The material behavior of cranial bone was defined as an isotropic linear-elastic model with age-dependent material properties. For the establishment of an age-matched corresponding elastic modulus (E-modulus) of the cranial bone, we inter- and extrapolated previously published data from McPherson and Kriwall.27 The calculated E-modulus ranged from 1,337 to 3,367 MPa for the newborn (date of birth), from 1,737 to 3,767 MPa for the 4-week-old infant, and from 2,738 to 4,768 MPa for the 3.5-month-old infant at a Poisson ratio of 0.28, respectively (Fig. 2). As previously reported, the germs of teeth with the partial beginning of mineralization only influence the results to an extremely limits amount. Thus, the teeth germs were modeled as empty space emphasizing the worst-case scenario, because the empty space simulation resulted in slightly larger stresses than the filled teeth germ simulations.26 A stress of 30,000 Pa was determined as the critical threshold value for resulting deformation over time as seen in positional plagiocephaly, as previously described.26 , 28 , 29
All supporting reactions were constrained to 0 with Dirichlet boundary conditions at the bitemporal level of the virtual skull. We applied a force of 0.7 N representing an ulceration force derived by a spring scale with a 3 mm2 cross-section at the vestibular region of the canines on both sides over an area of 40–60 mm2, representing the actual contact area between the NAM plate and the maxilla. The applied force of 0.7 N represents an ulceration force that causes local ischemia of the oral mucosa in a small case series of healthy adults (data not published). In cases a NAM plate causes ulceration, the plate is immediately adapted. Thus, the assumption of a long-term ulceration force in our simulation emphasizes the worst-case character of our study. Furthermore, we did not segment the open sutures to have a direct unphysiological force conduction neglecting dampening effects of the soft tissue.
For all simulated 5 cleft situations, the increased stresses occurred in the same characteristic areas: at the maxilla, vomer, and ossis nasale, lacrimale, ethmoidale, and frontale. In the model of the date of birth, the ossis parietale, temporale, and sphenoidale and the anterior fossa of the base of the skull were additionally involved. At the date of birth, von Mises stress distribution exceeded the previously defined threshold of 30,000 Pa, especially in the ipsilateral naso-orbito-ethmoidal complex, frontal sinus, and the anterior fossa of the base of the skull (Figs. 3, 4). The CT scan of the newborn showed finer osseous structures than the scans of the 4-week-old and 3.5-month-old neonates. The finest structures of the newborn lay within a single pixel diameter (0.32 mm; Fig. 3), whereas for the 4-week-old and 3.5-month-old neonates, the scans did not show such small structures and thus such peak stresses. The force flux ran via the palate from 1 force application area to the opposite area in the simulations of the healthy skulls.
The width of the cleft gap qualitatively influenced neither the force flux nor the occurring peak stresses.
A quantitative comparison was derived within 4 planes in the area of the viscerocranium (planes A–D) and the anterior and middle fossa of the base of the skull (planes E–H) by calculating the arithmetic mean stress for each plane of each simulation (Fig. 4). The resulting stress values were compared with the threshold value derived from a plagiocephaly case to validate the simulation in each plane and to detect any stress patterns that might cause deformations. The arithmetic means for the 4-week-old and 3.5-month-old neonates remained below the von Mises threshold value of 30,000 Pa and within a range of 15,000 Pa or less for von Mises stress, whereas the von Mises stress for the newborn reached 3 times the threshold von Mises stress value of 30,000 Pa.
Several studies of the last few decades have described the typical facial growth and appearance of patients presenting with CLP, based on radiological and clinical follow-up examinations.25 , 30 , 31 A standardized comparison of reported results is nearly impossible because of the wide heterogeneity of treatment algorithms and applied techniques and the lack of controlled randomized trials. Furthermore, and as stated earlier by Berkowitz,13 “all clefts cannot be lumped together as a single phenomenon.” Various preoperative orthofacial treatments have been described to affect the growing alveolar crest, maxilla, and nose positively with regard to growth, symmetry, and function.32 In particular, NAM therapy has been shown to be a valuable treatment, and the first reported long-term analyses have revealed that it might significantly reduce secondary corrections.4 , 6 On the other hand, NAM has also been criticized because of its unknown effectiveness or because of unrecognized significant clinical differences between infants with or without treatment by NAM, especially with regard to facial growth and symmetry, maxillary arch dimension, and occlusion.6 , 12 , 13 , 32–35 It is described that disrupting the premaxillary-vomerine suture may cause severe midfacial retrusion.36 Disruption may be a result of operative (eg, operative premaxillary setback) or inappropriate presurgical procedures (Latham apparatus or NAM) and needs maxillary advancement in follow-up.15 , 37 , 38 The forces and distribution of stress patterns that might evolve within the viscero- and neurocranium during NAM therapy are unknown. Interestingly, no simulations have been performed with regard to force distribution and possible impact (sutural hematoma and impairment of growth) on that sensitive region in case of exceeding forces. Only some clinical, retrospective analyses exist. Lee et al.39 have assessed the effects of NAM therapy with or without gingivoperiosteoplasty in 20 patients presenting with Unilateral Cleft Lip and Palate (UCLP) by analyzing lateral cephalograms at 6 years and 11.5 years of age. They have reported that midface growth in sagittal or vertical planes is not affected by presurgical alveolar molding. Other studies have concentrated on the analysis of the nasal symmetry of presurgically treated children with CLP.40 However, the results based on photographs and X-rays show no force distribution, especially in the regions of the naso-orbito-ethmoidal complex, frontal sinus, and the anterior fossa of the base of the skull.
