bmj open · imperial college, london, uk 2 south london and maudsley nhs foundation trust, london,...

For peer review only

Post-traumatic stress disorder, anxiety and depression following miscarriage or ectopic pregnancy: a prospective

cohort study

Journal: BMJ Open

Manuscript ID bmjopen-2016-011864

Article Type: Research

Date Submitted by the Author: 12-Mar-2016

Complete List of Authors: Farren, Jessica; Queen Charlotte's and Chelsea Hospital, Tommy's National Early Miscarriage Research Centre Jalmbrant, Maria; South London and Maudsley NHS Foundation Trust,

Ameye, Lieveke; KU Leuven, Department of Development and Regeneration Joash, Karen; Queen Charlotte\'s and Chelsea Hospital, Tommy's National Early Miscarriage Research Centre Mitchell-Jones, Nicola; Chelsea and Westminster Hospital Tapp, Sophie; Queen Charlotte\'s and Chelsea Hospital, Tommy's National Early Miscarriage Research Centre Timmerman, Dirk; University Hospitals KU Leuven , Department of Obstetrics and Gynaecology; KU Leuven , Department of Development and Regeneration Bourne, Tom; Queen Charlotte\'s and Chelsea Hospital, Tommy's National Early Miscarriage Research Centre; University Hospitals KU Leuven,

Department of Obstetrics and Gynaecology

<b>Primary Subject Heading</b>:

Mental health

Secondary Subject Heading: Obstetrics and gynaecology, Reproductive medicine

Keywords: Anxiety disorders < PSYCHIATRY, Depression & mood disorders < PSYCHIATRY, post-traumatic stress disorder, miscarriage, ectopic pregnancy

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TITLE PAGE

Post-traumatic stress disorder, anxiety and depression following

miscarriage or ectopic pregnancy: a prospective cohort study

Jessica Farren clinical research fellow1, Maria Jalmbrant clinical psychologist

2, Lieveke

Ameye medical statistician3, Karen Joash consultant gynaecologist

1, Nicola Mitchell-

Jones clinical research fellow4, Sophie Tapp

1 research assistant, Dirk Timmerman

professor of obstetrics and gynaecology3,5

, Tom Bourne adjunct professor and

consultant gynaecologist1,3,5

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]

Co-author affiliations:

1 Tommy’s National Early Miscarriage Research Centre, Queen Charlottes and Chelsea Hospital,

Imperial College, London, UK

2 South London and Maudsley NHS Foundation Trust, London, UK

3 KU Leuven, Department of Development and Regeneration, Leuven, Belgium

4 Chelsea and Westminster NHS Trust, London, UK

5 University Hospitals Leuven, Department of Obstetrics and Gynaecology, Leuven Belgium

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5 keywords or phrases: anxiety, depression, post-traumatic stress disorder, miscarriage, ectopic

pregnancy

Word count excluding title page/abstract/references/figures and tables: 4277

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ABSTRACT

Objectives: This is a pilot study to investigate the type and severity of emotional distress in

women after early pregnancy loss (EPL), compared to a control group with ongoing pregnancies.

The secondary aim was to assess whether miscarriage or ectopic pregnancy impacted differently

on the type and severity of psychological morbidity.

Design: This was a prospective survey study. Consecutive women were recruited between

January 2012 and July 2013. We emailed women a link to a survey one, three and nine months

after a diagnosis of EPL and one month after the diagnosis of a viable ongoing pregnancy.

Setting: The Early Pregnancy Assessment Unit (EPAU) of a central-London teaching hospital

Participants: We recruited 186 women. 128 had a diagnosis of EPL, and 58 of ongoing

pregnancies. 11 withdrew consent, and 11 provided an illegible or invalid e-mail address.

Main outcome measures: Post-traumatic stress disorder (PTSD) was measured using the Post-

traumatic Diagnostic Scale (PDS), and Anxiety and Depression using the Hospital Anxiety and

Depression Scale (HADS)

Results: Response rates were 69/114 at 1 month and 44/68 at three months in the EPL group,

and 20/50 in controls. Psychological morbidity was higher in the EPL group with 28% meeting

criteria for PTSD, 32% for anxiety, and 16% for depression at one month and 38%, 20%, and 5%

respectively at three months. In the control group, no women met criteria for PTSD and 10%

met criteria for anxiety and depression. There was little difference in type or severity of distress

following ectopic pregnancy or miscarriage.

Conclusions: We have shown a large number of women having experienced a miscarriage or

ectopic pregnancy fulfill the diagnostic criteria for PTSD. Many suffer from moderate to severe

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anxiety, and a lesser number depression. Psychological morbidity, and in particular PTSD

symptoms, persists at least three months following pregnancy loss.

