Cord blood from preemies may predict future bronchopulmonary dysplasia- associated pulmonary hypertension

Specific growth factors found in cord blood may one day help identify premature infants who may be at risk for developing bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH), according to research currently in press in the Journal of Pediatrics.

“We have many promising interventions and it would be exciting to start them at birth in babies at risk, before they become extremely sick,” said lead author Karen Mestan, MD, neonatologist, Ann & Robert H. Lurie Children’s Hospital of Chicago and Associate Professor at Northwestern University Feinberg School of Medicine, Chicago, IL. “Currently we do not use cord blood for prediction of disease, but our study shows that it has tremendous potential to save lives.”

Dr. Mestan and fellow researchers conducted this study to determine whether cord blood biomarkers associated with placental maternal vascular underperfusion (MVU) could predict BPD-PH. They assessed 15 different biomarkers in the cord blood from 190 premature infants enrolled in a large repository of cord blood and placental tissues that covered four gestational age strata (range: 23 to 36 weeks). They sought to assess correlations with lesions on the placenta that may have caused insufficient blood flow between mother and fetus.

Two growth factors were decreased in these placental lesions: granulocyte colony-stimulating factor (G-CSF) and placental growth factor (P1GF) in MVU (P < 0.003), and decreased with BPD-PH (P < 0.05). They validated these findings in 39 additional infants of extremely low gestational age.

In the combined group of 87 subjects, P1GF was decreased in 21 infants with BPD-PH compared with controls without PH (median: 3 pg/mL [IQR 2-7] vs median 15 pg/mL [IQR 6-30], respectively; P < 0.001). G-CSF was also decreased with BPD-PH (median: 55 pg/mL [IQR 38=85] vs median 243 pg/mL [IQR 48-15930, respectively; P=0.001). Upon ROC analysis, researchers also found that decreased P1GF and G-CSF were predictive of BPD-PH (AOC: 0.83 and 0.76, respectively).

“Our findings also have implications for what we do during pregnancy,” said Dr. Mestan. “The growth factors we identified potentially could be measured in the mom’s blood; and if they are low, that would signal lesions in the placenta that place the baby at risk for severe lung disease. Better understanding about fetal origins of disease, which is still a mystery, would help us find new ways to improve outcomes even before the child is born.”

These results do not prove that a deficiency in G-CSF and P1GF cause PBD-PH, but suggest a possible mechanism behind the development of BPD-PH.

“There are many undifferentiated stem cells in cord blood and these growth factors might help mobilize them to get assigned to specific immune functions involved in the healing process,” concluded Dr. Mestan. “Preemies who are deficient in G-CSF and PlGF might not be able to fight off the development of lung damage. But what if we could replenish these babies with healthier stem cells or even replenish the growth factors? We could then regenerate lung tissue. This is a thrilling area of research that could have huge impact.”

Dr. Mestan called for larger, multicenter studies to validate these findings.

This study was supported, in part, by grants from the National Heart, Lung, and Blood Institute.