abstract - imperial college london€¦ · web viewthe course of mental health after miscarriage...
TRANSCRIPT
The Psychological Impact of Early Pregnancy Loss
A narrative review of literature assessing for anxiety, depression and post-traumatic stress in
women and/or partners following miscarriage or ectopic pregnancy, with discussion of its
implications for early pregnancy care, and recommendations for future research
Jessica Farren clinical research fellow1,2, Nicola Mitchell-Jones clinical research fellow1,3, Jan Y
Verbakel assistant professor4, 5, Dirk Timmerman professor6, Maria Jalmbrant clinical
psychologist1, Tom Bourne adjunct professor and consultant gynaecologist1,6
Corresponding author: Professor Tom Bourne, Tommy’s National Early Miscarriage Research
Centre, Imperial College, Queen Charlottes and Chelsea Hospital, Du Cane Road, London
W12 0HS, email: [email protected]
orcid ID: https://orcid.org/0000-0003-1421-6059
Co-author affiliations:
1 Tommy’s National Centre for Miscarriage Research, Queen Charlottes and Chelsea
Hospital, Imperial College, London W12 0HS, UK
2 Imperial College Healthcare Trust, London W2 1NY, UK
3 Chelsea and Westminster NHS Trust, London SW10 9NH, UK
4 KU Leuven, ACHG, Department of Public Health and Primary Care, Kapucijnenvoer 33, 3000
Leuven, Belgium
4 University of Oxford, Nuffield Department of Primary Care Health Sciences, Woodstock
Road, Oxford OX2 6GG, UK
5 KU Leuven, Department of Obstetrics and Gynaecology, Herestraat 493000, Leuven,
Belgium
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Abstract
Background: Early pregnancy loss (EPL) is a common event, with scope for long term
personal and societal impact. There are three decades of published evidence of profound
psychological sequelae in a significant proportion of women. However, the wide variety of
outcomes, assessment instruments and timings, and geographical locations, makes forming
a coherent picture of the morbidity within the whole group, and its subgroups, challenging.
Objective and rationale:
The questions this review aims to investigate are:
- What is the evidence for depression, anxiety and post-traumatic stress disorder
(PTSD) following a miscarriage or an ectopic pregnancy in women and/or their
partners?
- What is the intensity and duration of these conditions, and how do they compare to
those without losses?
- Which patients have been found to be at highest risk of psychopathology?
Answers to these questions are salient not only in day-to-day clinical interaction with those
experiencing EPL, in whom psychological needs may not be prioritised, but should also form
the basis for tailoring healthcare policy in terms of screening for, and treating the associated
psychological morbidity.
Search methods: The following databases were searched, from the start of each database up
to July 2017:
MEDLINE (Ovid interface, 1948 onwards),
Embase classic + Embase (Ovid interface, 1947 onwards).
PsychINFO (Ovid interface, 1806 onwards)
Search strategies were developed using medical subject headings (MeSH). The concepts of
psychological morbidity (anxiety, depression or PTSD) and pregnancy loss (miscarriage or
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
ectopic pregnancy) were first expanded with the Boolean operator ‘or’, then linked together
using ‘and’.
Included studies were of prospective cohort design, including women or men following EPL
(with the majority to have experienced losses before 24 weeks gestation), and reported
standardised psychometric measures for anxiety, depression and post-traumatic stress
disorder. The timing of follow-up had to be specified, and standardised across participants.
Manuscript quality and risk of bias was assessed using the Newcastle-Ottawa Scale.
Outcomes: We found evidence of significant depression and anxiety in the first month
following EPL in women. Partners have also been shown to display anxiety and depression,
albeit to a generally lower level. There is also evidence of post-traumatic stress symptoms
relating to the EPL in three studies.
Wider implications: In view of their high frequency, EPLs can significantly contribute to the
overall burden of psychopathology within a population. Recognition of this impact is
important, so that severely affected individuals may be screened and treated appropriately.
Further research to establish risk factors to promptly identify and treat these patients, and
optimize their management, is crucial.
Key words
Miscarriage, Ectopic pregnancy, Depression, Anxiety, Post-traumatic Stress, Psychology
(HR Update Keywords: Abortion, Ectopic Pregnancy, Psychology, Recurrent Miscarriage,
Assisted Reproduction)
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
Table of ContentsAbstract.........................................................................................................................2
Key words......................................................................................................................3
Introduction...................................................................................................................6
Methods........................................................................................................................7
Eligibility criteria...............................................................................................................7
Information sources..........................................................................................................8
Search Strategy.................................................................................................................8
Study selection.................................................................................................................8
Data Collection, Data Items and Summary Measures.......................................................9
Quality Assessment..........................................................................................................9
Risk of bias across studies...............................................................................................10
Strength of recommendations........................................................................................10
Results.........................................................................................................................10
Study selection...............................................................................................................10
Study characteristics.......................................................................................................10
Risk of bias within studies............................................................................................14
Psychological Morbidity: Depression, Anxiety and PTSD...............................................15
Depression......................................................................................................................15
Anxiety............................................................................................................................17
PTSD and traumatic impact............................................................................................18
Correlation between outcomes......................................................................................19
Factors associated with psychological morbidity...........................................................19
Risk of bias across studies.............................................................................................21
Discussion....................................................................................................................22
Summary of evidence.....................................................................................................22
Limitations......................................................................................................................22
Conclusions..................................................................................................................27
6869
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
Authors’ Roles..............................................................................................................27
Acknowledgements......................................................................................................29
Funding........................................................................................................................29
Conflict of interest........................................................................................................29
Bibliography.................................................................................................................30
List of figures and tables...............................................................................................34
96
97
98
99
100
101
102
103
Introduction
Pregnancy loss is a common problem, with miscarriage estimated to affect 25% of women
who have been pregnant by 39 years of age (Blohm, et al., 2008), and ectopic pregnancy
occurring in approximately 1% of pregnancies (Varma and Gupta, 2012). There is scope for
long-term emotional impact (Beutel, et al., 1995). However, historically, this has been
overlooked. Reflecting this, it was little considered in the literature until the 1990s. Early
studies focused on grief, which is not a discrete psychiatric diagnosis and is variably defined
(Janssen, et al., 1997). They were also hampered by variable timings of assessment,
retrospective recruitment, unrepresentative study populations and qualitative data (Cecil
and Leslie, 1993, Harker, 1993, Seibel and Graves, 1980).