Strengths and limitations of this study:

- We have used validated instruments to obtain quantitative data on mental wellbeing

after early pregnancy loss

- We have included women who have suffered both miscarriages and ectopic pregnancies

- In addition to anxiety and depression we have tested for the presence or absence of

post-traumatic stress disorder

- The main limitation of this study was the drop-out rate for responses at one month and

in our control group

- Whilst it is a strength that we have included a control group, a potential weakness is

that these were women who were attending an early pregnancy unit for assessment

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INTRODUCTION

Early pregnancy loss (EPL) is common, with miscarriage affecting 25% of women who have been

pregnant by the age of 39, constituting 12 to 20% of all pregnancies1. Ectopic pregnancy is less

common, thought to occur in approximately 1% of pregnancies 2.

The psychological consequences associated with an EPL cannot necessarily be extrapolated from

our understanding of grief reactions in other contexts. They encompass both bereavement, and

an often traumatic (and in some cases life threatening) personal physical experience. They can

pose a potential threat to the dream or expectation to have a family. In contrast to other losses,

there are no standardized rituals to manage grief, and there is often no physical manifestation

of the loss to mourn. Societal norms may also encourage privacy, which may translate into less

support from friends or colleagues.

Previous studies evaluating the immediate psychological impact of miscarriage have shown a

significant proportion of women meet the criteria for depression (27%) and anxiety (28-41%)3-5

.

Such symptoms decline over time, to levels equivalent to the non-pregnant population at one

year6. In general, anxiety is more marked than depression

7 8.

Post-traumatic stress disorder (PTSD) may develop in response to experiencing a real or

perceived threat of death or injury to oneself or others. In the context of EPL, the threat of

serious injury, sight of blood or fetal tissue, or subjective perception of experiencing the death

of a baby may be sufficiently traumatic to result in PTSD. In previous studies, women have rated

EPL as their worst lifetime exposure to trauma9. There are few data relating to PTSD and

miscarriage. In one prospective study involving 113 women, 25% reported symptoms of PTSD at

one month and 7% four months following an EPL10

. However this study included late pregnancy

losses, so it is not possible to establish the prevalence of PTSD after a loss in early pregnancy

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from these results.

There are few published data evaluating psychological morbidity following ectopic pregnancy.

One retrospective study has suggested there may be an association between surgically treated

ectopic pregnancies and suicide11

. Ectopic pregnancy is a potentially life-threatening condition

that is more likely to lead to emergency hospital admission and surgical intervention, where the

pregnancy loss is often treated as secondary. Furthermore ectopic pregnancy is frequently

associated with a threat to future fertility. Given this enhanced threat of physical harm in

addition to the EPL itself, it might be expected that the psychological consequences are different.

An understanding of the type and frequency of emotional reactions to pregnancy loss is

important in order to target appropriate support to those that need it, thereby minimizing

psychological morbidity and its societal cost. In the current study the primary aim was to assess

the levels of PTSD, anxiety, and depression in women following EPL compared to a control group

of women with ongoing viable pregnancies. The secondary aim was to evaluate whether there

was any evidence to suggest different levels of PTSD, anxiety and depression in women who had

suffered a miscarriage compared to those with an ectopic pregnancy. A final aim was to explore

the feasibility and sample size required for a larger study to assess for risk factors, which could

be used to target screening or treatment of psychiatric morbidity in this context.

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METHODS

Design

This was a prospective cohort study. We recruited women presenting to the Early Pregnancy

Assessment Unit (EPAU) at Queen Charlottes and Chelsea hospital, which is a central London

university teaching hospital. Women attended the unit because of bleeding and/or pain, or for

reassurance or dating. The data presented are derived from a pilot to demonstrate the

feasibility of, and sample size for, a larger study examining risk factors for the development of

psychological morbidity following EPL.

On the days on which the study investigators were available (an average of one half day per

week), consecutive women were approached for recruitment. Initially, we approached all

women who had been diagnosed on the basis of a transvaginal ultrasound scan as having an

ectopic pregnancy or miscarriage. Women were approached on the day of their diagnosis, or at

subsequent follow-up visit. Following a change in the study protocol in December 2012 to

enable a control group to be recruited, we approached all women attending the EPAU, including

those with a pregnancy of unknown location (PUL) and ongoing viable pregnancies. Hospital

records were checked to confirm the outcome of the pregnancy.

Women were offered management in accordance with local protocols. Those with ongoing

viable pregnancies were discharged and requested to book their standard antenatal care. Those

with miscarriage (unless complete) were offered the clinically appropriate options out of

expectant, medical (with misoprostol administered by the patient, per vaginam, at home) or

surgical management (suction evacuation under general anaesthetic). Women with ectopic

pregnancies were offered expectant, medical (with a single dose of methotrexate) or surgical

(usually laparoscopic salpingectomy) management, according to what was clinically appropriate

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with respect to their symptoms, the findings on ultrasonography and serum human chorionic

gonadotrophin levels.

All women recruited to the study were sent a link to a survey by e-mail one month after

diagnosis of their EPL, or at first confirmation of viability (defined as visualisation of embryo

heart activity). Women with an EPL who completed the one-month questionnaire were also

requested to complete surveys at three and nine months following the diagnosis. These time-

points were chosen to measure prolonged distress, and also to avoid both the due date of the

lost pregnancy (which would usually be after 6-8 months), and the anniversary of the loss, both

of which might be expected to exacerbate distress.

