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Summary
Background Perinatal depression is a neglected global health priority, aecting 1015% of women in high-income Lancet 2015; 386: 87583
countries and a greater proportion in low-income countries. Outcomes for children include cognitive, behavioural, Published Online
and emotional diculties and, in low-income settings, perinatal depression is associated with stunting and physical June 11, 2015
http://dx.doi.org/10.1016/
illness. In the Victorian Intergenerational Health Cohort Study (VIHCS), we aimed to assess the extent to which
S0140-6736(14)62248-0
women with perinatal depressive symptoms had a history of mental health problems before conception.
This online publication has been
corrected. The corrected version
Methods VIHCS is a follow-up study of participants in the Victorian Adolescent Health Cohort Study (VAHCS), which rst appeared at thelancet.com
was initiated in August, 1992, in the state of Victoria, Australia. In VAHCS, participants were assessed for health on August 28, 2015
outcomes at nine timepoints (waves) from age 14 years to age 29 years. Depressive symptoms were measured with the See Comment page 835
Revised Clinical Interview Schedule and the General Health Questionnaire. Enrolment to VIHCS began in Centre for Adolescent Health,
September, 2006, during the ninth wave of VAHCS; depressive symptoms at this timepoint were measured with the Murdoch Childrens Research
Institute, University of
Composite International Diagnostic Interview. We contacted women every 6 months (from age 29 years to age 35 years) Melbourne, Royal Childrens
to identify any pregnancies. We assessed perinatal depressive symptoms with the Edinburgh Postnatal Depression Hospital Melbourne, Parkville,
Scale (EPDS) by computer-assisted telephone interview at 32 weeks of gestation, 8 weeks after birth, and 12 months VIC, Australia
after birth. We dened perinatal depression as an EPDS score of 10 or more. (Prof G C Patton MD, E Spry BA,
H Romaniuk PhD, C Coey PhD,
S Hearps BPsych); Clinical
Findings From a stratied random sample of 1000 female participants in VAHCS, we enrolled 384 women with Epidemiology and
564 pregnancies. 253 (66%) of these women had a previous history of mental health problems at some point in adolescence Biostatistics Unit, Murdoch
or young adulthood. 117 women with a history of mental health problems in both adolescence and young adulthood had Childrens Research Institute,
and Department of
168 pregnancies, and perinatal depressive symptoms were reported for 57 (34%) of these pregnancies, compared with Paediatrics, University of
16 (8%) of 201 pregnancies in 131 women with no preconception history of mental health problems (adjusted odds ratio Melbourne, Royal Childrens
836, 95% CI 3342087). Perinatal depressive symptoms were reported at one or more assessment points in Hospital Melbourne, Parkville,
VIC, Australia
109 pregnancies; a preconception history of mental health problems was reported in 93 (85%) of these pregnancies.
(Prof J B Carlin PhD,
H Romaniuk); Psychological
Interpretation Perinatal depressive symptoms are mostly preceded by mental health problems that begin before Sciences and Paediatrics,
pregnancy, in adolescence or young adulthood. Women with a history of persisting common mental disorders before Murdoch Childrens Research
Institute, University of
pregnancy are an identiable high-risk group, deserving of clinical support throughout the childbearing years.
Melbourne, Parkville, VIC,
Furthermore, the window for considering preventive intervention for perinatal depression should extend to the time Australia (Prof C Olsson PhD);
before conception. Centre for Social and Early
Emotional Development,
School of Psychology, Deakin
Funding National Health and Medical Research Council (Australia), Victorian Health Promotion Foundation, Colonial
University, Geelong, VIC,
Foundation, Australian Rotary Health Research and Perpetual Trustees. Australia (Prof C Olsson); Royal
Womens Hospital and
Introduction symptom prole,9 a particular endocrine sensitivity,10 and Murdoch Childrens Research
Institute, University of
Despite being one of the most common complications of a better prognosis than aective disorders diagnosed
Melbourne, Parkville, VIC,
pregnancy, perinatal depression remains a neglected global outside of pregnancy.8 In the past two decades, views have Australia (Prof L W Doyle MD);
health priority.1 In high-income countries, this disorder shifted. Depressive symptoms are recognised as common Department of Obstetrics and
aects 1015% of women2,3 and can have physical, cognitive, during pregnancy and, in turn, predictive of postnatal Gynaecology, University of
Melbourne, Melbourne, VIC,
and emotional eects on their childrens development, depression.11,12 Perinatal depression is now commonly Australia (Prof L W Doyle);
continuing into later life.4 Both antenatal and postnatal used to encompass syndromes that emerge either during School of Population and
depressive symptoms have been associated with poor early pregnancy or after birth.13 Mental disorders before Global Health, University of
child health and development.5 In low-income and middle- pregnancy are also recognised as an important risk factor Melbourne, Melbourne, VIC,
Australia (Prof J Oats DM); and
