FETAL AND NEONATAL MEDICINE

Interrelationship of atrial natriuretic peptide, atrial volume, and renal function in premature infants Terry M. Bierd, MD, John Kattwinkel, MD, Robert L. Chevalier, MD, Karen S. Rheuban, MD, D e b r a J. Smith, W. Gerald Teague, MD, Robert M. Carey, MD, a n d Joel Linden, MO From the Departments of Pediatrics, Internal Medicine, and Physiology, University of Virginia School of Medicine, Charlottesville, Virginia Infants experience dramatic changes in fluid balance during the first few days of life, which provides an opportunity to observe the interrelationships of changing atrial size, atrial natriuretic peptide (ANP) secretion, and renal function during a relatively short period. To study these relationships, we examined nine infant boys (mean birth weight 1180 gm and gestational age 30 weeks) at 20 to 28 hours of age and then at four 24-hour intervals. Measurements included plasma ANP concentration, two-dimensional echocardiographic estimations of left and right atrial volumes, Doppler determination of ductus arteriosus patency, creatinine clearance, urine flow rate, urinary sodium excretion, and cyclic guanosine monophosphate (cGMP) excretion. Plasma ANP concentration was found to decrease with age and to correlate with decreasing size of the right atrium, clo~ure of the ductus arteriosus, urinary cGMP excretion, and sodium excretion. We speculate that elevated plasma ANP values in a preterm neonate reflect an e x p a n d e d volume state. As volume contraction, reflected by decreasing atrial volume and body weight occurs, ANP levels decrease, which may diminish diuresis. These findings are compatible with a significant role for ANP in volume homeostasis of newborn infants. (J PEDIATR1990;116:753-9)

Atrial natriuretic peptide is a recently discovered hormone thought to help regulate sodium and volume homeostasis. 1-4 The peptide is stored in secretory granules of atrial myocytes5 and is released in response to a number of factors, including atrial distension, 6 intravascular volume expansion] and chronic sodium loading) A N P causes natriuresis, diuresis, 1 and smooth muscle relaxation. 9 The plasma A N P concentration is elevated in expanded volume Supported in part (Dr. Chevalier) by National Institutes of Health grant No. HL 40209 and by an Established Investigator Award from the American Heart Association. Submitted for publication Aug. 26, i988, accepted Nov. 22, 1989. Reprint requests: John Kattwinkel, MD, Department of Pediatrics, Box 386, University of Virginia School of Medicine, Charlottesville, VA 22908. 9/23/18337

states such as pregnancy] ~ congestive heart failure] ~ and end-stage renal disease. I2 It is also elevated in the early postnatal period t3, ~4 but decreases to adult leveis after the neonatal period. 15 Newborn infants normally undergo major vascular changes, including presumed right and left atrial distension ANP cGMP

Atrial natriuretic peptide Guanosine 3 ' 5 '-cyclic monophosphate

[

and profound diuresis, during the first few days after birth. In an extremely premature infant, atrial enlargement may be accentuated by a persistent patent ductus arteriosus and resultant left-to-right shunt. Therefore a newborn preterm infant should provide a n opportunity to observe the interrelationship of changing atrial size, A N P secretion, and renal function for a relatively short period.

753

754

Bierd et al.

The Journal of Pediatrics May 1990

Table I. C h a r a c t e r i s t i c s of study group Gesta- Mode Mode of Mean ventilairway PDA Pational of Apgar SurfacPatient atory pressure closure tient Birth a g e de- score tant Maternal No. weight (wk) livery (5 min) therapy history diagnoses support (cm H20) (hr) 1 2 3

890 1500 1190

27 33 30

C V V

7 8 7

Y Y Y

4 5

1100 1420

29 33

V C

7 5

Y Y

6

1200

30

C

4

N

7 8

1390 1090

34 28

C C

9 5

N Y

9

850

26

V

1

N

Abruption RDS Abruption Preterm PROM, Preterm chorioTTN amnionitis Abruption Preterm P1H Preterm TTN Abruption RDS, PHm PIH RDS Chronic RDS, PHt, hyperPIE, IVH tension PROM RDS, PIE, IVH

Plasma ANP Right atrial (pg/ml) volume (cc) 24 hr

120 hr

24 hr

120 hr

tPPV None None

5 NA NA

>120 > 120 24

305 250 391

79 107 94

0.46 1.10 0.80

0.29 0.62 0.44

None NCPAP

NA 5

48 48

200 392

43 57

1.02 0.68

0.63 0.58

14

72

210

NA

0.47

NA

6 8

24 96

152 1300

58 454

1.20 1.55

0.73 0.74

10

>120

1065

525

0.78

0.51

IPPV NCPAP 1PPV

IPPV

C, Cesarean section; V,vertex;PROM, premature rupture of mcmbranes;P1H, pregnancy-inducedhypertension;RDS, respiratorydistress syndrome;TTN, transient tachypnea of the newborn;PHm, puhnonary hemorrhage; PHt, pulmonary hypertension; PIE, pulmonary interstitial emphysema;IVH, intraventricular hemorrhage; IPPV, intermittent posltive-pressureventilation;NCPAP, nasal continuous positiveairway pressure; NA, not applicable.

In designing this study, we hypothesized that an acute increase in vascular volume would be reflected in atrial distension that would lead to elevated plasma A N P levels, increased urinary cyclic guanosine monophosphate excretion, and subsequent natriuresis. We further hypothesized that the resulting diuresis would lead to a diminution of these factors and that this interrelationship would be demonstrable in preterm infants immediately after birth. METHODS Patients. The protocol for the study was approved by the human investigation committee of the University of Virginia Medical Center, Charlottesville. Written informed consent for participation in the study was obtained from the infants' parents. Criteria for patient selection included birth weight -< 1800 gm, male gender (to facilitate urine collection), and stable fluid and electrolyte status, defined as urine output ~1 ml/kg/hr, serum sodium range of 125 to 145 mmol/L, and serum potassium level -