Urinary NT-proBNP Has Potential as Biomarker for PH in Premature Babies

Measuring the levels of the N‐terminal pro B-type natriuretic peptide (NT-proBNP) — a validated and widely accepted prognostic marker of pulmonary hypertension (PH) — in the urine of babies born prematurely is feasible, and may facilitate the screening of PH, a study suggests.

The study, “Urinary NT-proBNP as a potential noninvasive biomarker for screening of pulmonary hypertension in preterm infants: a pilot study,” was published in the Journal of Perinatology.

Bronchopulmonary dysplasia (BPD) is a lung disease that may compromise the survival and normal development of premature infants. Statistics indicate that 14–37% of babies with BPD develop PH, which is associated with increased morbidity and mortality.

The diagnosis of PH usually is confirmed through a procedure called cardiac catheterization, in which a long and thin tube (catheter) is inserted into an artery or vein in the groin, neck or arm, and threaded through blood vessels until it reaches the heart to measure blood pressures.

Because it is a highly invasive procedure, cardiac catheterization is not always feasible in infants. Consequently, non-invasive tests, such as echocardiograms (ECHO), usually are preferred. However, ECHOs also have limitations, including their cost, availability, and interpretation.

Therefore, there is a need to identify biomarkers that allow for a timely diagnosis and management of PH in young infants.

B-type natriuretic peptide (BNP) and its inactive version, known as NT-proBNP, are released from heart cells in response to heart strain. Recently, there has been increasing interest in exploring the utility of NT-proBNP as a screening tool for PH in preterm infants. In fact, some studies have demonstrated its diagnostic utility for both BPD and PH, with promising initial results.

Now, researchers at Indiana University and the University of Texas Medical Branch conducted a pilot study to determine whether measuring the levels of NT-proBNP in urine samples of preterm very low birth weight (VLBW) newborns would be feasible, and if NT-proBNP could be used as a non-invasive biomarker for PH.

The study included preterm infants who were born with less than 1,500 grams (about 3.3 pounds), and had less than 30 weeks of gestational age (the time elapsed since conception). Researchers performed urinary NT-proBNP measurements and ECHOs in infants at 28, 32, and 36 weeks of gestational age.

A total of 36 infants were included in the final analysis of the study. From these, six had BPD and PH (BPD-PH group), 20 had BPD only (BPD group), and 10 showed no signs of having these disorders (control group).

Results showed that the levels of NT-proBNP in urine were higher in infants from the BPD-PH group, compared to those from the BPD and control groups, at all time-points of gestational age.

Using a cutoff value of 2,345 pg/ml for the levels of NT-proBNP in urine, investigators found that at 28 weeks of gestational age, NT-proBNP had a sensitivity of 83.3% and a specificity of 84.2% as a marker to identify infants with BPD-PH. At later time-points of gestational age, the sensitivity remained higher than 80%.

(A cutoff value is a value over which a child would be diagnosed with PH; sensitivity refers to the ability of a test to correctly identify those who have a disease, while specificity is the ability to correctly identify those who do not have a disease.)

Researchers also noted that there was a decreasing trend in urinary NT-proBNP levels over time, which was accompanied by a reduction in sensitivity and specificity. This potentially could mean that NT-proBNP levels are more sensitive at an earlier gestational age rather than later on.

The researchers concluded: “Urinary NT-proBNP measurement is feasible in preterm infants, and appears to be a good noninvasive screening tool for PH.”

The team emphasized, however, that “further studies are needed to validate this work and identify any correlation between plasma [blood] and urinary levels of NT-proBNP for PH.”