However, since then, research in the field has proliferated, with a number of sizable studies
screening for psychiatric diagnoses (anxiety, depression and PTSD) following pregnancy loss
(Cumming, et al., 2007, Engelhard, et al., 2001, Neugebauer, et al., 1992) . These studies have
shown that women appear to be at very significant risk of psychological morbidity following
miscarriage – with up to 41% self-reporting clinically significant levels of anxiety (Prettyman,
et al., 1993), and 36% depression (Neugebauer, et al., 1992), within one month. Thirty-nine
percent of women self-reported meeting criteria for post-traumatic stress disorder (PTSD) at
three months in the author’s own study (Farren, et al., 2016). As an example, an estimated
250 000 miscarriages take place in the UK each year: these figures point to a significant
public health issue. It is clearly essential to understand the natural history of these reactions,
and when treatment may be indicated.
However, hindering overall interpretation of the morbidity reported in these studies is the
diverse nature of recruitment methodologies, assessment tools, timing of assessments, and
comparison groups. Studies have been published across a variety of journals (general,
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
gynaecological, or psychiatric), and over a period of three decades. There is also significant
clinical heterogeneity, with some studies choosing to exclude those with a past psychiatric
history, for example.
We aimed to conduct a narrative review of the existing literature on the psychological
impact of EPLs, focusing on the prevalence, intensity and duration of symptoms of anxiety,
depression and PTSD. We explore the variation in the literature and try to summarize
evidence of predisposing factors – both background and encounter related – for
psychological morbidity. A pertinent question is whether psychopathology is related to
delays to conception and involuntary childlessness, or to the loss itself, which we explore in
the available literature.
Methods
The methods set out below, in accordance with the PRISMA checklist, were specified in
advance and documented in the study protocol. This was registered with PROSPERO
(http://www.crd.york.ac.uk/PROSPERO, registration number CRD42017082754).
Eligibility criteria
Studies were considered eligible if they were of prospective cohort design, involving women
and/or men following a miscarriage or an ectopic pregnancy. Studies including participants
with late losses (>24 weeks) were eligible if the overwhelming majority (>=90%) had
experienced loss within the first 24 weeks of pregnancy.
There is strong evidence that psychopathology declines over time(Beutel, et al., 1995, Cordle
and Prettyman, 1994, Cumming, et al., 2007, Janssen, et al., 1996, Prettyman, et al., 1993) .
Therefore, only studies with set, specified, timings of assessment, standardized across all
participants, were included.
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
In order to comprehensively collate results, only empirical studies using a validated
psychometric measure or interview to define the proportion of the study group meeting
defined criteria for anxiety, depression or PTSD, or to compare to another group (pregnant
women, women after live birth, women after termination, non-pregnant women, partners,
or women who conceived with IVF) were included. Studies reporting on grief alone were
excluded.
Studies with abstracts in languages other than English were excluded.
Information sources
The following databases were used:
MEDLINE (Ovid interface, 1948 onwards),
Embase classic + Embase (Ovid interface, 1947 onwards).
PsychINFO (Ovid interface, 1806 onwards)
This search was limited to the English language, and last updated on 27 July 2017
Search Strategy
Literature search strategies were developed using medical subject headings (MeSH). The
concepts of psychological morbidity (anxiety, depression or PTSD) and pregnancy loss
(miscarriage or ectopic pregnancy) were first expanded with the Boolean operator ‘or’, then
linked together using ‘and’.
Details of the search strategies are included in the supplementary material. The reference
lists of included studies were also scanned to ensure complete literature saturation.
Study selection
Initially, titles and abstracts were screened against the eligibility criteria above. This was
performed independently by two researchers (JF and NMJ). If the article was clearly not
eligible based on the title and/or abstract alone, it was discarded. Otherwise, the full text
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
was reviewed by both researchers independently, and the eligibility criteria again applied.
Disagreements were resolved by consensus.
Data Collection, Data Items and Summary Measures
A spreadsheet was prospectively designed to accommodate the data, piloted on five papers
by two reviewers, and refined. The primary researcher (JF) extracted data into this, which
was then checked by a second reviewer (NMJ). Disagreements were resolved during
research meetings involving two senior researchers (MJ & TB).
Data was extracted on the study population, participation and response rate, and
assessment tools and timing. The proportion of participants reaching pre-defined, reported
thresholds (‘caseness’) for anxiety, depression, PTSD or Acute Stress Disorder (ASD) was
recorded, along with any comparison of measures in the EPL group vs the comparison group
(by absolute scores or caseness), and change over time. Statistically significant (P<0.05) risk
factors for morbidity were extracted into a further table.
Quality Assessment
Studies were assessed according to the Newcastle-Ottawa Quality Assessment Scale (NOAS)
for Cohort Studies (see supplementary material). This was performed by JF and checked by
NMJ, with disagreements resolved through discussion. Where a comparison cohort was not
used, this was documented under the ‘comparability’ section. Where the comparison group
was exposed partners, an assessment was made according to NOAS comparability criteria,
although originally designed for a non-exposed cohort. Stars for comparability were
awarded if the cohorts were controlled for a) parity and b) any additional factor.
The NOAS requirement for assessment of outcome to be blind was omitted given the
dominance of self-report measures and non-controlled studies. Follow-up duration of at
least one month was required for a star to be awarded. Follow-up was considered adequate
if above 75%, (based on clinical consensus among the research team), or if there was
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
comparison of the preceding psychological pathology in those who responded and those
who did not (only possible in studies performing psychological assessment at two time
points).
Risk of bias across studies
To avoid multiple publication bias, where different papers reported on different time points
or types of assessment for the same study group, these were reported in a single tabulated
row entry of the review. For example, Neugebauer’s group published four eligible articles on
the same group of participants (Klier, et al., 2000, Neugebauer, et al., 1992, Neugebauer, et
al., 1992, Neugebauer, et al., 1997). Data from these were reported within one row, as one
entry.
Results
Study selection
As shown in the PRISMA diagram (Figure 1), 109 articles underwent full-text review, and 27
were included in the final review (comprising 21 separate entries in total – 20 quantifying
psychological response, and one with conclusions relating to risk factors only). No relevant
unpublished studies were obtained.
Study characteristics
Baseline characteristics are presented in Table I.
Setting
The twenty-seven included articles were published between December 1989 and December
2016. Seven study groups originated from the UK, four from Hong Kong, two from each of
Germany, the USA and the Netherlands, and one study from each of Sri Lanka, Norway,
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
France and Ireland. One study was published in French (with an English abstract), and the
rest in English.
Participants
Details of participants in each study are provided in Figure 2.
Eight out of 21 study groups had results from less than 100 participants with pregnancy loss.
The smallest study had 22 participants (Daly, et al., 1996), and the largest 626 (Cumming, et
al., 2007)
Only one study included participants following an ectopic pregnancy (Farren, et al., 2016).
