Fatal non‐accidental pediatric cranial fracture risk and three‐layered cranial architecture development

Abstract

This study examines the influence of three‐layered cranial architecture development upon blunt force trauma (BFT) cranial outcomes associated with pediatric non‐accidental injury (NAI). Macroscopic and microscopic metric and morphological comparisons of subadult crania ranging from perinatal to 17 years of age chronicle the ontogenetic development and spatial and temporal variability in the emergence of a mature cranial architecture. Cranial vault thickness increases with subadult age, accelerating in the first 2 years of life due to rapid brain growth during this period. Three‐layer differentiation of the cranial tables and diploë initiates by 3–6 months but is not consistently observed until 18 months to 2 years; diploë formation is not well developed until after age 4 and does not manifest a mature appearance until after age 8. These results allow topographic documentation of cortical and diploic development and temporal and spatial variability across the growing cranium. The lateral cranial vault is identified as expressing delayed development and reduced expression of the three‐layer architecture, a pattern that continues into adulthood. Comparison of fracture locations from known BFT pediatric cases with identified cranial fracture high‐risk impact regions shows a concordance and suggests the presence of a higher fracture risk associated with non‐accidental BFT in the lateral vault region in subadults below the age of 2. The absence or lesser development of a three‐layered architecture in subadults leaves their cranial bones, particularly in the lateral vault, thin and vulnerable to the effects of BFT.

Highlights.

• Three‐layer pediatric cranial bone structure is an intrinsic protective variable in blunt trauma head injuries.

• The delayed and reduced expression of three‐layer development in the lateral vault makes it vulnerable to fracture.

• Bioengineering mapping of cranial vault development variability allows for pediatric fracture risk assessment.

1. INTRODUCTION

Approximately 75%–80% of all non‐accidental pediatric deaths in the U. S. involve cranial blunt force trauma (BFT), disproportionately affecting decedents below the age of 1 year [1, 2, 3]. Mortality rates for pediatric cranial non‐accidental injury (NAI) are at least 30% and are attributable to deleterious effects of direct impact or inertial brain motion from acceleration/deceleration and rotational forces [2]. Pediatric cranial NAI is often associated with cranial fracture, increasing the risk of fatal neurotrauma [4, 5, 6, 7, 8].

In cases of cranial fracture, factors that may influence skeletal trauma are to be considered in skeletal trauma interpretation. This includes both extrinsic and intrinsic variables. While prior research has focused on factors associated with fracture initiation, propagation, and fracture mechanics [9, 10, 11, 12, 13, 14, 15, 16, 17, 18], less attention has been paid to the influence of the intrinsic features of cranial bone structure and growth on inflicted BFT outcomes even though it has long been recognized that the three‐layered cranial architecture is an important functional feature in protecting the brain from trauma [19].

The current research investigates the role of cranial development in pediatric NAI and its outcomes. It considers ontogenetic development of the three‐layer bony architecture‐‐inner and outer cortical tables and diploë—in light of the pediatric cranium's ability to withstand non‐accidental fracture and associated neurotrauma and its potential application to assessing risk and predicting BFT outcome.

1.1. Three‐layer cranial architecture development

The bones of the adult human cranial vault are comprised of a spongy diploë (a cancellous repository for red marrow) sandwiched between an inner and outer table of cortical bone. However, this tri‐layered configuration is not present at birth or in the young infant. The infant cranium is thin and unilaminar, a consequence of its embryological origin. In contrast to the cartilaginous development of the cranial base, major portions of the cranial vault, including the parietals, frontal, temporal squama, and superior occipital squama, develop through intramembranous ossification from direct mesenchymal condensation within a fibrous membrane, the ectomenix [20, 21, 22].

With the help of the osteogenic outer layer of the meninges, ossification of a single cranial table occurs through the deposition of vascularized woven bone within cranial ossification centers [23, 24]. After birth, the transition to deposition of vascularized lamellar bone within the endosteal and periosteal membranes helps create the inner and outer tables, enlarged by the appositional growth of these layers [23, 25]. Concurrently, diploë formation occurs through a process of invasion of osteoclasts and then osteoblasts into the space between the inner and outer surfaces of these tables. The coordinated, coupled process of osteoclastic resorption and osteoblastic formation of woven and early lamellar bone creates the cavities of trabecular bone within the diploë layer, interspersed with vascularized canals for the diploic vein system [23].

There is a dearth of knowledge about initiation and maturation of the inner and outer table and diploë in terms of its timing and variability in expression in the growing subadult. It has been suggested that significant tri‐layer cranial architectural (including diploë) development occurs as early as 6 months of age [26] or the second [2, 22, 27], fourth [23, 25, 28], sixth [24], or even seventh year of life [29, 30]. The exact timing and mechanism of this process are not known and have not been fully studied on dry bone. Also unknown is the influence of three‐layer development on non‐accidental episodes of pediatric BFT.

