP-SPD). Our SPINT1 capture antibody was printed on a nitrocellulose membrane and assembled into test strips. Human plasma was diluted in running buffer, mixed with UCNP-SPD, and 50 µL of mixture added to the sample pad. The signal was read after 10 min using a strip reader equipped with a 980 nm laser. SPINT1 levels were quantified by generating a standard curve of known SPINT1 concentrations.
A case cohort of 36 week plasma samples was selected from a prospective population study in Melbourne. This included 30 cases who later delivered an infant with FGR (birthweight <3rd centile) and 111 randomly selected controls without FGR. Samples were run blinded, in triplicate.
Median SPINT1 level was 49.4 ng/ml (IQR 34.7-68.3 ng/mL) among 111 without FGR (the representative cohort). Median SPINT1 in those who later delivered with FGR was significantly lower (p =1.56x10-5) at 30.9 ng/mL (IQR 21.4- 46.5 ng/mL). The area under the receiver operator curve (AUC) was 0.76 and the detection was 43.3% (sensitivity) at 90% specificity.
Our SPINT1 point-of-care test identifies pregnancies at risk of FGR better than current clinical care. It could be integrated into prenatal clinics as a screening test to better identify pregnancies with placental insufficiency and at 10-fold increased risk of stillbirth.