The growth of the nasal septum in the 6–9 week period of foetal development—Warfarin embryopathy offers a new insight into prenatal facial development

Abstract

Background:The aim of this study was to determine the role of the nasal septum in embryonic facial development. Methods: Nasal septal growth and facial profile development were examined in sagittally-sectioned 6-9 week human foetuses and compared to previously published data for later prenatal periods. To complement this data a cephalometric study of a child with untreated warfarin embryopathy was undertaken since a previous study in rats had shown warfarin exposure interferes with septal growth. Results:The results showed that prenatal septal growth was maximal during the 6-9 week period and resulted in the establishment of a facial profile that was maintained until birth. This critical period of growth corresponds to the period of warfarin exposure of the human foetus that results in the warfarin embryopathy. The cephalometric examination of a child with untreated warfarin embryopathy showed a combination of short anterior cranial base and a short maxilla had contributed to a significant retrusion of the maxilla suggestive of failure of the midface to develop over the 6-9 week period. Conclusion: These findings would support the hypothesis that the nasal septum plays an active role in embryonic midfacial development.Key words: Facial development, nasal septum, warfarin embryopathy, cephalometric analysis.(Accepted for publication 5 March 2004.) Warfarin exposure during the first trimester of pregnancy can be associated with a distinct facies in the newborn characterized by a depressed nasal bridge, underdevelopment of the nasal cartilages causing a gross flattening of the nose and midfacial hypoplasia.

Septoplasty retards midfacial growth in a rabbit model

“…In humans, intrautero exposure to warfarin in the first trimester of pregnancy causes the septal cartilage to calcify. Subsequent nasal and midfacial hypoplasia has been demonstrated by a cephalometric study,3 suggesting that human embryonic maxillary and facial development is retarded by interference with the nasal septal cartilage. In vitro experimentation demonstrated that rat septal cartilage exerts growth pressures similar to or greater than epiphyseal growth plates.…”

Augmented BMP signaling in the neural crest inhibits nasal cartilage morphogenesis by inducing p53-mediated apoptosis

“…Cartilaginous nasal septum resection and transplantation experiments using rabbits demonstrated that the nasal septum acts as a growth site pushing the mid-facial bones downward and forward from the cranial base Sarnat, 1961, 1965;Copray, 1986). Hence, nasal septal defects in rabbits affect maxillary growth, and some human cases support this notion (Moss et al, 1968;Howe et al, 2004). The importance of nasal cartilage is further illustrated by defective nasal cartilage that results in diminished airway capacity, leading to nasal obstruction (Metzinger et al, 1994).…”

Warfarin embryopathy: fetal manifestations

“…Nasal hypoplasia was the most frequent external abnormality in our cases, but only one fetus had the alar grooves. In this context, it has been shown that prenatal septal growth is maximal at 6 to 9 weeks gestation and that the resultant facial profile is maintained until birth [6].…”