Written consent was gained for all participants. In every communication, including a

confirmatory email sent 48 hours after recruitment, the participant was reminded that their

participation was voluntary, and that they were free to withdraw.

In the three- and nine-month follow-up questionnaires, women were asked whether they were

trying to conceive, were pregnant, or had suffered another loss.

Participants

Patients were approached if they were above the age of 18 years, were able to give informed

consent, could speak English sufficiently to consent and respond to questions in the study, and if

the gestational age of the pregnancy was less than 20 weeks.

Between 1/1/2012 and 1/7/2013, 198 eligible women were consecutively approached and 186

women were recruited. Of those who declined to take part (12 cases), and voluntarily provided

a reason, the majority explained that they did not want to be reminded of the event by the

questionnaires. One woman explained that she had strong faith, and believed that the loss was

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‘in God’s hands’ – and explained that she felt participating and ‘questioning’ how she felt was

against her faith. 11 women subsequently withdrew their consent by email. None provided a

reason for doing so. 11 women provided illegible or invalid email addresses.

A total of 164 women received questionnaires: 114 had experienced an EPL and 50 had ongoing

viable pregnancies (the control group). Clinical information on each participant was collected at

enrolment, and updated on completion of follow-up. This included the reason for their initial

review, the initial and final diagnosis, and the clinical management. Information relating to the

gestational age and type of pregnancy loss and other demographic information about all study

recruits are seen in table 1.

Demographic and background information

Respondents were asked to provide demographic information including their age, level of

education, religion, income, marital status, length of time with current partner, religion,

previous mental health problems, and ethnic origin. They were then asked whether they had

ever had treatment in hospital, or emergency surgery, and to specify the details of this. The

participant was then asked whether or not they were still pregnant and they were separated

into two streams (control and EPL group) based on their responses.

Both groups were asked to detail any symptoms related to their visit (including the severity of

any pain and/or bleeding). They were asked details of their past obstetric history, including any

terminations of pregnancy, fertility treatment, the time taken to conceive the index pregnancy,

and how much the pregnancy was desired. They were asked whether they received clear

information from, and were emotionally supported by, healthcare professionals. They were

asked how satisfied they were with the healthcare they received, and whether they had

received any formal counselling, or would have liked to have been offered it. In addition, the

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EPL group were asked how worried they were for their own wellbeing during the loss, how

distressed they were, and how responsible they felt for the loss.

Measures

The participants were asked to complete a range of questionnaires presented in the same order,

as follows below. For the purposes of this pilot study, we limited our analysis to responses at

one and three months and for questionnaires relating to anxiety, depression and PTSD.

Post-traumatic diagnostic scale (PDS) This is a well-validated self-report questionnaire for the

presence of post-traumatic stress12

. It has good psychometric properties across a range of

populations and has a sensitivity of 0.89 and specificity of 0.7513

It contains 17 items based on

the DSM-IV diagnostic criteria for PTSD and measures probable PTSD diagnosis and symptom

severity (a score out of 51, with >10 designating at least moderate severity). The respondents in

the EPL group were asked to rate their symptoms in relation to the pregnancy loss, whilst the

control group was asked to complete the questionnaire in the standard way.

Hospital Anxiety and Depression Scale (HADS) All participants were asked to complete this 14-

item (seven questions related to each of anxiety and depression) questionnaire14

. Each subscale

measures symptom severity (a score out of 21, with ≥11 indicating moderate and ≥16 severe

symptoms). The HADS has good psychometric properties, and been used in a range of

populations; a review article identified 747 papers using HADS by May 200015

.

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Other self-report questionnaires completed by the participants but not included in this analysis

are the State Trait Anxiety Inventory (STAI), Norbeck Social Support Questionnaire (NSSQ), and

the Rumination Response Scale (RRS) and Self-compassion scale – short form (SCS).

The three- and nine-month questionnaires did not repeat demographic questions. They asked if

there had been any change in relationship status or new medical conditions, as well as whether

they had received any counselling and, if so, whether it had been helpful. It then asked whether

they had tried to conceive or were pregnant again. Respondents were then directed to HADS,

PDS, NSSQ, RRS and SCS.

Only a minority of participants responded to the 9-month questionnaire (18/68 (26%) of those

e-mailed). These results have therefore not been analysed for the pilot study and this has

highlighted to us the need to make an ethical amendment to allow us to send participants

reminder emails to chase responses.

Statistical analysis

For the purposes of this paper, we have limited ourselves to an analysis of the data for HADS

and PDS. To compare differences in binary variables we used the likelihood ratio, chi-square or

Fishers Exact test. We considered a P-value <0.05 as statistically significant. 95% confidence

intervals for rates of psychological morbidity were created using the Wilson method. All

statistical analyses were performed using SPSS version 20 and GraphPad Prism version 6.

