May 2023Original Research: Mental Disorders Among Mothers of Children Born Preterm: A Population-Based

Mental Disorders Among Mothers of Children Born Preterm: A Population-Based Cohort Study in CanadaTroubles mentaux chez les femmes d’enfants prématurés : une étude de cohorte dans la population au CanadaDeepak Louis, MD, DM¹

, Hammam Akil, MD¹, James M. Bolton, MD^2,3

, Fabiana Bacchini, MSc⁴, Karen Netzel⁵, Sapna Oberoi, MD, DM⁶, Christy Pylypjuk, MD⁷, Lisa Flaten, MSc³, Kristene Cheung, PhD⁸, Lisa M. Lix, PhD^3,9, Chelsea Ruth, MD^1,3, and Allan Garland, MD, MA^3,10img1

The Canadian Journal of Psychiatry / La Revue Canadienne de Psychiatrieimg4

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DOI: 10.1177/07067437221138237
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AbstractBackground: Our aim was to examine the association between preterm delivery and incident maternal mental disorders using a population-based cohort of mothers in Canada.Methods: Retrospective matched cohort study using Manitoba Centre for Health Policy (MCHP) administrative data in Manitoba. Mothers who delivered preterm babies (<37 weeks gestational age) between 1998 and 2013 were matched 1:5 to mothers of term babies using socio-demographic variables. Primary outcome was any incident mental disorder within 5 years of delivery defined as any of (a) mood and anxiety disorders, (b) psychotic disorders, (c) substance use disorders, and (d) suicide or suicide attempts. Multivariable Poisson regression model was used to estimate the 5-year adjusted incidence rate ratios (IRRs).Results: Mothers of preterm children (N = 5,361) had similar incidence rates of any mental disorder (17.4% vs. 16.6%, IRR = 0.99, 95% CI, 0.91 to 1.07) compared to mothers of term children (N = 24,932). Mothers of term children had a higher rate of any mental disorder in the first year while mothers of preterm children had higher rates from 2 to 5 years. Being the mother of a child born <28 week (IRR = 1.5, 95% CI, 1.14 to 2.04), but not 28–33 weeks (IRR = 1.03, 95% CI, 0.86 to 1.19) or 34–36 weeks (IRR = 0.96, 95% CI, 0.88 to 1.05), was associated with any mental disorder.Interpretation: Mothers of preterm and term children had similar rates of incident mental disorders within 5-years postdelivery. Extreme prematurity was a risk factor for any mental disorder. Targeted screening and support of this latter group may be beneficial.AbrégéContexte : Notre objectif était d’examiner l’association entre l’accouchement avant terme et les troubles mentaux maternels incidents à l’aide d’une cohorte de mères dans la population au Canada.Méthodes : Une étude de cohorte appariée rétrospective a utilisé les données administratives du Centre d’élaboration de la politique des soins de santé du Manitoba (MCHP). Les mères qui ont accouché de bébés avant terme (< 37 semaines d’âge gestationnel) entre 1998 et 2013 ont été appariées à raison d’une sur 5 à des mères de bébés à terme à l’aide de variables sociodémographiques. Le résultat principal était tout trouble mental incident dans les 5 ans après l’accouchement, défini comme étant l’un (a) des troubles anxieux ou de l’humeur (b) des troubles psychotiques, (c) des troubles liés aux substances, et (d) des suicides ou tentatives de suicide. Le modèle de régression multi-variable de Poisson a servi à estimer un ratio du taux d’incidence (RTI).Résultats : Les mères d’enfants prématurés (n = 5 361) avaient des taux d’incidence semblables de tout trouble mental [17,4% c. 16,.6%, RTI = 0,99, IC à 95% 0,91 à 1,07)] comparé aux mères d’enfants à terme (n = 24 932). Les mères d’enfants à terme avaient un taux plus élevé de tout trouble mental dans la première année alors que les mères de prématurés avaient des taux plus élevés de 2 à 5 ans. Être mère d’un enfant né avant < 28 semaines (RTI = 1,5, IC à 95% 1,14 à 2,04]), mais pas à 28–33 semaines (RTI = 1,03, IC à 95% 0,86 à 1,19]) ou à 34–36 semaines (RTI = 0,96, IC à 95% 0,88 à 1,05]), était associé à tout trouble mental.Interprétation : Les mères d’enfants prématurés et nés à terme avaient des taux semblables de troubles mentaux incidents dans les 5 ans suivant l’accouchement. La prématurité extrême était un facteur de risque pour tout trouble mental. Le dépistage ciblé et le soutien de ce dernier groupe peuvent être bénéfiques.Keywordsmaternal health, depressive disorders, anxiety, substance use disorders, postpartum, prematurityIntroductionApproximately 8% of all live births in Canada are preterm (<37 weeks), contributing to 30,000 births,¹ and costing eight billion dollars to the Canadian health care system annually.² Children born preterm can have multiple short-term and long-term morbidities. Long-term morbidities include neurosensory impairments (cerebral palsy, vision and hearing deficits), behavioural and developmental challenges, cognitive delays and learning disorders.^3–7Parenting a child born preterm therefore can be stressful for mothers making them prone to mental disorders.