income countries, estimates of prevalence vary from 15% for perinatal depression.8,1416 In a study of more than Healthy Mothers Healthy
to 50%.1 In these settings, associations extend to a failure to 1000 Italian women, in which perinatal depression was Families Research Group,
thrive in utero, childhood stunting, and childhood physical recorded from 3 months of gestation, 30% of women Murdoch Childrens Research
illness, with antenatal depressive symptoms also linked to with an incident perinatal episode reported a history of Institute, and General Practice
and Primary Health Care
preterm birth and low birthweight.3,6,7 depression.17 Yet, retrospective identication of episodes Academic Centre, University of
Postnatal depression was long held to be a discrete before pregnancy could lead to underestimates of earlier Melbourne, Parkville, VIC,
syndrome arising without previous history,8 with a unique mental disorder.18 Australia (S Brown PhD)
2 entry points
Adolescent risky behaviours were also measured in assessment measures nested within pregnancy and
VAHCS.19 Cigarette smoking was recorded with a pregnancies nested within women. For models assessing
self-report diary over the previous 7 days; daily smokers the persistence of perinatal mental disorders for every
were classied as those smoking on 6 or 7 days in the pregnancy, we used a two-level variance structure with
previous week. Risky alcohol use was assessed over a pregnancies nested within women. We used linear
period of 1 week in a beverage-specic and quantity- multilevel models with random intercepts for continuous
specic self-report diary; drinking ve or more standard measures of perinatal depression and logistic multilevel
drinks (one standard drink being equal to 10 g alcohol) models with random intercepts for binary measures.
on any day was dened as binge drinking, the most Initially, we adjusted models for perinatal assessment
common form of alcohol misuse in adolescents. point only (partial adjustment); in subsequent models
Participants who reported cannabis use at least once a we also adjusted for parental divorce or separation,
week were also identied by self-report. Antisocial pregnancy history, and adolescent risky behaviours.
behaviour during adolescence was measured with We estimated marginal means and probabilities from the
ten items on the Mott and Silva self-report early fully adjusted models at the mean values of the covariates.
delinquency scale25 relating to property damage, We used multiple imputation to handle incomplete data.
interpersonal conict, and theft in the previous 6 months. We obtained all proportions and model parameter
Antisocial behaviour was dened if one behaviour was estimates by averaging results across 20 imputed datasets
reported more than once or two dierent behaviours (appendix p 1),31 with inferences under multiple imputation See Online for appendix
were noted at least once. obtained using Rubins rules.32 We calculated frequency
We asked participants to complete computer-assisted estimates with imputed percentage estimates and
telephone interviews at three perinatal assessment total number of female participants or pregnancies.
points: at 32 weeks of gestation, 8 weeks after birth, and We assessed two-way interactions between perinatal
12 months after birth. We assessed perinatal depressive assessment point, persistence of disorder, and parity in
symptoms for every pregnancy with the Edinburgh fully adjusted models, but these were not retained in
Postnatal Depression Scale (EPDS).26 The EPDS is a nal models. We assessed all main eects and interactions
ten-item rating scale with high internal consistency, using p values from Wald tests. We did sensitivity analyses
designed for postnatal depression screening but validated with available case data from the current study for women
for antenatal use.26 Scores on the EPDS range from who had complete VAHCS data at waves 29. We analysed
0 to 30; we used a threshold of 10 or more to dene data with Stata version 13.
perinatal depression. This cuto generally indicates
minor depression in English-speaking women with a Role of the funding source
pencil and paper format,27,28 but on telephone interview The funding sources had no role in study design, data
it has been judged the optimum point at which to collection, data analysis, data interpretation, or writing of
identify depressive disorder assessed on a structured the report. The corresponding author had full access to
psychiatric interview.29 We also categorised the persis- all data in the study and had responsibility for the nal
tence of perinatal depressive symptoms for every decision to submit for publication.
pregnancy in the perinatal periodie, a score on the
EPDS of 10 or more at no or one perinatal assessment Results
point or at two or three assessment points. Between November, 2006, and July, 2013, women were
Every participants pregnancy history was recorded in screened for participation in VIHCS. Of 1000 young
VAHCS during young adulthood (waves 79), including women who had participated in VAHCS at least once
previous full-term pregnancies, miscarriages, termin- during adolescence, 872 (87%) were still active in
ations, and stillbirths. We also recorded pregnancy history VAHCS and were eligible for our study (gure 2).
