The effect in premature infants of prenatal corticosteroids on endogenous surfactant synthesis as measured with stable isotopes

• Published in: American journal of respiratory and critical care medicine 2000-09, Vol.162 (3), p.844-849
• Main Authors: BUNT, Jan Erik H, CARNIELLI, Virgilio P, DARCOS WATTIMENA, J. L, HOP, Wim C, SAUER, Pieter J. J, ZIMMERMANN, Luc J. I
• Format: Article
• Language: English
• Subjects: Betamethasone - administration & dosage; Betamethasone - adverse effects; Biological and medical sciences; Dose-Response Relationship, Drug; Female; Glucocorticoids - administration & dosage; Glucocorticoids - adverse effects; Humans; Infant, Newborn; Injections, Intramuscular; Male; Medical sciences; Pharmacology. Drug treatments; Phosphatidylcholines - biosynthesis; Pregnancy; Prenatal Care; Pulmonary Surfactants - biosynthesis; Respiratory Distress Syndrome, Newborn - physiopathology; Respiratory Distress Syndrome, Newborn - prevention & control; Respiratory system; Treatment Outcome
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.162.3.9906139

Most in vitro studies show that prenatal administration of corticosteroids stimulates the synthesis of surfactant phosphatidylcholine (PC), but studies in animals are controversial. Whether prenatal corticosteroids stimulate surfactant PC synthesis in humans has not been studied. We studied endogenous surfactant PC synthesis in relation to prenatal corticosteroid treatment in 27 preterm infants with respiratory distress syndrome. Infants received a 24-h infusion of the stable isotope [U-(13)C]glucose, starting approximately 5 h after birth. We measured (13)C-incorporation into palmitic acid in surfactant PC from serial tracheal aspirates and in plasma triglycerides and phospholipids by isotope-ratio mass spectrometry. Premature infants had received either zero (n = 11), one (n = 4), or two doses (n = 12) of prenatal betamethasone (12 mg intramuscularly). The fractional synthesis rate (FSR) of surfactant PC from glucose was 1.7 +/- 0.3%/d without corticosteroid treatment, 2.9 +/- 1.4%/d with one dose of prenatal corticosteroid, and 5.8 +/- 1.3%/d after two doses of prenatal corticosteroid. Using multiple regression analysis, we found that the FSR of surfactant PC increased by 40% (confidence interval: 7 to 82%/d, p < 0.02) per dose of corticosteroid and doubled after two doses of corticosteroid. The (13)C-enrichment of plasma triglycerides and phospholipids was not increased by corticosteroid. These data show for the first time that prenatal corticosteroid treatment stimulates surfactant synthesis in the preterm infant.