Pediatric traumatic brain injury may consider expanding to include perinatal events and exposures involved in complicated childbirth, since research reveals adverse influences for child neurodevelopmental trajectory. Epidemiological studies link specific intrapartum complexities presenting during labor and delivery with rising child neuropsychiatric outcomes, justifying the novel concept of perinatal neurotrauma. These overlapping, interacting factors combined with elevated maternal gestational BMI, confer a disruptive cascade of neural events which may risk lifelong impairments for children. Rising neuropsychiatric conditions including ADHD and Autism have unconfirmed etiologies, yet complicated childbirth associations. Concomitant cognitive dysexecutive symptoms, emotional dysregulation, social and academic issues often persist into adulthood. While research has considered genetic etiology, it is unlikely genetics alone trigger these outcomes. Plausibly, events introduced during most sensitive developmental periods may affect the malleable fetal brain with risky downstream effects, altering child neurodevelopment. Birth complications typically involve well-respected measures aimed at expediting childbirth. One first-line, synthetic uterine simulant effectively assists > 50% of all U.S. childbirths, despite its poorly understood fetal impact. Exponential increases in exogenous uterine stimulation and dosage inconsistencies raise concerns of consequential maternal-fetal transmission. Labor duration and pharmacological dosages are important algorithms to disentangle since these are all modifiable factors. Established repercussions of this early environmental exposure include fetal distress, low Apgar scores, uterine hyperactivity, FHR abnormalities, NICU admissions and ischemia/asphyxia/hypoxia. Putative neuropathophysiological models include fetal intolerance to prolonged dosages, labor impact; epigenetic triggering, oxytocin receptor hyperstimulation and/or receptor oversaturation. Other considerations include neuroinflammation; hypertonic uterine contraction pressure imposing neuropathogenic alterations and diffuse axonal injury. Plausibly, disharmonious compounds, GABA downregulation; blood-brain barrier breach and/or placental permeability may interactively compromise fetal neuroprotective integrity. Additionally, the underexplored neuropathophysiological interpretation of pharmacokinetics involving synthetic properties may play a key role in fetal brain impact. Interestingly, maternal BMI/adiposity, a modifiable gestational health factor, increases odds for medically assisted childbirth owing to diminished uterine contractility in obese mothers. The shared effects of maternal BMI with chemically expedited labor, and its two-fold impact on offspring brain development is under-investigated, begging further exploration since its potential future contribution to the study of pediatric traumatic brain injury is imperative. While a signature, underlying, neuropathophysiological mechanism(s) linking childbirth complications and maternal gestational BMI to pediatric brain injury lacks confirmation, mixed evidence associates these factors directly with child neuropsychiatric phenotypes. Logically, the vulnerable fetal brain’s reaction to early, overlapping events and exposures is important to better understand. It is crucial to appreciate that a constellation of perinatal factors may risk future functional and behavioral impairments for children. Early vulnerabilities, potentially linked to in-utero exposures and obstetric dynamics, may destabilize and/or disrupt fetal brain development, warranting aggressive research and inclusion in the burgeoning field of pediatric brain injury as a critical child public health issue.

BACKGROUND: Prognostic prediction models (PPMs) can estimate a pediatric patient’s risk for delayed recovery following mild traumatic brain injury (mTBI). Since 2015, literature has emerged to guide reporting and reviewing PPMs. Identifying these PPMs and critically examining them would help guide use and future research.

METHODS: This review follows the Cochrane Prognosis Methods Group process. Literature searches of Ovid Medline, Embase, Ovid PsycInfo, Web of Science Core Collection, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Google Scholar were conducted on November 21, 2022. Studies of pediatric patients with mTBI that used a PPM to evaluate the risk of delayed recovery were included. The prediction horizon was restricted to at least 28 days but no more than 1 year after injury. Moment of prediction was any time before the 28th day after injury. Setting was not restricted. Additional inclusion criteria included the reporting of model performance; peer-reviewed original research; published in English language; and a cohort, nested case-control, or case cohort design. The Prediction model Risk of Bias (RoB) ASsessment Tool (PROBAST) and a modified Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used to inform PPM quality. Meta-analysis was used to aggregate parameter estimates of model performance among studies reporting the same measures for the same PPM. The remaining literature was qualitatively synthesized.

RESULTS: Searches yielded 17,433 references with 6,250 duplicates; 11,183 studies were screened, and 78 references were retrieved, with 72 studies being deemed ineligible. Six studies of 9 PPMs were included. Three PPMs demonstrated statistically significant predictive capability - the Predicting and Preventing Postconcussive Problems in Pediatrics (5P) clinical risk score, the Buffalo Concussion Physical Examination (BCPE) risk for delayed recovery (RDR) score, and the model developed by Grubenhoff et al. 2014. Most used the Concussion in Sport Group consensus guidelines for mTBI diagnosis. Operational definitions of delayed recovery varied. Logistic regression was the most common modeling method. The selected predictors can be grouped into 3 domains – history, exam, and symptoms. All studies were evaluated as being at high risk of bias. Meta-analysis of the 5P model demonstrated a poor to moderate effect size (aggregate AUC 0.69) without heterogeneity; however, this result should be considered preliminary given the low number of studies. GRADE rating was highest for 5P (Moderate).

