Okajimas Folia Anat. Jpn., 71(5): 311-318, December, 1994

Investigations on the Growth Pattern of the in Japanese Human Fetuses

By

Thomas KOPPE, Toshio YAMAMOTO, Osamu TANAKA and Hiroshi NAGAI

Department of Anatomy, Okayama University, School of Dentistry Department of Anatomy, First Division, Shimane Medical University

-Received for Publication, August 31, 1994-

Key Words: Pneumatization, Maxillary sinus, Growth, Human fetuses

Summary: The growth pattern of the maxillary sinus was analyzed using 18 human fetuses of both sexes between 9 and 21 weeks of age postconception. The paraffin embedded specimens were cut in series in the frontal and the transversal plane, respectively. The inner surface of the maxillary sinuses was redrawn and surrounded with a digitizer and then the volumes were calculated. A correlation analysis as well as a simple linear regression analysis between the values of the maxillary sinus, different linear values of the and the crown-rump length (CRL) served to prove possible growth relations. The maxillary sinus' Anlage was already identifiable in the 29.8 mm (CRL) fetus. From this first appearance, the maxillary sinus expands not only in posterior direction but also in anterior direction from 11 weeks onwards. The maxillary sinus volume increased from 0.0008 mm3 at the age of 9 weeks to more than 9 mm3 at the age of 21 weeks. The results of the statistical analysis indicated, that the relationship between the maxillary sinus' Anlage and the nasal cavity were strongly influenced by the body size (CRL). This study suggests, that the growth of the maxillary sinus follows special regularities in the early fetal development.

The show a considerable varia- A number of investigators showed, that biomath- bility in size and shape. This variability can already ematical methods are useful to show the fetal growth be proved at the moment of birth. According to relations of different facial skeleton structures (Houpt, Cullen and Vidie (1972) and Anderhuber et al. (1992), 1970; Kvinnsland, 1970; Lavelle and Moore, 1970; the shape of the maxillary sinus in fetuses and new- Diewert, 1985; Siegel et al. , 1987; Burdi et al. , 1988; - born , ranges from elliptical, to round and triangular Kimes et al., 1988; Lee et al., 1992; Mandarim-de- forms. However, there is no satisfying interpretation Lacerda and Urania-Alves, 1992). However, no re- of these observations. port is available about the biomathematical analysis The principal development of the maxillary sinus, of the fetal maxillary sinus. The purpose of the which is the first of the paranasal sinuses to be present study was, therefore, to describe the normal developed in the fetal period after the 2"d month development and the growth of the maxillary sinus (Killian, 1895; 1896; Schaeffer, 1910; Peter, 1912; in human fetuses using quantitative methods. Van Aleya, 1936; Vidie, 1971), can be considered as quite well known. Although many authors, have worked on the morphology of the fetal maxillary Material and Methods sinus (Killian, 1895; 1896; Schaeffer, 1910; Peter, 1912; Richter, 1936; Salinger, 1936; Stern, 1939; Eighteen formalin fixed normal human fetuses of Vidie, 1971; Libersa et al. , 1981; Lang and Papke, both sexes were used in the present study (Tab. 1). 1984), their studies are mostly restricted to the re- Their age ranged from 9 to 21 weeks of age postcon- lation between the maxillary sinus' Anlage and the ception to exclude an influence of the developing cartilage of the nose capsule, the developing maxilla, tooth germs on the development of the maxillary and the developing glands, respectively. There are sinus (Schaeffer, 1910). In the case of fetuses without relatively few quantitative data on this paranasal indication of the age it was calculated according to sinus (Schaeffer, 1910; Vidic, 1971). Jakobovits et al. (1972).

Correspondence address: Dr. Th. Koppe. Department of Anatomy, Okayama University Dental School, Shikata-cho 2-5-1, Okayama 700, Japan

311 312 T. Koppe et al.

Table 1. Classification of the experimental material' maxillary sinus The relations between the studied measurements were described with the Pearson correlation coef- ficient. Also, partial correlation coefficients were calculated in order to exclude the influence of the body size (CRL) on the correlation coefficient (Lohse et al., 1986). A simple linear regression analysis was performed for the selected parameters. In the cases, in which it was not possible to apply the linear model of the regression analysis, the respective linear trans- formations of the values were done (Chatterjee and Price, 1977; Sherwood et al. , 1992). The calculated regression lines were evaluated by inspection of the residuals. Additionally the standard error Sx,), was calculated and the regression slope was statistically proved.