This study has two research objectives. The first goal is to chronicle the temporal and spatial development of three‐layered architecture in the subadult cranium. The second objective is to investigate the implications of this development for pediatric NAI cranial fracture and outcomes. It is hypothesized that regions of the pediatric cranium manifesting incomplete, delayed, or inadequate development of the three‐layer architecture will exhibit greater vulnerability to fracture and neurotrauma than regions with a more fully developed three‐layer structure.

2. MATERIALS AND METHODS

Development of three‐layered cranial architecture is chronicled through both macroscopic and microscopic observations of crania and cranial portions of 55 male and female subadults, aged fetal to 17 years (Table 1). The majority (n = 52) are derived from the Scheuer collection at the University of Dundee Centre for Anatomy and Human Identification. This sample includes historic and anatomical specimens of known age, with the age range being independently verified by the authors at the time of study using standard subadult aging criteria. Since sex was recorded for some individuals, but not others, sexes were combined in this study. Cranial samples included isolated fragments of frontals, parietals, and occipitals which provided observation of the interior bone structure and thickness of the cranial vault. Samples also included eight fairly complete Scheuer subadult crania with circumferential calvarial autopsy cuts, allowing a superior endocranial view of internal bone structure along the contour of the cranial vault. In addition, the total sample included three individuals (all aged 3 months or less) derived from the Radford University Forensic Science Institute (RUFSI).

TABLE 1.

Cranial samples examined by age categories.

Age	n
Fetal	7
Perinatal – 2.9 months	12
3–5.9 months	3
6–11.9 months	1
12–17.9 months	2
18–23.9 months	7
2–3.9 years	7
4–5.9 years	6
6–7.9 years	3
8–11.9 years	5
12–17.9 years	2
Total	55

Recorded metric and morphological variables focused on the transformation of the uni‐layered cranial vault into a tri‐layered one. A preliminary review of all Scheuer cranial samples in temporal order (from fetal to oldest adolescent) at 5× magnification allowed the creation of 10 arbitrary age groupings (Table 1) which best chronicled this transformation and, at the same time, mitigated small sample sizes for some ages. All variables were recorded by the primary author with the aid of a portable 3D high‐resolution digital light microscope at 5–40× magnification and, when possible, a stationary high‐resolution 3‐D digital combined stereoscopic and electron microscope at 5–200×. For the complete skulls with cross‐sectional autopsy cuts, measurements of maximum thickness dimensions for the cranial table(s) and diploë, if present, were taken at common CT‐based standardized points for measuring cranial thickness and determining halo pin placement [31, 32], including the anterior and posterior and right and left anterolateral, mid‐parietal lateral, and posterolateral positions on the exposed cranial cross‐section along the circumferential cut (Figure 1). These points were approximated for the fragmentary specimens in anatomical position; the mid‐parietal medial position was added where possible.

FIGURE 1.

Cranial locations examined: A, anterior (most anterior point on the frontal, typically at the midline); AL, anterolateral (most lateral point on the frontal); L, Parieto‐lateral (most lateral point on the parietal); PL, posterolateral (most lateral point on the posterior occipital); P, posterior (most posterior point on the occipital, typically at the midline). [Color figure can be viewed at wileyonlinelibrary.com]

With the aid of a digital grid, ordinal scales were used to describe each sample's cranial table and diploë morphological development within a 5 × 5 mm area in each of the above regions (Table 2). Development of these ordinal scales was based on visualization of morphological features associated with the cranial table and diploë formation, differentiation, and remodeling and best captured the dynamic process of osteoblastic deposition of woven and subsequently lamellar bone accompanied by osteoclastic resorption. Variables record the degree of three‐layer differentiation and diploë bone deposition, resorption, uniformity, and distribution across each bone sample and are presented as percentage estimations (<25%, 25%–75%, and >75%). These data are compared across age groups and cranial locations to illustrate and map the progression and character of diploë and inner and outer table development both within and across these temporal and spatial groupings.

TABLE 2.

Microscopically‐defined morphological variables examined across age categories and bone location.

