Metopic synostosis is being diagnosed and treated at increasing rates,1–7 with recent studies estimating that metopic synostosis accounts for 30% of new craniosynostosis diagnoses.8,9 Metopic synostosis is the premature fusion of the metopic suture, leading to compensatory growth parallel to the fused suture.10,11 This results in features such as trigonocephaly, hypotelorism, and biparietal widening.1,4,9,12–15 Surgical treatment for metopic synostosis can include either strip craniectomy with orthotic therapy or fronto-orbital advancement.5,16 Minimally invasive approaches with either postoperative helmeting or spring distraction are being used more frequently with increasing acceptance in the craniofacial community.7,17–19
Age is an important factor for the endoscopic technique because of its reliance on calvarial pliability and early brain growth to correct the aberrant cranial bone morphology.7,17,20–22 Therefore, most craniofacial centers elect to perform strip craniectomies at 2–4 months of age. While delayed presentation generally limits the feasibility of this strategy,20 some series have reported reasonable outcomes in patients treated between 6 and 9 months of age.2,17 Clarifying the influence of age on outcomes of endoscopic repair is necessary to guide appropriate management of metopic synostosis. Here, we examine postoperative outcomes of endoscopic repair of metopic craniosynostosis at our institution to quantify the impact of age on morphological outcomes after endoscopic repair.
Methods
Institutional review board approval was obtained for this study. Consecutive patients with isolated metopic craniosynostosis treated endoscopically from October 2007 to April 2019 were retrospectively reviewed and aggregated in a dedicated database. Patients were included if they were diagnosed based on clinical examination and CT findings interpreted by experienced members of our craniofacial team. Patients with syndromic craniosynostosis and/or multisuture craniosynostosis were excluded.
Treatment
Both endoscopic and open (fronto-orbital advancement) repair of metopic craniosynostosis were offered to patients up to 6 months of age per clinical routine. Family preference and social factors were taken into consideration when choosing the treatment option. Endoscopic repair of metopic craniosynostosis was performed using a 2.5-cm skin incision to allow for a 1-cm-wide craniectomy extending from the anterior fontanelle to the nasofrontal junction as previously described.7 All patients were admitted postoperatively with the plan for discharge on postoperative day 1. Standardized helmet therapy was initiated 1 to 3 days after discharge and involved wearing the orthotic helmet for 23 hours daily until 1 year of age. Helmet adjustments and replacements are performed as the patient grows to sufficiently manipulate cranial shape.
Patient Characteristics and Outcomes
Patient demographics and perioperative outcomes, including sex, estimated gestational age, age at surgery, weight at surgery, operative time, need for blood transfusion, length of hospital stay, and complications, were obtained from the electronic medical record.
Anthropometric Analysis
Image analysis of 3D reconstructed preoperative and 1-year postoperative CT scans was conducted using Analyze 12.0 software (Mayo Clinic). Using a bone threshold, the frontal width was measured as a straight line between the left and right frontotemporal points (Fig. 1A) to the nearest 0.1 mm. To assess the degree of trigonocephaly, the interfrontal divergence angle (IFDA) was measured as described by Wood et al.1 Scans were first aligned on the midsagittal plane by adjusting the nasion and gnathion to be vertically aligned. For scans that did not include the mandible or had mandibular motion artifact, the subnasale was used instead of the nasion. Next, the CT scans were aligned so the opisthion and posterior clinoid processes lay in a horizontal plane. After orientation, the IFDA was calculated based on the points marked on the outer bone cortex as seen in Fig. 1B. One author (E.C.P.) performed all image analysis, which was not blinded to patient age.
Definitions of anthropometric measurements utilized. A: Measurement of the frontal width (red line) on a 3D reconstructed CT scan using a bone threshold. B: Measurement of the IFDA on a reconstructed axial CT image that contains both the opisthion and the dorsum sellae. Bilateral coronal sutures are marked A and B, as is the metopic suture (point C). Perpendicular lines are extended anteriorly from the midpoints of the lines connecting coronal and metopic sutures (points D and E), until they reach the frontal bone (points F and G). The angle FCG is the IFDA. Figure is available in color online only.