⁸ Previous studies exploring the association between prematurity and maternal mental disorders were limited by small sample sizes, residual confounding, selection and attrition biases,^9,10 and the use of self-report questionnaires for diagnosing mental disorders.^11–13 Our aim was to study the association between prematurity and incident mental disorders using a population-based cohort of mothers.MethodsThis retrospective cohort study used the Population Research Data Repository at the Manitoba Centre for Health Policy (MCHP), University of Manitoba, Canada.¹⁴ The Repository contains linked education, social, health and justice data collected by government and healthcare providers for all Manitoba residents. Validated maternal-child linkages between the datasets were used to build the study cohort.^15,16 These data have almost complete population coverage for Manitoba, which has a publicly funded, single payer healthcare system. Study approvals were obtained from the Research Ethics Board and other data custodians. eTable 1 lists the datasets and corresponding variables used in the study.All women who delivered liveborn singleton or twin babies in Manitoba between 1998 and 2013 formed the study population. From them, we included mothers who had delivered preterm babies (<37 weeks gestational age) (a) who were continuously registered with Manitoba Health at least 5 years before and 5 years after the index birth event, and (b) whose children were continuously registered with Manitoba Health for 5 years after the index birth event. For mothers with more than one preterm delivery, only the first preterm birth was included as long as the subsequent one occurred > 5 years later.We excluded preterm mothers: (a) who had pre-existing mental disorders (i.e., within the 5 years prior to the index birth event), (b) whose children died within 5 years of the index delivery or (c) for whom we could not find term mothers as matches.We used two different definitions for mental disorders in the study, one to exclude mothers with pre-existing mental disorders, and the other to identify incident mental disorders among the included mothers. For the former, we used validated administrative data definitions available in the Repository based on outpatient physician diagnoses using ICD codes, medication prescriptions and hospital admissions for mental health with high sensitivity to avoid false-negative classification of mental disorders (eTable 2) and applied them to a 5-year blackout period prior to the index birth event.^17,18For mothers who delivered term babies, we used the same inclusion and exclusion criteria as for preterm mothers except that preterm birth was replaced by term birth (≥ 37 weeks gestational age). Unlike mothers of preterm babies, mothers who had more than one term baby during the 5-year period were included.For each mother of preterm child, we sought five matched mothers of term children based on the following criteria at the time of the index birth event: (a) year of delivery (±3 years), (b) singleton versus twin birth, (c) maternal age (±1 year), (d) SEFI-2 score (±0.3 standard deviation),¹⁹ (e) sex of the child, (f) parity of the mother (1 vs. >1), (g) marital status (married/common law vs. single), and (h) rural vs. urban residence.²⁰For mothers of preterm children with less than five matches, matching with replacement was performed; specifically, the same term birth event was allowed to be matched to more than one preterm birth event from separate mothers, and a given mother’s separate term birth events could also be used as a match for separate preterm birth events. For those preterm mothers who did not have five matches, frequency weighting was used during the analysis. The statistical power and efficiency of matched cohort studies plateau beyond a matching ratio of 1: 4 to 1:5 as per literature²¹ and it also becomes challenging to find the appropriate number of matches.OutcomeOur primary outcome was any de novo mental disorder among mothers within the 5 years of the index birth event. Any mental disorder included any one or more of the following: (a) mood and anxiety disorders, (b) psychotic disorders, (c) substance use disorders including alcohol use disorders, and (d) suicide or suicide attempts. To identify mothers with new mental disorders, we used administrative data definitions based on outpatient physician diagnoses using ICD codes, medication prescriptions, and hospital admissions for mental health with the highest agreement (kappa value) to clinical diagnoses so as to avoid both false-positive and false-negative diagnoses (eTable 2).^17,18Secondary outcomes included each mental disorder separately, and the time to diagnosis of any mental disorder, the latter defined by the first date of hospitalization or physician visit or prescription filled for any of the mental disorders.CovariatesThese included mother’s age at index delivery, year of delivery, residence, maternal diabetes (gestational or pre-existing), maternal hypertension (gestational or pre-existing), smoking, income assistance at delivery, SEFI-2 score, marital status, birth order, Caesarean delivery, infant’s sex, small for gestational age,²² and singleton versus twins. These variables were identified from previous literature.