Do Elevated BNP Levels Predict Hemodynamically Significant PDAs

B type natriuretic peptide (BNP) is mainly synthesized in the ventricles of the heart and
released in response to volume and pressure loading and ventricular stress and, therefore,
plays an important role in regulation of extracellular fluid volume. BNP causes diuresis,
natriuresis, arterial and venous vasodilation and antagonizes the renin-angiotensin system
resulting in a reduction in intravascular volume and decreased ventricular preload and
afterload.

In adults, BNP levels have been routinely used to diagnose and measure the degree of
congestive heart failure. In healthy term infants, BNP levels are initially elevated in the
first few days of life but then decline over the ensuing week after birth to near adult
levels by 3 months of age. However, in premature newborn infants there are still no
normative values for BNP and, therefore, no agreed-upon cut off points to diagnose
ventricular overload without confirmatory echocardiography. Patent ductus arteriosus (PDA)
is the most common cause of ventricular overload and congestive heart failure in premature
neonates and can be a cause of significant morbidity. Excessive pulmonary blood flow due to
the aortopulmonary shunting can result in increased ventilatory dependency and thereby
contribute to chronic lung disease. Other possible sequelae from a PDA include renal
hypoperfusion, necrotizing entercolitis, and pulmonary hemorrhage. Early closure of a PDA
has been shown to reduce these risks.

Delayed ductal closure is inversely related to GA at birth with the incidence varying from
20% in babies greater than 32 weeks gestation and up to 60% in babies less than 28 weeks
gestation. Currently, infants are screened for a PDA by echocardiography. This requires
that centers have access to cardiologists to perform and analyze these studies. A simple
blood test that could help diagnose a hemodynamically significant PDA would be extremely
helpful in low birth weight infants, especially in more remote centers that do not have
routine access to cardiology services. To date, there is no accepted blood test although
numerous studies are emerging suggesting that BNP might be such a test. It has been shown
that the magnitude of shunting through a PDA is a major determinant of BNP level, however,
the levels published in various studies for what is hemodynamically significant varies
greatly. In addition, the studies that have been done previously are on small sample sizes
(less than 70 patients, with one retrospective study that had 88 patients) and on various
gestational ages and, therefore, it is difficult to extrapolate normative data.

It is already known that BNP levels are elevated in neonates with a hsPDA, however, there is
little agreement on how high a BNP level needs to get to imply a hsPDA. We propose a study
to measure the BNP values in all infants born less than 32 weeks gestation with and without
a PDA. We will also do serial BNP levels with concurrent echocardiograms in infants with a
PDA to determine a cutoff value of BNP above which an infant is likely to have a hsPDA. We
hope that our study, with a larger sample size and on all infants with and without a PDA,
will be able to not only gather more definitive data on what the cutoff BNP level is, but
also gather normative BNP data on premature infants without PDAs.

Inclusion Criteria:

- gestational age between 24 0/7 weeks gestation and 31 6/7 weeks gestation. -
Infants must be enrolled by 24 hours of life.

Exclusion Criteria:

- congenital heart disease,

- necrotizing enterocolitis,

- culture positive sepsis or culture negative but treated for presumed sepsis.