New anatomical data on the growing C4 vertebra and its three ossification centers in human fetuses

Abstract

PurposeDetailed knowledge on the normative growth of the spine is of great relevance in the prenatal diagnosis of its abnormalities. The present study was conducted to compile age-specific reference data for vertebra C4 and its three ossification centers in human fetuses.Materials and methodsWith the use of CT (Biograph mCT), digital image analysis (Osirix 3.9) and statistical analysis (Wilcoxon signed-rank test, Kolmogorov–Smirnov test, Levene’s test, Student’s t test, one-way ANOVA, post hoc RIR Tukey test, linear and nonlinear regression analysis), the normative growth of vertebra C4 and its three ossification centers in 55 spontaneously aborted human fetuses (27 males, 28 females) aged 17–30 weeks was examined.ResultsSignificant differences in neither sex nor laterality were found. The height and transverse and sagittal diameters of the C4 vertebral body increased logarithmically as: y = −3.866 + 2.225 × ln(Age) ± 0.238 (R2 = 0.69), y = −7.077 + 3.547 × ln(Age) ± 0.356 (R2 = 0.72) and y = −3.886 + 2.272 × ln(Age) ± 0.222 (R2 = 0.73), respectively. The C4 vertebral body grew linearly in cross-sectional area as y = −7.205 + 0.812 × Age ± 1.668 (R2 = 0.76) and four-degree polynomially in volume as y = 14.108 + 0.00007 × Age4 ± 6.289 (R2 = 0.83). The transverse and sagittal diameters, cross-sectional area and volume of the ossification center of the C4 vertebral body generated the following functions: y = −8.836 + 3.708 × ln(Age) ± 0.334 (R2 = 0.76), y = −7.748 + 3.240 × ln(Age) ± 0.237 (R2 = 0.83), y = −4.690 + 0.437 × Age ± 1.172 (R2 = 0.63) and y = −5.917 + 0.582 × Age ± 1.157 (R2 = 0.77), respectively. The ossification center-to-vertebral body volume ratio gradually declined with age. On the right and left, the neural ossification centers showed the following growth: y = −19.601 + 8.018 × ln(Age) ± 0.369 (R2 = 0.92) and y = −15.804 + 6.912 × ln(Age) ± 0.471 (R2 = 0.85) for length, y = −5.806 + 2.587 × ln(Age) ± 0.146 (R2 = 0.88) and y = −5.621 + 2.519 × ln(Age) ± 0.146 (R2 = 0.88) for width, y = −9.188 + 0.856 × Age ± 2.174 (R2 = 0.67) and y = −7.570 + 0.768 × Age ± 2.200 (R2 = 0.60) for cross-sectional area, and y = −13.802 + 1.222 × Age ± 1.872 (R2 = 0.84) and y = −11.038 + 1.061 × Age ± 1.964 (R2 = 0.80) for volume, respectively.ConclusionsThe morphometric parameters of vertebra C4 and its three ossification centers show no sex differences. The C4 vertebral body increases logarithmically in height and both sagittal and transverse diameters, linearly in cross-sectional area, and four-degree polynomially in volume. The three ossification centers of vertebra C4 grow logarithmically in both transverse and sagittal diameters, and linearly in both cross-sectional area and volume. The age-specific reference intervals for evolving vertebra C4 may be useful in the prenatal diagnosis of congenital spinal defects.

Digital image analysis of ossification centers in the axial dens and body in the human fetus

“…Vignolo et al [26] reported that ossification started earlier in female fetuses, thus male fetuses were more difficult to assess in this respect. The present paper and our previous findings [4, 5, 22–24] have not confirmed any sex differences in ossification of the spine. Therefore, in the present study both numerical data and statistical analysis are presented aggregately without taking sex into account.…”

“…Of note, such a proportionate increase in cross-sectional area was previously proved by Baumgart et al [5] for vertebra C4 as y  = −4.690 + 0.437 × age, and by Szpinda et al [23, 24] for both vertebrae T6: y  = −15.591 + 1.200 × age and L3: y  = −32.423 + 2.071 × age.…”

“…As reported in the medical literature, the vertebral body ossification centers revealed a natural logarithmic increase in both transverse and sagittal diameters. This was substantiated by Baumgart et al [5] in relation to vertebra C4 ( y  = −8.836 + 3.708 × ln(age) and y  = −7.748 + 3.240 × ln(age), respectively) and by Szpinda et al [23, 24] in relation to both vertebrae T6 ( y  = −14.784 + 6.115 × ln(age) and y  = −12.065 + 5.019 × ln(age), respectively) and L3 ( y  = −27.610 + 10.341 × ln(age) and y  = −13.858 + 5.636 × ln(age), respectively).…”

“…Its volume gradually increased from the C1 to L3 vertebra, and sharply decreased from the L4 to S5 vertebra. Of note, on the same fetal material Szpinda and his collaborators carried out a comprehensive morphometric analysis including growth curves for typical vertebrae C4 [5], T6 [23] and L3 [24]. However, Castellana and Kosa [7] were the only authors to measure the axial ossification centers in a large sample, consisting of 106 human fetuses aged 16–40 weeks.…”

“…Because of flexion–extension at the atlantooccipital joint and rotation at the atlantoaxial joint, 3-dimensional sonographic evaluation of the atlas and axis in utero fetuses may frequently misjudge their malalignment or offset phenomena [12]. To date, the quantitative analysis of some linear, planar and spatial dimensions of ossification centers of the spine has been established in detail using computed tomography and digital image analysis only for the C4 [5], T6 [23] and L3 [24] vertebrae. Therefore, this study involved advanced morphometric analysis of the non-typical axial vertebra, the dens of which from a developmental point of view is actually the atlantal body.…”