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RESULTS

Demographic and background characteristics of the study sample

The groups (viable pregnancy, miscarriage and ectopic pregnancy) were similar in terms of age

at presentation (See Table 1). Gestation at presentation was lower in the ectopic pregnancy

group. Similar proportions were IVF pregnancies in the control and miscarriage group, but no

women with an ectopic pregnancy had had IVF. Most ectopic pregnancies were diagnosed on

the first ultrasound scan (18/24, 75%). Most miscarriages had an initially inconclusive ultrasound

scan (57/95, 60%). The majority of ectopic pregnancies (21/24, 88%) were ultimately treated

surgically, whereas 50/95 (54%) of miscarriages were successfully managed expectantly or with

outpatient medical management.

Response rates

At one month the response rate for women with EPL was 69/114 (61%). This includes one

woman who, according to our clinical records had been diagnosed with a viable pregnancy, but

in her responses indicated that a miscarriage had taken place while abroad. This participant did

not receive the subsequent questionnaires. The response rate for the control group was

significantly lower: 20/50 (40%) (p=0.02).

At three months, 44/68 (65%) of women responded. In addition, there were three completed

questionnaires (one at one month (who self-reported a loss), and two at three-months) in which

the respondent did not fill in their study number. These were excluded from the analysis.

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Respondents

Supplementary table 1 details background information on respondents in both the viable and

EPL groups. Both groups had similar characteristics in terms of past obstetric and psychiatric

history.

Levels of Post-traumatic Stress

At one month, 19/69 (28%) women in the EPL group met the PDS criteria for moderate or severe

PTSD. In addition, 9/69 (13%) women met all criteria for moderate or severe PTSD (13%) except

the criterion requiring the symptoms they reported to have been present for more than four

weeks. At three months 17/44 (39%) met the criteria for moderate or severe PTSD. The mean

severity score for all respondents with EPL was 15.3 (SD 9.9) at one month, and 11.6 (SD 9.5) at

three months.

We examined the endorsement of separate symptom clusters. Re-experiencing was the most

commonly endorsed, followed by avoidance, and then hyper-arousal. At one month, of all

questions asked, the most commonly endorsed statement was - ‘Feeling emotionally upset

when you were reminded of the loss of your pregnancy’ (40/69 (58%) women describing this

happening at least 2-4 times per week), followed by - ‘Having upsetting thoughts or images

about the loss of your pregnancy that came into your head when you didn’t want them’ (30/69

(43%) women describing this at least 2-4 times per week). At three months, re-experiencing

remained the most commonly endorsed symptom cluster. Endorsement of avoidance symptoms

had declined (50/69 (72%) to 22/44 (55%), p=0.07), and become the least common. The

reported impact of the endorsed symptoms on areas of respondents’ lives is detailed in Table 2.

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The dropout rate between one and three months was slightly (non-significantly) higher for those

with moderate-severe PTSD at one month (8/19 (42%)), than for those with no or mild PTSD

(16/49 (33%)).

In the control group, no women met the criteria for a diagnosis of PTSD for self-reported

traumatic life events (not specifically probing for previous EPLs).

Levels of Anxiety and Depression

Table 3 and Figure 2 illustrate that the incidence of moderate or severe anxiety was higher in

the EPL compared to the control group at one month: 22/69 (32%) versus 2/20 (10%) (p = 0.04),

and declined over time in the EPL group to 9/44 (20%) at 3 months. The incidence of moderate

and severe depression was similar in both groups for all time-points: 11/69 (16%) for women

with an EPL compared to 2/20 (10%) for controls, dropping to lower than the control group

(2/44 (5%)) at 3 months.

The mean severity score at 1 month in the EPL group was 7.8 for anxiety (SD 4.8) and 5.7 (SD

4.4) for depression, whilst the control group had a mean severity score of 6.6 (SD 3.0) for

anxiety and 3.9 (SD 4.2) for depression. At 3 months the mean severity score in the EPL group

for anxiety was 6.8 (SD 4.2), and 4.1 for depression (SD 3.6).

The drop out rate between one and three months was higher in women with moderate-severe

anxiety and depression compared to those with no or mild anxiety or depression, although

these results did not reach significance (11/22 (50%) drop-out for those with moderate/severe

anxiety vs 13/46 (28%) with none/mild anxiety, 6/11 (55%) vs 18/57 (32%) respectively for

depression).

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Ectopic pregnancy compared to miscarriage

Table 4 compares the psychological distress following ectopic pregnancy and miscarriage. When

comparing the ectopic pregnancy and the miscarriage groups, six of the 16 women who had

experienced an ectopic pregnancy met criteria for PTSD (38%), compared to 13/53 (25%) in the

miscarriage group. 4/8 (25%) met the criteria for moderate/severe anxiety, compared to 18/53

(34%) in the miscarriage group. 2/16 (13%) met criteria for moderate/severe depression,

compared to 9/53 (17%) in the miscarriage group. None of these differences reached statistical

significance.

