Retinol status of newborn infants with congenital diaphragmatic hernia

Abstract

The etiology of congenital diaphragmatic hernia (CDH) is not yet known. Studies in the literature from 1941 have reported that nutritional deficiency of vitamin A during pregnancy could lead to CDH, associated or not with other malformations in young rats. More recently, possible correlations between expression patterns of cellular retinoid-binding protein and retinoic-acid receptors and morphologic effects of vitamin A deficiency have been suggested. The purpose of this study was to verify in human newborns the possible link between vitamin A deficiency and CDH previously observed in experimental animals. Blood samples were obtained during the first hours after birth from 11 term CDH newborns and 11 healthy controls matched for gestational age, and also from 7 mothers in each group, for a total of 7 newborn-mother pairs of matched CDH-controls. Plasma retinol was measured by high-performance liquid chromatography and retinol-binding protein (RBP) by nephelometry. In the 11 matched CDH-control newborns, plasma retinol and RBP levels in CDH newborns were 50% less than control values (P< 0.0002 and <0.006, respectively); in contrast, retinol levels in CDH mothers were significantly higher than those of control mothers (P < 0.005). The observation that the plasma concentrations of retinol and RBP are low in infants with CDH relative to controls may be clinically very relevant and may help to elucidate the mechanism of development of this congenital anomaly.

Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia

“…Although the mechanism by which nitrofen induces the diaphragmatic defect and lung hypoplasia is not fully understood, recent evidences suggest the involvement of abnormalities linked with the retinoid signaling pathway in this model and also in human CDH etiology (42)(43)(44)(45). Indeed, one clinical study demonstrated the presence of decreased levels of retinol and retinol-binding protein in human CDH, suggesting a possible deterioration of retinol transport across the placenta (46). Regarding the nitrofen-induced CDH model, it was already demonstrated that nitrofen inhibits retinal dehydrogenase 2 (RALDH2), a key enzyme responsible for the conversion of retinal to retinoic acid (47).…”

Retinal Dehydrogenase-2 Is Inhibited by Compounds that Induce Congenital Diaphragmatic Hernias in Rodents

“…9,10 In 1994, Mendelsohn and colleagues 11 published data showing that in a subset of double-retinoic acid receptor subtype knockouts, fetuses had diaphragmatic hernias. Major and colleagues 12 provided preliminary evidence supporting a role of vitamin A as a factor in human CDH. In a small study of human mothers and infants born with or without CDH, it was reported that the retinol levels in the maternal and infant plasma were abnormal when CDH was present.…”

Dietary vitamin A intake below the recommended daily intake during pregnancy and the risk of congenital diaphragmatic hernia in the offspring

“…Newborns with CDH show reduced concentrations of retinol and retinol binding protein (RBP) in cord blood compared with healthy newborns (Major et al, 1998;Beurskens et al, 2010). However, the retinol and RBP concentrations at birth seem not to be deranged in the mothers of these children (Major et al, 1998;Yang et al, 2008;Beurskens et al, 2010).…”