Two studies included stillbirth: for one (Engelhard, et al., 2001) the authors provided data
enabling extraction of results for just the EPL group (<24 weeks). In the other, 90% were
before 20 weeks (Janssen, et al., 1996). The remaining studies included cases of miscarriage
only. If described, the mean gestation at time of loss was in the first trimester (when the vast
majority of miscarriages take place).
Comparison groups, where present, were variable: pregnant women, women or partners
after live birth, women after termination, or non-pregnant women (contacted via random
digit telephoning, or when looking for contraceptive advice).
In studies of women alone, all but one study (Bowles, et al., 2006) specified the proportion
of women approached who agreed to participation – this ranged from 83% (Friedman and
Gath, 1989) to 97% (Prettyman, et al., 1993) in all but Nordal Broen’s study, in which the
figure was 50%. This was proposed to be related to staff motivation (Nordal Broen, et al.,
2005). In Cumming’s study, which required potential participants to return a consent form
by post, an overall participation of 47.5% in women and partners was described (Cumming,
et al., 2007). Participation rates of partners were lower in one study: 75% of women versus
30% of partners (Kong, et al., 2010).
Figure 2
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
Where participation was not defined by first response, response rates at first assessment in
women varied from 61% (at one month (Farren, et al., 2016)) to 94% (at one week
(Prettyman, et al., 1993)).
Outcomes
Depression was the most studied outcome, reported by all but two groups (Bowles, et al.,
2006, Cheung, et al., 2013).
Additional data (not included in the original article) was obtained from the study authors for
two publications and presented (Cumming, et al., 2007, Engelhard, et al., 2001).
Methods of assessment
Supplementary Table I summarises the methods of assessment used.
The majority of groups used self-report measures. Five groups used a structured assessment
by interview in addition to self-report measures – four used both in all participants
(Friedman and Gath, 1989, Klier, et al., 2000, Lee, et al., 1997, Neugebauer, et al., 1997,
Walker and Davidson, 2001), and the other performed this in those who scored >=4 on the
General Health Questionnaire (GHQ) (Sham, et al., 2010). Garel used only an interview
(Garel, et al., 1996). Cumming compared outcome from the Hospital Anxiety and Depression
Scale (HADS) with the Composite International Diagnostic Interview (CIDI) in 37 randomly
selected participants, in order to confirm its validity in this context (Cumming, et al., 2007).
Cut-offs to define morbidity were variably defined by study groups, as detailed within
Supplementary Table I.
Follow-up
The follow-up period ranged from 1 month (Bowles, et al., 2006, Friedman and Gath, 1989)
to five years (Nordal Broen, et al., 2005). Nine of the study groups reported outcomes at one
year or more, with only two studies reporting beyond 18 months.
Supplementary
Table I
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
In studies with multiple assessments, response rates declined over time (Beutel, et al., 1995,
Cordle and Prettyman, 1994, Engelhard, et al., 2001, Farren, et al., 2016, Garel, et al., 1996,
Nordal Broen, et al., 2005, Nordal Broen, et al., 2006, Prettyman, et al., 1993). Janssen, who
recruited via adverts in magazines, maintained a 94% response rate at 18 months (Janssen,
et al., 1996).
Of those with follow-up of three months or more, one assessed for pregnancy at follow-up
(Cordle and Prettyman, 1994), one excluded women who were pregnant (Garel, et al., 1996),
and two assessed for the impact of future pregnancies on morbidity (Farren, et al., 2016,
Nordal Broen, et al., 2005). The majority of studies did not assess for this.
Suitability for meta-analysis
We considered the feasibility and value of meta-analysis.
It was not possible to obtain individual participant data for the vast majority of studies.
Consideration was given to using aggregate data from those studies with a comparison
group. However, there is significant clinical diversity, as can be seen in Table I. For example,
in psychiatric history (two studies excluded women with any psychiatric history), parity
(between one and two thirds of woman had children), and exposure (one study included late
losses). The majority of data is derived from cohorts in Western Europe and the USA, with
approximately one fifth from Hong Kong. There has been discussion of the possibility of
significant cultural differences in approach to EPL, which calls into question the
appropriateness of any summary measures (Garel, et al., 1996, Sham, et al., 2010). The data
is also derived over a period of three decades.
There was also significant methodological diversity in terms of study design (timing of
assessment, measure, comparison group used).
With such differences in both the subjects and the outcomes reported, it was deemed
inappropriate to attempt to provide a meaningful summary estimate through meta-analysis.
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
Risk of bias within studies
Supplementary Table II details the quality assessment of each study using the Newcastle-
Ottawa Scale (see supplementary material). Quality issues relating to selection were noted
as follows: three studies used a self-selected population (Engelhard, et al., 2001, Janssen, et
al., 1996, Johnson and Baker, 2004), and three studies did not specify the derivation of their
cohorts (Cheung, et al., 2013, Daly, et al., 1996, Kulathilaka, et al., 2016). Participant groups
were generally said to be representative of the EPL population attending the units, but in
two studies, at least 50% declined participation, without discussion of the
representativeness of those who agreed (Cumming, et al., 2007, Nordal Broen, et al., 2005,
Nordal Broen, et al., 2006). One study group able to collect data on those who declined
showed that women were significantly older, and both women and partners had been
married for longer, had a lower level of formal education, and a greater number of children,
than those who had participated (Kong, et al., 2010, Lok, et al., 2010). Partners were also
more likely to take part if they reported planning/wanting the pregnancy. Beutel’s study of
couples found that partners who participated were more frequently married, and their
female partners were less likely to believe that they had desired the pregnancy less than
they had (Beutel, et al., 1996).
Ascertainment of exposure to EPL was by hospital records in all but two studies (Engelhard,
et al., 2001, Janssen, et al., 1996).
Few studies recruited prior to the diagnosis of EPL, thus precluding proof that
psychopathology was not present prior to exposure to EPL. Only one study, in partners,
(Johnson and Baker, 2004) showed similar early pregnancy assessments in those whose
partners went on to experience healthy pregnancies.
No studies matched exposed and non-exposed individuals in the design of the study
(although in two studies, couples were recruited together, and thus matched in terms of
Supplementary Material
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
exposure (Beutel, et al., 1996, Kong, et al., 2010)). Studies frequently found the loss group
was older, or had more previous losses (Beutel, et al., 1995, Janssen, et al., 1996). One study
found a significantly higher rate of history of prior depression (42.4% vs. 18.8%) in the
miscarriage group (Beutel, et al., 1995). Five study groups controlled for potential
confounders (Janssen, et al., 1996, Kulathilaka, et al., 2016, Lok, et al., 2010, Neugebauer, et
al., 1992, Neugebauer, et al., 1992, Nordal Broen, et al., 2005, Nordal Broen, et al., 2006).