^12,23–26Statistical and Sensitivity AnalysisThe unit of analysis was the index birth event. Descriptive statistics were used for baseline variables. Standardized mean differences were calculated to compare them, with values >0.1 considered substantial.²⁷ To test the association between preterm birth and maternal mental disorders (primary analysis), matched preterm and term birth events along with the covariates were entered into multivariable Poisson regression models. We fit two models to the data: (i) prematurity defined as <37 weeks gestational age, and (ii) prematurity categorized as <28 weeks, 28–33 weeks, and 34–36 weeks. We assessed multicollinearity among covariates using the variance inflation factor (VIF); all VIF were <4.²⁸ Since prematurity was our primary exposure variable, we adjusted the P-values for the four prematurity variables mentioned above across the two models using Sime’s false discovery rate step-up method^29,30 while all other P-values remain unadjusted for multiple comparisons. As all subjects had the same 5-year follow-up period, the exponentiated coefficient of the primary exposure variable represented the 5-year incidence rate ratio (IRR).A sensitivity analysis was planned a priori, including mothers whose children died within 5 years of the index birth event. Statistical analyses were conducted using SAS 9.4 (SAS Institute Inc., Cary, NC, USA).ResultsOf the 14,362 women who had preterm babies during the study period, 5,361 were eligible and included in the study cohort (Figure 1). Among the 169,192 term mothers, 94,497 were eligible and 24,932 were matched to mothers of preterm children. Most (87%) preterm mothers had five matches, 2.7% had four, 2.6% had three, 4.3% had two, and 3.6% had one match. The groups were similar except for mother’s age at index delivery and first child birth, prevalence of diabetes, hypertension, and delivery by Caesarean section, all of which were higher among mothers of preterm children (Table 1).Primary and secondary outcomes of the cohort with prematurity defined as <37 weeks are shown in Table 2. There were no differences in the outcomes between preterm mothers and term mothers. Mothers of extremely preterm babies (<28 weeks) had higher incidence rates of any mental disorder, mood and anxiety disorders, and substance use disorders compared to mothers of other preterm groups (28–33 weeks and 34–36 weeks) and term children (Table 3).eTable 3 shows the regression model based on gestational age categories. We found that compared to mothers of term children, being a mother of <28 week infant was associated with developing any mental disorder, while mothers of infants born at 28–33 weeks and 34–36 weeks gestational age were not.Fig1Figure 1. Flow of study cohort.Sensitivity analysis including mothers whose children died within 5 years after birth identified two additional mothers in the preterm group and eight in the term group; the results were similar to the primary cohort (eTable 4).The time of diagnosis of any mental disorder is shown in Figure 2. In the first year after the index delivery, term mothers had a higher incidence for any mental disorder compared to preterm mothers. After the first year, preterm mothers had a higher rate for mental disorders compared to term mothers.DiscussionIn this population-based matched cohort study, the incidence rate of mental disorders did not differ between mothers of preterm and term children when preterm group was analyzed as a single category. However, we found an association between mothers of extremely preterm infants (<28 weeks) and the incidence rate of any mental disorder. A majority of mothers of preterm children were diagnosed with mental disorders beyond the first year after delivery while for mothers of term children, a plurality was diagnosed within the first year after delivery.Preterm delivery and subsequent care of children born preterm can be stressful for parents, especially mothers, adversely affecting their mental health. Maternal mental health strongly impacts the entire family. Beyond their own physical health and well-being,^31–33 maternal mental disorders can adversely affect their partners’ mental health,^34,35 and their infants’ socio-emotional and behavioral development.^36,37 The latter is particularly relevant for preterm infants, who have a higher baseline risk for developmental impairment compared to term infants.^38,39Our study improved on the methodologies of previous population-based studies.^{23–25,34,40–42} This included using a matched cohort allowing us to account for multiple confounders, the use of a more stringent 5-year blackout period to exclude mothers with pre-existing mental disorders, excluding mothers with any pre-existing mental disorder rather than a specific mental disorder, and using a composite of any mental disorder as our primary outcome. In addition, while the postpartum follow-up period of most studies was 1 year, our use of 5 years more completely captured the long-lived maternal exposure to stress following preterm delivery.