History of Concussion and Risk of Severe Maternal Mental Illness: A Population-Based Cohort Study
Maternal mental illness is common, with an estimated prevalence of 25% in birthing people who have children aged 0–16 years.1 Maternal mental illness has a negative impact on the affected individual and their offspring.2–4 Severe mental illness outcomes, including psychiatric emergency department visits, psychiatric hospital admissions, and self-harm or suicide, affect only 1% of birthing people but have significant negative impacts on individuals and families.5,6 There are several known risk factors for severe maternal mental illness, including history of mental illness,7 lack of social support,8 and history of abuse or violence9; however, many birthing people experience severe mental illness outcomes without these risk factors.5 Most available research on maternal mental illness focuses on the postpartum period.5,10 Less information is available on long-term outcomes beyond the first year postpartum.1
Concussion, the most common form of traumatic brain injury (TBI), is a risk factor for mental illness in the general population,11–15 including severe outcomes even years after the concussion.16 Concussion is a term for a set of symptoms that develop after an acute brain injury, including impaired balance and cognition.17 Concussion disrupts brain function and has the potential to cause long-term physical health concerns,18 sleep disturbances,19 and decreased cognitive functioning.20 About 15%–25% of birthing people report a history of concussion.21 One study found an increased risk for postpartum complications, including depression, among birthing people with a history of moderate to severe TBI vs those without TBI.22 However, no studies, to our knowledge, have examined the impact of concussion on long-term severe maternal mental illness. This is an important gap; concussion may increase the risk of maternal mental illness via an interaction between parenting stressors such as poor sleep and noise and injury-related difficulties such as diminished cognitive and executive functioning.23–25
Our objective was, therefore, to examine the association between a predelivery history of concussion and long-term risk of severe maternal mental illness. We hypothesized that concussion would be associated with elevated risk of severe maternal mental illness and that this association would be moderated by mental illness history.
METHODS
Study Design and Data Sources
This was a population-based cohort study using Ontario, Canada health administrative data accessed from the Institute of Clinical Evaluative Sciences (ICES). This research was part of the first author’s Master’s thesis.26 The datasets, described in Supplementary Table 1, were linked using unique encoded identifiers and analyzed at ICES. ICES is a prescribed entity under Ontario’s Personal Health Information Protection Act (PHIPA).27 Section 45 of PHIPA authorizes ICES to collect personal health information, without consent, for analyses that inform health care system management, planning, and evaluation. The use of the data in this project was authorized under section 45 and approved by ICES’ Privacy and Legal Office. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2013. All procedures involving human subjects/patients were approved by the University of Toronto Research Ethics Board (application # 42750).
Study Population
The cohort included all birthing people with a singleton livebirth between April 1, 2007, and March 31, 2017, excluding those ineligible for Ontario health insurance in the 2 years before delivery. Fewer than 1% of those living in Ontario are ineligible for the Ontario Health Insurance Plan (OHIP); they mainly include those who are new immigrants or nonstatus (ie, students, temporary migrant workers, and newcomers without immigration status).28 We excluded individuals with a history of TBI other than concussion or unspecified head injury,13 and those admitted to the hospital within 2 days of the concussion encounter. The latter exclusion was made because these individuals would likely have more severe TBI,16 and we wanted to focus on concussion, as it is the most common form of head injury and may have less comprehensive follow-up than severe TBI as it does not typically require hospital admission. To handle clustering of multiple pregnancies to the same person, 1 pregnancy was randomly selected. In this remaining cohort, those with a history of unspecified head injury were excluded from primary analyses.29
The exposure of interest was a history of a concussion-related health care encounter (without hospital admission) before the index pregnancy’s delivery date. Concussions were identified in ≥1 outpatient visits (OHIP billing code: 850) or emergency department visits (International Classification of Diseases, Ninth Revision [ICD-9], physician billing code for emergency department visits prior to 2002: 850; ICD-10 diagnostic code for emergency department visits in the National Ambulatory Care Reporting System after 2002: S06.0).16,29,30 The concussion diagnosis code could be in any field and did not need to be the primary diagnosis position, given that a person could be seen for polytrauma where the concussion was not the most acute condition at the health care encounter. Those without an encounter for concussion or unspecified head injury from database inception to the delivery date were the unexposed.
In additional analyses, concussion exposure was subclassified by proximity of the most recent concussion health care encounter to the delivery: ≥5 years prior to conception, 2–5 years prior to conception, or <2 years prior to conception and up to delivery.