Outcome assessment was always by assessment for psychopathology performed exclusively
for the purposes of the study (usually by self-assessment using standardized self-report
measures). Follow-up duration was adequate (>=1 month) in all but two studies (Daly, et al.,
1996, Friedman and Gath, 1989). Drop out ranged from 6% over 18 months (involving
volunteers responding to an advert (Janssen, et al., 1996)) to 61% over three months (in a
study with consecutive recruitment from an early pregnancy unit (Farren, et al., 2016)).
Most studies assessed for a relationship between drop out from first assessment and
baseline psychometric scores. Some found no evidence selective drop out on this basis
(Beutel, et al., 1995, Lee, et al., 1997, Lok, et al., 2010, Prettyman, et al., 1993, Thapar and
Thapar, 1992). Other studies suggested that those most affected may drop out (Engelhard,
et al., 2001, Farren, et al., 2016, Janssen, et al., 1996). Contrastingly, one French study found
that those with more distress initially were more likely to take part in the three-month
assessment (Garel, et al., 1996).
Psychological Morbidity: Depression, Anxiety and PTSD
Table II & III detail psychological morbidity according to the time point of assessment. Table
II summarises studies without comparison groups, and table III studies with comparison
groups.
Table II & III
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
Depression
Within the first two weeks after a miscarriage, studies have shown 22% (Prettyman, et al.,
1993), 28% (Nordal Broen, et al., 2005) and 36% (Neugebauer, et al., 1992) of women
reaching a threshold for depression. Studies have shown significantly higher depression
scores (Beutel, et al., 1995, Thapar and Thapar, 1992) and a higher proportion of cases –
with relative risks of meeting criteria between 3.1 (Lok, et al., 2010) and 4.3 (Neugebauer, et
al., 1992) times that in a non-pregnant comparison group. No significant difference was
found between women following miscarriage and termination (Nordal Broen, et al., 2005). In
partners, one study in Hong Kong showed a 17% prevalence of probable depression (Kong,
et al., 2010), with significantly lower depression scores, but not proportion meeting criteria,
than in women (Beutel, et al., 1996, Kong, et al., 2010), and no difference in scores
compared to partners following live birth (Johnson and Baker, 2004).
Between one and two and a half months after loss, eight study groups published rates
between 8% and 20% of women with EPL meeting a defined cut-off for moderate depressive
symptoms (Cumming, et al., 2007, Engelhard, et al., 2001, Farren, et al., 2016, Friedman and
Gath, 1989, Kulathilaka, et al., 2016, Lee, et al., 1997, Neugebauer, et al., 1992, Prettyman,
et al., 1993). A higher proportion of 35% was found in a study utilizing volunteers, and in
which 10% were >20 weeks (Janssen, et al., 1996). In studies utilizing a comparison group,
GHQ depression subscale (but not HADS-depression) and SCL-90 depression subscale scores
were significantly higher than in the comparison group (Janssen, et al., 1996, Thapar and
Thapar, 1992). A subgroup of women interviewed for the first time at six weeks (excluding
those also interviewed at two weeks) were 2.6 (95% CI 1.5-4.4) times more likely than non-
pregnant controls to be highly symptomatic for depression (Neugebauer, et al., 1992). In a
Sri Lankan study, after controlling for gestation and age, the higher proportion of cases in
women between six and ten weeks after losses versus pregnant controls was no longer
significant (Kulathilaka, et al., 2016). 4% of partners met a threshold for moderate
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
depression at one month, with no difference in scores compared to women (Cumming, et
al., 2007).
Assessed at 3 months post miscarriage, one French study found that 51% women had
experienced a major depressive episode, although they noted selective drop-out of those
less affected (Garel, et al., 1996).
Overall, depression caseness has been found to decline between consecutive assessments in
women (for example, from 10% at one month to 3% at six months (Cumming, et al., 2007),
and 27% immediately to 19% at three months (Lok, et al., 2010)) . Three studies found
results comparable to those without EPL by one year (Cumming, et al., 2007, Janssen, et al.,
1996, Nordal Broen, et al., 2005). One study suggesting increased pathology at one year
reported a significantly higher prevalence of psychiatric history in the miscarriage group as
compared to the non-pregnant comparison group (Beutel, et al., 1995). Depression scores in
partners also decline over time (Beutel, et al., 1996, Cumming, et al., 2007, Lok, et al., 2010).
One study comparing partners a year after miscarriage and live birth showed higher
depression scores in the former (Johnson and Baker, 2004).
Anxiety
Studies looking at both anxiety and depression using HADS show anxiety to be the more
frequent and sustained morbidity(Cordle and Prettyman, 1994, Cumming, et al., 2007,
Farren, et al., 2016, Nordal Broen, et al., 2006, Prettyman, et al., 1993, Thapar and Thapar,
1992). Immediately after loss, 41% participants met criteria for anxiety (Prettyman, et al.,
1993), with scores significantly higher than in an antenatal comparison group (Thapar and
Thapar, 1992). The proportion of women meeting criteria for anxiety was significantly higher
than in the control group at one month in the author’s own study (Farren, et al., 2016).
Scores declined over time in all except one study, which found a further increase in anxiety
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
scores at 12 weeks, which they hypothesized related to resumed efforts to conceive
(Prettyman, et al., 1993). Scores were found to normalize compared to non-pregnant
community participants at 6 months in two studies (Beutel, et al., 1995, Nordal Broen, et al.,
2005, Nordal Broen, et al., 2006), but not until 12 months in Janssen’s study when compared
to women at an equivalent time point after delivery (Janssen, et al., 1996).
Sham’s study, in which Chinese women were assessed in person at 3 months post-
miscarriage, showed a lower prevalence of only three patients (1.8%) with anxiety disorders
(including one with PTSD) (Sham, et al., 2010).
Partners showed significantly less anxiety cases than women at one, six and 13-month
assessments (Cumming, et al., 2007). Partners of women with miscarriage also showed no
difference in anxiety scores to those of women with live births, either within 3 weeks or at
one year post loss or birth (Johnson and Baker, 2004).
PTSD and traumatic impact
The largest study of PTSD following miscarriage showed a 25% incidence at 1 month, and 6%
incidence at 4 months (Engelhard, et al., 2001). The author’s own study group, in a pilot
study using more lenient criteria for diagnosis, found 38% of women with EPL met criteria
for PTSD at three months (45% in miscarriage, 18% in ectopic pregnancy) (Farren, et al.,
2016). A small study (25 women) by Bowles found a 39% incidence at one month after
miscarriage (Bowles, et al., 2006). They also reported a 28% incidence of Acute Stress
Disorder (ASD) (often seen as a precursor to PTSD) at seven days. Another small study
reported an incidence of ASD of 15% at three weeks (Walker and Davidson, 2001). A study of
161 women three months after miscarriage in Hong Kong using structured clinical
assessment found only one patient with PTSD (0.6%) and three with adjustment disorder
(1.8%) on interview (Sham, et al., 2010).
