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Golding and Thomas G. O'Connor
Emma Robertson Blackmore, Denise Côté-Arsenault, Wan Tang, Vivette Glover, Jonathan Evans, Jean
Previous prenatal loss as a predictor of perinatal depression and
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The Royal College of PsychiatristsPublished by
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Pregnancy loss associated with miscarriage or stillbirth is
common, affecting more than an estimated 1 million women in
the USA and 70000–90000 women in the UK each year.1Between
14 and 20% of clinically recognised pregnancies end in
miscarriage,2defined as the loss of an intrauterine pregnancy from
natural causes before the 24th (in the UK) or 20th (in the USA)
week of pregnancy. Stillbirth, or the loss of a pregnancy prior to
delivery after the 20th week (USA) or 24th week (UK) of gestation
due to natural causes, is estimated to occur in nearly 1 in 200
significantly elevated levels of depression and anxiety in the weeks
and months following the loss, compared with samples of
pregnant, community or postpartum women.5–10Between 50
and 80% of women who experience prenatal loss become pregnant
again.11–14That is significant because women with a history of
prenatal loss are consistently reported to exhibit significantly
elevated rates of anxiety and depressive symptoms during a
subsequent pregnancy.14–18What is not clear from existing studies
of the impact of prenatal loss is whether or not symptoms
associated with a previous loss persist beyond the birth of a
subsequent (healthy) child (see also Hughes et al,14Armstrong
et al,18Hunfeld et al19). That is, does the birth of a healthy baby
resolve the affective symptoms associated with previous loss or
do the symptoms persist? Prior research has been unable to answer
this important question because of limited follow-up periods,
small sample sizes, selection biases, lack of control groups and lack
of data on subsequent birth outcomes that may alter postnatal
adjustment. The current study capitalised on a large community
sample (Avon Longitudinal Study of Parents and Children
(ALSPAC)) that had several research design advantages that
allowed us to differentiate between two competing hypotheses
with substantial clinical and public health significance: a history
of prenatal loss would be associated with elevated depressive
and anxiety symptoms that would be limited to the prenatal
period, i.e. the birth of a healthy child would resolve the impact
of the previous loss; and a history of prenatal loss would have a
persisting effect on depressive and anxiety symptoms that
extended beyond the birth of a subsequent healthy child.
Data for this study were obtained as part of ALSPAC, an ongoing
population-based study designed to investigate the effects of a
wide range of influences on the health and development of
Pregnant women residing in the Avon area of south-west England
who had an estimated date of delivery between 1 April 1991 and
31 December 1992, were invited to participate in the study. It was
estimated that 85–90% of the eligible population participated.20
All data used for this study were collected via postal question-
naires. The study cohort consisted of 14541 pregnancies and
13998 children who were still alive at 12 months of age. The study
protocol has been published previously,20and further details can
be found at: www.bris.ac.uk/alspac. Ethical approval for all
measures was obtained from the ALSPAC Ethics and Law
Committee and from local research ethics committees. The
current study focuses on the 13133 women for whom we had data
on previous prenatal loss. The data for the current study are based
on six assessments, two during pregnancy at 18 and 32 weeks’
Previous prenatal loss as a predictor of perinatal
depression and anxiety
Emma Robertson Blackmore, Denise Co ˆte ´-Arsenault, Wan Tang, Vivette Glover, Jonathan Evans,
Jean Golding and Thomas G. O’Connor
Prenatal loss, the death of a fetus/child through miscarriage
or stillbirth, is associated with significant depression and
anxiety, particularly in a subsequent pregnancy.
This study examined the degree to which symptoms of
depression and anxiety associated with a previous loss
persisted following a subsequent successful pregnancy.
Data were derived from the Avon Longitudinal Study of
Parents and Children cohort, a longitudinal cohort study in
the west of England that has followed mothers from
pregnancy into the postnatal period. A total of 13133
mothers reported on the number and conditions of previous
perinatal losses and provided self-report measures of
depression and anxiety at 18 and 32 weeks’ gestation and at
8 weeks and 8, 21 and 33 months postnatally. Controls for
pregnancy outcome and obstetric and psychosocial factors
Generalised estimating equations indicated that the number
of previous miscarriages/stillbirths significantly predicted
symptoms of depression (b=0.18, s.e.=0.07, P50.01) and
anxiety (b=0.14, s.e.=0.05, P50.01) in a subsequent
pregnancy, independent of key psychosocial and obstetric
factors. This association remained constant across the pre-
and postnatal period, indicating that the impact of a previous
prenatal loss did not diminish significantly following the birth
of a healthy child.
