Pulmonary hypoplasia: alternative pathogenesis and antenatal therapy in diaphragmatic hernia
Editor—We wish to comment on some aspects of the important problem raised by Porter et al,1 relating to congenital diaphragmatic hernia (CDH).
Pulmonary hypoplasia in CDH may not be attributable to the diaphragmatic defect and visceral herniation alone. There is evidence from CDH models to indicate that, before the established hernia, lung development is abnormal from the outset in the embryonic period.2 3 This has substantial implications for the type and timing of potential treatments.
Intrauterine tracheal occlusion for CDH is the subject of a US National Institutes of Health clinical trial (Harrison MR, personal communication). Numerous studies in experimental CDH have shown that although antenatal glucocorticoid treatment does not correct overall lung size, it improves structural, biochemical, molecular and functional abnormalities in the hypoplastic lung. As a potential pharmacological fetal treatment, antenatal steroids are therefore also under evaluation as part of an international human CDH trial (CDH Study Group, personal communication).4
Finally, the role of growth factors in increasing lung development remains unclear. Unravelling the control of normal pulmonary development is crucial to the design of effective medical treatments for this frustrating human disease.5