Three‐layer differentiation	Degree of definition and differentiation of inner and outer cranial tables and intermediate diploe layer: 0 = No observable differentiation of cranial layers (unilaminar) 1 = beginning differentiation of cranial layers (<25%) 2 = moderate differentiation of cranial layers, with an inner and outer table visible but not clearly distinct or measurable (25%–75%) 3 = advanced differentiation of cranial layers—Distinct tri‐laminar cranial architecture is observed and each layer is measurable as a discrete entity (>75%)
Diploë bone deposition	Amount of osteoblastic deposition of cancellous bone in the space between inner and outer cranial tables: 0 = No observable bone deposition 1 = Beginning woven bone deposition between inner and outer tables (<25%) 2 = Moderate cancellous bone deposition, characterized by measurable amounts of woven bone between inner and outer tables; beginning transformation into lamellar bone (25%–75%) 3 = Advanced cancellous bone deposition between inner and outer tables, characterized by transformation into vascularized lamellar bone (>75%)
Diploë bone resorption	Amount of osteoclastic bone resorption between inner and outer cranial tables: 0 = no osteoclastic bone resorption 1 = slight resorption (<25% of the analyzed bone region is resorbed) 2 = moderate resorption (25%–75% of the analyzed bone region is resorbed) 3 = advanced resorption (>75% of the analyzed bone region is resorbed)
Diploë uniformity	Uniformity of cancellous bone between the inner and outer tables: 0 = no observable cancellous bone formation 1 = non‐uniform, irregular cancellous (woven) bone (>75% of bone is disorganized, unpatterned) 2 = moderate uniformity of cancellous bone (25%–75% of bone is disorganized, unpatterned) 3 = advanced uniformity of cancellous (lamellar) bone (<25% of bone is disorganized, unpatterned)
Diploë distribution	Distribution of diploë across cranial bone sample: 0 = no diploë development 1 = sparse (<25%) diploë distribution across the bone sample 2 = moderate (25%–75%) diploë distribution across the bone sample 3 = concentrated (>75%) diploë distribution across the bone sample

With the aid of over 300 micrographs derived from the Scheuer and RUFSI samples (taken by the first author), the samples were re‐scored by the first and third authors approximately 7 months after the initial scoring. This occurred without the knowledge of the initial scores. Inconsistent scores between the first and second trials (and between the first and third authors) were averaged to produce the final ordinal scoring for each sample.

RUFSI cases of pediatric cranial NAI (both antemortem and acute) are compared to the temporal and spatial patterning of developing three‐layer cranial architecture. The RUFSI sample consists of 19 individuals with cranial NAI, ranging in age from 28 days to 4 years of age. Nearly 150 digital microscopic and macroscopic cranial fracture and internal bone structure images were derived from fully macerated cranial samples post‐autopsy and were taken by the primary author. A variety of known BFT mechanisms were associated with this sample, including contact with blunt objects (e.g., adult fists, couch arms) and acceleration/deceleration forces. Specific impact points to the cranium were identifiable in a minority (n = 5) of the sample.

Comparison of these NAI data allows testing of the hypothesis that regions of the pediatric cranium manifesting incomplete development of the three‐layer architecture exhibit a higher incidence of (and by extrapolation, greater vulnerability to) fracture than regions with a developed three‐layer structure.

3. RESULTS

3.1. Cranial vault thickness

Maximum thickness means for the cranial vault (cranial table[s] plus diploë) are comparable to those recorded in the clinical literature [29, 32, 33] for analogous ages. Comparison of mean thicknesses across age groups and the region shows an increase with age for each bone considered. However, this trend is not temporally or spatially uniform—it is accelerated in the first 2 years of life and shows greater expression at all ages in the anterior and posterior cranial vault (i.e., frontals and occipitals). Subadult crania show reduced parietal thicknesses in all age categories examined.

3.2. Three‐layer cranial architecture differentiation and development

All samples aged from fetal or perinatal up to approximately 3 months exhibit unilaminar bone morphology (Table 3; Figure 2). The beginning development of inner and outer tables is not observed until the 3–5.9 month age category. This is first observed as an osteoblastic‐driven thickening and subsequent expansion of the unilaminar tabular margins (Figure 3A), followed by a dynamic process of osteoclastic cavitation of bone within the unilaminar space and eventual differentiation of the tabular margins into an inner and outer cranial table. Above the age of 6 months of age, most samples show some degree of layer thickening and beginning differentiation; however, it is not until 18 months – 2 years of age and onward that it is consistent and appreciable (>25%) differentiation of outer and inner tables for all regions (Figure 3B). Samples above 4 years of age show readily discernible advanced (Stage 3 ≥ 75%) three‐layer differentiation.

TABLE 3.

Mean three‐layer cranial differentiation scores across age and cranial location.

Age category	Cranial location
	A	AL	L	PL	P
Fetal	0	0	0	0	0
Perinatal–2.9 months	0	0	0	0	0
3–5.9 months	1	1	0	0.5	0.5
6–11.9 months	1	1	1	1	1
12–17.9 months	2	2	1	2	2
18–23.9 months	3	2	2	2	3
2–3.9 years	3	2.5	2	2	3
4–7.9 years	3	3	2	2.5	3
8–11.9 years	3	3	2.5	3	3
12–17.9 years	3	3	2.5	3	3

Note: Cranial location: A = anterior (most anterior point on the frontal, typically at the midline); AL = anterolateral (most lateral point on the frontal); L = parieto‐lateral (most lateral point on the parietal); PL = posterolateral (most lateral point on the posterior occipital); P = posterior (most posterior point on the occipital, typically at the midline).

Three‐layer differentiation: 0 = no differentiation; 1 = beginning/slight differentiation (<25%); 2 = moderate differentiation (25%–75%); 3 = advanced differentiation (>75%).

