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Prediction of perinatal depression from adolescence and before conception (VIHCS): 20-year prospective cohort study George C Patton, Helena Romaniuk, Elizabeth Spry, Carolyn Coffey, Craig Olsson, Lex W Doyle, Jeremy Oats, Stephen Hearps, John B Carlin, Stephanie Brown

Summary Background Perinatal depression is a neglected global health priority, affecting 10–15% of women in high-income countries and a greater proportion in low-income countries. Outcomes for children include cognitive, behavioural, and emotional difficulties and, in low-income settings, perinatal depression is associated with stunting and physical illness. In the Victorian Intergenerational Health Cohort Study (VIHCS), we aimed to assess the extent to which women with perinatal depressive symptoms had a history of mental health problems before conception.

Published Online June 11, 2015 http://dx.doi.org/10.1016/ S0140-6736(14)62248-0

Methods VIHCS is a follow-up study of participants in the Victorian Adolescent Health Cohort Study (VAHCS), which was initiated in August, 1992, in the state of Victoria, Australia. In VAHCS, participants were assessed for health outcomes at nine timepoints (waves) from age 14 years to age 29 years. Depressive symptoms were measured with the Revised Clinical Interview Schedule and the General Health Questionnaire. Enrolment to VIHCS began in September, 2006, during the ninth wave of VAHCS; depressive symptoms at this timepoint were measured with the Composite International Diagnostic Interview. We contacted women every 6 months (from age 29 years to age 35 years) to identify any pregnancies. We assessed perinatal depressive symptoms with the Edinburgh Postnatal Depression Scale (EPDS) by computer-assisted telephone interview at 32 weeks of gestation, 8 weeks after birth, and 12 months after birth. We defined perinatal depression as an EPDS score of 10 or more.

Centre for Adolescent Health, Murdoch Childrens Research Institute, University of Melbourne, Royal Children’s Hospital Melbourne, Parkville, VIC, Australia (Prof G C Patton MD, E Spry BA, H Romaniuk PhD, C Coffey PhD, S Hearps BPsych); Clinical Epidemiology and Biostatistics Unit, Murdoch Childrens Research Institute, and Department of Paediatrics, University of Melbourne, Royal Children’s Hospital Melbourne, Parkville, VIC, Australia (Prof J B Carlin PhD, H Romaniuk); Psychological Sciences and Paediatrics, Murdoch Childrens Research Institute, University of Melbourne, Parkville, VIC, Australia (Prof C Olsson PhD); Centre for Social and Early Emotional Development, School of Psychology, Deakin University, Geelong, VIC, Australia (Prof C Olsson); Royal Women’s Hospital and Murdoch Childrens Research Institute, University of Melbourne, Parkville, VIC, Australia (Prof L W Doyle MD); School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia (Prof J Oats DM); and Healthy Mothers Healthy Families Research Group, Murdoch Childrens Research Institute, and General Practice and Primary Health Care Academic Centre, University of Melbourne, Parkville, VIC, Australia (S Brown PhD)

Findings From a stratified random sample of 1000 female participants in VAHCS, we enrolled 384 women with 564 pregnancies. 253 (66%) of these women had a previous history of mental health problems at some point in adolescence or young adulthood. 117 women with a history of mental health problems in both adolescence and young adulthood had 168 pregnancies, and perinatal depressive symptoms were reported for 57 (34%) of these pregnancies, compared with 16 (8%) of 201 pregnancies in 131 women with no preconception history of mental health problems (adjusted odds ratio 8·36, 95% CI 3·34–20·87). Perinatal depressive symptoms were reported at one or more assessment points in 109 pregnancies; a preconception history of mental health problems was reported in 93 (85%) of these pregnancies. Interpretation Perinatal depressive symptoms are mostly preceded by mental health problems that begin before pregnancy, in adolescence or young adulthood. Women with a history of persisting common mental disorders before pregnancy are an identifiable high-risk group, deserving of clinical support throughout the childbearing years. Furthermore, the window for considering preventive intervention for perinatal depression should extend to the time before conception. Funding National Health and Medical Research Council (Australia), Victorian Health Promotion Foundation, Colonial Foundation, Australian Rotary Health Research and Perpetual Trustees.

Introduction Despite being one of the most common complications of pregnancy, perinatal depression remains a neglected global health priority.1 In high-income countries, this disorder affects 10–15% of women2,3 and can have physical, cognitive, and emotional effects on their children’s development, continuing into later life.4 Both antenatal and postnatal depressive symptoms have been associated with poor early child health and development.5 In low-income and middleincome countries, estimates of prevalence vary from 15% to 50%.1 In these settings, associations extend to a failure to thrive in utero, childhood stunting, and childhood physical illness, with antenatal depressive symptoms also linked to preterm birth and low birthweight.3,6,7 Postnatal depression was long held to be a discrete syndrome arising without previous history,8 with a unique

symptom profile,9 a particular endocrine sensitivity,10 and a better prognosis than affective disorders diagnosed outside of pregnancy.8 In the past two decades, views have shifted. Depressive symptoms are recognised as common during pregnancy and, in turn, predictive of postnatal depression.11,12 Perinatal depression is now commonly used to encompass syndromes that emerge either during pregnancy or after birth.13 Mental disorders before pregnancy are also recognised as an important risk factor for perinatal depression.8,14–16 In a study of more than 1000 Italian women, in which perinatal depression was recorded from 3 months of gestation, 30% of women with an incident perinatal episode reported a history of depression.17 Yet, retrospective identification of episodes before pregnancy could lead to underestimates of earlier mental disorder.18

www.thelancet.com Published online June 11, 2015 http://dx.doi.org/10.1016/S0140-6736(14)62248-0