Depression and anxiety associated with a previous prenatal
loss shows a persisting pattern that continues after the birth
of a subsequent (healthy) child. Interventions targeting
women with previous prenatal loss may improve the health
outcomes of women and their children.
Declaration of interest
The British Journal of Psychiatry (2011)
198, 373–378. doi: 10.1192/bjp.bp.110.083105
gestation, and four in the postpartum period, at 8 weeks and 8, 21
and 33 months.
At the assessment at 18 weeks’ gestation, respondents were asked
to report the number of previous miscarriages and the number of
previous stillbirths that they had experienced. Although the terms
‘miscarriage’ and ‘stillbirth’ were not explicitly defined, in the UK
a stillbirth certificate is issued where there was a prenatal death
after 24 weeks’ gestation; accordingly, respondents who did
experience a stillbirth would have had that document to designate
formally a stillbirth. We also collected data on the number of
previous elective terminations; these were counted separately.
Maternal anxiety at each occasion was measured using the anxiety
items from the Crown–Crisp Experiential Index (CCEI), a
validated self-rating inventory.21It has been shown to correlate
with the State (0.70) and Trait (0.76) subscales of the Spielberger
State–Trait Anxiety Inventory.22There is no established clinical
cut-off, and so for categorical analyses we defined a mother as
anxious if she scored in the top 15% of the sample.
Depression Scale (EPDS), a 10-item self-report questionnaire that
has been extensively used and shown to be valid in and outside the
postnatal period.23A cut-off score of 512 is recommended to
identify cases of probable major depression.24
A series of covariates were chosen because of their known links
with depression and/or anxiety or because they were thought
a priori to be a possible confound linking prenatal loss and
depressive and anxiety symptoms. Specific covariates included
maternal age at initial interview, currently living with husband
or partner, number of living children, education level, ethnicity
and use of tobacco and alcohol during the first 3 months of the
pregnancy. Respondents were also asked ‘Have you ever had a
severe depression?’ Those who answered ‘yes, in the past not
now’ were classified as having a previous depressive episode. Birth
weight was used as an indicator of healthy birth outcome; we
dichotomised weight into 42500g or 42500g representing low
or normal birth weight. Gestational age at birth was dichotomised
into 532 weeks or 432 weeks. A household crowding index was
ascertained, which represents the number of residents per room. A
high crowding index score is well established as an indicator of
low socioeconomic status, a highly stressful situation, and is
associated with high morbidity and mortality risks in a range of
Generalised estimating equations (or GEE) is a method used for
longitudinal data modelling. This method is semi-parametric
and therefore does not require normal distribution assumptions
to be met. Given that depression and anxiety can be treated as
discrete or continuous data they do not meet normality
assumptions for parametric data analysis. The GEE was performed
to model the change of depression and anxiety over time. A
backward elimination procedure was applied to control covariates
and interactions. It should be noted that there were a significant
number of missing values for depression and anxiety, especially
for the last two visits. Specifically, sample sizes at the six visits were
12121, 12096, 11710, 11195, 10259 and 9683. The impact of
missing data was characterised by model estimates through two
well-established missing data mechanisms: the missing completely
at random assumption and the missing at random assumption.26
The missing completely at random assumption was tested by
modelling the missingness as a function of observed responses
and baseline covariates using logistic regression. It was found that
depression at previous visit was a strong predictor, thus the
missing completely at random assumption is inappropriate and
weighted generalised estimating equations (WGEE) were used
with weights estimated from the logistic model for missing data.26
Online Table DS1 provides descriptive data on the sample. The
majority (n=10310, 79%) of women reported no miscarriages.
Rates of previous stillbirths were low, with n=106 (0.8%)
reporting one and just three women reporting two prior stillbirths.