FIGURE 2.

Unilaminar cranial table (anterior frontal; perinatal; 10×). [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3.

(A) Three‐layer initial architecture development and differentiation—Initial thickening of the unilaminar table (anterolateral frontal, 4–6 months; 20×). (B) Advanced three‐layer architecture development and differentiation (anterolateral frontal, 18–23 months; 10×). (C) Spatial variability in three‐layer development and differentiation—Immature cavitation and cranial table differentiation in parietal (18–23 months; 20×). [Color figure can be viewed at wileyonlinelibrary.com]

This tri‐layer initiation and differentiation are not spatially uniform‐‐portions of the anterior and posterior cranium, particularly along the midline, manifest the earliest and most prominently discernible thickening and beginning tri‐layer appearance, followed by anterolateral and posterolateral regions of the vault. Portions of the parieto‐lateral cranial table, particularly in the region of the temporal fossa, remain unilaminar longer and show incomplete differentiation of the inner and outer tables and diploë through adolescence (Table 3; Figure 3C).

3.3. Diploë formation

The very beginnings of diploë formation can be observed as an osteoblastic thickening, followed by slight osteoclastic resorption, of the differentiated layer between the inner and outer cranial tables of the anterior and anterolateral portions of the frontal samples (Table 4; Figure 4A). This paired process of bone deposition and resorption within the differentiated space is variable in terms of its distribution and uniformity until the 12–17.9 month‐old samples (Table 5). Even then, diploë is sporadic and comprises <25% of the assessed intermediate bone space. Early microscopic manifestations of the cancellous layer reveal an immature structure characterized by a fairly disorganized, irregular, and non‐uniform appearance, reflecting the mixture of both woven and lamellar bone in the nascent creation of the diploë. Although there is variability across age groups, moderate (25%–75%) diploë formation becomes more consistently visualized across the cranial vault by 18 months; with the more advanced (>75% of the examined area) development of diploë trabeculae not consistently seen until after 4 years of age (Figure 4B). It is not until 8 years of age and later that a more mature, uniform diploë arrangement is observed, resembling a homogenous honeycomb structure and reflecting the transformation of woven into more organized lamellar bone.

TABLE 4.

Mean diploë osteoblastic bone deposition and resorption scores across age and cranial location.

Age category	Cranial location
	A	AL	L	PL	P
Diploë deposition
Fetal	0	0	0	0	0
Perinatal–2.9 months	0	0	0	0	0
3–5.9 months	1	1	0	0.5	0.5
6–11.9 months	1	1	1	1	1
12–17.9 months	2	1.5	1	1.5	1.5
18–23.9 months	3	2	2	2	2
2–3.9 years	3	2.5	2	2	3
4–7.9 years	3	2.5	2	2.5	3
8–11.9 years	3	3	2	2.5	3
12–17.9 years	3	3	2	2.5	3
Diploë resorption
Fetal	0	0	0	0	0
Perinatal–2.9 months	0	0	0	0	0
3–5.9 months	1	1	0	0.5	0.5
6–11.9 months	1	1	1	1	1
12–17.9 months	2	1.5	1	1.5	1.5
18–23.9 months	2	2	2	2	2
2–3.9 years	2	2	2	2	2
4–7.9 years	2	2	2	2	2
8–11.9 years	3	3	2	2.5	3
12–17.9 years	3	3	2	2.5	3

Note: Cranial location: A = anterior (most anterior point on the frontal, typically at the midline); AL = anterolateral (most lateral point on the frontal); L = parieto‐lateral (most lateral point on the parietal); PL = posterolateral (most lateral point on the posterior occipital); P = posterior (most posterior point on the occipital, typically at the midline).

Diploë deposition: 0 = no bone deposition (unilaminar); 1 = beginning/slight deposition (<25%); 2 = moderate deposition (25%–75%); 3 = advanced deposition (>75%).

Diploë resorption: 0 = no resorption; 1 = beginning/slight resorption (<25%); 2 = moderate resorption (25%–75%); 3 = advanced resorption (>75%).

FIGURE 4.

(A) Initial diploe development (anteromedial frontal, 3–6 months; 20×). (B) Advanced diploe development (medial occipital, 5–6 years; 10×). (C) Spatial variability in diploe development (anteromedial frontal, 18–23 months; 40×). (D) Spatial variability in diploe development (lateral parietal, 3 years; 40×). [Color figure can be viewed at wileyonlinelibrary.com]

TABLE 5.

Mean diploë uniformity and distribution scores across age and cranial location.