Results

I Specimen , belonging to the collection of the Department of Morphology of the maxillary sinus Anatomy, Shimane Medical University, The maxillary sinus' Anlage was already observed * Specimen , belonging to the Department of Anatomy, Okayama at the age of 9 weeks. Whereas the Anlage of the University School of Dentistry CRL — crown-rump length. Specimen 7 and 13 have been cut maxillary sinus in the 29.8 mm fetus was restricted to transversely. F — female, M — male. the region of the ethmoidal infundibulum, the 39 mm fetus already showed a posterior recess. From the 11th weeks onwards an anterior recess in addition to The heads of the fetuses were cut in sagittal a posterior recess was observed in all specimens. At direction conserving the , and the left the age of 11 weeks the first Anlagen of glands halves were embedded in paraffin. Serial sections at appeared, especially in the posterior recess. 7 pm and 10 pin, according to the size of the speci- mens, were made at the frontal plane. Two specimens Table 2. Positionrelations between the posteriorrecess of the were cut in the transversal plane. Every third section maxillarysinus and the inferiornasal meatus was stained with hematoxylin and eosin. The inner surface of the maxillary sinus on every section were traced and surrounded three times by employing a digitizer. The corresponding areas were measured and afterwards the volume (V) was calcu- lated. In addition, the following variables were de- termined out of the section series: Li —length of the maxillary sinus L2 —length of the anterior recess of the maxillary sinus L3 —length of the part of the maxillary sinus in the region of the maxillary hiatus LA —length of the posterior recess of the maxillary sinus H1 —height of the maxillary sinus in the region of the ethmoidal infundibulum H2 —highest height of the posterior recess H3 —height of the nasal cavity in the region of the

ethmoidal infundibulum A — posterior recess, above the inferior WI —distance between the lateral wall of the carti- B — posterior recess, at the upper margin of the inferior nasal laginous nose capsule and the cartilaginous nasal meatus septum at the horizontal level C — posterior recess, below the upper margin of the inferior nasal W2 — maximum width of the posterior recess of the meatus Growth of the Maxillary Sinus in Human Fetuses 313

Though the resorption of the nose capsule's carti- also between specimens (Fig. 2). Within this, the lage was performed from posterior to anterior, the form changed from a long ovate into an elliptical and maxillary sinus mainly developed from anterior to sometimes even into a circular or a triangular form. posterior. The growth of the maxillary sinus into caudal direction was not always the same between Growth of the maxillary sinus specimens of the same age (Tab. 2). The maxillary The maxillary sinus volume increased from sinus had already advanced to the height of the 0.0008rrun3 at the age of 9 weeks to more than inferior nasal meatus at the age of 18 weeks (Fig. 1). 9 mm3 at the age of 21 weeks (Tab. 3). Specimen In 21 week-old fetuses the sinus exceeded the inferior number 15 showed an extremely high value of already by more than 1.3 mm (Tab. 2). 11.4nun3. At the same time the length Ll of the The shape of the posterior recess changed from maxillary sinus enlarged from 0.27mm to 7mm. anterior to posterior characteristically, but differed Figure 3 shows the changing of the length relations

Fig. 1. a. Frontal section through the posterior recess of the maxillary sinus in a 18-week old human fetus. The posterior recess (P) has already advanced the inferior nasal meatus (asterik). C — cartilage of the nose capsule, M — maxillary bone. b. Frontal section through the posterior recess of the maxillary sinus in a 20-week old human fetus. Note the developing glands (arrowheads) in association with the posterior recess (P) M — maxillary bone. Osteoclasts are marked by arrows. Bar — 200 am. 314 T. Koppe et al.