Statistical Analysis
Independent-samples t-tests and Fisher’s exact tests were used to compare continuous and categorical data, respectively, between patients who underwent repair before 4 months of age and those who underwent repair at 4 months of age or later. Forced-entry linear regression analysis was performed to determine if age at repair predicts postoperative frontal width after controlling for preoperative frontal width and age at postoperative measurement. A similar regression was performed to determine predictors of postoperative IFDA. Spearman correlations were performed to examine for association of postoperative frontal width and IFDA with estimated gestational age and weight at surgery. Finally, linear regression for postoperative IFDA was performed as above with the additional inclusion of gestational age and weight. Multicollinearity was examined via scatterplots and the variance inflation factor, where a factor ≥ 2.5 suggests collinearity.23
Pairwise deletion was used in bivariate analyses and listwise deletion in linear regressions. Data are represented as means ± SDs and counts (percent). An a priori power analysis was run using the Student t-test based on previous data from our institution.16 Intrarater reliability for frontal width and IFDA measurements was determined by the interclass correlation coefficient (ICC) using the single-measures two-way random-effects consistency model. All tests were two-tailed with a prespecified significance level of 0.05. Statistical analyses were performed using SAS Studio version 3.8 (SAS Institute Inc.).
Groups are divided visually into < 4 months, 4 months, and 5 months of age at repair in figures to facilitate understanding of the differences each passing month contributes, but all statistical comparisons were performed with groups of < 4 months and ≥ 4 months at repair to maximize power.
Results
Patient Demographics and Perioperative Outcomes
In total, 36 (8 female [22%] and 28 male [78%]) patients were included in this study. Twenty-eight patients underwent surgery when they were younger than 4 months of age (76%), and 8 underwent surgery between 4 and 6 months of age (5 patients at 4 months and 3 patients at 5 months of age). Patient sex, weight, and perioperative outcomes did not differ significantly by age group (Table 1). However, patients in the older group tended to have been born at an earlier gestational age (mean 35 ± 4.3 vs 39 ± 1.2 weeks, p = 0.04). The rate of blood transfusions was 7% in the younger cohort and 12% in the older cohort (p = 0.54). Mild perioperative complications occurred in 4 (14%) of 28 patients treated at < 4 months of age and 1 patient (12%) treated beyond 4 months of age (p > 0.9). The older cohort required on average 2 helmets versus 3 in the younger group (Table 1). Two patients in the younger cohort (7.1%) later underwent exchange cranioplasty for a persistent defect at the craniectomy site, with no cranioplasties required in the older cohort.
Demographics and perioperative outcomes of patients treated endoscopically for metopic craniosynostosis at our institution
| Age at Op | OR (95% CI) | MD (95% CI) | p Value | ||
|---|---|---|---|---|---|
| <4 mos (n = 28) | 4–6 mos (n = 8) | ||||
| Baseline characteristics | |||||
| Female sex | 5 (18) | 3 (38) | 2.76 (0.49–15.53) | 0.34 | |
| Gestational age, wks | 39 ± 1.2 | 35 ± 4.3 | −3.7 (−7.4 to −0.1) | 0.04 | |
| Weight at op, kg | 6.0 ± 0.8 | 5.8 ± 0.9 | −0.2 (−0.9 to 0.5) | 0.59 | |
| Periop outcomes | |||||
| Op time, mins | 55 ± 21 | 58 ± 18 | 2.1 (−14 to 19) | 0.79 | |
| Need for transfusion | 2 (7.1) | 1 (12) | 1.86 (0.15–23.58) | 0.54 | |
| Estimated blood loss, mL | 45 ± 33 | 31 ± 37 | −13 (−41 to 14) | 0.33 | |
| Length of stay, days | 1.0 ± 0 | 1.1 ± 0.4 | 0.1 (−0.2 to 0.4) | 0.35 | |
| Periop complications | 4 (14) | 1 (12) | 0.86 (0.08–8.97) | >0.9 | |
| Follow-up | |||||
| No. of helmets | 2.7 ± 0.8 | 1.8 ± 0.5 | −0.9 (−1.8 to −0.1) | 0.04 | |
| Time in helmet, mos | 9.1 ± 1.4 | 7.8 ± 0.9 | −1.3 (−2.7 to 0.1) | 0.06 | |
| Age at latest follow-up, yrs | 4.2 ± 2.6 | 4.2 ± 3.0 | 0.001 (−2.2 to 2.2) | >0.9 | |
MD = mean difference.
