Maternal Blood Test May Help Diagnose Fetal Growth Restriction in Late Preterm Pregnancies

BcL-2, a protein that regulates cell death, has been identified as a potential marker for intrauterine growth restriction, an obstetric condition that can lead to cerebral palsy in affected children, a study suggests.

Higher levels of this protein were found in maternal and umbilical cord blood in late preterm pregnancies with uterine growth restriction (IUGR), suggesting that it may serve as a marker to confirm the diagnosis and to assess general fetal well-being.

The study, “Serum Bcl-2, caspase-9 and soluble FasL levels as perinatal markers in late preterm pregnancies with intrauterine growth restriction,” was published in The Turkish Journal of Pediatrics.

IURG is a complex obstetric condition in which the fetus does not reach the size and weight expected for the number of weeks of pregnancy. The condition increases the risk of stillbirth when it remains undetected before birth. IURG may also lead to a number of other conditions after birth, including cerebral palsy, motor dysfunction, speech and cognitive delays, chronic disorders, and metabolic diseases.

Apoptosis, or programmed cell death, is thought to play a key role in IURG. While apoptosis is a normal cellular process, in the case of IURG, it becomes abnormally increased, leading to fetal tissue cell destruction and placental dysfunction, which in turn affects fetal growth. However, decreased apoptosis has also been reported in the context of IURG.

Placental dysfunction, in which apoptosis is thought to play a role, may not always be detected by fetal biometry (measuring fetal body parts by ultrasound), biophysical profiling (prenatal test that checks a baby’s well-being), or a non-stress test, which is used to assess fetal movement and heart rate, the researchers wrote.

In addition to diagnostic methods, such as ultrasound surveillance, commonly used to diagnose IUGR, the researchers examined the levels of cell death markers, namely Bcl-2, caspase-9, and soluble Fas ligand (sFasL), in the maternal and umbilical cord serum of late preterm pregnancies.

They hypothesized that these markers would allow them to assess fetal well-being and decrease neonatal mortality and morbidity. Of note, Bcl-2 is an inhibitor of apoptosis, while caspase-9 and sFasL both trigger apoptosis.

A total of 159 pregnant women, who gave birth between 34 and 37 weeks of gestation (considered late preterm pregancies), were included in the study. Of these, 80 were diagnosed with IURG (mean age of 31.6 years) and 79 were used as controls (mean age of 28.3).

Before conceiving, the women in the IURG group weighed significantly less than women in the control group. They also weighed less and gained less weight during their pregnancies than the other women, who had more pregnancies and childbirths. For women in the IUGR group, it was their first pregnancies.

Of note, the smoking rate in IURG pregnancies was found to be six times higher than in the controls.

In terms of prenatal testing, the researchers reported that the incidence of a non-reactive non-stress test, meaning the baby’s heart rate did not measure as expected, was significantly higher in women with IUGR than in the control group. Moreover, the IUGR group had significantly decreased amniotic fluid index, indicative of fetal distress.

Fewer women had vaginal deliveries in the IURG group compared to the control group (11% vs 24%), and infants affected by IURG had a significantly longer hospital stay in the intensive care unit.

Maternal blood and umbilical cord levels of Bcl-2 were both significantly higher in the IUGR group than the control group, which is in accordance with the literature. Moreover, Bcl-2 levels were correlated between the blood serum of the mother and the umbilical cord in both the IUGR and control groups.

The researchers theorized that increased Bcl-2 levels may be the result of chronic hipoxia (low oxygen levels) tolerance and indicate the presence of an immature placenta due to increased apoptosis.

“One of the most important findings of the study is that the level of Bcl-2 in the maternal blood level is related to the Bcl-2 level in the umbilical cord. This suggests that Bcl-2, which is maternally diagnosed, can help in the diagnosis of IUGR,” they added.

In other words, this means that a simple, non-invasive maternal blood test could be used to confirm an IUGR diagnosis.

No significant differences in both caspase-9 and sFasL levels were found between the two groups, in maternal blood and the umbilical cord.

“In this study, we showed that looking at the Bcl-2 level in the maternal serum can be used as an additional method in the future to confirm the IUGR diagnosis,” the researchers wrote. “In addition, the results make us think that Bcl-2 may be used as a marker to assess fetal well-being regardless of IUGR.”