Blood test predicts preterm birth risk
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A novel biomarker test predicted the risk for spontaneous and medically indicated preterm birth, as well as extended hospital stays and severe adverse outcomes among infants, according to recent results of the TREETOP study.
The PreTRM test (Sera Prognostics Inc.) is based on a ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin (IBP4/SHBG) in serum. It is the only commercially available blood test that uses IBP4/SHBG to predict the risk for preterm birth, according to a press release from the manufacturer.
Previous research has shown that IBP4 regulates insulin-like growth factors that help facilitate nutrient delivery to the fetal compartment, according to Glenn R. Markenson, MD, professor of obstetrics and gynecology at Boston University School of Medicine, and colleagues.
“IBP4 is expressed by the placenta and has been reported to be upregulated (increased in the circulation) in women with growth-restricted fetuses, upregulated in the placentas of small-for-gestational-age neonates and downregulated in the placentas of large-for-gestational-age neonates,” they wrote in the American Journal of Obstetrics & Gynecology MFM. “These observations suggest IBP4 may be a biomarker for conditions of uteroplacental insufficiency.”
SHBG is also expressed by the placenta, according to the researchers. It regulates levels of sex steroids and has been shown to be downregulated by proinflammatory cytokines.
“Clinically meaningful prediction of [preterm birth] risk may require that biomarkers be sensitive to conditions of placental dysfunction and inflammation,” Markenson and colleagues wrote.
The current study is a preplanned subanalysis of a larger prospective observational study conducted at 18 centers across the United States. The subanalysis included 847 women with singleton pregnancies and no symptoms of preterm labor or membrane rupture. All of the women had blood drawn between 19 and 20 weeks gestation.
Markenson and colleagues measured IBP4/SHBG in serum to assess the value of the PreTRM test in predicting “very preterm birth,” defined as birth at less than 32 weeks of gestation, as well as adverse outcomes among infants. The severity of adverse neonatal outcomes was defined by a morbidity and mortality scoring system that ranged from 0 to 4, with more severe cases being scored as 3 or 4.
In the subanalysis, Markenson and colleagues reported nine cases of very preterm birth, eight of which were medically induced. In addition, 21 out of the 847 infants had a composite morbidity and mortality index score of 3 or greater, including four who died. Seven of the nine preterm birth cases had a severe index score of 3; the other two preterm birth cases had a score of 4 and died.
The IBP4/SHBG ratio was significantly higher among women with very preterm births (P = .032) and correlated with severe morbidity and mortality scores (P = .02), according to the researchers. Higher IBP4/SHBG scores were associated with younger gestational age at birth (P < .001).
The PreTRM test was a significant predictor of very preterm birth (area under the curve = 0.71; 95% CI, 0.55-0.87), the researchers reported. It also predicted severe vs. nonsevere morbidity and mortality scores (AUC = 0.67; 95% CI, 0.57-0.77), severe vs. mild-to-moderate scores (AUC = 0.65; 95% CI, 0.52-0.77) and mortality (AUC = 0.78; 95% CI, 0.63-0.93). In addition, the researchers observed a significant association between IBP4/SHBG and longer neonatal hospital stays.
The findings build on previous research demonstrating the value of IBP4/SHBG in predicting preterm birth before 37 weeks of gestation, according to Markenson and colleagues.
“Biomarker-based risk stratification may prove to be clinically and economically impactful if paired with currently utilized interventions,” they wrote. “Interventions such as corticosteroids and magnesium sulfate for a woman exhibiting signs and symptoms of preterm labor have well established benefits to neonatal health.”
Gregory C. Critchfield, MD, chair, president and CEO of Sera Prognostics, told Healio Primary Care that additional study results on the clinical utility of the PreTRM test along with early interventions are expected to be released later this year. The company is coordinating efforts so the test will be available across the United States.
“Our commercialization strategy execution involves step-by-step continued clinical utility implementation and is underway in the marketplace real-time,” Critchfield said. “We are rolling out coverage with evidence development initiatives with commercial and government payers, accountable care organizations and self-insured companies.” – by Stephanie Viguers
Disclosures: Critchfield is an employee of Sera Prognostics. Markenson reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.