Fig. 2. Redrawings of the outline of the posterior recess of the maxillary sinus in different frontal cut areas, using selected specimen. Note the form variability of the posterior recess. The numbers in the circles correspond to the specimen numbers. The order of the redrawings corresponds to a division into 3 parts of the posterior recess from the front to the back side: A — beginning of the posterior recess; B — middle part of the posterior recess; C — back part of the posterior recess. in the anterior recess (L2) and the posterior recess CRL. (LA) related to the whole length of the maxillary Table 4 and 5 contain the results of the calculated sinus (L1) in different specimens. partial correlation coefficients and the Pearson cor- The statistical analysis of the measured values relation coefficients. After elimination of the factor indicated, that the values of the maxillary sinus body size (CRL) on the Pearson correlation, most of correlated in a different degree with the CRL and the correlation coefficients between the values of the the variables of the nose cavity (Tab. 4). Although maxillary sinus and the nose cavity became smaller. the volume of the maxillary sinus correlated with the Only the variables of the posterior recess showed CRL, the respective correlation coefficientwas rela- significant correlations with the width of the nose tively low. In contrast, there was a close relation capsule WI (Tab. 4). However, the volume of the between the length of the maxillary sinus Li and the maxillary sinus correlated significantly with the lengths Growth of the Maxillary Sinus in Human Fetuses 315

Table 3. Results of the measurements of the maxillary sinus and the nasal cavity

V — in mm3; L1 to H3 — in mm

Fig. 3. Diagram representing the relations between the length's measurements L2, L3 and L4. It was possible to observe apart from a posterior recess (L4) an anterior recess (L2) from the 11th week onwards.

Li and widths W2 (Tab. 5). Discussion Figure 4 and table 6 show the results of selected calculations of simple linear regressions. They indi- The morphological findings corresponded princi- cate at the same time the different growth rates of pally with the results of previous reports (Schaeffer, the observed values. 1910; Richter, 1936; Vidid, 1971). They especially support the observations made by Vidit (1971), who found the first Anlage of a maxillary sinus in a 32 mm 316 T. Koppe et al.

Table 4. Correlations r and partial correlations r' between the fetuses is relatively low after the 24th week. More- measures of the maxillary sinus, the nose cavity and over, Mandarim-de-Lacerda and Urania-Alves (1993) CRL (Body size = constant) reported, that the different components of the mid and lower face in Human fetus, such as the maxilla, the palatine and the ethmoid expand with different growth rates. Earlier qualitative studies on the development of the maxillary sinus have shown, that the maxillary sinus elongates, coming from the ethmoidal infun- dibulum backwards in the form of a posterior recess (Schaeffer, 1910; Starck, 1965). However, the pres- ent study indicated, that from 11 weeks onwards, ap < 0.001, bp < 0.01, cp < 0.05, " not significant. there was also an anterior recess identifiable. To describe the growth direction of the maxillary sinus in this study, the total length Li of the maxillary sinus was divided into 3 partial lengths (Fig. 2). In Table 5 Correlations r and partial correlations r' most cases the posterior recess showed the biggest between the volume and linear measure- ments of the maxillary sinus .(Body size = length of all partial length values constant) The results of the correlation and regression analy- sis showed in some parts close relations between the studied variables and the CRL (Tab. 4). Especially the length of the maxillary sinus correlated highly to the CRL (Tab. 4), suggesting, that the length of the maxillary sinus represents a reasonable measurement to characterize the size and the growth of the fetal maxillary sinus. ap< 30 .001,bp < 0.01, 'pc 0.05n,"s not significant. The calculated partial correlations showed signifi- cant differences in comparison with the correlation coefficients according to Pearson (Tab. 4, 5). It was obvious, that the correlations between the values of long fetus and the first appearance of glands' Anlagen the maxillary sinus and those of the nose capsule in a 49 mm long fetus. In the present study those were highly influenced by the body size (CRL). Only Anlagen were found in 29.8 mm and 45.9 mm long the values of the posterior recess showed significant fetuses, respectively. correlations to the width of the nose capsule (Tab. In this study, the length Li of the maxillary sinus 4). It has been stated in previous reports (Sperber, increased from 0.3 mm to more than 7 mm in fetuses 1980; Wolf et al., 1993), that the growth of the at the age of 21 weeks. There are no comparable human paranasal sinuses is directly linked to the data on fetuses smaller than 50 mm CRL. According development of the skull and to the dentition. How- to Schaeffer (1910), Onodi (1911), Anderhuber et ever, the results of this study indicate, that the fetal al. (1992) and Ritter and Fritsch (1992) the length of growth of the maxillary sinus has its own growth the maxillary sinus is not bigger than 7.5 mm to pattern, at least until the age of 21 weeks. 10 mm at the moment of birth. However, no report Cullen and Vidie (1972) and Anderhuber et al. is available about the volume of the maxillary sinus (1992) report on an incredible form variability of in human fetuses. the maxillary sinus in human fetuses and newborn. The results of the length's measurements obvi- Cullen and Vidie (1972) suggest a subdivision of 5 ously indicate, that the size of the maxillary sinus types. The results of both, the Pearson correlation changes very little after 21 weeks of age. Some coefficients and the partial correlation coefficients in authors claim, that after 20 weeks of intrauterine age the present study, showed, that the volume increase an obvious growth phase starts in different regions of of the maxillary sinus was closely related to the the facial skeleton (Lavelle and Moore, 1970; Siegel development of the length of the maxillary sinus. et al. , 1987; Kimes et al. , 1988). The present study However, this study also revealed close correlations indicates, that this growth pattern apparently does between the volume of the maxillary sinus and the not work in all structures of the human facial skel- widths of the posterior recess (Tab. 5). These results eton. These findings support the observation made lead to the conclusion, that the form variability, by Siebert (1986), who points at the fact, that the which is discussed by Cullen and Vidie (1972) and growth rate of the median facial region in human Anderhuber et al. (1992) and which is also shown in Growth of the Maxillary Sinus in Human Fetuses 317