In sensitivity analyses, those with unspecified head injury codes were included in the exposed group to address the potential misclassification that may occur wherein those with a concussion may have been coded as having an unspecified head injury.29
Outcome
The primary outcome was a composite measure of severe maternal mental illness, defined as any psychiatric emergency department visit, psychiatric hospital admission, or self-harm or suicide between the day after delivery and March 31, 2021 (Supplementary Table 2). This provided a follow-up period of 4–14 years, with a median of 8.54 years for the total cohort. Secondary outcomes were defined as follows: (1) each of psychiatric emergency department visits, psychiatric hospital admissions, and self-harm or suicide, separately, and (2) for psychiatric emergency department visits and hospital admissions, the specific diagnosis (ie, psychotic, depressive and other moods, anxiety and related, or substance and alcohol use disorders) (Supplementary Table 3).
Covariates
Confounders were age, parity, neighborhood income quintile, rurality, immigration status (Immigration, Refugees, and Citizenship Canada Permanent Residents Database), stable and unstable chronic conditions (Johns Hopkins Adjusted Clinical Groups v. 10.0),31 predelivery history of assault resulting in an emergency department visit, and predelivery history of mental illness. Predelivery history of mental illness was divided into (1) no history of mental illness in pregnancy or 5 years before conception, (2) history of outpatient care for mental illness in pregnancy or 2 years before conception without a history of acute care for mental illness in pregnancy or 5 years before conception, and (3) history of acute care for mental illness in pregnancy or 5 years before conception. (History of acute care included psychiatric emergency department visits, psychiatric hospital admissions, and self-harm.)
Pregnancy and child variables were measured to describe the cohort and were not adjusted for in the main analyses since they might be mediators (Supplementary Figure 1).5,22 Pregnancy variables were pregnancy induced hypertension, gestational diabetes, instrumental delivery, and caesarean delivery. Child variables were preterm birth <37 weeks, small for gestational age <10th percentile, neonatal intensive care unit admission, and child mortality.
Statistical Analysis
All statistical analyses were performed using SAS software, version 9.4 (SAS Institute Inc, Cary, NC, USA). The characteristics of birthing people with and without a history of concussion were described and compared using standardized differences.32
The outcomes were displayed as the number of events per 1,000 person-years of follow-up. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% CI for severe maternal mental illness, comparing birthing people with a predelivery history of concussion to those without such a history. Participants were censored at death, loss of OHIP eligibility, or March 31, 2021, whichever came first. Additional analyses examined each element of the composite and specific psychiatric diagnoses within acute health care encounters separately. Adjusted HRs (aHRs) were produced controlling for maternal age, parity, neighborhood income quintile, rurality, immigration status, chronic conditions, history of assault, and history of mental illness. Due to the known association between a history of mental illness and both concussion and recurrence of mental illness after delivery,14,33 an interaction term between history of concussion and history of mental illness was assessed, with statistically significant interaction terms followed by analyses stratified by history of mental illness.
The proportional hazards assumption was assessed by visualizing the cumulative incidence function, log negative-log of survival by log time, and log-negative-log of survival by time graphs and by assessing the concussion-time interaction in the Cox proportional hazards regression model.34 No major departures were visualized in the exposure-outcome relationship and the concussion-time interaction variable resulted in a P value of .81, supporting the proportionality of the hazards of serious maternal mental illness over the follow-up period.
Several sensitivity analyses were performed: (1) concussion exposure was examined by proximity of the concussion health care encounter to delivery; (2) concussion exposure was limited to those with a concussion health care encounter in the 5 years before conception up to delivery to ensure an equal lookback period for the cohort; (3) those with unspecified head injury codes were added to the concussion group to address misclassification of concussion miscoded as unspecified head injury29; (4) observations with concussion or TBI after delivery were excluded to ensure results were due to predelivery concussion; (5) the follow-up period was truncated to end on March 12, 2020, to account for possible changes in health care use during the COVID-19 pandemic35; (6) pregnancy and child variables were added to the multivariable models; and (7) an E-value was calculated to assess the minimum magnitude of association an unmeasured confounder must have with the exposure and outcome to bring the HR to the null.36
RESULTS
There were 1,288,480 singleton livebirths between April 1, 2007, and March 31, 2017 (Supplementary Figure 1). After exclusions, 1,178,248 deliveries to 806,330 unique people met the inclusion criteria. Of the final cohort, 18,064 (2.2%) had a predelivery history of concussion, 51,577 (6.4%) had a predelivery history of unspecified head injury, and 736,689 (91.4%) had no predelivery history of concussion or unspecified head injury. Birthing people with a predelivery history of concussion were more likely than those without such a history to live in a rural area, be long-term residents, and have a history of assault or mental illness. There were no notable differences in other variables including pregnancy and child characteristics (Table 1).
