Administration of prenatal betamethasone suppresses the adrenal-hypophyseal axis in newborns with congenital diaphragmatic hernia.
BACKGROUND
Congenital diaphragmatic hernia (CDH) is a condition that is characterized by pulmonary hypoplasia and pulmonary hypertension. Prenatal betamethasone often is administered to fetuses with CDH to improve pulmonary function. In this study, the authors investigate the possible role of the adrenal-hypophyseal axis in CDH in an animal model and subsequently in human infants with CDH.


METHODS
Twin fetal sheep underwent creation of DH or a sham thoracotomy, and levels of plasma and lung ACTH and plasma cortisol were compared. For the human studies, plasma levels of ACTH, cortisol, and DHEA were measured in cord blood samples collected from 9 CDH (5 that received prenatal betamethasone) and compared with those of 14 normal newborns. In both studies, ACTH and cortisol levels were determined by radioimmunoassay (RIA). Human (DHEA) levels were determined by ELISA.


RESULTS
Plasma ACTH and cortisol levels were elevated in fetal DH sheep compared with sham-operated controls; however, levels of ACTH in lung tissues were not different. Human newborns with CDH who have been exposed to prenatal steroids have significantly lower plasma ACTH, cortisol, and DHEA levels than normal newborns and CDH newborns not exposed to prenatal betamethasone.


CONCLUSIONS
In an ovine model of CDH, the adrenal-hypophyseal axis appears up-regulated in DH fetuses compared with sham-operated animals. Conversely, the adrenal-hypophyseal axis in human CDH newborns appears normal but is suppressed by the administration of prenatal betamethasone.
Paddock
Heather
H
Department of Surgery, University of Florida School of Medicine, Shands at Jacksonville, Jacksonville, FL, USA.
Beierle
Elizabeth A
EA
Chen
Mike K
MK
Mullett
Timothy
T
Wood
Charles M
CM
Kays
David W
DW
Langham
Max R
MR
D000324:Adrenocorticotropic Hormone / Q000032:analysis* / Q000097:blood; D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D001034:Apgar Score; D001623:Betamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005315:Fetal Diseases / Q000188:drug therapy / Q000503:physiopathology*; D005865:Gestational Age; D006548:Hernia, Diaphragmatic / Q000097:blood / Q000188:drug therapy / Q000196:embryology / Q000401:mortality / Q000503:physiopathology; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007231:Infant, Newborn; D008168:Lung / Q000737:chemistry* / Q000196:embryology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000503:physiopathology; D011247:Pregnancy; D012756:Sheep; D015996:Survival Rate
D000324:Adrenocorticotropic Hormone; D001623:Betamethasone; D006854:Hydrocortisone