Fig. 4. Bivariate plots of different parameters in relation to the crown-rump length (CRL) and the volume of the maxillary sinus (V). The figures also show the corresponding regression lines. R2 — coefficient of determi- nation. Li — length of the maxillary sinus, H3 — height of the nasal cavity, WI — distance between the lateral wall of the nose capsule and the nasal septum, W2 — width of the posterior recess of the maxillary sinus.

the Figure 2 of this study, may be an expression of a the growth of its supporting structure, the maxillary different growth intensity of the maxillary sinus. bone (Dixon, 1953). Further studies should be con- The present study clarified, that during the early centrated on possible changes of the growth pattern fetal development, the maxillary sinus may have its of the maxillary sinus, which are related to growth own growth pattern. However, the latter develop- direction into the developing maxilla. ment and growth of the maxillary sinus is related to 318 T. Koppe et al.

Table 6. Results of the regression analysis between the measures Cleft Palate J 1988;40;282-287. of the maxillary sinus, the nose cavity and the CRL 12) Kvinnsland S. The relationship between the cartilaginous nasal septum and maxillary growth during human fetal life. Cleft Palate J 1970;7:523-532. 13) Lang J, Papke J. Uber die klinische Anatomic des Panes inferior orbitae und dessen Nachbarstrukturen. Gegenbaurs Morphol Jahrb 1984;130:1-47. 14) Lavelle CLB, Moore WJ. Proportionate growth of the human jaws between the fourth and seventh months of intrauterine life. Archs Oral Biol 1970;15:453-459. 15) Lee SK, Kim YS, Lim CY, Chi JG. Prenatal growth pattern of the human maxilla. Acta Anat 1992;145:1-10. 1 All results were significant at p < 0 .001. 16) Libersa C, Laude M, Libersa JC. The pneumatization of the accessory cavities of the nasal fossae during growth. Anat Clinica 1981;2:265-273. 17) Lohse H, Ludwig R, Rtihr M. Statistische Verfahren. pp. Acknowledgement 176-207, Volk und Wissen, Berlin, 1986. 18) Mandarim-de-Lacerda CA, Urania-Alves MU. Human man- dibular prenatal growth: bivariate and multivariate growth We would like to thank Prof. Dr. T. Sugimoto, allometry comparing different mandibular dimensions. Anat 2nd Department of Anatomy of the Okayama Uni- Embryol 1992;186:537-541. versity School of Dentistry, for his helpful advice 19) Mandarim-de-Lacerda CA, Urania-Alves M. Growth al- and support concerning the quantitative analysis of lometry of the human face: analysis of the osseus components the histological sections. The authors also wish to of the mid and lower face in 'Brazilian fetuses. Ann Anat 1993;175:475-479. thank Mrs. Dr. Sabine Koppe and Mr. Alessandro 20) Onodi A. Die Nebenhdhlen der Nase beim Kinde. Kabitzsch, Cartieri for the translation of the manuscript and Wiirzburg, 1911. editorial assistance, respectively. A part of this 21) Peter K. Die Entwicklung der Nasenmuscheln bei Menschen study was presented at the 89. Versammlung der und Saugetieren. Arch Mikr Anat 1912;80:478-559. Anatomischen Gesellschaft, Marburg, March 22-25, 22) Richter H. Grundsatzliches fiber die Entwicklung der NasennebenhOhlen. Arch Ohren-Nasen-Kehlkopfkd 1936; 1994. ' 14:54 -60 . 