DISCUSSION: Empirical support for PPM use in this population is limited due to a high risk of bias for existing studies and predominantly Very Low GRADE quality of published PPMs. The 5P clinical risk score has the most robust evidence for use. Issues inherent to the current and varied definitions of delayed recovery following mTBI will likely limit further progress in this area of study until a consensus-based, operational definition is reached.

Concussions involve symptoms that arise following mild traumatic brain injury (mTBI). There is limited understanding about the evolution of concussion symptoms, particularly among children. This limits clinicians’ ability to predict concussion duration, or even define persisting post-concussive symptoms (PPCS). The objective of this study was to characterize the trajectory of concussion symptoms among youths and define the prevalence of PPCS.

This cohort study included 1132 youths, 12-21 years. There were 399 youths with mTBI (enrolled 2.9 ± 2 days after mTBI) and 733 without mTBI. Both groups were recruited at emergency departments and outpatient clinics. The Post-Concussion Symptom Inventory (PCSI) was used to assess 22 concussion symptoms. In total, 2074 PCSI were completed: 1076 uninjured ratings (865 from youths without mTBI, and 211 retrospective estimates from youths with mTBI); 998 longitudinal ratings from youths with mTBI: 390 at enrollment, 351 at 1-2 weeks, and 257 at 1 month. Uninjured ratings were used to determine mean symptom burden in the absence of mTBI. Longitudinal ratings were used to characterize symptoms after mTBI. Incidence of PPCS 1 month after mTBI was assessed with 3 approaches: 1) compared to individual uninjured symptoms; 2) compared to the mean symptom severity of uninjured youths; 3) using one question, “What percentage of normal do you feel?” (>95% at 1 month = recovered).

Participants were 49% male, 77% white, and 9% Hispanic. The majority were in in high school (44%) or middle school (32%), and 69% were athletes. History of headaches (29%), attention problems (30%), and depression (25%) were common. Many (22%) had a prior mTBI. Uninjured youths endorsed 6.7 of 22 symptoms, with a mean symptom severity of 16 out of 132. Following mTBI (n=399), mean symptom severity was 36 at enrollment, 19 at 1 week, and 9 at 1 month. Headache was the most common symptom at enrollment (88%), 1 week (66%), and 1 month (38%). Difficulty concentrating (33%) was also common at 1 month. One month after mTBI, 35% met PPCS criteria compared to personal uninjured ratings, 25% met PPCS criteria compared to the mean symptom severity of uninjured youths, and 30% met PPCS criteria based on estimated “percent normal.” There was significant agreement between measures (ĸ = 0.62, p < 0.001).

Many youths endorse concussion-like symptoms, even without mTBI. Headache is the predominant symptom in the first month after mTBI. Rates of PPCS in youths are 25-35%, and may be captured with a single self-report question, “What percentage of normal do you feel?”

Clinical guideline recommendations for pediatric post-concussion care and management have undergone major updates in 2023. The Living Guideline team includes 48 concussion clinical experts, researchers, and individuals with lived experience from across the US and Canada. This team collaborates on the Living Guideline for Pediatric Concussion Care (PedsConcussion) project to review new evidence and update the 80+ clinical recommendations, clinical algorithms, return-to-sport/activity, and return-to-learn/school concussion protocols as the evidence evolves. The best evidence from 2023 was collated and assessed, and new critical papers were shared in a living evidence map (EPPIreviewer). A quorum of 88% or more of the 48 experts voted on each update and consensus at 97-100% agreement was attained for all updates that were implemented. Significant updates to guideline recommendations involve revisions to the steps of the return-to-sport and activity protocol, highlighting the benefits of aerobic exercise in concussion treatment. Activities that pose no risk of sustaining a second concussion should be gradually resumed after 1-2 days even if mild symptoms are present. These symptoms may worsen mildly during activity as tolerated. Definitions of relative rest, mild to moderate intensity aerobic exercise, and mild symptom exacerbation have been harmonized with the Amsterdam International Consensus Statement on Concussion in Sport. Additionally, updates have been made to the timing of medical clearance and the definitions associated with it. The new return-to-school protocol reinforces the importance of promptly resuming school activities that do not have a risk of falling or being hit on the head, as tolerated, with the provision for academic accommodations if needed. It also emphasizes that the return to non-contact and low-risk school activities should not be restricted if the individual is effectively tolerating cognitive activities. The importance of restricting screen time in the early stage of recovery is now supported by strengthened evidence. Any activity with a risk of head impact or falling must still be entirely avoided until reassessment and medical clearance are obtained. All patients with a diagnosed concussion are recommended to return for a repeat medical assessment 7-10 days after the initial diagnosis and patients should be referred to specialized care with an interdisciplinary concussion team if post-concussion symptoms do not resolve by 2-4 weeks. Youth at increased risk of prolonged recovery require immediate referral. For more detailed information, including consensus voting details and complete recommendations, the pedsconcussion.com website serves as a valuable resource. Dissemination and implementation of these updates is essential to continue to improve outcomes for all pediatric patients with concussion. The collective efforts of the Living Guideline team highlight a commitment to continually advancing and improving pediatric post-concussion care practices.