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
Two other studies reported on Impact of Event Scale (IES) scores. The IES is a scale of
subjective distress related to a specific event, with questions reflecting PTSD criteria,
although not diagnostic of the condition. Nordal Broen compared IES scores following
miscarriage to termination, and found significantly higher intrusion scores in the miscarriage
group initially (with 47.5% women meeting criteria for intrusion at 10 days), and lower
avoidance scores at later time points (two and five years) (Nordal Broen, et al., 2005).
Another study looking only at partners, comparing those following miscarriage to those after
live birth, showed higher overall IES scores in the miscarriage group at 3 weeks and 1 year
(Johnson and Baker, 2004). The clinical significance of these differences in scores was not
discussed.
Correlation between outcomes
In studies reporting on more than one outcome, a minority reported assessing for
correlation between outcomes. Prettyman reported a statistically significant positive
correlation between higher depression and anxiety scores (Prettyman, et al., 1993).
Engelhard found that those meeting criteria for PTSD were significantly more likely to meet
criteria for depression (Engelhard, et al., 2001). Johnson and Baker reported correlation
between scores on the BDI, State Trait Anxiety Inventory (STAI) and IES in partners (Johnson
and Baker, 2004).
Factors associated with psychological morbidity
Although a minority of studies were sufficiently powered to assess risk factors for
psychological morbidity, we have summarized the findings showing a significant association
in table IV. Generally, in studies with more than one assessment, factors were correlated to
levels of distress at the earliest assessment.
One uncontrolled study found a significant protective impact of older age on depression
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
caseness (Sham, et al., 2010). Another study demonstrated that women with no children or
previous miscarriage have significantly higher anxiety scores immediately after loss (Thapar
and Thapar, 1992). Women have been found to be more at risk of depression the fewer
existing children they have, if they have a history of infertility, or if they have had previous
miscarriage (Engelhard, et al., 2001, Neugebauer, et al., 1992, Sham, et al., 2010, Thapar and
Thapar, 1992). A longer gestation has been related to higher anxiety, depression and PDS
scores (for depression scores, this relationship was found to persist at 1 year) (Engelhard, et
al., 2001, Janssen, et al., 1996). A pregnancy achieved through assisted reproduction was
associated with higher IES avoidance and hyperarousal scores (Cheung, et al., 2013). Having
previously seen a viable fetus on ultrasound increased the likelihood of depression caseness
in women (Kong, et al., 2010).
In partners, a planned pregnancy was associated with a high prevalence of depression
caseness in one study (Kong, et al., 2010). By contrast, in women, an unplanned pregnancy
has been associated with more cases of anxiety at 12 weeks, and higher depression and IES
scores immediately (Prettyman, et al., 1993, Thapar and Thapar, 1992, Walker and Davidson,
2001) .
Being single at the time of the loss has been related to higher levels of depression shortly
afterwards, and both anxiety and depression at 5 years (Friedman and Gath, 1989, Nordal
Broen, et al., 2006). Measures of lower marital satisfaction, or higher marital discord, have
been associated with increased caseness of depression (measured simultaneously) (Kong, et
al., 2010, Lee, et al., 1997). Lower perceived spousal support at the time of EPL has been
associated with both anxiety and depression scores (assessed simultaneously, both soon
after loss (Beutel, et al., 1996, Lee, et al., 1997), and retrospectively at 5 years (Cordle and
Prettyman, 1994)).
Past psychiatric history (or self-reported poor psychiatric health prior to the EPL) has been
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
found to be significantly associated with both anxiety and depression after EPL (Cumming, et
al., 2007, Friedman and Gath, 1989, Nordal Broen, et al., 2006, Sham, et al., 2010, Walker
and Davidson, 2001).
A history of abuse, as well as reporting feeling personally responsible for the loss or a lack of
control over one’s life, has been associated with increased acute stress symptoms at seven
days (Bowles, et al., 2006). Gestational length has been found to be a risk factor for
increased symptoms of PTSD occurring at one and four months (Engelhard, et al., 2001).
Only two studies assessed for the impact of further pregnancies in the follow-up period.
Neither reported any impact, though were underpowered to do so (Farren, et al., 2016,
Nordal Broen, et al., 2006).
Risk of bias across studies
Across studies, a large proportion declined participation (up to 52.5% (Cumming, et al.,
2007)) or dropped out (up to 39% at first assessment (Farren, et al., 2016)). Only one study
group collected background sociodemographic and clinical data on those who declined
participation, and did find some differences as detailed above (Lok, et al., 2010). In the
author’s own study, collection of data on those who declined participation was not ethically
permitted: it is likely that other studies were similarly constrained. The unassessed group
may have different psychological outcomes: either more or less affected. Participation was
lower in partners: 22% versus 75% (Kong, et al., 2010) and 35% versus 50% (Cumming, et al.,
2007) , and thus the potential for bias higher.
There may also be concern of unintended therapeutic effect of study involvement across
studies. This was specifically assessed by Neugebauer’s team (Neugebauer, et al., 1992), who
found evidence in support of this – but not considered in other studies. Care should thus be
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
taken in the interpretation of repeated assessments, in which resolution of symptoms may
rely on the impact of the assessment rather than time itself.
A minority relied on interviews as opposed to written assessments, generally excluding non-
native language speakers or individuals with low literacy. However, some authors discussed
potential ‘conscious non-disclosure of genuine symptoms’ due to a fear of stigmatization
during interviews (Sham, et al., 2010).
Discussion
Summary of evidence
Studies performed over three decades, in a variety of locations, and involving over 2500
women with EPL, have consistently demonstrated an association between pregnancy loss
and psychological morbidity. We found that four to six weeks after loss, studies reported
between eight and 20% of women experiencing symptoms above a threshold for moderate
depression. Anxiety appeared to have a prevalence of between 18 and 32%. For both
conditions, resolution to background rates seems complete within one year. Partners show a
lower intensity of depressive and anxiety reactions initially: for anxiety, this difference seems
to be sustained for at least a year. Three studies reported incidences of between 25% and
39% of women reaching a threshold for the diagnosis of PTSD at one month. The duration
and degree of resolution of post-traumatic stress is not clear.
An unselected EPL group appears to have higher pre-loss psychological morbidity (which
may relate to previous loss or subfertility), but there is evidence from controlled studies that
post-loss morbidity cannot be explained by baseline characteristics alone.