Comparison according to pregnancy status at three months

At three months, 22/44 (50%) of respondents reported trying to conceive but not yet being

pregnant. 9/22 (41%) who were trying to conceive met criteria for PTSD, compared to 2/6 (33%)

who were pregnant again, and 6/16 (38%) who had not tried to conceive. 5/22 (23%) of those

who were trying to conceive met the criteria for moderate/severe anxiety, compared to none

(0/6) of the group who were pregnant again, and 4/16 (25%) in the group who were not trying

to conceive. For depression, 1/22 (5%) who was trying to conceive, 1/6 (17%) who was pregnant

again, and none (0/16) of the group who were not trying to conceive met criteria.

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DISCUSSION

We have shown in our cohort of women attending an inner London EPAU that 39% of women

three months after suffering an early pregnancy loss meet the criteria for moderate to severe

PTSD. Furthermore 20% meet the criteria for moderate to severe anxiety compared to 10% in

our control population. Levels of anxiety and depression dropped between one and three

months, but the symptoms associated with PTSD persisted. We also found that women with

ectopic pregnancy suffer from significant levels of emotional distress, with slightly higher levels

of PTSD compared to women who experience a miscarriage, but lower levels of anxiety and

depression.

This pilot study, has demonstrated the feasibility of a larger scale study into the psychological

morbidity associated with EPL. Women were generally happy to be approached and take part.

All women who got as far as entering their study number at the start of the online questionnaire

completed all questions, reassuring us that the required time commitment was appropriate. The

drop out rate has implications for future study size, and has resulted in us submitting an

amendment to allow up to two reminder emails in an effort to improve this.

A strength of this study is that women were consecutively recruited rather than self-referring

themselves for involvement. Knowledge of their clinical data and outcomes enabled us to send

the questionnaires at appropriate set time points after diagnosis. We also involved a relatively

large number of women compared to other studies of its type. A further strength is in the

inclusion of women with ectopic pregnancies, a group largely unreported in the literature to

date.

The primary weakness of the study is in the significant drop out rate, including both a failure to

respond to the initial questionnaire, and the drop out of initial responders to subsequent

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questionnaires. In line with our protocol, it was not possible to find out the reasons for this. It

does raise the concern of a potential ascertainment bias artificially inflating rates of pathology.

However whilst it is possible that women with a more significant emotional response to EPL

were more likely to respond, it is perhaps more likely that women with the greatest trauma

avoid engagement with a process that makes them confront the event. The observed selective

drop out of those with higher PTSD, anxiety and depression levels perhaps supports the view

that there may have been a group of women who did not want to be reminded of their feelings

about their EPL. A further weakness is the possibility of an unintended, moderating therapeutic

effect from taking part in the study – a hypothesis supported by results from Neugebauer and

colleagues’ study16

. Finally, we recognise that this study relies on the use of self-report screening

questionnaires, whereas confirmed diagnosis of these disorders requires more extensive

interview with appropriately trained personnel.

Respondents in our control group who did not suffer an EPL in the index pregnancy had a high

rate of previous miscarriage (45%). This can be explained by the fact that in the United Kingdom,

attendance for medical review in early pregnancy is often for reassurance in women with a

previous history of EPL. It also seems likely that women with a past pregnancy loss would be

more likely to invest time in the questionnaire. The result is that, whilst our control group is a

useful comparator, we would probably be underestimating overall levels of distress related to

early pregnancy loss if we were to rely on it as a normative baseline.

We were surprised by the incidence of PTSD in our study. Even in women not meeting the full

criteria for PTSD, there was a significant endorsement of all symptom clusters by the majority of

participants, along with impairment across social and occupational domains, and in general

satisfaction. This incidence of PTSD is higher than previously reported 10

. However, in the paper

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by Engelhard et al the participants were not limited to women with losses in early pregnancy.

Furthermore, the PDS scale was scored differently in our paper. We scored according to Foa’s

original recommendation – where a symptom was considered endorsed if it occurs ‘once a week

or less/once in a while’ – whereas Engelhard required a symptom to occur ‘2-4 times a

week/half the time’.

It will be noted that there is an apparent increase in PTSD between month one (28% of

respondents) and month three (38%). This reflects the timing of the questionnaires, which were

sent out one month after the EPL. Accordingly women may have endorsed the symptom clusters

that constitute a diagnosis of PTSD, but would not at that stage have fulfilled the requirement

for the symptoms to have been present for at least one month. We considered classifying these

women as having an acute stress disorder, however strictly speaking the PDS is not validated for

this purpose. In any event the number of women who endorse the symptoms clusters for PTSD

other than the duration criterion at one month is 41% of initial respondents, suggesting that

there is no appreciable fall off in PTSD symptoms between month one and three.

