7 Blood Biomarkers Seen to Predict PH and Worse Outcomes in Babies Born with Rare Defect in Diaphragm

Blood biomarkers may help to predict poor outcomes in babies born with a rare congenital defect of the diaphragm that often leads to pulmonary hypertension (PH).

The seven biomarkers, identified by researchers in Germany and evident in the blood within 24 hours of birth, were associated with a higher risk of death and chronic lung disease within one month in these newborns. They may also serve as targets of potential treatments.

The study, “Circulating microRNAs are associated with Pulmonary Hypertension and Development of Chronic Lung Disease in Congenital Diaphragmatic Hernia,” was published in the journal Nature Scientific Reports.

Congenital diaphragmatic hernia (CDH) is a rare, life-threatening defect of the diaphragm — the muscle sheet under the lungs — that causes growth defects and malformations in the lungs during fetal development.

Most infants born with the condition also develop PH, which further elevates the risk of premature death and contributes to the development of chronic lung disease.

The cellular and molecular mechanisms that lead to PH and chronic lung disease in these babies are not fully understood. But a better understanding of them may help to identify biomarkers that predict which CDH babies are most likely to have a poorer prognosis.

Early identification is important, as early interventions (ventilation or supportive techniques) can limit lung trauma in newborns.

Previous studies with animal models suggest that a class of messenger molecules called microRNAs (miRNAs) may be useful biomarkers of PH severity and a propensity for developing chronic lung disease.

miRNAs are a type of small messengers of genetic information, capable of blocking gene activity and protein production.

Based on previous positive results, researchers examined if miRNAs could be useful biomarkers of severe outcomes in CDH newborns.

They measured the expression of several miRNAs in blood samples of 18 newborns with CDH and PH, taken 24 hours after birth.

Seven miRNAs were found to be significantly more expressed in babies who died or developed chronic lung disease within 28 days of birth, compared to those who survived that same stretch of days without lung disease.

Biological pathway studies indicated that these seven miRNAs play roles in cell replication, inflammation and development, and in targeting molecules associated with growth factors, immune mediators, and cellular stress response.

Based on predicted interaction networks between miRNA targets, the team was able to rank these miRNAs according to their relative importance. That is, they reported that dysregulation of miRNAs let-7b-5p, let-7c-5p, miR-1307-3p, miR-185-3p, miR-8084, miR-331-3p, and miR-210-3p may negatively impact lung development and function, and potentially contribute to chronic lung disease in infants born with CDH.

“Whether these miRNAs might serve as prognostic circulating biomarkers for the development of CLD [chronic lung disease] in CDH newborns, and might be useful therapeutic targets, needs to be investigated in a larger cohort,” the researchers wrote.

This study “provides encouraging evidence to ensure further validation of our present findings,” they concluded.