Analysis of placental biomarkers in blood could prevent unnecessary ultrasound scans in fetal growth restriction

The Fetal Maternal Medicine group at Vall d'Hebron Research Institute (VHIR) and the Obstetrics Department of Vall d'Hebron University Hospital have demonstrated the usefulness of placental biomarkers for fetal growth restriction surveillance. The analysis of these markers in blood provides information on the risk of having a premature birth in the following weeks and, therefore, informs on the need to carry out a more or less exhaustive follow-up according to each case and to avoid performing unnecessary ultrasound examinations. The results of the study have been published in BJOG: An International Journal of Obstetrics & Gynaecology.

The study involved 134 pregnant women between 20 and 36 weeks of gestation with small-for-gestational-age fetuses or with early-onset fetal growth restriction. Small fetuses are considered those with a weight below the 10th centile. In fetal growth restriction, this low weight is usually accompanied by other abnormalities in the fetus or placenta. In both cases there may be complications during pregnancy and, for this reason, ultrasound follow-up is necessary to reduce the risks. However, there is no clear consensus on the optimal frequency of ultrasound examinations in each case. So far, it is usual to perform a weekly ultrasound scan in cases with growth restriction and one every two weeks in small-for-gestational-age fetuses.

To improve the surveillance of these patients, the researchers have studied the relationship between the blood levels of two placental biomarkers (sFlt-1/PlGF ratio), known to be altered when there is a problem in pregnancy. These two biomarkers were analyzed in blood samples from patients at the time of diagnosis and compared with the time of delivery. In all cases, the type and timing of delivery were decided according to standard hospital protocols.

Regarding small-for-gestational-age fetuses, in all cases the sFlt-1/PlGF1 ratio was below 38 at the time of diagnosis and delivery occurred more than 3 weeks later. In the cases of fetuses with growth retardation, no woman with a value below 38 delivered before 2 weeks, and only 2% of these delivered before 4 weeks. This shows that having a ratio below 38 points rules out the need to advance labor by at least 2-3 weeks. "These pregnancies are considered less risky and therefore the number of ultrasounds scans performed on these women could be reduced. This would decrease the discomfort and anxiety associated with performing many medical tests and also the burden on the health system", explains Dr. Erika Bonacina, specialist of the Obstetrics Department of the Vall d'Hebron University Hospital, researcher of the Fetal Maternal Medicine group at VHIR and first author of the article.

On the other hand, researchers demonstrated that, as sFlt-1/PlGF ratio values increase, the time to delivery is reduced in fetal growth restriction. Specifically, more than 50% of cases with an sFlt-1/PlGF ratio higher than 85 required delivery to be advanced within less than one week. This happened in 100% of the cases with a value greater than 655. Therefore, these women require closer follow-up to avoid fetal complications up to the time of delivery.

"This study demonstrates the usefulness of analyzing the sFlt-1/PlGF ratio to classify the severity of fetuses with growth restriction and to approximate the time to delivery. The vast majority of centers in Spain have the capacity to analyze these markers in blood, therefore, once we validate its usefulness, it would be a useful method to apply in routine clinical practice", concludes Dr. Manel Mendoza, specialist of the Obstetrics Department, head of the Placental Insufficiency Unit at Vall d'Hebron University Hospital and researcher of the Fetal Maternal Fetal Medicine group at VHIR.