^43,44 This allowed the capture of a more precise and harmonious sample, despite the exclusion of 63% of eligible mothers who delivered preterm children.Previous studies based on clinical interviews report the prevalence of postpartum depression (PPD) to be 0.5–1.4%.^23–25 In contrast, we found a higher incidence of any mental disorder (∼17%) among both mothers of preterm and term children, with mood and anxiety disorders contributing the most (∼13%). Potential reasons for our high rates include the longer duration of follow up (5 years vs. 1 year in other studies), the use of a composite of mental disorders as the outcome, and the relatively high prevalence of mental disorders prevalent in Manitoba and Canada compared to other high-income countries.⁴⁵ A 2018 report showed that the 5-year prevalence of any mental disorder in Manitoba among 18–24 and 25–44-year-old women was 36% and 42%, respectively.¹⁸ Similarly, a national mental health survey of Canadian mothers found a 23% prevalence of PPD and anxiety.⁴⁶Tab1Table 1. Baseline Characteristics of the Study Cohort.Results of previous population-based studies evaluating prematurity and mental disorders have been mixed, with some showing preterm delivery as a risk factor for PPD^24,25,40,41 while others did not find such an effect.^23,34,42 Despite these differences, most of them evaluated prematurity as a single category, that is, <37 weeks gestational age.^25,41,42 In the only study that showed an association between degree of prematurity and PPD, Silverman et al.²⁴ found that preterm birth born <32 weeks (OR: 1.53, 95% CI, 1.12 to 2.10), but not 32–36 weeks (OR: 1.07, 0.91–1.26), was associated with PPD. These findings were similar to our results, except that we found mothers of <28-week infants to be at an increased risk for any mental disorder (IRR: 1.53, 1.14–2.04) while mothers of 28–33 weeks and 34–36 weeks infants were not. These findings are not unexpected given the longer duration of hospital stay of these extremely preterm infants and the higher rates of short-term and long-term morbidities in them.In addition to extreme prematurity, other risk factors for mental disorders in our cohort included higher birth order, maternal age <20 years, maternal diabetes, Caesarean delivery, receipt of income assistance, and mothers who were single, all of which are congruent with previous literature.⁴⁷ Our findings highlight a vulnerable group of mothers who may have fewer resources (both through internal coping mechanisms as well as external support) to deal with the challenges of having a preterm infant. However, these risk factors should be considered hypothesis generating and needs further exploration.Tab2Table 2. Primary and Secondary Outcomes of the Cohort (Prematurity Defined as <37 Weeks).Tab3Table 3. Mental Disorders Based on Gestational age Categories Among Preterm Mothers.Fig2Figure 2. Time to diagnoses of mental disorders among preterm and term mothers.We also found that most mental disorders among preterm mothers were diagnosed after the first postpartum year, unlike term mothers where most were diagnosed in the first year. The potential reasons for this finding include the singular focus of mothers on their preterm child after delivery and sometimes mothers not realizing the changes occurring to their mental health during this very stressful period. These mothers also receive support from the medical team including social work and other parents initially whereas they lose these supports after discharge from the hospital. The emerging developmental issues in their child also might contribute to their mental health challenges. Overall, the findings of this study underscore the need for continued mental health surveillance of mothers in the first few years after preterm delivery.Our study has notable strengths. To the best of our knowledge, this is the first study that evaluated such a broad group of mental disorders among mothers of preterm children. A number of methodologic factors were used to minimize bias and confounding, including: use of a large populationbased cohort, use of stringent inclusion and exclusion criteria, use of matching and numerous covariates in regression modeling, exclusion of mothers who delivered triplets or higher-order births, and exclusion of mothers who had multiple preterm babies within the 5-year follow-up period. Our physician-identified diagnoses are more specific than symptom-based scales for mental disorders used in previous studies. Unlike most other studies, we were also able to look at varying degrees of prematurity and its association with mental health outcomes.Our study has certain limitations. Mothers with mental disorders, especially substance use disorders, may have been undercounted as administrative data only captures those who are diagnosed by a physician or nurse practitioner. We were unable to delineate the effect of