The observation that such a significant proportion of women suffer from symptoms of PTSD

after losing a pregnancy, and that this is more common than both anxiety and depression is

important. In other contexts, we know that untreated PTSD has a significant impact on quality of

life, relationships, ability to work, suicide risk, and physical health17-19

. PTSD also has implications

for future pregnancies, including poor health behaviour, reduced gestational length, and issues

with infant bonding20-22

. The treatment for PTSD is specific and relies on trauma focused

cognitive behavioural therapy or eye movement desensitisation and reprocessing23

. It is perhaps

not surprising therefore that the outcome of a broad-brush approach of offering “counselling”

(in variable formats) to all women following miscarriage has been disappointing 24

. Given the

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serious impact of untreated PTSD, screening women for the disorder following EPL may be a

more effective use of resources. Conversely, we have shown that there are a number of women

who do not suffer significant morbidity. These may not require any intervention following their

loss.

There are some issues to be considered with respect to the diagnosis of PTSD using the PDS.

First, the diagnostic criteria for PTSD changed slightly during the trial. In the 2013 DSM-5, the

requirement for the trauma to result in fear, helplessness or horror was removed18

. All of our

patients with the other features of PTSD met this criterion; thus its removal would not change

our results. In addition, a fourth symptom cluster relating to negative alterations in mood was

included. The PDS does not contain questions pertaining to this cluster, and there are currently

no validated screening questionnaires relating to it. In any event, although diagnostic thresholds

are important to define the nature of any pathology, this change does not detract from the

frequency or severity of distress we have observed. Third, there may be debate about

miscarriage or ectopic pregnancy fulfilling criteria for a ‘traumatic event’ according to DSM 5 18

,

which requires either participation in a life-threatening event, including a catastrophic medical

event, or observing the death or serious injury to others. Clearly, some EPLs do result in sudden,

life-threatening haemorrhage or emergency surgery and may thus be classified as a catastrophic

medical event. The interpretation of whether an EPL fulfills the criteria of vicarious trauma by

observing death or serious injury is subjective. Some women and couples start relating to their

embryo as a child as soon as they have received a positive pregnancy test, and for them losing

that embryo and perhaps observing the embryo or fetus being passed during the miscarriage

may be equated with the catastrophic death of a child.

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Future research would be aimed at assessing for risk factors for PTSD. Based on this pilot study,

we have estimated that a total of 440 women with losses would need to complete Part 1 of the

study to demonstrate a 20% difference in incidence between women with assisted reproduction

and those without (chosen as the least common potential risk factor of interest) (power 0.80

and alpha 0.05). Accounting for rates of declined participation, withdrawal and non-response,

811 women with EPL should be recruited.

Our findings are highly relevant to healthcare professionals who deal with early pregnancy loss.

Exposure to EPL on a daily basis may lead clinicians to normalize the experience and overlook

the possible profound psychological sequelae. Given the high rates of PTSD symptomatology

found in this patient group, we believe that consideration should be given to screening all

women who have suffered an EPL for PTSD. There is also a need for tools to help predict those

women who are most at risk of serious psychological morbidity, in order to facilitate early

intervention and appropriate treatment.

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ACKNOWLEDGEMENTS

The research team would like to thank the women that generously donated their time to

participate, as well as all the staff in the EPU for their support with this study.

CONTRIBUTORSHIP

TB, MJ and KJ devised the original study protocol. JF recruited patients to the study. JF and LA

were responsible for statistical analysis of the results. TB, JF and MJ wrote the first draft of the

manuscript that was then critically reviewed and revised by the other co-authors. DT, NMJ and

ST commented on drafts of the paper. All authors approved the final version of the manuscript

for submission. All authors had full access to all of the data (including statistical reports and

tables) in the study and can take responsibility for the integrity of the data and the accuracy of

the data analysis. TB is the guarantor, and affirms that that the manuscript is an honest,

accurate, and transparent account of the study being reported; that no important aspects of the

study have been omitted; and that any discrepancies from the study as planned have been

explained.

COMPETING INTERESTS

None to declare

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. DT is Senior Clinical Investigator of FWO (Research Foundation – Flanders).

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DATA SHARING STATEMENT

No additional data are available

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REFERENCES

1. Blohm F, Friden B, Milsom I. A prospective longitudinal population-based study of clinical

miscarriage in an urban Swedish population. BJOG 2008;115(2):176-82; discussion 83.

2. NICE. Ectopic pregnancy and miscarriage: diagnosis and initial management, 2012.

3. Lok IH, Yip AS, Lee DT, et al. A 1-year longitudinal study of psychological morbidity after

miscarriage. Fertil Steril 2010;93(6):1966-75.

4. Cumming GP, Klein S, Bolsover D, et al. The emotional burden of miscarriage for women and

their partners: trajectories of anxiety and depression over 13 months. BJOG

2007;114(9):1138-45.

5. Prettyman RJ, Cordle CJ, Cook GD. A three-month follow-up of psychological morbidity after

early miscarriage. Br J Med Psychol 1993;66 ( Pt 4):363-72.

6. Janssen HJ, Cuisinier MC, Hoogduin KA, et al. Controlled prospective study on the mental

health of women following pregnancy loss. Am J Psychiatry 1996;153(2):226-30.

7. 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(356):94-6.

8. Nikcevic AV, Tunkel SA, Nicolaides KH. Psychological outcomes following missed abortions and

provision of follow-up care. Ultrasound Obstet Gynecol 1998;11(2):123-8.

