Association of lipid peroxidation with antenatal betamethasone and oxygen radial disorders in preterm infants.
BACKGROUND
Premature infants are highly susceptible to 'oxygen radical diseases' (ORD), including bronchopulmonary dysplasia, intraventricular hemorrhage/white matter injury, retinopathy of prematurity, and necrotizing enterocolitis. The incidence of ORD is reduced following antenatal treatment with betamethasone. Oxidant-mediated injury is characterized at the cellular level by peroxidation of lipid membranes. This results in the generation of malondialdehyde (MDA), which can be quantified indirectly by measurement of thiobarbituric acid-reacting substances (TBARS). There is currently no effective way to quantify the risk for ORD. In this study, we analyzed the correlation of early urinary MDA and TBARS with prenatal betamethasone administration and with the development of ORD.


METHODS
Preterm infants (<30 weeks gestation, n = 25) born at St. Peter's University Hospital were enrolled. Urine samples were collected during the first 10 days of life and stored at -70 degrees C for 0-21 days. TBARS were quantified by spectrophotometric assay, and malondialdehyde levels measured by HPLC. Subjects were screened for the subsequent development of ORD. Betamethasone administration was defined as one or more doses > or =24 h prior to delivery.


RESULTS
Urinary MDA levels increased on days 2-3 and 5-10 relative to day 1 from birth. Maximal urinary MDA concentrations were significantly higher in the ORD group compared to controls, and there was a trend toward increased urinary TBARS in the presence of ORD. Infants receiving prenatal betamethasone demonstrated higher maximal urinary TBARS values during the first 10 days of life than control infants. The length of sample storage from 0 to 3 weeks at -70 degrees C did not significantly affect TBARS measurements.


CONCLUSIONS
Elevated urinary MDA measurements in the first 10 days are correlated with the risk for ORD. Urinary TBARS concentrations, which are correlated with MDA measurements, can be quantified rapidly and are stable for short-term storage. Our findings suggest that urinary TBARS may be adaptable as a practical tool for assessing the risk for ORD in neonatal intensive care unit patients, allowing clinicians to optimize the use of preventive strategies. Antenatal betamethasone is associated with increased urinary TBARS in the first 10 days of life, indicating that the protective effects of corticosteroids are not mediated through reductions in oxidant-mediated lipid peroxidation.
Weinberger
Barry
B
Division of Neonatology, Department of Pediatrics, UMDNJ-Robert Wood Johnson Medical School, St. Peter's University Hospital, New Brunswick, NJ 08901, USA. barryw@pol.net
Anwar
Mujahid
M
Henien
Samir
S
Sosnovsky
Ana
A
Hiatt
Mark
M
Jochnowitz
Nina
N
Witz
Gisela
G
Hegyi
Thomas
T
D000375:Aging / Q000652:urine; D001623:Betamethasone / Q000008:administration & dosage*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology* / Q000652:urine; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000652:urine; D011295:Prenatal Care; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D005938:Glucocorticoids; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D001623:Betamethasone