Age category	Cranial location
	A	AL	L	PL	P
Diploë uniformity
Fetal	0	0	0	0	0
Perinatal–2.9 months	0	0	0	0	0
3–5.9 months	1	1	0	0.5	0.5
6–11.9 months	1	1	1	1	1
12–17.9 months	2	1.5	1	1.5	1.5
18–23.9 months	2	2	2	2	2
2–3.9 years	2	2	2	2	2
4–7.9 years	2	2	2	2	2
8–11.9 years	3	3	2	2.5	3
12–17.9 years	3	3	2	2.5	3
Diploë distribution
Fetal	0	0	0	0	0
Perinatal–2.9 months	0	0	0	0	0
3–5.9 months	1	1	0	0.5	0.5
6–11.9 months	1	1	1	1	1
12–17.9 months	1	1	1	1	1
18–23.9 months	2	2	1	2	2
2–3.9 years	3	2.5	2	2	3
4–7.9 years	3	2.5	2	2.5	3
8–11.9 years	3	2.5	2	2.5	3
12–17.9 years	3	3	2	2.5	3

Note: Cranial location: A = anterior (most anterior point on the frontal, typically at the midline); AL = anterolateral (most lateral point on the frontal); L = parieto‐lateral (most lateral point on the parietal); PL = posterolateral (most lateral point on the posterior occipital); P = posterior (most posterior point on the occipital, typically at the midline).

Diploë uniformity: 0 = no diploë formation; 1 = beginning/slight uniformity (>75% of bone is non‐uniform, irregular); 2 = moderate uniformity (25%–75% of bone shows uniform, regular patterning); 3 = advanced uniformity (>75% of bone shows uniform, regular patterning).

Diploë distribution: 0 = no diploë development; 1 = sparse diploë distribution (<25%); 2 = moderate diploë distribution (25%–75%); 3 = advanced diploë distribution (>75%).

Spatial variability in diploë formation is apparent across age categories. The early formation is first observed in the anterior (frontomedial) and posterior (occipitomedial) regions of the cranial vault, followed by the anterolateral aspect (Figure 4C). Lagging behind in its expression, even into the older subadult age categories, is the mid‐lateral (parieto‐lateral) vault (Figure 4D). Diploë development is also not often visible near sutural regions.

Beginning with the 18–23.9 month age category, diploë visualization becomes more consistent across the cranial vault. At this age, diploë thickness comprises over half of the total cranial vault thickness for the frontals and occipitals examined, but not the parietals (Table 6). With increasing subadult age, this percentage generally increases, although variability is noted. This mirrors the significant degree of intra‐ and inter‐individual adult variability in diploë thickness observed by Voie et al. [34]. Parietals show the smallest diploë thicknesses and percentages for all age categories—a finding consistent with Sabancioğullari et al. [35].

TABLE 6.

Mean diploë thickness and percentage of total cranial thickness across age categories and bone.

Age category	Frontal		Parietal		Occipital
18–23.9 months	3.17 mm	53.5%	1.97 mm	52.1%	2.81 mm	68.0%
2–3.9 years	3.03 mm	58.1%	1.49 mm	41.5%	3.05 mm	66.4%
4–7.9 years	4.26 mm	81.6%	1.91 mm	49.0%	*	*
8–11.9 years	3.92 mm	70.9%	2.30 mm	55.8%	4.30 mm	59.1%

^*Insufficient data.

3.4. Tri‐layer cranial topographic variation

Patterned variability in three‐layer architectural development across bone location is most evident through an examination of cross‐sectional circumferential autopsy‐cut cranial contour, which provides a window into cranial ontogenetic topography. Beginning in the anteromedial frontal near glabella, there is an early thickening of the unilaminar table at the region of the frontal crest by 3–6 months of age. Diploë formation is often first visualized in this region. Moving anterolaterally, there is a fairly consistent undulating pattern of diploë development and inhibition established by 18 months to 2 years of age (Figure 5A). This is characterized by thickened tables and embellished diploë in the anterolateral cranial vault, particularly evident at the juncture of the anterior and medial cranial fossae, in contrast to the more poorly developed mid‐parietal squama (including the temporal fossa) region of the lateral vault. Posterolateral regions of the cranial vault also manifest poorly developed three‐layer development, followed by thickening and embellishment (similar to that seen anterolaterally) at the juncture of the medial and posterior cranial fossae. This differential pattern of cranial architecture development continues with advancing subadult age (Figure 5B), even into adulthood.

FIGURE 5.

(A) Tri‐layer cranial topographic contour (anterolateral frontal and lateral parietal, 18–23 months; 5×). (B) Tri‐layer cranial topographic contour (4–5 years old). [Color figure can be viewed at wileyonlinelibrary.com]

3.5. Clinical correlations

Approximately 63% (12/19) of the BFT RUFSI cases involving cranial NAI manifest cranial fracture (Table 7). Three of these individuals (all below the age of 6 months) manifested multiple cranial fractures, resulting in a total of 16 cranial fractures in the examined comparative sample. The majority were associated with cranial hemorrhage. Using Wiersema et al.'s [36] standardized cranial fracture classification scheme, five of the observed fractures were either complex (4) or comminuted (1), all derived from individuals below 13 months of age. Fracture patterning was variable—almost half (7/16) were incomplete linear or curvilinear fractures, four were completely linear, and five were depressed fractures—all were visible endocranially as well as ectocranially. All fracture locations centered on the parietal (one also involved the superior temporal)—the majority were inferolateral or posterolateral parietal fractures, often extending superiorly toward (and ending in) the sagittal suture. The remaining parietal fractures were situated either in the mid‐parietal squama or medially, near the sagittal suture. The majority (62.5%) of fractures were acute. All three individuals showing multiple cranial fractures manifested a combination of both acute and antemortem defects.