See Online/Comment http://dx.doi.org/10.1016/ S0140-6736(15)61033-9

Correspondence to: Prof George C Patton, Centre for Adolescent Health, Murdoch Childrens Research Institute, University of Melbourne, Royal Children’s Hospital, Parkville, VIC 3052, Australia [email protected]

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We designed the Victorian Intergenerational Health Cohort Study (VIHCS) to ascertain the extent to which parental health, lifestyle, and social adjustment before conception might affect maternal perinatal health and neonatal development. Here, we aimed to assess the extent to which women with perinatal depressive symptoms had a history of depression and anxiety before conception.

Methods Participants We recruited female participants from the Victorian Adolescent Health Cohort Study (VAHCS),19 a prospective cohort study of health in young people living in the state of Victoria, Australia, which was initiated in August, 1992. The VAHCS population consisted of a representative sample of male and female adolescents who were selected with two-stage cluster sampling. In stage one, 45 schools were chosen at random from a stratified frame of government, Catholic, and independent schools with a probability proportional to the number of year 9 students (typically aged 14–15 years) in the schools in every stratum. In stage two, two distinct complete classes were selected at random from every participating school. One class entered the study in the latter part of the ninth school year (wave 1; August, 1992) and the second class entered 6 months later (wave 2; February, 1993). Participants were reviewed at four subsequent 6-month intervals (waves 3–6; August, 1993, to February, 1995), with three follow-up reviews in young adulthood: at age 20–21 years (wave 7; 1998), 24–25 years (wave 8; 2001–03), and 28–29 years (wave 9; 2006–08). School retention rates to year 9 in the year of sampling were 98%. One of the 45 schools did not continue beyond wave 1, with a loss of 13 participants. From a total of 2032 adolescents, 1943 (96%) participated at least once during the first six (adolescent) waves, 1000 of whom were young women. Figure 1 shows the flow of female participants through VAHCS. Written consent for participation in VAHCS was provided initially by parents. At every survey point (wave), informed verbal consent was sought explicitly from every participant. The human research ethics committee at the Royal Children’s Hospital Melbourne approved data collection protocols for both VAHCS and VIHCS.

Procedures We began our study in September, 2006, during the ninth wave of follow-up of VAHCS. We contacted all young women who were still active in VAHCS to obtain their verbal consent for participation in VIHCS. Every 6 months, we contacted participants by text message, email, or telephone to identify pregnancies; we asked participants if they were currently pregnant, were planning a pregnancy, or had a child younger than 1 year who was not enrolled in VIHCS. We invited women who affirmed they were pregnant or had an infant younger than 1 year to participate in our study. In VAHCS during waves 1–7, common mental disorders were assessed with the Revised Clinical Interview Schedule (CIS-R), a psychiatric interview designed to assess symptoms of depression and anxiety in non-clinical populations.20 Presence of a common mental disorder was adjudicated as a score of 12 or more on the CIS-R, which is the level at which intervention by a family doctor would be appropriate. In our study, we categorised the persistence of common mental disorders during adolescence—ie, a score of 12 or more on the CIS-R in no waves, in one wave, or in two or more waves. In VAHCS during waves 8 and 9, symptoms of depression and anxiety were assessed with the 12-item General Health Questionnaire (GHQ-12), with high symptoms of common mental disorder defined as a score of 3 or more.21,22 Further, in wave 9, depression and anxiety were assessed using the Composite International Diagnostic Interview (CIDI): major depressive disorder was measured with CIDI-auto23 and anxiety disorder with CIDI-short form.24 We defined major depressive disorder and anxiety disorder according to the International Classification of Diseases, 10th revision (ICD-10). We classed participants as having anxiety disorder if they were diagnosed with generalised anxiety disorder, social phobia, agoraphobia, or panic disorder. We categorised the persistence of common mental disorders in young adulthood using all three measures (CIS-R, GHQ-12, and CIDI) to identify symptoms of major depressive disorder and anxiety disorder in no waves, one wave, or two or more waves. We defined continuity of mental health disorder from adolescence to young adulthood as no disorder, adolescent disorder only, young adult disorder only, and both adolescent and young adult disorder. Young adult

Adolescent Survey timepoint Year Mean age Sample

Wave 1 1992 14·9 years n=466

Wave 2 1993 15·4 years n=907

Wave 3 1993 15·9 years n=888

Wave 4 1994 16·3 years n=875

Wave 5 1994 16·8 years n=854

Wave 6 1995 17·4 years n=848

Wave 7 1998 20·6 years n=866

Wave 8 2001–03 24·0 years n=824

Wave 9 2006–08 29·0 years n=806

2 entry points

Figure 1: Sampling and retention of female participants in VAHCS, 1992–2008 Participants were recruited during waves 1 and 2 and followed up at seven timepoints (waves 3–9). VAHCS=Victorian Adolescent Health Cohort Study.