Values are presented as the number of patients (%) or mean ± SD unless stated otherwise.
Anthropomorphic Measurements
Using a power level of 0.8 and alpha of 0.05, an a priori power analysis determined that the study sample was powered to detect a difference of 9° in IFDA and 5 mm in frontal width. The ICC was calculated for preoperative and postoperative frontal width and IFDA measurements for 5 patients (10 measurements). The ICC value for single measures was 0.982 (95% CI 0.930–0.996) for frontal width and 0.989 (95% CI 0.955–0.997) for IFDA.
Preoperatively, patients’ frontal widths and IFDAs were not significantly different (Table 2 and Fig. 2A and B). Postoperative anthropomorphic measurements did not differ between groups: frontal width increased postoperatively to 83 ± 4.4 mm in the younger group and 84 ± 5.2 mm in the 4- to 6-month-old group (p = 0.47) (mean 83 ± 4.4 mm in 4-month-old patients and 86 ± 7.0 mm in 5-month-old patients; Fig. 2C and D). IFDAs were generally below normal preoperatively and increased into the normal range postoperatively (142° ± 5.0° in < 4-month-old patients, 141° ± 4.4° in 4-month-old patients, and 137° ± 2.3° in 5-month-old patients; Fig. 2E and F). With age as a continuous measure, there were no clear trends in postoperative frontal width or IFDA (Fig. 2G and H).
Preoperative and postoperative measurements across age groups
| Mean Age at Op | MD (95% CI) | p Value | ||
|---|---|---|---|---|
| <4 mos (n = 28) | 4–6 mos (n = 8) | |||
| Preop measurements | ||||
| Age at CT, days | 44 ± 30 | 112 ± 50 | 67 (37 to 97) | <0.001 |
| Frontal width, mm | 52 ± 3.5 | 54 ± 5.0 | 2.5 (−0.8 to 5.8) | 0.14 |
| IFDA, ° | 119 ± 7.9 | 124 ± 5.2 | 4.0 (−2.4 to 10) | 0.21 |
| Postop measurements | ||||
| Age at CT, yrs | 1.3 ± 0.2 | 1.6 ± 0.3 | 0.3 (0.1 to 0.4) | <0.001 |
| Frontal width, mm | 83 ± 4.4 | 84 ± 5.2 | 1.3 (−2.4 to 5.0) | 0.47 |
| IFDA, ° | 142 ± 5.0 | 140 ± 4.2 | −2.1 (−6.1 to 1.8) | 0.28 |
| Change in measurements | ||||
| Change in frontal width, mm | 31 ± 4.9 | 30 ± 6.2 | −0.8 (−5.3 to 3.7) | 0.71 |
| Change in IFDA, ° | 23 ± 9.1 | 17 ± 5.8 | −5.7 (−13 to 1.7) | 0.13 |
Mean values are presented as mean ± SD.
