Comparing Conservative to Surgical Treatment of Trigonocephaly Craniofacial Surgery in Children With Trigonocephaly: an Observational Cohort Study on Clinical Outcomes, Psychosocial Wellbeing, and Costs (Treat Trigono)

Comparing Effectiveness of a Conservative Policy to Craniofacial Surgery in Children With Trigonocephaly: an Observational Cohort Study on Clinical Outcomes, Psychosocial Wellbeing, and Costs

RESEARCH QUESTION Is the effectiveness of conservative policy comparable to that of surgery in children with trigonocephaly, with regard to clinical outcomes and psychosocial functioning, stress for parents, and costs? DESIGN Observational cohort study in children, aged 0 to 8 years old, with trigonocephaly, excluding metopic ridging (physiologic early closure of metopic suture), treated conservatively or surgically.

OUTCOME MEASURES Primary: Head growth decline, indicating raised intracranial pressure Secondary: fundoscopy, cognition, behavior, refraction and vision, forehead shape, quality of life, posttraumatic stress, decisional conflict, costs.

Study Overview

• Status: Recruiting
• Conditions: Metopic Synostosis
• Intervention / Treatment: Procedure: craniofacial surgery

Detailed Description

HYPOTHESIS Conservative treatment is non-inferior to surgery with regard to clinical outcomes, causes less burden of disease, and is cost-effective.

STUDY DESIGN Observational cohort study STUDY POPULATION Children, aged 0 to 8 years old, with trigonocephaly, excluding metopic ridging (physiologic early closure of metopic suture) INTERVENTION Conservative policy USUAL CARE/COMPARISON Craniofacial surgery OUTCOME MEASURES Primary: Head growth decline (head circumference in SD), indicating raised intracranial pressure Secondary: fundoscopy, cognition, behavior, refraction and vision, forehead shape, quality of life, posttraumatic stress, decisional conflict, costs. Repeated measures at 0, 2, 4, 6, 8 years of age SAMPLE SIZE/DATA ANALYSIS Eligible patients <= 3 years of age are included since Sept 2022 Sample size 440 patients <1 year of age: 195 surgery and 245 conservative

Non-inferiority with regard to head growth from 0-4 years (annual measurement) is determined using a linear mixed model adjusted for confounders:

severity of phenotype, sex, syndrome and parental factors (e.g., education). COST-EFFECTIVINESS ANALYSIS/BIA An economic evaluation is performed with the incorporation of medical costs and costs due to loss of productivity for the parents. A detailed costs-study is done for medical specialist care, surgical costs, hospitalization and other costs directly associated with the interventions. Cost prizes of surgery will be determined by the bottom-up micro-costing method. Cost-utility will be measured with QALY (based on EQ-5D utility score) gained, with confidence ellipses and acceptability curves. The impact of conservative policy versus surgery will be investigated on assurance perspective and central level. From the viewpoint of the (health care) government, a societal perspective and perspective of the "budgettair kader zorg" will be highlighted. We will provide a valid framework with budget consequences by a range of predictions. Sensitivity analysis is done.

TIME SCHEDULE Inclusion between Sept 2022 and Sept 2030. Analysis and reporting for each outcome parameter related to age is distributed from January 2025 to September 2031. New recommendation for treatment of trigonocephaly in guideline ready in 2031.

• Study Type: Observational
• Enrollment (Estimated): 440

Contacts and Locations

• Study Contact: Name: Irene MJ Mathijssen, MD, PhD, MBA-H; Phone Number: +31655758441; Email: i.mathijssen@erasmusmc.nl

Study Locations

• Netherlands
  • Rotterdam, Netherlands, 3012LE
    • Recruiting
    • Erasmus MC
    • Contact: Irene MJ Mathijssen, MD, PhD, MBA-H; Phone Number: +31655758441; Email: i.mathijssen@erasmusmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children with mild, moderate or severe trigonocephaly, between 0 and 8 years of age, excluding metopic ridge (i.e. physiologic early closure of metopic suture).

Description

Inclusion Criteria:

• diagnosis of trigonocephaly

Exclusion Criteria:

• metopic ridge (physiologic early closure of metopic suture)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Conservative group; Children with trigonocephaly that are treated conservatively.
Surgical group; Children with trigonocephaly that are treated surgically.	Procedure: craniofacial surgery; Surgical treatment, either stripcraniectomy or fronto-orbital advancement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Head growth	Annual measurement of head circumference in SD for gender and age. Decline in head growth may indicate raised intracranial pressure	from 0 to 8 years old

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fundoscopy	Annual screening for presence of papilledema as sign of raised intracranial pressure	from 1 to 4 years old
Cognition and behavior	Validated tests for cognition and behavior of the child	at 0, 2, 4 and 8 years old
refraction and vision	tests taken by orthoptist	at 1, 4 and 8 years old
forehead shape	3D photos (objective) and VAS score by parents (subjective) to grade the forehead shape	at 0, 2, 4, 6 and 8 years old
Quality of life and post-traumatic stress	Validated tests to measure quality of life of the child and parents and presence of PTS in parents	at 0, 2, 4, 6 and 8 years old
Decisional conflict	questionnaire to determine whether or not parents are still content with their decision on type of treatment	at 8 years old

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Sint Franciscus Gasthuis; IJsselland ziekenhuis; LAPOSA
• Investigators: Principal Investigator: Irene MJ Mathijssen, MD, PhD, MBA-H, Erasmus Medical Center

Publications and helpful links

General Publications

• Cornelissen MJ, Loudon SE, van Doorn FEC, Muller RPM, van Veelen MC, Mathijssen IMJ. Very Low Prevalence of Intracranial Hypertension in Trigonocephaly. Plast Reconstr Surg. 2017 Jan;139(1):97e-104e. doi: 10.1097/PRS.0000000000002866.
• de Planque CA, Petr J, Gaillard L, Mutsaerts HJMM, van Veelen MC, Versnel SL, Dremmen MHG, Mathijssen IMJ. Cerebral Blood Flow of the Frontal Lobe in Untreated Children with Trigonocephaly versus Healthy Controls: An Arterial Spin Labeling Study. Plast Reconstr Surg. 2022 Apr 1;149(4):931-937. doi: 10.1097/PRS.0000000000008931.
• Mathijssen IMJ; Working Group Guideline Craniosynostosis. Updated Guideline on Treatment and Management of Craniosynostosis. J Craniofac Surg. 2021 Jan-Feb 01;32(1):371-450. doi: 10.1097/SCS.0000000000007035. No abstract available.
• Abdel-Alim T, Iping R, Wolvius EB, Mathijssen IMJ, Dirven CMF, Niessen WJ, van Veelen MC, Roshchupkin GV. Three-Dimensional Stereophotogrammetry in the Evaluation of Craniosynostosis: Current and Potential Use Cases. J Craniofac Surg. 2021 May 1;32(3):956-963. doi: 10.1097/SCS.0000000000007379.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): February 28, 2031
• Study Completion (Estimated): August 31, 2031

Study Registration Dates

• First Submitted: October 2, 2023
• First Submitted That Met QC Criteria: October 2, 2023
• First Posted (Actual): October 5, 2023

Study Record Updates

• Last Update Posted (Actual): August 11, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Congenital Abnormalities; Bone Diseases, Developmental; Dysostoses; Craniosynostoses; Synostosis
• Other Study ID Numbers: PaNaMaID 9517

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No