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www.thelancet.com Published online June 11, 2015 http://dx.doi.org/10.1016/S0140-6736(14)62248-0

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Adolescent risky behaviours were also measured in VAHCS.19 Cigarette smoking was recorded with a self-report diary over the previous 7 days; daily smokers were classified as those smoking on 6 or 7 days in the previous week. Risky alcohol use was assessed over a period of 1 week in a beverage-specific and quantityspecific self-report diary; drinking five or more standard drinks (one standard drink being equal to 10 g alcohol) on any day was defined as binge drinking, the most common form of alcohol misuse in adolescents. Participants who reported cannabis use at least once a week were also identified by self-report. Antisocial behaviour during adolescence was measured with ten items on the Moffitt and Silva self-report early delinquency scale25 relating to property damage, interpersonal conflict, and theft in the previous 6 months. Antisocial behaviour was defined if one behaviour was reported more than once or two different behaviours were noted at least once. We asked participants to complete computer-assisted telephone interviews at three perinatal assessment points: at 32 weeks of gestation, 8 weeks after birth, and 12 months after birth. We assessed perinatal depressive symptoms for every pregnancy with the Edinburgh Postnatal Depression Scale (EPDS).26 The EPDS is a ten-item rating scale with high internal consistency, designed for postnatal depression screening but validated for antenatal use.26 Scores on the EPDS range from 0 to 30; we used a threshold of 10 or more to define perinatal depression. This cutoff generally indicates minor depression in English-speaking women with a pencil and paper format,27,28 but on telephone interview it has been judged the optimum point at which to identify depressive disorder assessed on a structured psychiatric interview.29 We also categorised the persistence of perinatal depressive symptoms for every pregnancy in the perinatal period—ie, a score on the EPDS of 10 or more at no or one perinatal assessment point or at two or three assessment points. Every participant’s pregnancy history was recorded in VAHCS during young adulthood (waves 7–9), including previous full-term pregnancies, miscarriages, terminations, and stillbirths. We also recorded pregnancy history at the first perinatal assessment for every pregnancy.

Statistical analysis We estimated the frequency of preconception exposures for every woman, using data for their first pregnancy (to avoid double counting in case of multiple pregnancies). For every pregnancy in our study, we estimated mean EPDS scores and the frequency of perinatal depressive symptoms. We used multilevel models to investigate the association between preconception disorders and perinatal mental health and to accommodate data structured hierarchically.30 For models examining perinatal depressive symptoms at every perinatal assessment, we used a three-level variance structure with repeated

assessment measures nested within pregnancy and pregnancies nested within women. For models assessing the persistence of perinatal mental disorders for every pregnancy, we used a two-level variance structure with pregnancies nested within women. We used linear multilevel models with random intercepts for continuous measures of perinatal depression and logistic multilevel models with random intercepts for binary measures. Initially, we adjusted models for perinatal assessment point only (partial adjustment); in subsequent models we also adjusted for parental divorce or separation, pregnancy history, and adolescent risky behaviours. We estimated marginal means and probabilities from the fully adjusted models at the mean values of the covariates. We used multiple imputation to handle incomplete data. We obtained all proportions and model parameter estimates by averaging results across 20 imputed datasets (appendix p 1),31 with inferences under multiple imputation obtained using Rubin’s rules.32 We calculated frequency estimates with imputed percentage estimates and total number of female participants or pregnancies. We assessed two-way interactions between perinatal assessment point, persistence of disorder, and parity in fully adjusted models, but these were not retained in final models. We assessed all main effects and interactions using p values from Wald tests. We did sensitivity analyses with available case data from the current study for women who had complete VAHCS data at waves 2–9. We analysed data with Stata version 13.

See Online for appendix

Role of the funding source The funding sources had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all data in the study and had responsibility for the final decision to submit for publication.

Results Between November, 2006, and July, 2013, women were screened for participation in VIHCS. Of 1000 young women who had participated in VAHCS at least once during adolescence, 872 (87%) were still active in VAHCS and were eligible for our study (figure 2). Of 128 women who were no longer active in VAHCS at wave 9, two had died, 87 declined to participate further, and 39 were lost to follow-up. Baseline measurements gathered at the first assessment did not differ between women still active in VAHCS and those no longer involved (appendix pp 2–3), with the exception of place of birth, with women not born in Australia less likely to remain active in VAHCS by wave 9 (odds ratio 3·5, 95% CI 2·1–5·8; p

Prediction of perinatal depression from adolescence and before conception (VIHCS): 20-year prospective cohort study.

Perinatal depression is a neglected global health priority, affecting 10-15% of women in high-income countries and a greater proportion in low-income ...
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