Anthropometric measurements and representative images across age groups. A: Preoperative reconstructed CT scan, vertex view, obtained in a patient who was later treated at 3.4 months of age. B: Preoperative reconstructed CT scan, vertex view, obtained in a patient who was later treated at 5.0 months of age. C and D: Preoperative and postoperative frontal widths. E and F: Preoperative and postoperative IFDAs. G and H: Postoperative frontal width and IFDA with age as a continuous measure. IFDAs larger than 134° (dotted line) are considered normal.
When accounting for age at measurement and preoperative frontal width utilizing linear regression, no association between postoperative frontal width and age cohort was found (β = −0.81, 95% CI −5.39 to 3.77, p = 0.72; Table 3). Similarly, postoperative IFDA was not associated with age at operation, adjusting for the respective preoperative measures, and age at imaging (Table 4).
Results of linear regression for postoperative frontal width
| Covariate | Coefficient (95% CI) | p Value |
|---|---|---|
| Age 4–6 mos at repair (ref: <4 mos) | −0.81 (−5.39 to 3.77) | 0.72 |
| Preop frontal width | 0.27 (−0.16 to 0.70) | 0.21 |
| Age at postop CT | 5.98 (−1.95 to 13.91) | 0.12 |
R2 = 0.15.
Results of linear regression for postoperative IFDA
| Covariate | Coefficient (95% CI) | p Value |
|---|---|---|
| Age 4–6 mos at repair (ref: <4 mos) | −1.89 (−6.84 to 3.06) | 0.44 |
| Preop IFDA | 0.05 (−0.20 to 0.29) | 0.70 |
| Age at postop CT | 0.28 (−8.49 to 9.05) | >0.9 |
R2 = 0.03.
Gestational age was not associated with postoperative measurements (ρ = 0.21 for frontal width, ρ = 0.01 for IFDA), while weight did appear to be negatively correlated with postoperative IFDA (ρ = −0.35, p = 0.04; Fig. 3). However, on multivariable logistic regression, neither gestational age nor weight was associated with postoperative IFDA (Table 5). None of the predictors included in this regression were significantly colinear (variance inflation factors < 1.97; Supplemental Fig. 1).
Postoperative outcomes and correlation with estimated gestational age and weight at surgery. Gestational age is not correlated with frontal width (A) (ρ = 0.21, p = 0.23) or IFDA (B) (ρ = 0.01, p = 0.56). Weight is not correlated with frontal width (C) (ρ = 0.12, p = 0.47); however, the postoperative IFDA appears to decrease with increasing weight (D) (ρ = −0.35, p = 0.04). Angles larger than 134° (dotted line) are considered normal.
Results of linear regression for postoperative IFDA with the addition of gestational age and weight
| Covariate | Coefficient (95% CI) | p Value |
|---|---|---|
| Age 4–6 mos at repair (ref: <4 mos) | −2.23 (−8.09 to 3.61) | 0.44 |
| Preop IFDA | 0.07 (−0.17 to 0.30) | 0.70 |
| Age at postop CT | −1.05 (−9.87 to 7.77) | 0.81 |
| Estimated gestational age, wks | −0.08 (−0.91 to 0.75) | 0.84 |
| Weight at op, kg | −1.77 (−4.06 to 0.51) | 0.12 |
R2 = 0.12.
Discussion
In this study, we sought to quantify the impact of age on outcomes following endoscopic repair of craniosynostosis. We found that postoperative IFDAs and frontal widths did not significantly differ between patients treated at younger than 4 months of age and those treated later than 4 months of age.