at the rst perinatal assessment for every pregnancy. Of 128 women who were no longer active in VAHCS at
wave 9, two had died, 87 declined to participate further,
Statistical analysis and 39 were lost to follow-up. Baseline measurements
We estimated the frequency of preconception exposures gathered at the rst assessment did not dier between
for every woman, using data for their rst pregnancy (to women still active in VAHCS and those no longer
avoid double counting in case of multiple pregnancies). involved (appendix pp 23), with the exception of place of
For every pregnancy in our study, we estimated mean birth, with women not born in Australia less likely to
EPDS scores and the frequency of perinatal depressive remain active in VAHCS by wave 9 (odds ratio 35,
symptoms. We used multilevel models to investigate 95% CI 2158; p<00001).
the association between preconception disorders and Of the 872 women eligible for our study, 466 (53%)
perinatal mental health and to accommodate data reported 744 pregnancies during the study window
structured hierarchically.30 For models examining perinatal (median follow-up 63 years, IQR 5970). 12 infants
depressive symptoms at every perinatal assessment, we died in utero before 32 weeks of gestation, resulting in
used a three-level variance structure with repeated 732 livebirths to 465 women, similar to the expected
birth rate in Victoria by maternal age for the active points. The 67 women who did not participate in our
female sample (724 expected births).33 398 (86%) of study had a higher prevalence of depressive symptoms at
465 women who had 600 (82%) of 732 eligible pregnan- waves 7 and 9, and of anxiety at wave 9 (appendix pp 46).
cies participated at one or more perinatal assessment Furthermore, compared with those who did take part in
our study, these women were more likely to be born
outside Australia and to have used cannabis more often
1000 participants in VAHCS as a young adult.
128 no longer active in VAHCS 36 pregnancies were conceived around the time of the
87 declined
39 lost to follow-up
wave 9 VAHCS interview, and these were excluded from
2 died our analysis to clearly distinguish VAHCS wave 9 mental
872 screened for VIHCS entry health measures from perinatal mental health measures,
resulting in an analysis sample of 384 women and
406 ineligible (not pregnant)
564 pregnancies. Of women in the analysis sample,
Recruitment
466 woman had 744 pregnancies 256 (67%) had not had a previous child and 128 (33%)
had had a previous pregnancy resulting in a livebirth.
12 pregnancies were ineligible (death in utero)*
289 women with 388 pregnancies at Alcohol misuse 135 35% (3040)
32 weeks of gestation
Daily cigarette smoking 84 22% (1826)
347 women with 499 pregnancies at
8 weeks after birth Regular cannabis use 28 7% (510)
368 women with 526 pregnancies at Young adulthood
12 months after birth
Persistence of mental health problems
No waves 211 55% (5060)
32 weeks of gestation
306 women with 414 pregnancies were assessed One wave 109 28% (2433)
128 pregnancies identified after eligibility
window Two or more waves 64 17% (1321)
24 pregnancies, mother was too busy Mental health problems, by wave
34 pregnancies, unable to contact mother
Wave 7* 71 18% (1422)
Wave 8 90 23% (1928)
1 pregnancy lost to follow-up Wave 9 44 12% (815)
8 weeks after birth
5 pregnancies lost to follow-up (3 women Both adolescent and young adult 117 30% (2635)
withdrew consent) disorder
382 women with 560 pregnancies were assessed Estimates were obtained from imputed data for the rst child included in VIHCS.
12 pregnancies, mother was too busy Frequency estimates were calculated from imputed percentage estimates and
22 pregnancies, unable to contact mother total number of participants. CIS-R=Revised Clinical Interview Schedule.
GHQ=12-item General Health Questionnaire. CIDI=Composite International
Diagnostic Interview. *Mean age 207 years; mental health problems dened as
Figure 2: Sampling and ascertainment of pregnancies during the study period
CIS-R score 12. Mean age 241 years. Mental health problems dened as GHQ
Participants were recruited from the VAHCS population and screened for eligibility in VIHCS. VAHCS=Victorian
score 3. Mean age 291 years. Dened with CIDI.
Adolescent Health Cohort Study. VIHCS=Victorian Intergenerational Health Cohort Study. *128 pregnancies were
excluded, 12 because of death in utero, 79 because the pregnancy was reported retrospectively, and 37 because Table 1: Common mental disorders and health risks in adolescence and
consent was not given. Of these exclusions, 60 women were retained in VIHCS because of another pregnancy. young adulthood before conception in women with at least
36 pregnancies excluded from the analysis sample because the wave 9 assessment took place around the one pregnancy during the study period
estimated point of conception.