prematurity separately for maternal depression and anxiety because of the way ICD-9 outpatient physician visit codes are recorded in the Repository. Posttraumatic stress disorder is an important mental disorder among these mothers that we could not evaluate, for this reason.To conclude, our population-based control study showed that among mothers without previous mental disorders identified within the 5 years before birth, the rate of new mental disorders is not different between mothers of preterm and term children. There was a dose response relationship between prematurity and any mental disorder, mood and anxiety disorders, and substance use disorders. Our regression analysis showed that extreme prematurity (<28 weeks) was associated with the outcome of any mental disorder. The results of this research outline the relationship between preterm birth and maternal mental vulnerability suggesting clinicians be more cognizant, especially of those mothers whose premature babies were born at less than 28 weeks. This may warrant routine screening for mental disorders and follow up among mothers of preterm babies born at such an early gestation.AcknowledgmentsThe authors acknowledge the Manitoba Centre for Health Policy for use of data contained in the Manitoba Population Research Data Repository under project #2020-017 (HIPC#2020/2021-76). The results and conclusions are those of the authors and no official endorsement by the Manitoba Centre for Health Policy, Manitoba Health, or other data providers is intended or should be inferred. Data used in this study are from the Manitoba Population Research Data Repository housed at the Manitoba Centre for Health Policy, University of Manitoba and were derived from data provided by Manitoba Health and Senior Care, Winnipeg Regional Health Authority, Department of Families, Healthy Child Manitoba Office, Statistics Canada and Manitoba Education and Training. We would like to acknowledge the Diabetes Education Resource for Children and Adolescents (DERCA) for use of their Pediatric Diabetes Database. We would like to acknowledge the contributions of Monica Sirski, data analyst at MCHP, for helping with building the study cohorts and performing the data analyses.Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.FundingThe authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Manitoba Medical Service Foundation (MMSF) grant (grant no: 8-2021-07) awarded to Deepak Louis in 2021.ORCID iDsDeepak Louis

https://orcid.org/0000-0002-8535-4208
James M. Bolton

https://orcid.org/0000-0001-6319-5181
Supplemental MaterialSupplemental material for this article is available online.References

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¹ Section of Neonatology, Department of Pediatrics and Child Health, Rady Faculty of Medicine, University of Manitoba, Winnipeg, Canada² Department of Psychiatry, Rady Faculty of Medicine, University of Manitoba, Winnipeg, Canada³ Manitoba Centre for Health Policy, University of Manitoba, Winnipeg, Canada⁴ Canadian Premature Babies Foundation, Toronto, Canada⁵ Neonatal Intensive Care Unit, Women’s Hospital, Winnipeg, Canada⁶ Department of Pediatric Hematology Oncology, Rady Faculty of Medicine, University of Manitoba, Winnipeg, Canada⁷ Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Rady Faculty of Medicine, University of Manitoba, Winnipeg, Canada⁸ Department of Clinical Health Psychology, Rady Faculty of Medicine, University of Manitoba, Winnipeg, Canada⁹ Department of Community Health Sciences, Rady Faculty of Medicine, University of Manitoba, Winnipeg, Canada¹⁰ Department of Medicine, Rady Faculty of Medicine, University of Manitoba, Winnipeg, CanadaCorresponding author:Deepak Louis, MD, DM, Department of Pediatrics and Child Health, University of Manitoba, WN-2064, 820 Sherbrook Street, Winnipeg, Manitoba, Canada R3A 1R9. Email: dlouis@hsc.mb.caJournal CoverOtsuka Lundbeck AdEditorial BoardBluewater Health AdEisai Dayvigo AdJournal infoThe University of British Columbia AdSAGE JournalsSAGE Peer Reviewer RewardsSystematic Review: Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force ReportCommentary: Underfunding of Innovative Mental Health Research: A Call for ActionOriginal Research: Feasibility, Acceptabiity, and Safety of Faecal Microbiota TransplantationOriginal Research: Cross-sectional Study of Factors Associated With Suicide Ideation in OntarioOriginal Research: Mental Disorders Among Mothers of Children Born Preterm: A Population-BasedOriginal Research: Neuropsychiatric Symptom Burden across Neurodegenerative DisordersOutcomes Among People With Schizophrenia Participating in General-Population Smoking CessationLetter to the Editor: Evidence-based Treatment for Stimulant Use Disorder: Time to Hit the CommunityPosition Paper: Collaborative Mental Health Care in Canada: Challenges, Opportunitiesénoncé de Principe: Les soins de santé mentale en collaboration au Canada: Défis, possibilitésSAGE VideoExplore and discover more from SAGECPA's 2023 Annual Conference Save the DateThank You to CPA Members