Prior studies of endoscopic repair for metopic craniosynostosis have demonstrated aesthetic outcomes that are comparable to those of open repair.7,16,18,19 Benefits of the endoscopic approach include decreased anesthesia time, less blood loss, shorter hospital stays, and lower overall cost.24–27 However, this operation is offered to only a limited patient population based on age at presentation. Traditionally, endoscopic repair has been offered to infants before the first 2–4 months of life, while fronto-orbital advancement can be performed beginning at around 6 months of age.6,24,28,29 Indeed, it has been reported that endoscopic strip craniectomies are less efficacious after 3 months of age, with a substantial increase in difficulty after 6 months of age because of increased bone thickness.22,24,30
None of the 8 patients in the older group had a persistent defect along the craniectomy site. However, 2 of 28 patients in the younger group required an exchange cranioplasty using autologous bone at school age because of a critical-sized defect in the middle to lower one-third of the craniectomy site. We believe that these defects occurred because of injury to the frontalis muscle during the subgaleal dissection toward the nasofrontal junction from the hairline incision. We have since modified our dissection toward the nasofrontal junction to transition from subgaleal to subperiosteal in the midforehead. The subperiosteal dissection over the fused metopic suture can be done once appropriate bone is removed up to the midforehead.
Our measurements are consistent with those of previous studies showing normalization of the IFDA and frontal width after endoscopic repair, and we further demonstrate that the endoscopic technique can be performed up to 6 months of age.1,16,18,31 Similarly, our results showed no significant difference between age groups in terms of operative time, blood loss, or perioperative complications. Gestational age and weight similarly do not appear to affect outcomes. Because of our findings, our practice is thus now able to offer endoscopic repair with orthotic therapy to any patient with metopic synostosis who is younger than 6 months of age.
Limitations of this study include its relatively small sample size and its inclusion of only one academic medical center. It is possible that preoperative severity may differ in those treated before and after 4 months of age to a degree that we were underpowered to detect, thus confounding our analysis. Furthermore, the patients in the older cohort tended to be of younger gestational ages, which is a potential confounder of our findings. Some studies have shown, however, that the first 6 months and indeed the first 2 months of life are a period of catch-up head growth, suggesting that these older infants may have anatomy that is similar to those their full-term peers.32,33 Future follow-up with a larger, multi-institutional collaborative study may strengthen the results presented here. In addition, the literature does not provide a consensus on a measurement to compare metopic synostosis severity and outcomes; many different measurements have been proposed, including frontal width, head circumference, interfrontal angle, intercanthal distance, IFDA, cranial index, and interpupillary distance.6,7,34 Here, we chose to examine IFDA and frontal width, as these assessments encapsulate the essential morphological features of metopic craniosynostosis: trigonocephaly and decreased frontal width.1,35 However, a minimally clinically important difference in these measures has yet to be defined. Finally, while all patients had at least 1 year of follow-up, ideally, these children would be followed until cranial maturity to study the effects of surgery on final head shape and durability of the results presented here.
Conclusions
Using objective measurements of trigonocephaly and frontal width after repair of metopic craniosynostosis, we found that anthropometric outcomes of endoscopic repair beyond 4 months of age do not differ significantly from those of repair at < 4 months of age. Further study with longer follow-up will be necessary to confirm the longevity of these results at skeletal maturity.
Acknowledgments
We thank the St. Louis Children’s Hospital Foundation Board for their support of the Washington University School of Medicine Cleft Palate Craniofacial Institute. We also thank the WUSM Dean’s Medical Student Research Fellowship for the MPHS Yearlong Research Program for their support.
Disclosures
Dr. Naidoo: honoraria from Hanger Clinic. Dr. Patel: consultant for Stryker CMF.
Author Contributions
Conception and design: Patel, Peterson, McEvoy, Naidoo, Smyth. Acquisition of data: Chiang, Peterson, Skolnick. Analysis and interpretation of data: Chiang, Peterson, Lauzier. Drafting the article: Patel, Chiang, Peterson. Critically revising the article: Patel, Lauzier, McEvoy, Skolnick, Naidoo, Smyth. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Patel. Statistical analysis: Chiang, Peterson. Administrative/technical/material support: Skolnick.
Supplemental Information
Online-Only Content
Supplemental material is available with the online version of the article.
Supplemental Figure 1. https://thejns.org/doi/suppl/10.3171/2022.8.PEDS22214.
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