The most consistently identified risk factors relate to past psychiatric history and low marital
satisfaction or support. An unplanned pregnancy might be associated with a higher risk of
anxiety, depression and PTSD in women. Other identified risk factors for anxiety and
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
depression include being single, having no children, or having had a previous miscarriage.
Longer gestation appeared to be a risk factor in studies including later losses.
Limitations
There is variability in rates of disorders across studies. This is most marked for PTSD at 3
months: one study using a clinician administered scale found only one case (a rate of 0.6%)
(Sham, et al., 2010); another, using the PDS, found a rate of 7%, (Engelhard, et al., 2001);
and, in the author’s own pilot study, a rate of 39% (Farren, et al., 2016). The difference
between the latter two studies may in part relate to different recruitment and scoring
methods used, but variation also brings into question whether research conducted in
different geographical locations, with different demographics and cultural norms, can be
appropriately and usefully interpreted in other populations.
There is also limited concordance across studies with regard to risk factors identified. This is
likely to reflect the small size of the majority of the studies, thus limiting power to detect
statistically significant factors. The absence of consistent relationships of morbidity to
background factors could also suggest that better elucidation and stratification of groups at
risk is necessary – for which a study assessing all three outcomes (anxiety, depression and
PTSD) would be helpful. Different groups may be at risk of different disorders, and merit
different management.
There is evidence for selective participation and retention of participants across studies,
both under-representation of those most affected (who may avoid the questionnaires as
upsetting reminders of the event) or least affected (who may be less motivated to take part).
In other literature there is evidence for selective non-participation by those likely to be most
affected by industrial disasters and termination of pregnancy (Soderberg, et al., 1998,
Weisaeth, 1989). While unavoidable, this introduces an important selection bias throughout
this body of research.
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
There are clear gaps in the literature. There has been minimal research into the impact of
ectopic pregnancy, which was only reported in one study, making up <1% of the participants
included in this review. No studies have assessed for PTSD in partners. Studies are also
generally old: only four of the study groups published in the past decade. The importance of
this is twofold. First, the management of EPL has changed over time - with a shift to earlier
diagnosis and more conservative management. Second, there may have been fundamental
changes in the psyche of the population – for example with regards to expectations,
women’s roles outside the home, or in terms of stigmatization of EPL. Both of these may
significantly alter the response to EPL. With the exception of two studies, recruitment was
derived from early pregnancy units or hospitals. Historically, many miscarriages were
managed in the community. It is likely therefore that women with clinically severe
encounters (at later gestation, with heavier bleeding, requiring active intervention) are over-
represented in earlier studies.
Risk factors for psychological morbidity at first assessment (soon after the EPL) have
generally been identified. However, arguably, more important are risk factors for longer
term morbidity – which cannot be assumed to be the same. Furthermore, there has been
limited investigation with regard to risk factors for PTSD. An understanding of this will be
especially important in targeting appropriate treatment.
A pertinent question to healthcare professionals and researchers working in early pregnancy
is whether management strategy may affect emotional response. Only one reported
assessing for the impact of the management of miscarriage (Sham, et al., 2010). In this
study, a very small minority had medical management, and there was no difference in the
proportions of women having conservative or surgical management in the groups with or
without depressive disorders. The impact of management is more appropriately assessed in
interventional studies, where women are randomized to conservative, medical and surgical
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
approaches. However, there is two-fold difficulty in performing these trials. First, many
women will have a clear preference, precluding randomization in a substantial (and
potentially characteristically different) group of women. Indeed, Wieringa-de Ward’s
analysis of their substantial non-randomised group showed those who opted for expectant
management had better mental health scores at the outset (Wieringa-De Waard, et al.,
2002). Second, many of those randomized will deviate from their allocated management
strategy, for clinical reasons or newly demonstrated preferences. At present, there is no
evidence to guide management except to support a woman’s preference.
Fundamental to research of this nature is a reliance on self-report measures, which use
arbitrary cut-offs to define pathology that have not been validated in EPL populations.
Furthermore, the diagnoses of depression, anxiety and PTSD – while helpful in defining an
under-recognised and unmet need in the EPL population – may be of limited usefulness in
terms of understanding the exact nature of the distress. For example, anxiety may be
generalized, specifically associated with concerns about involuntary childlessness (in which
case having further children may be expected to resolve it), or focused on the trauma of the
event (i.e. adjustment disorder or PTSD).
Studies without a comparison group enable quantification of the overall psychological
pathology in the population with EPL, but cannot prove association with the loss itself. The
risk of miscarriage is related to age, previous miscarriage and previous subfertility
(Maconochie, et al., 2007). As such, an EPL population is likely to be older, have had more
miscarriages, or higher rates of antecedent subfertility than a comparison group outside or
within healthy pregnancy – all of which may themselves be related to psychological
morbidity. Comparability between the cohorts was a consistent issue in the included studies,
most studies commented that comparison groups were broadly similar in terms of age, past
EPL, and number of children, but did not control from them. Two study groups retained
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
statistically significant results after controlling for possible confounders (Lok, et al., 2010,
Neugebauer, et al., 1992a, Neugebauer, et al., 1992b).
It is also important to consider that the psychological conditions seen may relate to the
uncertain period of involuntary subfertility or childlessness while waiting to conceive again.
In support of this is the evidence (though not demonstrated in all studies) that existing
children are protective from depression after miscarriage (Neugebauer, et al., 1997, Thapar
and Thapar, 1992). One would also expect improvement with future successful procreation –
though there is yet no evidence of this (Nordal Broen, et al., 2006). There is, however,
sizable evidence included in this review that those who conceived without delay or planning
experience notable distress after a miscarriage – supporting a notion that the loss itself is at
least partially causative.
The significant decline in anxiety and depression scores over time may also be pertinent in
ascribing morbidity to the EPL itself, rather than solely to any predisposing factors (Beutel, et
al., 1995, Cumming, et al., 2007, Janssen, et al., 1996, Lok, et al., 2010, Neugebauer, et al.,
1992, Prettyman, et al., 1993). However, hampering interpretation of this is the fact that few
studies with prolonged follow-up have assessed for further pregnancies (healthy or
otherwise). In order to fully understand the natural trajectory of psychological sequelae
after a loss, it is necessary to separate out women who are newly pregnant, or who have
experienced further loss.
Although this review supports a strong association between EPL and psychopathology,
categorical proof of the direction of causation is lacking. This would require pre-loss
psychological assessment. Only one study was methodologically capable of this (Janssen, et
al., 1996), and this study found higher depression and anxiety scores in the group of women
who subsequently lost the pregnancy. This was incompletely explained by the higher rate of
past loss in this group. It is possible that symptoms such as bleeding or pain led this group to
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
expect a poor outcome prior to diagnosis. However, the possibility that psychopathology
itself could (directly or indirectly) increase risk of EPL cannot be excluded (available
literature both supports (Sugiura-Ogasawara, et al., 2002) and refutes (Kolte, et al., 2015,
Nelson, et al., 2003) this). Overall, however, even if causation cannot be proven, the body of
research presented identifies a group at high risk of psychological morbidity.