The first analysis examined whether stillbirths predicted
subsequent depressive and anxiety symptoms more strongly than
miscarriage. The non-parametric Wilcoxon rank sum test was
applied to each visit to check whether there was any difference
in depression and anxiety symptom scores between mothers
who experienced a previous miscarriage and mothers who
experienced a previous stillbirth. Results indicated that the
difference between stillbirth and miscarriage was not significant
(P=0.27). Thus, stillbirth and miscarriage were combined in the
Figure 1(a) and (b) present the mean (95% CI) scores of
depressive and anxiety symptoms across the assessment period
according to the number of previous losses (miscarriages and
Table 1 presents results from the GEE model. Results indicate
that, as expected, many of the psychosocial and sociodemographic
covariates were associated with depressive and anxiety symptom
scores. In addition, there was a significant prediction from the
number of prenatal losses for both depressive and anxiety
symptom scores. The magnitude of the effect was moderate: for
each additional prenatal loss there was a corresponding increase
of approximately one-quarter of a standard deviation in mood
symptoms. Analyses to test the hypothesis that previous prenatal
loss was a stronger predictor for pre- than postnatal assessments
was carried out using an interaction between time of assessment
and prenatal loss. For neither depressive nor anxiety symptoms
was there an interaction between time of assessment and prenatal
loss; that is, the association between prenatal loss and depressive
and anxiety symptoms was not significantly different across the
pre- and postnatal assessments (the interactions are not included
in the final models in Table 1).
Table 2 shows the percentage and number of women who
scored greater than 12 on the EPDS, which is indicative of a case
of probable major depression, grouped by the number of losses.
Analyses were re-run using categorical cut-off scores for
depression and anxiety rather than a continuous scale. We found
substantively comparable results using this alternate scaling. Given
the overlap between depressive and anxious symptoms across the
reproductive period, a final set of regression analyses (not
reported; details available from the author) was carried out to
investigate whether the effect of prenatal loss on anxious
Robertson Blackmore et al
Prenatal loss and depression and anxiety
symptoms was distinguishable from that for depressive symptoms
and vice versa. It was not. The association between prenatal
loss and anxious symptoms was confounded by the association
between prenatal loss and depressive symptoms and the high
degree of covariation between anxious and depressive symptoms
(4r=0.70 at each assessment).
We found no evidence that affective symptoms associated with
previous prenatal loss resolve with the birth of a healthy child.
Rather, previous prenatal loss showed a persisting prediction
of depressive and anxiety symptoms well after what would
conventionally be defined as the postnatal period. There were
changes over time in the perinatal period in depression and
anxiety, but these did not vary significantly for women with
different histories of prenatal loss. The predictions of anxious
and depressive symptoms were similar and inseparable, the
result of comparable effect sizes and the high degree of overlap
between the two dimensions. Previous studies had documented
that women who had experienced miscarriage or stillbirth had
significantly higher levels of anxiety and depression in a
subsequent pregnancy.5,9,6,27The current study extends this
work by showing that the impact persists well past the
subsequent pregnancy and despite the birth of a healthy child
(indexed here by birth weight and gestational age of the
Findings from other studies
Our findings of prolonged and elevated depressive and anxious
symptoms in women with a prior prenatal loss nearly 3 years after
the birth of a subsequent child contrast with some previous
studies. Hughes et al14found that, compared with controls,
women who were pregnant subsequent to a stillbirth had
significantly higher levels of depression and state anxiety during
pregnancy, but did not differ from controls at 6 and 26 weeks
postpartum. Interestingly, the subset of women who conceived less
than a year following the stillbirth had significantly higher
depression and anxiety scores across all time points than women
who conceived after a year. The possibility that time since previous
prenatal loss moderates the persisting impact of distress could not
be examined in this study because we did not have reliable
information on the timing of the previous loss. It may be that a
more recent loss is associated with higher levels of affective
symptoms that continue in the postpartum period, perhaps as a
function of bereavement.6,14
Although Armstrong et al18also reported that depressive and
anxious symptoms during pregnancy decreased following the
birth of a healthy child, they noted that mothers with higher levels
18 weeks 32 weeks2 months 8 months 21 months
18 weeks32 weeks 2 months8 months21 months
prenatal losses (miscarriages + stillbirths).
Mean (95% CI) of (a) depression and (b) anxiety symptom scores throughout the perinatal period according to number of previous
Numbers of participants are as follows: zero losses, n=10250; one, n=2158; two, n=515; three, n=131; and four or more, n=79.
Robertson Blackmore et al
of depression and anxiety in the postpartum period reported
increased concerns about their investment in and health concerns
about their infant. This raises the important issue of how and
whether previous perinatal loss and associated mood symptoms
may alter child outcomes. Limited available data suggest that
mothers may have more concerns about and greater difficulty
managing the needs of a child born after a prenatal loss;19,28also,
12-month-old infants born following prenatal loss were reported
to show higher rates of disorganised attachment patterns to their
mothers than children born into families without a loss history.
