Little evidence of association between severity of trigonocephaly and cognitive development in infants with single-suture metopic synostosis

Abstract

Objectives: To measure severity of trigonocephaly among infants with single-suture metopic craniosynostosis by using a novel shape descriptor, the trigonocephaly severity index (TSI), and to evaluate whether degree of trigonocephaly correlates with their neurodevelopmental test scores.

Methods: We conducted a multicenter cross-sectional and longitudinal study, identifying and recruiting 65 infants with metopic synostosis before their corrective surgery. We obtained computed tomography images for 49 infants and measured the presurgical TSI, a 3-dimensional outline-based cranial shape descriptor. We evaluated neurodevelopment by administering the Bayley Scales of Infant Development, Second Edition, and the Preschool Language Scale, Third Edition, before surgery and at 18 and 36 months of age. We fit linear regression models to estimate associations between test scores and TSI values adjusted for age at testing and race/ethnicity. We fit logistic regression models to estimate whether the odds of developmental delay were increased among children with more severe trigonocephaly.

Results: We observed little adjusted association between neurodevelopmental test scores and TSI values, and no associations that persisted at 3 years. Trigonocephaly was less severe among children referred at older ages.

Conclusion: We observed little evidence of an association between the severity of trigonocephaly among metopic synostosis patients and their neurodevelopmental test scores. Detecting such a relationship with precision may require larger sample sizes or alternative phenotypic quantifiers. Until studies are conducted to explore these possibilities, it appears that although associated with the presence of metopic synostosis, the risk of developmental delays in young children is unrelated to further variation in trigonocephalic shape.

Figures

FIGURE 1

Volumetric reformations of the cranium of a patient diagnosed with isolated metopic craniosynostosis.

FIGURE 2

Identification of the plane used for image analysis and measurement of the trigonocephaly severity index. We identified the nasa suture (NS) (arrow) and opisthion (O) (arrow) to locate the cranial base. We then shifted this plane superiorly until positioned at the level of the maximal dimension of the fourth cerebral ventricle (termed the M plane).

FIGURE 3

The first step in measuring the trigonocephaly severity index is to extract quantitative information from a bone computed tomography image (A) about the cranial outline (B) in the polar coordinate system. The origin in the polar coordinate system is defined by its centroid (O). Any given point on the outline, such as p, can then be represented in polar coordinates (r, θ), where r is the distance from the origin to p and θ is the angle between the line segment Op and the polar axis (the line OR). After normalizing the axial distance from the origin by dividing by head length, α, the normalized polar representation is a scatterplot of r/α vs θ (C).

FIGURE 4

The cranial shape outline (left) gives rise to the normalized polar representation (right), from which the trigonocephaly severity index can be calculated. The angle γ and the ordinate hM are parameters used to compute the TSI. The lines labeled CS indicate the approximate location of the coronal sutures. A,B, represent trigonocephalic and nontrigonocephalic cranial shapes, respectively.

FIGURE 5

Normalized polar representation of a trigonocephalic outline shape (ρ = r/α) (A). The trigonocephaly severity index (TSI) is computed as the base of an isosceles triangle that approximates the profile of the normalized polar representation’s main section (ie, the curve above the shaded area), which encodes the shape information for the frontal bones (B). The angle γ is a parameter used to compute the TSI. The base is computed as 2A/(180)hM, where A is the area of the triangle, hM is the height of the triangle, and 180 is a normalization factor that ensures that the TSI takes values between 0 and 1. A triangle can be fitted to the outline representation (C).

FIGURE 6

Cranial outlines with successively milder trigonocephaly, corresponding to increasing trigonocephaly severity index values. A, a patient with metopic synostosis and severe trigonocephaly (trigonocephaly severity index [TSI] = 0.20). B, a patient with metopic synostosis and moderate trigonocephaly (TSI = 0.31). C, a control subject unaffected by craniosynostosis (TSI = 0.52).

FIGURE 7

Trigonocephaly severity index (TSI) values are positively associated with age at referral. Because higher TSI values represent less severe trigonocephaly, this indicates that patients with more severe trigonocephaly tended to present at younger ages.