The results of the primary analysis are shown in Table 2. Overall, 2,033 (11.3%) of the 18,064 observations with a predelivery history of concussion experienced severe maternal mental illness (14.7 per 1,000 person years), compared to 49,928 (6.8%) of the 736,689 observations without a predelivery history of concussion (7.9 per 1,000) (HR 1.82, 95% CI, 1.74–1.90). These results remained statistically significant after adjustment, with an aHR of 1.25 (95% CI, 1.20–1.31). After stratification by predelivery history of mental illness, the association was strongest in individuals with no mental illness history (aHR 1.33, 95% CI, 1.23–1.44), followed by those with a history of outpatient care for mental illness (aHR 1.30, 95% CI, 1.20–1.40) and with a history of acute care for mental illness (aHR 1.14, 95% CI, 1.06–1.24) (interaction P < .0001).
Results of the secondary outcomes, including each element of the composite (Table 3) and psychiatric diagnosis at the acute health care encounter (Table 4), were similar, with the exception of psychotic disorders, which had a nonsignificant aHR. Results stratified by mental illness history were mostly similar, with some exceptions possibly due to lower statistical power.
In sensitivity analyses examining proximity of the concussion health care encounter to delivery, aHRs were elevated for distal, mid, and proximal history of concussion (Supplementary Table 4). Analyses restricting the lookback to 5 years preconception (Supplementary Table 5), including unspecified head injuries in the concussion group (Supplementary Table 6), excluding those with postdelivery concussion or TBI (Supplementary Table 7), truncating follow-up prior to the COVID-19 pandemic (Supplementary Table 8), and including pregnancy and child variables (Supplementary Table 9) showed similar results. Finally, the E-value for the aHR for the primary analyses was 1.81 for the point estimate and 1.69 for the lower bound of the 95% CI.
DISCUSSION
In this large, population-based study in Ontario, Canada, we found that a predelivery history of concussion was associated with an increased risk of severe maternal mental illness. The relative increase in risk for those with concussion was greater among those with no history of mental illness than among those with a predelivery history of mental illness. Results were consistent across additional and sensitivity analyses. These results have critical clinical implications for the prevention of concussion in people with reproductive capacity, antenatal screening for a history of concussion, and delivery of trauma-informed care for those with a history of concussion who develop mental illness after the birth of a child.
Previous Research
This research aligns with previous research in pediatric populations,12,13 professional athletes,11 and veterans37 that also showed an increased risk of mental illness, including serious outcomes such as psychiatric emergency department visits, psychiatric hospital admissions, self-harm, and suicide, even years after concussion.11–16 Only 1 study examined postpartum mental illness, finding an increased risk of postpartum depression following TBI; however, neither concussion nor long-term maternal mental health outcomes were examined.22 Our sensitivity analyses also align with previous research showing that the observed association is not unduly influenced by misclassification of concussion as unspecified head injury.29 Sensitivity analyses further adjusting for pregnancy and child variables, as well as omitting concussion or TBI after delivery, support the unique impact of predelivery concussion, and no other trauma, on serious maternal mental illness. The current study therefore contributes new data by showing a strong relation between a history of concussion and long-term risk of severe maternal mental illness.
Potential Mechanisms
There is considerable literature to support the biological plausibility of an association between concussion and severe maternal mental illness. Concussion can lead to neurotransmitter, blood flow, neuronal, and inflammatory changes,38 poor sleep quality,39 and long term cognitive impairment.40 Each of these factors could lead to the development of mental illness.41,42 Pregnancy, labor and birth, and parenting may add complexity to the relationship between concussion and mental illness. Research has shown that people with TBI, including concussion, have light and sound sensitivities and a resulting increase in fatigue.23,24 Sleep is also integral to healing following a head injury25 but may be compromised among parents of young children. Not only does a history of concussion have the potential to make parenting more difficult due to neurological deficits and sensitivities,23–25,43 but the demands of parenting could also worsen concussion symptoms, including increasing the long-term risk of mental illness.44
Strengths and Limitations
This population-based cohort study was the first study to examine the relation between a predelivery history of concussion and serious maternal mental illness outcomes and has many strengths. A relatively large sample size provided enough statistical power to stratify the cohort by mental illness history. We were able to capture outpatient concussion health care encounters, which research has shown make up the majority of concussion health care encounters.30
However, there is likely geographical and provider heterogeneity in concussion diagnosis, indicating the need for consistent diagnosis guidelines. We were unable to distinguish between health care encounters for new concussion vs ongoing management of prior concussion in order to capture the number of concussions. This is an important limitation because there is a potential dose-response effect of the number of concussions on mental illness risk.11 The data also do not capture the occurrence of concussions where no health care was sought, or care was sought outside of Ontario. Therefore, it is possible that there are observations in the unexposed group who had a history of concussion. Finally, we excluded individuals admitted to the hospital following a concussion health care encounter to exclude more severe head injuries potentially misclassified as concussion. Theoretically, this exclusion would dilute our findings, as a more severe TBI would be expected to have an even stronger association with severe maternal mental illness.