Conclusions
Women, and to a lesser extent, their partners, are at significant risk of symptoms of anxiety,
depression and PTSD after an EPL. Clinicians should be especially alert to this risk in women
who have a history of psychiatric illness, who have less support, who have had multiple
miscarriages, who have experienced subfertility and/or are left childless by the loss.
It is important to remember that reactions are diverse. Amongst the distributions of
responses to EPL will be those who are unaffected, and those who are completely
debilitated. Different groups of women may be at risk of different disorders; and beneath
the heading of one ‘disorder’ may be a variety of reactions with different predispositions,
patterns of progression or resolution, and response to treatments. A priority for future
research is to establish what types of emotional support are appropriate and efficacious
(Prior, et al., 2017). Evidence on the benefits of general counselling in an unselected
population has so far been disappointing (Murphy, et al., 2012). Larger studies, and studies
assessing all outcomes, will help separate and define groups at risk, as well as the impact of
our clinical management, and may be the first step in individualizing treatment, and seeing
benefit.
While awaiting such research, clinicians should be sensitive to the risk of psychopathology in
this population. We suggest enquiring about emotional well-being at any routine follow-up,
and encouraging those who have experienced EPL to contact their general practitioner if
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
633
634
635
636
they experience severe or prolonged psychological symptoms. A policy for systematic
screening of these women should be considered and evaluated.
Authors’ Roles
JF originally proposed the review. All authors contributed to the protocol design during
research meetings, during which consensus was reached for any discrepancies found during
screening or data extraction. JF performed the initial literature searches, and JF and NMJ
assessed the results of these searches against inclusion criteria. JF extracted data and made
the initial assessment of study quality, with advice from JV, which was checked by NMJ. JF
and TB wrote the first draft of the manuscript, that was then critically reviewed and revised
by JV, MJ, DT and NMJ. All authors approved the final version of the manuscript for
submission.
637
638
639
640
641
642
643
644
645
646
647
Acknowledgements
The research team would like to thank the researchers who responded to queries, and
provided additional data for this review. We would also like to thank Jaqueline Cousins, and
the staff at Imperial College library, for their support in performing a systematic search
procedure and obtaining original texts.
Funding
JF was supported by Imperial College Healthcare Charity grant number 141517. TB is
supported by the National Institute for Health Research (NIHR) Biomedical Research Centre
based at Imperial College Healthcare NHS Trust and Imperial College London. The views
expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the
Department of Health. The Tommy’s National Centre for Miscarriage Research at Imperial
College NHS Trust is supported by the Tommy’s charity.
Conflict of interest
The authors do not have any conflict of interest.
648
649
650
651
652
653
654
655
656
657
658
659
660
661
Bibliography
Beutel M, Deckardt R, von Rad M, Weiner H. Grief and depression after miscarriage: their separation, antecedents, and course. Psychosom Med 1995;57: 517-526.
Beutel M, Willner H, Deckardt R, Von Rad M, Weiner H. Similarities and differences in couples' grief reactions following a miscarriage: results from a longitudinal study. J Psychosom Res 1996;40: 245-253.
Blohm F, Friden B, Milsom I. A prospective longitudinal population-based study of clinical miscarriage in an urban Swedish population. BJOG 2008;115: 176-182; discussion 183.
Bowles SV, Bernard RS, Epperly T, Woodward S, Ginzburg K, Folen R, Perez T, Koopman C. Traumatic stress disorders following first-trimester spontaneous abortion. Journal of Family Practice 2006;55: 969-973.
Cecil R, Leslie Jc. Early miscarriage: Preliminary results from a study in Northern Ireland. Journal of Reproductive and Infant Psychology 1993;11: 89-95.
Cheung CS, Chan CH, Ng EH. Stress and anxiety-depression levels following first-trimester miscarriage: a comparison between women who conceived naturally and women who conceived with assisted reproduction. Bjog 2013;120: 1090-1097.
Cordle C, Prettyman R. A 2-year follow-up of women who have experienced early miscarriage. Journal of Reproductive and Infant Psychology 1994;12: 37-43.
Cumming GP, Klein S, Bolsover D, Lee AJ, Alexander DA, Maclean M, Jurgens JD. The emotional burden of miscarriage for women and their partners: trajectories of anxiety and depression over 13 months. Bjog 2007;114: 1138-1145.
Daly SF, Harte L, O'Beirne E, McGee H, Turner MJ. Does miscarriage affect the father? Journal of Obstetrics and Gynaecology 1996;16: 260-261.
Engelhard IM, van den Hout MA, Arntz A. Posttraumatic stress disorder after pregnancy loss. Gen Hosp Psychiatry 2001;23: 62-66.
Farren J, Jalmbrant M, Ameye L, Joash K, Mitchell-Jones N, Tapp S, Timmerman D, Bourne T. Post-traumatic stress, anxiety and depression following miscarriage or ectopic pregnancy: a prospective cohort study. BMJ Open 2016;6: e011864.
Friedman T, Gath D. The psychiatric consequences of spontaneous abortion. The British Journal of Psychiatry 1989;155: 810-813.
Garel M, Lelong N, Brondel B. Psychological difficulties following spontaneous abortion. [French]. Reproduction Humaine et Hormones 1996;9: 478-481.
662
663664
665666667
668669
670671672
673674
675676677
678679
680681682
683684
685686
687688689
690691
692693
Harker L. Emotional wellbeing following miscarriage. Journal of Obstetrics and Gynaecology 1993;13: 262-265.
Janssen HJ, Cuisinier MC, de Graauw KP, Hoogduin KA. A prospective study of risk factors predicting grief intensity following pregnancy loss. Arch Gen Psychiatry 1997;54: 56-61.
Janssen HJ, Cuisinier MC, Hoogduin KA, de Graauw KP. Controlled prospective study on the mental health of women following pregnancy loss. The American Journal of Psychiatry 1996;153: 226-230.
Johnson MP, Baker SR. Implications of coping repertoire as predictors of men's stress, anxiety and depression following pregnancy, childbirth and miscarriage: A longitudinal study. J Psychosom Obstet Gynaecol 2004;25: 87-98.
Klier CM, Geller PA, Neugebauer R. Minor depressive disorder in the context of miscarriage. J Affect Disord 2000;59: 13-21.
Kolte AM, Olsen LR, Christiansen OB, Nielsen HS. Stress and depression at referral do not entail a lower chance of live birth/ongoing pregnancy for women with recurrent pregnancy loss. Hum Reprod 2015;30: i73.