TABLE 7.

RUFSI pediatric BFT cranial fracture case summary.

Individ.	Age	Fracture location/origin	Fracture category; timing	Fracture pattern	Fracture description
1	28 days	R parietal (inferolateral)	Complex; acute	Incomplete linear	Extends superiorly toward the mid‐sagittal suture
2	2 months	R parietal (inferolateral)	Simple; acute	Incomplete linear	Extends anteroposteriorly 28 mm
		L frontal (posterolateral)	Simple; antemortem	Depressed	Depressed defect
3	3 months	R parietal (posterolateral)	Comminuted; antemortem	Complete	Extends superomedially from the most inferior edge of the parietal toward the sagittal suture
4	3 months	R parietal (inferolateral)	Complex; acute	Complete linear, with slight displacement	Extends anteroposteriorly from coronal to lambdoidal suture, with accessory posterior fx line extending medially
5	3 months	R parietal (posterolateral)	Simple; antemortem	Incomplete linear	Extends 54 mm from lambdoidal to squamosal suture
		R parietal (posterior)	Simple; acute	Depressed	Rounded depressed defect near lambda associated with 7 mm curvilinear fx line extending laterally
		L parietal (posterior)	Simple; acute	Depressed	Rounded depressed defect near lambda; fx line extending 7 mm superolateral
6	3 months	R parietal (inferolateral)	Simple; antemortem	Incomplete linear	Originates at posteroinferior parietal; extends 72 mm anteromedially, ending in a meningeal artery near anterosagittal suture
7	4.75 months	R parietal (posterolateral)	Complex; antemortem	Depressed, with slight displacement and two radiating fx lines	fx lines extend to the lambdoidal suture; one ends at the suture, and the other crosses it
8	5 months	L parietal (lateral)	Simple; acute	Depressed w associated linear fx line	Extends 48 mm from lateral parietal squama superiorly to mid‐sagittal suture
9	5 months	L, R parietal (medial)	Simple; acute	Incomplete linear	Three associated fx lines: one extends mediolaterally across the sagittal suture; one extends from L parietal medially to the sagittal suture; one extends from R parietal medially to the sagittal suture
		R parietal (posterior)	Simple; antemortem	Incomplete linear	Extends into lambdoidal suture
10	13 months	R parietal (inferolateral)	Complex; acute	Complete, associated with two incomplete curvilinear fx lines	Irregular curvilinear fx extends anteroposteriorly; associated with two incomplete lateral fractures (65 and 70 mm, respectively) extending longitudinally across the inferior parietal
11	2 years	L parietal (mid‐parietal squama)	Simple; acute	Complete linear	Extends medially toward the sagittal suture
12	4 years	L parietal and superior temporal (posteroinferior)	Simple; acute	Incomplete linear	Irregular fx of inferior parietal near squamosal suture extends 39 mm medially toward the sagittal suture

Macroscopic and microscopic imaging of the internal architecture of these parietals shows a unilaminar cranial surface in the youngest individual, the 28‐day‐old. In the 3‐month‐old crania (n = 4), initial inner and outer table differentiation is noted for all of the samples, a result in concordance with our prior findings of three‐layer cranial architecture initiation by 3–5.9 months of age. Anterior and posterior cranial vault regions manifest thickening and beginning osteoclastic resorption of bone within the differentiated layers. This process is not generally observed in the lateral cranial vault. In the 4.75‐month‐old cranium, thin but distinct endocranial and ectocranial layers are noted in the fractured parietal region, with slight osteoclastic resorption of the nascent diploic layer in between. This pattern continues through the fifth month. A circumferential cross‐sectional view of the cranial architecture is possible for one of the fifth‐month crania, showing the undulating patterning of greater thickness and more advanced diploë development anteriorly and anterolaterally compared to laterally and posterolaterally as seen in the Scheuer samples. Cross‐sectional views of the 4‐year‐old cranium show a thickened diploë and clear delineation of the three‐layered architecture in the anterolateral aspect, but a thinner, less developed profile in the lateral (parietal) aspect. Although these clinical cases are small in number, both the location of fractures and the morphological structure of bone at these locations are concordant with the temporal and spatial patterning of three‐layer cranial architectural development recorded in our study sample and lend support to the identification of the lateral cranial vault as a high‐risk region for pediatric fracture and associated poor outcomes.