There are confounders that are not captured in Ontario health administrative data (eg, race/ethnicity, education level, health practices). This limitation speaks to the importance of collecting data on these contextual factors in health administrative data in the future. However, the large E-value indicated that a strong association would be needed between an unmeasured confounder and both concussion and severe maternal mental illness to attenuate the results.
Finally, we were unable to examine the specific mechanisms underlying the observed association, and it is possible other factors that lie along the causal pathway between concussion and severe maternal mental illness explain the results. More research is needed to address these mechanisms to assist in our understanding of this relationship and prevent development of serious maternal mental illness.
Conclusion
Concussion in reproductive-aged people is common,30 and our findings show the potential long-term effect of concussion on severe mental health outcomes in an important population group. The importance of concussion prevention for all people with reproductive capacity is integral and requires awareness of their long-term risk of severe mental illness. Screening for a history of concussion should also be a part of routine antenatal and postnatal care, enabling adequate supports to be arranged for postdelivery care as a means of preventing maternal mental illness. Such supports could include sleep relief to aid in concussion healing25 and plans to address light and sound sensitivities common after concussion.23,24 As a high-risk group, birthing people with a history of concussion could also benefit from ongoing screening for mental illness by their primary care provider in the months and years after childbirth. Last, those with a history of concussion and maternal mental illness may benefit from trauma-informed mental health care, as routine care has the potential to trigger memories of traumatic experience and exacerbate symptoms of mental illness.45 Together, these clinical considerations could address the association between predelivery history of concussion and severe maternal mental illness and potentially decrease the incidence of these important outcomes.
Article Information
Published Online: November 4, 2024. https://doi.org/10.4088/JCP.24m15373
© 2024 Physicians Postgraduate Press, Inc.
Submitted: April 5, 2024; accepted September 6, 2024.
To Cite: Krueger S, Vigod SN, Chan V, et al. History of concussion and risk of severe maternal mental illness: a population-based cohort study. J Clin Psychiatry. 2024;85(4):24m15373.
Author Affiliations: Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada (Krueger, Vigod, Chan, Brown); ICES, Toronto, Ontario, Canada (Krueger, Vigod, Alonzo, Chung, Brown); Women’s College Hospital and Research Institute, Toronto, Ontario, Canada (Vigod, Brown); Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada (Vigod); KITE Research Institute-Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada (Chan, Mollayeva); Rehabilitation Sciences Institute, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada (Chan, Mollayeva); Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada (Mollayeva, Brown); Department of Health and Society, University of Toronto Scarborough, Toronto, Ontario, Canada (Brown).
Corresponding Author: Hilary K. Brown, PhD, Department of Health & Society, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A5, Canada (hk.brown@utoronto.ca).
Relevant Financial Relationships: Dr Vigod receives royalties from UpToDate Inc for authorship of materials related to depression and pregnancy. The other authors report no conflicts of interest.
Funding/Support: This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC). Research reported in this publication was also supported by the Canadian
Institutes of Health Research under award #FRN173436. This research was undertaken, in part, thanks to funding from the Canada Research Chairs Program to Drs Brown and Mollayeva. Ms Krueger is supported by a Canadian Institutes of Health Research Canada Graduate Scholarship—Masters Award.
Role of the Sponsor: The sponsors had no role in the conduct of the study design, management, analysis, or interpretation of the data, or in the preparation, review, or approval of the manuscript.
Disclaimers: This document used data adapted from the Statistics Canada Postal CodeOM Conversion File, 2006, 2011, and 2016, which are based on data licensed from Canada Post Corporation, and/or data adapted from the Ontario Ministry of Health Postal Code Conversion File, which contains data copied under license from ©Canada Post Corporation and Statistics Canada. Parts of this material are based on data and/or information compiled and provided by the Canadian Institute of Health Information, Ontario Ministry of Health, Immigration, Refugees and Citizenship Canada (IRCC) current to September 2020, Ontario Registrar General (ORG) information on deaths, the original source of which is ServiceOntario, and Statistics Canada, 2016 Census. The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the data sources, the ORG or the Ministry of Public and Business Service Delivery; no endorsement is intended or should be inferred. The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding sponsors.
Previous Presentation: This research was presented at the Canadian National Perinatal Research Meeting; May 23–26, 2023; Montebello, Quebec, Canada.
ORCID: Samantha Krueger: https://orcid.org/0009-0002-8626-990X
Supplementary Material: Available at Psychiatrist.com.
Clinical Points
- Concussion has been associated with mental illness in the general population, but this is the first study to examine how a predelivery history of concussion impacts serious maternal mental illness risk.
- Health care providers should consider prevention of concussion in people with reproductive capacity, antenatal screening for a history of concussion, and delivery of trauma-informed care for those with a history of concussion who develop mental illness after the birth of a child.
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