9. Hamama L, Rauch SA, Sperlich M, et al. Previous experience of spontaneous or elective

abortion and risk for posttraumatic stress and depression during subsequent pregnancy.

Depress Anxiety 2010;27(8):699-707.

10. Engelhard IM, van den Hout MA, Arntz A. Posttraumatic stress disorder after pregnancy loss.

Gen Hosp Psychiatry 2001;23(2):62-6.

11. Farhi J, Ben-Rafael Z, Dicker D. Suicide after ectopic pregnancy. N Engl J Med

1994;330(10):714.

12. Foa EB, Riggs DS, Dancu CV, et al. Reliability and validity of a brief instrument for assessing

post-traumatic stress disorder. Journal of Traumatic Stress 1993;6(4):459-73.

13. Foa E, Cashman L, Jaycox L, et al. The validation of a self-report measure of posttraumatic

stress disorder: The Posttraumatic Diagnostic Scale. Psychological Assessment

1997;9(4):445-51.

14. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta psychiatrica

Scandinavica 1983;67(6):361-70.

15. Bjelland I, Dahl AA, Haug TT, et al. The validity of the Hospital Anxiety and Depression Scale:

An updated literature review. Journal of Psychosomatic Research 2002;52(2):69-77.

16. Neugebauer R, Kline J, O'Connor P, et al. Depressive symptoms in women in the six months

after miscarriage. Am J Obstet Gynecol 1992;166(1 Pt 1):104-9.

17. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin

Psychiatry 2000;61 Suppl 5:4-12; discussion 13-4.

18. American Psychiatric A, American Psychiatric Association DSMTF. Diagnostic and statistical

manual of mental disorders : DSM-5. Arlington, Va. ; London: American Psychiatric

Association, 2013.

19. Rapaport MH, Clary C, Fayyad R, et al. Quality-of-life impairment in depressive and anxiety

disorders. Am J Psychiatry 2005;162(6):1171-8.

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20. Rogal SS, Poschman K, Belanger K, et al. Effects of posttraumatic stress disorder on

pregnancy outcomes. Journal of affective disorders 2007;102(1-3):137-43.

21. Dunkel Schetter C, Tanner L. Anxiety, depression and stress in pregnancy: implications for

mothers, children, research, and practice. Current opinion in psychiatry 2012;25(2):141-

8.

22. Klier CM, Geller PA, Ritsher JB. Affective disorders in the aftermath of miscarriage: a

comprehensive review. Archives of women's mental health 2002;5(4):129-49.

23. NICE. Post-traumatic stress disorder: management 2005.

24. Murphy FA, Lipp A, Powles DL. Follow-up for improving psychological well being for women

after a miscarriage. The Cochrane database of systematic reviews 2012;3:Cd008679.

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TABLES

Table 1. Demographic and background characteristics of the study sample

All Recruits Viable pregnancy Miscarriage Ectopic

Number recruited

175 56

95

(including 13

resolved PUL)

24

Mean age

(years)

33.8

34.1 33.0 34.9

Mean gestation at diagnosis

(weeks)

9.2 10.3 9.1 7.1

IVF pregnancy 10/175 (6%) 4/56 (7%) 6/95 (6%) 0/24

First ultrasound inconclusive 76/175 (43%) 13/56 (23%) 57/95 (60%) 6/24 (25%)

Final Management

None required/Expectant

Medical management*

Surgical management

Lost to follow-up

N/A

35 (37%)

15 (16%)

43** (45%)

2 (2%)

1 (4%)

2 (8%)

21*** (88%)

0

*Medical management refers to the use of misoprostol to treat miscarriage, or the use of methotrexate to treat

ectopic pregnancy

** including one molar pregnancy, and one PUL investigated with laparoscopy and suction evacuation, ultimately

found to be intra-uterine

*** including one cervical ectopic treated with suction evacuation

PUL -Pregnancy of Unknown Location; IVF - In Vitro Fertilization

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Table 2. Proportion of respondents meeting criteria for post-traumatic stress disorder at 1 and 3

months (subdivided according to severity, including and excluding the duration criterion),

individual symptom clusters within PDS endorsed, and areas of life symptoms reported to have

impacted upon

One month

Three months

Including duration

criterion**

Excluding duration

criterion**

Total proportion meeting PDS

criteria

22/69 (32%) 31/69 (45%) 19/44 (43%)

Mild 3/69 (4%) 3/69 (4%) 2/44 (5%)

Moderate 6/69 (9%) 11/69 (9%) 9/44 (20%)

Moderate-Severe 10/69 (14%) 14/69 (20%) 7/44 (16%)

Severe 3/69 (4%) 3/69 (4%) 1/44 (2%)

Symptom clusters endorsed*

Re-experiencing 64/69 (93%) 39/44 (89%)

Avoidance 50/69 (72%) 24/44 (55%)

Hyper-arousal 39/69 (57%) 27/44 (61%)