4. DISCUSSION

This study has documented the ontogenetic sequence and timing of three‐layer architectural development in the subadult cranium. It is characterized by an initial increase in unilaminar cranial thickness and a fairly rapid acceleration in this thickness within the first 2 years of life. This is in agreement with findings suggested by prior research studies [25, 29, 32, 37, 38, 39, 40, 41] and undoubtedly reflects the period of accelerated cranial growth and brain development during this time. Cranial thickness continues to increase into adulthood, albeit more slowly and with some variability, particularly in older ages [35, 42, 43, 44, 45, 46, 47, 48, 49]. Lillie et al. [7, 50], for example, record a 36%–60% reduction in cortical thickness in the endocranial and ectocranial tables in adult females with advancing age.

Initial unilaminar thickness increases are followed by separation and continued thickening of the inner and outer tables and osteoblastic‐ and osteoclastic‐driven formation of the spongy diploë between these tables. This process exhibits important patterned temporal and spatial variability, however, which has anatomical and biomechanical correlates and clinical implications.

4.1. Three‐layer cranial architecture temporal and spatial developmental variability

Three‐layer cranial differentiation and diploë development can be observed initiating quite early in infancy (by 3–6 months of age) in the anterior and posterior cranial vault; however, it is immature and incomplete in the earliest 4 years of life. Its more mature manifestation is not seen until the 8‐year‐old samples, but variability in diploë expression is still noted in older ages. This is in agreement with Garcia et al.'s [51] histological examination of diploë, which notes a decrease in its expression in adolescence in coordination with expanded mineralization. This is followed by expanded diploë into adulthood, albeit through a nonlinear, dynamic process which leads to a significant degree of variability in diploë expression [13, 52, 53].

Portions of the anterior and posterior vault show more advanced three‐layer architectural development and resultant greater cranial thicknesses compared to the mid‐ and inferoparietal (and to a lesser degree, postero‐parietal) regions of the lateral cranial vault. This pattern is, for the most part, in agreement with clinical CT and MRI‐based cranial studies. Although both intra‐ and inter‐individual variability in cranial thickness has been documented [27, 31, 33, 35, 46, 48, 54], the lateral vault has been identified as typically the thinnest, with these thinner areas not changing significantly with increasing age. For example, Anzelmo et al. [44] and Garfin et al. [33] found consistently greater thicknesses in the antero‐ and posteromedial cranial vault (including the superior frontal [glabella], posterior frontal, and lambda regions) compared to the thinner lateral vault across all CT subadult samples examined. Middle regions of the lateral vault were noted to be more diploë‐deficient than anterolateral and posterolateral portions of the subadult cranium, although variability in its visibility was noted.

Regional variation in three‐layer cranial architecture is likely related to a variety of anatomical variables, including cranial growth. Domenech‐Fernandez et al. [32] record a gradual growth‐related increase in cranial thickness with subadult age but significantly centered on the anterior and posterior (including antero‐ and posterolateral) dimensions. Cranial thickness dimensions of these regions increase 50% over this period; in contrast, the mid‐lateral dimension showed the least increase. The temporal fossa region was noted as thin, vulnerable, and often lacking cancellous bone even in older children. This is especially evident in children below the age of 4 years. The thickest portion of the cranium at the growth's end was located in the posterior midline and the thinnest in the lateral dimension—their observation that 93% of their sample showed thicknesses of <3 mm in the posterolateral dimension of the cranial vault at 4 years of age is consistent with our findings.

Structural development of bony buttressing systems, sinuses, and sutures also influences diploë and three‐layer architectural development and distribution, producing variability in their expression. Diploë is not well developed along sutural regions [34], which are primarily composed of cortical bone. It does not generally form within the sphenoid ala, cribriform and orbital plates (pars orbitalis), middle cranial fossa floor, posterior cranial fossa between the mastoid and sigmoid and transverse sulci, and the squamous portion of the temporal [8, 22]. In contrast, significant cranial thickening and diploë development is observed along heavily enhanced regions near glabella and opisthocranion. Sperber [28] attributes thickened bone at glabella to the invasion of the frontal sinus by 6–7 years of age, although our study found increased thickness in this region much earlier than this, possibly correlating with the beginning expansion of the frontal sinuses by 3.5 years, as documented by Scheuer and Black [22].

4.2. Three‐layer cranial architecture biomechanics and fracture vulnerability

Although extrinsic phenomena such as force, mass, impact surface area and type, and, ultimately, the energy associated with a BFT event are clearly important biomechanical variables in fracture initiation and propagation, the differential distribution of three‐layer architecture across the cranium also plays an important role, particularly in the developing pediatric cranium. The three‐layer architectural unit actually represents three separate systems, each responding to its own set of anatomical and structural demands and demonstrating different biomechanical properties, yet still working as one functional unit. Thus, cranial thickness varies across the inner and outer table, with the inner table manifesting less thickness and density [7, 19, 24, 55, 56, 57]. Whereas the inner table is more responsive to the requirements of brain development and accommodations for cranial vessels and dura mater, the generally thicker outer table is more reflective of the external environment, including muscle development [44].

