Early preterm birth risk linked to low PlGF levels during pregnancy screening

Early preterm birth risk linked to low PlGF levels during pregnancy screening | Image Credit: © Phushutter - © Phushutter - stock.adobe.com.

The risk of early preterm birth may be identified based on low placental growth factor (PlGF) level during routine gestational diabetes screening.¹

Approximately 9% of singleton births are preterm, defined as birth before 37 weeks’ gestation. Of preterm births, 1 in 4 are early preterm, defined as birth before 34 weeks’ gestation. Early preterm birth has been linked to significant risk of adverse infant and childhood outcomes, making it a major health concern in higher-resource nations.

Preterm birth either occurs spontaneously or through medical intervention. Of preterm births, over half are iatrogenic.² This often impacts the ability of the placenta to release PLGF.1 Therefore, early identification of preterm birth is necessary to improve maternal and perinatal health outcomes.

During first trimester multimodal screening in the United Kingdom, PlGF level in the maternal blood is measured to identify early preterm birth risk. However, this practice has not been widely adopted.

To determine the efficacy of maternal circulating PlGF at a midpregnancy screening test as a predictor of early preterm birth, investigators conducted a single-center, prospective cohort study. Participants included women aged at least 18 years with singleton pregnancy receiving care from obstetricians, midwives, or family physicians at Mount Sinai Hospital.

Exclusion criteria included pregestational diabetes, kidney disease, multiple gestations, and preexisting signs of placental dysfunction. PlGF blood testing was provided to participants during gestational diabetes screening, which often occurred at 24 to 28 weeks’ gestation.

Hospital central laboratories performed PlGF testing daily, with results posted to the hospital electronic medical record (EMR). The EMR was also assessed for maternal demographics, laboratory values, vital signs, and delivery information.

Early preterm birth was reported as the primary outcome of the analysis. Secondary outcomes included gestational age at birth, all preterm birth, spontaneous preterm birth, iatrogenic preterm birth, stillbirth, preeclampsia, severe preeclampsia, hemolysis, elevated liver-enzyme levels, and low platelet count syndrome, small for gestational age, birth weight, and mode of birth.

There were 9037 pregnant patients included in the final analysis, 8930 of whom had a PlGF level of 100 pg/mL or higher while 107 had a PlGF level under 100 pg/mL. Of participants, 7% were Asian, 2% Black, 18% White, 19% other race, and 53% unknown race.

Significant increases in advanced parity rates were observed among patients with PlGF levels under 100 pg/mL vs 100 pg/mL or higher. Additionally, gestational diabetes rates in these patients were 14% and 4%, respectively, and the median prepregnancy weights were 72 and 62 kg, respectively.

The area under the curve of PlGF was 0.80 for early preterm birth, with an optimal PlGF threshold of 290 pg/mL identified by the Youden Index. This indicated a sensitivity of 64.7%, specificity of 87.9%, positive predictive value (PPV) of 8.6%, and negative predictive value (NPV) of 98.9%.

A low PlGF level was reported in 12.9% of the cohort when the cutoff was 290 pg/mL. In comparison, a low PlGF level was reported in 1% when the cutoff was 100 pg/mL, with a sensitivity of 39.7%, specificity of 99.5%, PPV of 57.9%, and NPV of 98.9%.

The adjusted relative risk of early preterm birth was 10.56 for a PlGF threshold under 290 ph/mL. Patients with low PlGF were also at a significantly increased risk of all secondary outcomes except for spontaneous preterm birth.

These results indicated efficacy from PlGF testing toward identifying early preterm birth risk in pregnant patients. Investigators concluded this test may be used by clinicians to improve delivery of evidence-based interventions that mitigate adverse outcomes associated with preterm birth.

References

1. Gladstone RA, Ahmed S, Huszti E, et al. Midpregnancy placental growth factor screening and early preterm birth. JAMA Netw Open. 2024;7(11):e2444454. doi:10.1001/jamanetworkopen.2024.44454
2. Aughey H, Jardine J, Knight H, et al.Iatrogenic and spontaneous preterm birth in England: a population-based cohort study.BJOG. 2023;130(1):33-41. doi:10.1111/1471-0528.17291