Thus, even if there is no persistence of mood disturbance into the
postnatal period, there may still be adverse effects of a previous
prenatal loss on the parent–child relationship and child outcomes.
This possibility requires further attention.
Brockington31has argued that pregnancy and childbirth
should be seen as a general stressor, like any other life event
that can potentially trigger an affective illness episode.32The
current findings underscore the view that pregnancy and
childbirth are major life events, a careful assessment of which
may reveal information of value in understanding psychiatric
There are important clinical implications of this work. Currently,
prenatal loss is not routinely considered a risk factor for antenatal
or postpartum depression in the same way as, for instance,
personal or family history of depression, exposure to stressful life
events or lack of social support. Our findings suggest that
routinely assessing loss history, which could be accomplished
briefly and without some of the report bias that accompanies
other assessments, would be valuable as a predictor of current
Regression analyses predicting depression and anxiety symptoms from previous prenatal losses and covariates
s.e. 95% CI
Tobacco smoked in first 3 months of pregnancy
0.46 to 0.91
0.00 to 0.00
0.31 to 0.63
0.00 to 0.00
Previously experienced depression
2.80 to 3.54
0.00 to 0.00
2.39 to 2.91
0.00 to 0.00
Alcohol consumption in the first 3 months of pregnancy
<1 glass per week
1+ glass per week
172 glasses per day
3+ glasses per day
0.00 to 0.00
0.10 to 0.45
0.16 to 0.66
0.16 to 1.73
1.64 to 6.59
0.00 to 0.00
0.05 to 0.37
0.07 to 0.44
0.25 to 1.32
0.99 to 4.43
Crowding index0.290.060.17 to 0.41
50.00010.210.040.12 to 0.29
70.06 to 70.02
70.04 to 70.010.0012
Number of living children0.180.06 0.06 to 0.30
70.03 to 0.140.18
Currently living with partner
0.00 to 0.00
0.43 to 0.89
70.16 to 1.22
0.57 to 3.83
0.00 to 0.00
0.36 to 0.70
70.24 to 0.75
0.35 to 2.30
Maternal level of education
70.11 to 0.030.310.05 0.020.00 to 0.10 0.05
Number of perinatal losses0.180.070.03 to 0.32 0.010.14 0.050.03 to 0.24
18 weeks’ gestation
32 weeks’ gestation
2 months postnatal
8 months postnatal
21 months postnatal
33 months postnatal
0.00 to 0.00
0.01 to 0.18
70.93 to 70.72
71.55 to 71.34
71.20 to 70.96
70.70 to 70.44
0.00 to 0.00
0.15 to 0.27
71.53 to 71.39
71.29 to 71.14
71.11 to 70.95
70.23 to 70.04
Birth weight (for the current pregnancy)
0.06 to 1.08
0.00 to 0.00
0.03 to 0.76
0.00 to 0.00
Participants with an Edinburgh Postnatal Depression Scale score >12 grouped by number of losses and assessment point
Number of losses, % (n)
Assessment point 01234+
18 weeks’ gestation13.3 (1238) 14.1 (278)19.7 (90)25.2 (30) 23.1 (15)
32 weeks’ gestation 14.2 (1305)15.4 (293)20.3 (90) 22.7 (25)34.4 (22)
2 months postpartum9.3 (819) 11.6 (217)17.0 (74)11.3 (12)21.3 (13)
8 months postpartum8.2 (690)9.8 (174) 12.4 (50)9.7 (10) 17.5 (10)
21 months postpartum9.2 (713) 11.5 (188)12.6 (47) 13.2 (12) 15.1 (8)
33 months postpartum11.9 (876)12.7 (194) 18.6 (66)10.1 (8) 21.3 (10)
Prenatal loss and depression and anxiety
and postpartum risk and as a possible marker for intervention.
Approximately 15% of women experience clinically significant
antenatal depression and anxiety33and so recognition of and
effective treatment for perinatal mood disturbance are of the
utmost importance. Both prenatal depression and anxiety are
among the biggest predictors of postpartum depression,34,35which
in turn has deleterious effects on maternal–child attachment, child
behaviour, and cognitive and neuroendocrine outcomes that
persist into adolescence.36–40Given the adverse outcomes of
persistent maternal depression on both child and family
outcomes, early recognition of symptoms can lead to preventive
interventions to reduce the burden of illness, provide coping
strategies to reduce anxiety and depression and promote healthy
adjustment of the mother, family and child.