Sandwiched between these cortical layers and comprising the largest component of adult cranial thickness, the diploë is recognized as a critical aspect of biomechanical modeling of cranial trauma [47, 58]. In the adult, the diploë serves to not only increase cranial vault thickness but also increase its bending strength and energy absorbing capabilities. It provides cushioning and shear strength which increases the inertial bending strength (stiffness) that allows the cranium to withstand bending loads [7, 9, 14, 29, 50, 59]. When combined with the more dense inner and outer tables, the result is a strong architectural structure with high stiffness‐to‐weight ratio and the ability to respond as one functional unit to protect the brain [28].

Infant and adult crania differ significantly in their elastic modulus, including stress and strain. When placed under bending stress and tension, age plays a key role in the elasticity of cranial bones [60]. In experimental studies of adult cadaver heads undergoing BFT [61], as skull thickness increases, skull deformation decreases. Much of this elasticity can be related to diploë morphology— the diploë contributes the most to the overall cranial thickness and density and their variability [34, 62, 63] compared to the inner and outer tables. It has been observed that the diploë of younger adult individuals, 30–40 years of age, is tight and uniform between the inner and outer tables and is transversely isotropic [9, 64]. This results in less propensity for the adult cranium to significantly deform before it fractures [60]. These features change with advancing age, however. The diploë of older adult individuals, 60–70 years, has been described as more porous, irregular, and showing signs of degradation and decreased trabecular intensity [35, 58], resulting in a diminished capacity to withstand fracture.

In contrast, elastic modulus testing of infant cranial bones has documented large strains associated with external loading of pediatric cranial bone, leading to the potential for increased capacity for cranial and brain deformation compared to adult crania [26, 60, 65, 66]. Under external loading, intrinsic features of the pediatric skull, including the absence or immature development of the three‐layer architecture throughout the first 4 years of life, contribute to its compliant nature and lead to the potential for significant deformation and intracranial injury. This is particularly seen in the lateral cranial vault, where this architectural development is differentially delayed.

The vascular system within the diploë is not well developed in early ontogeny—it is visible in the late fetal/newborn period, but not fully established until 5 years of age [19, 67]. Since the diploë is lightweight and vascular, with a network of veins draining into the endocranial venous sinuses and emissary veins ectocranially, it can be associated with a significant potential for bleeding with intracranial injury. Although the course of the diploic veins shows a fair degree of variability, these veins (along with the middle meningeal arteries) manifest their greatest expression within the parietals compared to the remainder of the cranial vault [62, 68]. Anastomoses of the complex network of diploic vessels within the spongy cancellous middle cranial layer with the extracranial emissary veins and intracranial middle meningeal vessels and dural sinuses are common, particularly in the region of pterion [67, 68]. The absence of valves in diploic vessels provides the opportunity for blood to flow bidirectionally across the endocranial and ectocranial space, increasing the bleeding risk from cranial trauma to this region.

5. CONCLUSIONS

This study has chronicled the ontogenetic development of three‐layer cranial architecture and documented its spatial and temporal variability. Three‐layer differentiation, including diploë development, initiates at 3 to 6 months but remains inconsistently present until at least 2 years of age and is not well‐developed until age four. Prior to this time, a thin cranial vault combined with incomplete inner and outer table differentiation and sporadic and incomplete diploë development leave the pediatric cranium, particularly the region of the temporal fossa, intrinsically vulnerable to fracture.

Documentation of reduced or delayed three‐layered architecture in the region of the lateral vault identifies it as a vulnerable (and by inference, high‐risk) region of the developing cranium. This is correlated with a clinical pattern of non‐accidental fractures, many of them multiple and complex, preferentially affecting the lateral aspect of the cranial vault of subadult crania, a finding seen in the current study as well as others [2]. While a host of other factors, particularly extrinsic ones, undoubtedly influence the predilection for the lateral vault as a common pediatric fracture location, our study suggests the presence of a higher risk associated with non‐accidental BFT in this region. It also identifies infants below the age of 2 years as a vulnerable population more highly susceptible to the fatal effects of cranial trauma.

These findings illustrate the importance of the subadult cranium's bony architectural development on BFT fracture and add to our understanding of intrinsic variables influencing brain injury and fatal BFT outcomes. Additional pediatric cranial bone architecture samples of differing ages, analyzed microscopically, histologically, and through microCT and finite element models, will allow more fine‐tuned topographic mapping of age‐specific high‐risk trauma regions. These data can be applied toward improving mortality outcomes, including providing education about pediatric BFT cranial trauma outcomes, prevention, and prediction of injury to task forces and public health groups on both a local and national level.

Boyd DC, Cheek KG, Boyd CC. Fatal non‐accidental pediatric cranial fracture risk and three‐layered cranial architecture development. J Forensic Sci. 2023;68:46–58. 10.1111/1556-4029.15183