Kong GW, Chung TK, Lai BP, Lok IH. Gender comparison of psychological reaction after miscarriage-a 1-year longitudinal study. Bjog 2010;117: 1211-1219.
Kulathilaka S, Hanwella R, de Silva VA. Depressive disorder and grief following spontaneous abortion. BMC Psychiatry Vol 16 2016, ArtID 100 2016;16.
Lee DT, Wong CK, Cheung LP, Leung HC, Haines CJ, Chung TK. Psychiatric morbidity following miscarriage: a prevalence study of Chinese women in Hong Kong. J Affect Disord 1997;43: 63-68.
Lok IH, Yip AS, Lee DT, Sahota D, Chung TK. A 1-year longitudinal study of psychological morbidity after miscarriage. Fertil Steril 2010;93: 1966-1975.
Maconochie N, Doyle P, Prior S, Simmons R. Risk factors for first trimester miscarriage--results from a UK-population-based case-control study. Bjog 2007;114: 170-186.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Bmj 2009;339: b2535.
Murphy FA, Lipp A, Powles DL. Follow-up for improving psychological well being for women after a miscarriage. Cochrane Database Syst Rev 2012;3: CD008679.
Nelson DB, McMahon K, Joffe M, Brensinger C. The effect of depressive symptoms and optimism on the risk of spontaneous abortion among innercity women. J Womens Health (Larchmt) 2003;12: 569-576.
694695
696697
698699700
701702703
704705
706707708
709710
711712
713714715
716717
718719
720721
722723
724725726
Neugebauer R, Kline J, O'Connor P, Shrout P, Johnson J, Skodol A, Wicks J, Susser M. Depressive symptoms in women in the six months after miscarriage. Am J Obstet Gynecol 1992;166: 104-109.
Neugebauer R, Kline J, O'Connor P, Shrout P, Johnson J, Skodol A, Wicks J, Susser M. Determinants of depressive symptoms in the early weeks after miscarriage. Am J Public Health 1992;82: 1332-1339.
Neugebauer R, Kline J, Shrout P, Skodol A, O'Connor P, Geller PA, Stein Z, Susser M. Major depressive disorder in the 6 months after miscarriage. JAMA: Journal of the American Medical Association 1997;277: 383-388.
Nordal Broen A, Moum T, Bodtker AS, Ekeberg O. The course of mental health after miscarriage and induced abortion: a longitudinal, five-year follow-up study. BMC Med 2005;3: 18.
Nordal Broen A, Moum T, Sejersted Bodtker A, Ekeberg O. Predictors of anxiety and depression following pregnancy termination: A longitudinal five-year follow-up study. Acta Obstet Gynecol Scand 2006;85: 317-323.
Prettyman R, Cordle C, Cook G. A three-month follow-up of psychological morbidity after early miscarriage. Br J Med Psychol 1993;66: 363-372.
Prior M, Bagness C, Brewin J, Coomarasamy A, Easthope L, Hepworth-Jones B, Hinshaw K, O'Toole E, Orford J, Regan L et al. Priorities for research in miscarriage: a priority setting partnership between people affected by miscarriage and professionals following the James Lind Alliance methodology. BMJ Open 2017;7: e016571.
Seibel M, Graves WL. The psychological implications of spontaneous abortions. J Reprod Med 1980;25: 161-165.
Sham A, Yiu M, Ho W. Psychiatric morbidity following miscarriage in Hong Kong. Gen Hosp Psychiatry 2010;32: 284-293.
Soderberg H, Andersson C, Janzon L, Sjoberg NO. Selection bias in a study on how women experienced induced abortion. Eur J Obstet Gynecol Reprod Biol 1998;77: 67-70.
Sugiura-Ogasawara M, Furukawa TA, Nakano Y, Hori S, Aoki K, Kitamura T. Depression as a potential causal factor in subsequent miscarriage in recurrent spontaneous aborters. Hum Reprod 2002;17: 2580-2584.
Thapar AK, Thapar A. Psychological sequelae of miscarriage: a controlled study using the general health questionnaire and the hospital anxiety and depression scale. Br J Gen Pract 1992;42: 94-96.
Varma R, Gupta J. Tubal ectopic pregnancy. BMJ Clin Evid 2012;2012.
727728729
730731732
733734735
736737738
739740741
742743
744745746747
748749
750751
752753
754755756
757758759
760
Walker TM, Davidson KM. A preliminary investigation of psychological distress following surgical management of early pregnancy loss detected at initial ultrasound scanning: A trauma perspective. Journal of Reproductive and Infant Psychology 2001;19: 7-16.
Weisaeth L. Importance of high response rates in traumatic stress research. Acta Psychiatr Scand Suppl 1989;355: 131-137.
Wieringa-De Waard M, Hartman EE, Ankum WM, Reitsma JB, Bindels PJ, Bonsel GJ. Expectant management versus surgical evacuation in first trimester miscarriage: health-related quality of life in randomized and non-randomized patients. Human reproduction (Oxford, England) 2002;17: 1638-1642.
761762763
764765
766767768769
List of figures and tables
Figure 1: PRISMA diagram (Moher, et al., 2009)
Figure 2: Numbers and types of participants in each paper included within qualitative
synthesis, in reverse order of year of publication
Table I Baseline characteristics of included studies (studies reporting on the same cohort
(with multiple publications for different time points) combined as one entry)
Table II Cohort studies that have applied standardized psychometric questionnaires or
diagnostic interviews at set time points after a miscarriage or ectopic pregnancy to assess
proportion of participants reaching a threshold for psychological morbidity (Depression (D),
Anxiety (A) or measures of acute stress disorder (ASD), or post-traumatic stress disorder
(PTSD))
Table III Cohort studies that have applied standardized psychometric questionnaires or
diagnostic interviews at set time points after a miscarriage or ectopic pregnancy to assess
psychological morbidity (Depression (D), Anxiety (A) or measures of acute stress, post-
traumatic stress or traumatic impact (T)): caseness of disorders (given to 0 decimal places),
and difference in caseness (C) or scores (S) compared to comparison group (with p value, if
available)
Table IV Factors identified to have a statistically significant (at an alpha of 0.05) association
with higher outcome measures of anxiety, depression, or traumatic impact (scores (S) or
caseness (C)) in women following miscarriage
Supplementary Table I Methods of psychometric assessment, and cut-offs used to define
caseness, in studies included in this narrative review
Supplementary Table II Newcastle-Ottawa Scale assessment of quality of studies
Supplementary Material I: Systematic Review Search Criteria
Supplementary Material II: Newcastle-Ottawa Quality Assessment Scale for Cohort Studies
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794