FEA is a suitable method for simulations and for providing clinical observations and therapies with reproducible analyses. Nevertheless, FEA involving fetal cranial bone and with special regard to growth and the effect of various therapeutic modalities in neonates are lacking. On the 1 hand, fetal cranial bone is a thin, curved, and inhomogeneous material. For this reason, its mechanical properties are difficult to determine. Furthermore, fetal or newborn cranial bone is rarely biomechanically examined, because of ethical reasons. The mechanical properties reported in the literature are therefore also heterogeneous.41–45 We decided to use the mechanical properties reported by McPherson and Kriwall,27 because of their systematic analyses of fetal cranial bone, which seemed conclusive and valid. Furthermore, their results allowed us an extrapolation based on the common assumption that the mechanical properties change according to an isotropic linear-elastic model. According to the literature, it is not clearly defined whether a linear-elastic or plastic model would have been the right to choose. Gačnik et al.46 described a linear-elastic behavior of the mandibular bone if the strain was within 1–2%. Jiang et al.47 used also a linear-elastic constitutive model to simulate the skull and sutures in their analysis of fracture characteristics in infant skulls. An accurate modeling of biological tissues requires the experimental characterization of the inhomogenous structures.48 Simulations, established to describe the inhomogeneous facial structures, are also based on numerous assumptions [Roth 2010]. For that reason, our presented FE model and analysis represent a worst-case scenario. We did not segment the sutures of the viscero- and neurocranium as reported by others,44 and we applied a force (0.7 N) that would result in mucogingival ulceration, if it was not corrected immediately.49 Therefore, our results from the stress distribution patterns are expected to be higher than those in vivo. In particular, in the case of the scan of the newborn, a lower stress distribution can be expected, because such small structures (0.32 mm) as observed in the model are in reality supported by surrounding tissue, which would partially absorb or transmit the incoming load state. The reason for the small structures in the scan of the newborn can also be explained by the resolution of the scan, which had a third of the layer thickness compared with the other scans. A higher layer resolution leads to finer osseous structures, resulting in increased peak stress because the occurring force needs to pass these fine structures.
Our results show increased von Mises values exceeding the previously defined threshold (30,000 Pa) along the expected force flux. Exceeding peak values were registered in the regions of the ipsilateral naso-orbito-ethmoidal complex, frontal sinus, and the anterior fossa of the base of the skull. This result has to be kept in mind when it comes to the timing and initiation of NAM therapy. For this reason, we have corrected the time at which we start our NAM therapy to the second week of life, in contrast to an earlier study.2 Furthermore, we now adapt the beginning of NAM therapy in cases of preterm birth and apply a regular drinking plate until the correlated age of 1 week. Our results also showed that the resulting force at the age of 4 weeks and 3.5 months was less than the previously defined threshold value; this therefore allows regular NAM therapy until cheiloplasty at 3 months of age.
In contrast to other active treatment modalities, such as the Latham method with its bony fixation and screw for the activated expansion of the palate,50 NAM represents a passive plate without active components. The main intention of NAM therapy is guided growth. Consequently, the resulting forces and stress distributions are expected to be much lower than those in active applications. On the basis of our results, no immediate adverse effects can be expected with regard to the development of the viscero- and neurocranium. The beneficial effect of improved alveolar and nasal symmetry and the potential reduction of secondary correction might outweigh possible adverse effects as reported by others.
As claimed earlier, long-term analyses of children treated with NAM and other presurgical modalities have to be conducted.51 In particular, the incidence of suspected unwanted effects, such as retraction of the premaxilla, midfacial retrusion and the increased need for LeFort I osteotomies,13 occlusal sequela, and the missing effectiveness compared with untreated infants therapy need to be analyzed in further, standardized studies with accurate evaluation of facial and alveolar growth.
FEA is only a close approximation to reality and is not able to analyze the in vivo situation. However, our presented results are valid, because the performed convergence analysis shows good consistency within the model. In this study, we have only examined the worst-case scenario with a high force being applied and without segmentation of the sutures. The absorption of force conduction is also not illustrated. Thus, the actual values of the von Mises stress distribution are expected to be even lower. The generation of realistic FE models of skulls of neonates is, however, generally difficult, because of the limited valid data regarding the E-modulus and the precise age-matched material properties of bone, cartilage, and soft tissue of newborns and neonates.
No adverse effects of NAM therapy on the development of the viscero- and neurocranium are to be expected when NAM is started later than the date of birth. In cases of preterm birth, initial treatment should be restricted to conventional feeding plates only until the corrected age.
All persons who have contributed to the study are listed as authors, because everyone has met the listed criteria for authorship.
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