Strengths and limitations
Strengths of the study include the large community sample and
detailed and repeated assessments of depressive and anxiety
symptoms in the prenatal and postnatal period; the follow-up well
past the postnatal period is a particular novelty in this area of
study. There are, however, limitations. Participants were asked
about the number of miscarriages and stillbirths experienced
retrospectively, which could be subject to recall bias. However,
the objective nature of the event provides some protection against
this possibility, and the persistence of effect years after the enquiry
about perinatal loss makes a simple recall bias account unlikely.
Self-reports of prenatal loss may be underestimated insofar as
mothers are often unaware of spontaneous early miscarriages.4
Accordingly, the current study is able to assess the psychological
impact of prenatal loss, but is not positioned to examine
biological hypotheses that there may be risk underlying both
prenatal loss and the experience of depressive and anxiety
symptoms. Finally, as noted, we were unable to assess the impact
of time since loss as a potential predictor of postpartum mood.
Emma Robertson Blackmore, PhD, Department of Psychiatry, University of
Rochester Medical Center, New York; Denise Co ˆte ´-Arsenault, PhD, School of
Nursing, University of Rochester Medical Center, New York; Wan Tang, PhD,
Department of Biostatistics and Computational Biology, University of Rochester
Medical Center, New York, USA; Vivette Glover, PhD, Institute of Reproductive and
Developmental Biology, Imperial College School of Medicine, London, UK; Jonathan
Evans, PhD, Academic Unit of Psychiatry, School of Social and Community Medicine,
University of Bristol; Jean Golding, PhD, Centre for Child and Adolescent Health,
University of Bristol, UK; Thomas G. O’Connor, PhD, Department of Psychiatry,
University of Rochester Medical Center, New York, USA
Correspondence: Emma Robertson Blackmore, PhD, University of Rochester
Medical Center, BOX PSYCH 4-9200, 300 Crittenden Blvd, Rochester,
NY 14642–8409, USA. Email: Emma_robertsonblackmore@urmc.rochester.edu
First received 26 May 2010, final revision 13 Oct 2010, accepted 9 Dec 2010
The UK Medical Research Council, the Wellcome Trust and the University of Bristol
currently provide core support for ALSPAC. This particular project was funded in part by
National Institutes of Health (NIH) grants R01 MH073842 and K23 MH080290.
We are extremely grateful to all the families who took part in this study, the midwives for
their help in recruiting them and the whole ALSPAC team, which includes interviewers,
computer and laboratory technicians, clerical workers, research scientists, volunteers,
managers, receptionists and nurses.
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Melancholia in Chaha ˆr Maqa ˆle, a 12th-century Persian text
Little is known about the life of Ahmed ibn ‘Umar ibn ‘Alı ˆ, better known as Niza ˆmı ˆ ‘Aru ˆzı ˆ. The only information resides in his own text
outlining travels throughout Uzbekistan and Afghanistan to collect biographies of famous poets. He reached Iran and became the
court poet of the sultan Sanjar in 1116/1117 AD. His monumental Chaha ˆr Maqa ˆle (Four Discourses) addresses the four professions
indispensable for a sound ruler: poet, civil secretary, astrologer and physician. The work entered the literary canon within the
Four Discourses is rich in cultural history. For example, ‘Aru ˆzı ˆ lists essential works for the mastery of medicine. Moreover, his
narratives resemble case presentations. Contemporary readers can therefore compare symptoms across time and space.
In one anecdote on melancholia, a person dear to the Buyid ruler ‘Ala ˆ al-Dawla becomes so delusional that he considers himself
a cow. He asks people to kill and eat him even as he fasts. Since no physician could treat him, the ruler entreats his trusted vizier
Ibn Sı ˆna (Avicenna), who dispatches two men with word of a butcher’s arrival. The young man rejoices. As they bind his limbs,
Ibn Sı ˆna inspects him like a butcher, but protests that he is too thin for slaughter. Ibn Sı ˆna orders specific foods and medicines
to fatten him up. The young man cheerfully obliges. Ibn Sı ˆna continues to consult and within a month the man’s health returns.
Notable lessons can be drawn from this anecdote. Like today, one millennium ago physicians struggled to manage psychotic
depression. Ibn Sı ˆna’s status as minister also reveals the historical esteem of physicians. Finally, physicians working within the
patient’s psychological world tend to succeed, even through unorthodox means. This helps explain Ibn Sı ˆna’s lasting reputation.
The British Journal of Psychiatry (2011)
198, 378. doi: 10.1192/bjp.198.5.378