23) Ritter FR, Fritsch MH. Atlas of paranasal sinus surgery. pp. 6-12, Igaku-Shoin, Tokyo, New York, 1992. References 24) Salinger S. The paranasal sinuses. Arch Otolaryngol 1936; 24:204 -240 . 1) Anderhuber W, Weiglein A, Wolf G. Cavitasnaji und Sinus 25) Schaeffer JP. The sinus maxillaris and its relations in the maxillaris im Neugeborenen- und Kindesalter. Acta Anat embryo, child and adult Man. Am J Anat 1910;10:313-368. 1992;144:120- 126. 26) Sherwood RJ, Robinson HB, May RL, Meindl RS. Stan- 2) Burdi AR, Lawton TJ, Grosslight J. Prenatal pattern emerg- dardized residuals as a mean for detection of growth alter- ence in early human facial development. Cleft palate J ation in the pathologic human fetus. Teratology 1992;46: 1988;25:8-15. 419-427. 3) Chatterjee S, Price B. Regression analysis by example. New 27) Siebert JR. Prenatal growth of the median face. Am J Med York, John Wiley & Sons, New York, 1977. Genet 1986;25:369-379. 4) Cullen RL, VidW B. The dimensions and shape of the 28) Siegel MI, Mooney MP, Kimes KR, Toghunter J. Analysis human maxillary sinus in the perinatal period. Acta Anat of the size variability of the human normal and cleft palate 1972;83:411-415. fetal nasal capsule by means of three-dimensional recon- 5) Diewert VM. Development of human craniofacial mor- struction of histologic preparations. Cleft Palate J phology during the late embryonic and early fetal periods. 1987;24:190 - 199. Am J Orthodont 1985;88:64-76. 29) Sperber GH. Applied anatomy of the maxillary sinus. J 6) Dixon AD. The early development of the maxilla. Dent Canad Dent Assn 1980;6:381-386. Pract 1952;3:331-336. 30) Starck D. Embryologie. 2. Auflage, pp. 458-460, G. Thieme, 7) Houpt MI. Growth of the craniofacial complex of the human Stuttgart, 1965. fetus. Am J Orhodont 1970;58:373-383. 31) Stern L. ROntgenologische Betrachtung der Entwicklung 8) Jakobovits A, Iffy L, Wingate MB, Slate MG, Chatterton und Ausdehnung der Nasennebenhalen. Hals- Nasen- und RT, Kerner P. The rate of early fetal growth in the human Ohrenarzt Teil I 1939;30:169-199. subject. Acta Anat 1972;83:50-59. 32) Van Aleya OE. The ostium maxillare. Arch Otolaryngol 9) Killian G. Zur Anatomie der Nase menschlicher Embryonen. 1936;24:553-569. Arch Laryngol 1895;3:17-47. 33) Vidie B. The morphogenesis of the lateral nasal wall in the 10) Killian G. Zur Anatomie der Nase menschlicher Embryonen. early prenatal life of Man. Am J Anat 1971;130:121-140. Arch Laryngol 1896;4:1-45. 34) Wolf G, Anderhuber W, Kuhn F. Development of the 11) Kimes KR, Siegel MI, Mooney MP, Todhunter J. Relative paranasal sinuses in children: implications for paranasal contributions of the nasal septum and airways to total nasal sinus surgery. Ann Otol Rhino! Laryngol 1993;102:705-711. capsule volume in normal and cleft lip palate fetal specimens.