Prenatal glucocorticoids improve pulmonary morphometrics in fetal sheep with congenital diaphragmatic hernia.
OBJECTIVE
Prenatal glucocorticoids reverse pulmonary immaturity in rodents with pharmacologically induced congenital diaphragmatic hernia (CDH). The authors applied quantitative stereologic morphometric techniques to test whether these effects could be reproduced in large animals (sheep) with surgically created CDH.


METHODS
Diaphragmatic hernias were created surgically in fetal lambs at gestational day 80. The fetuses were treated with intravenous cortisol (n = 6) or normal saline control (n = 5) from days 133 to 135. Lungs distended at 15 cm pressure from each group were harvested at day 136, processed histologically, and studied by brightfield microscopy at 400 x using a 42-point equidistant counting grid. Ten morphometric parameters (Mean +/- SEM) were measured by point-counting 60 fields/lung, and analysis of variance was performed.


RESULTS
The CDH-cortisol-treated lungs showed striking significant maturational improvements when compared with lungs of CDH-normal saline controls by seven of ten morphometric parameters.


CONCLUSIONS
(1) Prenatal glucocorticoids accelerate lung maturity in fetal lambs with CDH by seven quantitative morphometric parameters. (2) The observation that prenatal glucocorticoid therapy improves measures of maturity for both CDH rodent and sheep models encourages proceeding with a Phase I human clinical trial in ultrasound-confirmed CDH.
Hedrick
H L
HL
Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Kaban
J M
JM
Pacheco
B A
BA
Losty
P D
PD
Doody
D P
DP
Ryan
D P
DP
Manganaro
T F
TF
Donahoe
P K
PK
Schnitzer
J J
JJ
D000818:Animals; D004195:Disease Models, Animal; D005315:Fetal Diseases / Q000188:drug therapy*; D005325:Fetal Organ Maturity / Q000187:drug effects*; D005865:Gestational Age; D006548:Hernia, Diaphragmatic / Q000188:drug therapy* / Q000473:pathology; D065630:Hernias, Diaphragmatic, Congenital; D006854:Hydrocortisone / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D012756:Sheep
D006854:Hydrocortisone