Of these 128 women, 82 had one previous livebirth, two-thirds of all participants reported a mental health
40 had two previous livebirths, four had three previous problem either during adolescence or young adulthood.19
livebirths, and two women had ve and six previous Table 2 shows data for depressive symptoms reported
livebirths each. On average, participants were 32 years during the three perinatal assessments. Of 256 primi-
old when their rst child included in VIHCS was born parous mothers, 56 (22%, 95% CI 1627) reported
(SD 2; range 2936). depressive symptoms at any perinatal assessment and
Table 1 shows data for preconception mental health 20 (8%, 411) had signs of depression or anxiety at two or
disorders and health risks in the 384 women included in three assessments. In the 265 multiparous women with
the analysis sample. 80 women (21%, 95% CI 1625) 308 second and subsequent pregnancies, depressive
reported an adolescent disorder only, 56 (15%, 1118) had symptoms were reported during 53 (17%, 1222)
a young adult disorder only, and 117 (30%, 2635) had pregnancies at any perinatal assessment and during
both an adolescent and young adult disorder. Overall, 14 (5%, 27) pregnancies at two or three assessments.
Data are either number of pregnancies (% [95% CI]) or mean (SD [95% CI]). Frequency estimates were calculated from imputed percentage estimate and total number of
pregnancies. Perinatal depressive symptoms dened as an EPDS score 10. Perinatal period was from 32 weeks of gestation to 8 weeks after birth. Antenatal assessment was
at 32 weeks of gestation. Postnatal assessments were at 8 weeks and 12 months after birth. EPDS=Edinburgh Postnatal Depression Scale.
Data are number of pregnancies (% [95% CI]). Frequency estimates were calculated with imputed percentage estimate and total number of pregnancies. Perinatal depressive
symptoms dened as an EPDS score 10. Perinatal period was from 32 weeks of gestation to 8 weeks after birth. Antenatal assessment was at 32 weeks of gestation.
Postnatal assessments were at 8 weeks and 12 months after birth. EPDS=Edinburgh Postnatal Depression Scale.
Mean
13 pregnancies among women with no history of 45
depressive symptoms before conception. By comparison, 40
35
women with mental health problems persisting from
30
adolescence to young adulthood reported depressive
25
symptoms in more than one in three pregnancies.
In total, a history of mental health problems before 0
conception was noted in 85% of pregnancies in which
High perinatal depressive symptoms
perinatal depressive symptoms were evident. Most 020 No disorder Young adult disorder only
episodes were either a recurrence or continuation of Adolescent disorder only Adolescent and young
mental health problems that began before conception. adult disorder
problems. Figure 3: Continuity of mental health disorders from adolescence and young adulthood to the perinatal
Despite strengths in the prospective design of our period in 564 pregnancies of 384 participants
study and multiple points of assessment across (Upper) Estimated mean EPDS scores across adolescence and young adulthood. Error bars show 95% CI. (Lower)
Probability of depressive symptoms continuing from adolescence and young adulthood to the perinatal period.
adolescence and young adulthood in VAHCS, we might
Perinatal depressive symptoms dened as a score 10 on the EPDS. EPDS=Edinburgh Postnatal Depression Scale.
still have missed some earlier cases of depressive
disorder. Adolescent assessments focused on the Error in outcome measurement is a further potential
previous 7 days, potentially missing brief episodes that limitation. The EPDS is the most widely used
might have arisen between follow-up assessments. assessment of perinatal depressive symptoms but is
Moreover, assessments in young adulthood also focused likely to capture anxiety symptoms as well.28 Using a
on the period immediately before interview, with the threshold of 10 or more on the EPDS, we recorded
exception of the CIDI assessments at wave 9, which perinatal depression during at least one of the three
covered the previous 12 months. Thus, we might have perinatal assessments in around 20% of pregnancies.
underestimated the prevalence of perinatal depression Although this proportion is similar to those reported in
after earlier mental health problems before conception. meta-analyses of prevalence, the point estimates are
Although overall attrition was low in VIHCS, lower than in most studies using the EPDS in
non-response is a further limitation of our study. 87% community samples.29 Telephone administration of the
of the original sample from VAHCS were still active EPDS seems likely to be one explanation. A threshold of
participants at the start of our study, and they diered 10 or more generally corresponds to minor depression,
from non-responders mainly in the proportion who but by telephone administration, this score is the
were not born in Australia. However, 14% of women optimum cuto point for screening for depressive
who had pregnancies during the study window did not disorder.30 Diminished participation of women with
participate. This group diered from those who did mental health disorders before conception is another
take part not only in being more likely to be born possible contributor to lower prevalence estimates.
outside Australia but also in patterns of cannabis use Finally, women becoming pregnant at this time of life
before conception and, most importantly, previous (mean age 32 years) might have a better mental health
mental health problems. Use of multiple imputation prole than those who are pregnant at a younger or
should have reduced biases arising from missing older age.35 Although such factors might aect the
interviews in all phases of the study but it cannot strength of associations, the persistence of strong
address the dierential response in the perinatal phase associations when perinatal depression was dened
of the study. This drawback might have contributed to either as symptoms persisting across two assessments
some misspecication of associations with disorders or as a continuous variable suggests that our ndings
before pregnancy. are robust.
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