Areas of life symptoms impacted on

Work 36/69 (52%) 13/44 (30%)

Household chores 22/69 (32%) 9/44 (20%)

Relationships with family 28/69 (41%) 16/44 (36%)

Relationships with friends 34/69 (49%) 17/44 (39%)

Fun and leisure activities 38/69 (55%) 21/44 (48%)

Sex life 48/69 (70%) 21/44 (48%)

General satisfaction with life 48/69 (70%) 26/44 (59%)

Overall level of functioning 35/69 (51%) 20/44 (45%)

*endorsed so as to meet criteria i.e. Re-experiencing – one or more positive responses to 5 questions, Avoidance –

three or more positive responses to 7 questions, Hyper-arousal – two or more positive responses to 5 questions

** the duration criterion requires a respondent to verify that the symptoms they are reporting have been present for

“more than one month”. Where excluded, this requirement is disregarded

PTSD - post traumatic stress disorder; PDS – Post-traumatic diagnostic scale

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Table 3. Proportion meeting criteria for anxiety and depression, and severity scores, according

to HADS, at 1 and 3 months.

HADS – Hospital Anxiety and Depression Scale; EPL – early pregnancy loss; CI - Confidence interval; SD - Standard

deviation

Controls EPL 1 month EPL 3 months

Anxiety: proportion of moderate & severe cases; %

(95% CI)

2/20

10% (3% to 30%)

22/69

32% (22% to 44%)

9/44

20% (11% to 35%)

Anxiety score (/21); mean (SD) 6.6 (3.0) 7.8 (4.8) 6.8 (4.2)

Depression : proportion of moderate & severe cases; %

(95% CI)

2/20

10% (3% to 30%)

11/69

16% (9% to 26%)

2/44

5% (1% to 15%)

Depression score (/21); mean (SD)

3.9 (4.2) 5.7 (4.4) 4.2 (3.6)

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Table 4. PDS, anxiety and depression scores for ectopic pregnancy compared to miscarriage

1 month 3 months

All EPL Miscarriage Ectopic All EPL Miscarriage Ectopic

PDS

(moderate, moderate-severe,

severe)

19/69

28%

13/53

25%

6/16

38%

17/44

39%

15/33

45%

2/11

18%

Mean PDS score 15.3 (9.9) 16.1 (9.9) 12.6 (9.7) 11.6 (9.5) 12.4 (9.2) 9.1 (10.2)

Anxiety

(moderate & severe cases)

22/69

32%

18/53

34%

4/16

25%

9/44

20%

8/33

24%

1/11

9%

Mean anxiety score (/21)

(SD)

7.8 (4.8) 8.1 (4.8) 6.9 (4.7) 6.8 (4.2) 7.2 (4.1) 5.6 (4.4)

Depression


11/69

16%

9/53

17%

2/16

13%

2/44

5%

1/33

3%

1/11

9%

Mean Depression score (/21)

(SD)

5.7 (4.4) 6.0 (4.4) 4.9 (4.6) 4.2 (3.5) 4.3 (3.3) 3.7 (4.2)

PDS - Post-traumatic Diagnostic Scale; SD - Standard Deviation

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LEGENDS FOR FIGURES

Figure 1. Flowchart showing numbers invited to participate, reasons for withdrawal, and

response rates to 1- and 3-month questionnaires

Figure 2. Bar chart illustrating proportion of women meeting criteria for moderate or severe

anxiety/depression, according to HADS, with 95% confidence limits

SUPPLEMENTARY FILE

Supplementary table 1. A comparison of response rates, and reported demographic and

background variables according to pregnancy outcome (viable pregnancy, early pregnancy loss

(then subdivided into miscarriage and ectopic))

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Figure 1. Flowchart showing numbers invited to participate, reasons for withdrawal, and response rates to 1- and 3-month questionnaires

254x254mm (72 x 72 DPI)

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Figure 2. Bar chart illustrating proportion of women meeting criteria for moderate or severe anxiety/depression, according to HADS, with 95% confidence limits

Figure 2 83x69mm (300 x 300 DPI)

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Supplementary table 1. A comparison of response rates, and reported demographic and background

variables according to pregnancy outcome (viable pregnancy, early pregnancy loss (then subdivided

into miscarriage and ectopic))

Viable pregnancy All EPL Miscarriage Ectopic

Number recruited 58 128 104 24

Active withdrawal 2 9 9 0

Invalid email 6 5 5 0

Response rate 20/50 (40%) 69/114 (61%) 53/90 (59%) 16/24 (67%)

Self-reported background characteristics:

Length of time trying to

conceive <3 months

9/20 (45%) 41/69 (59%) 32/53 (60%) 9/16 (65%)

IVF pregnancy 2/20 (10%) 5/69 (7%) 3/53 (6%) 0/16 (0%)

Existing children 5/20 (25%) 26/69 (38%) 22/53 (42%) 4/16 (25%)

Previous miscarriage 9/20 (45%) 27/69 (39%) 22/53 (42%) 5/16 (31%)

Previous ectopic 0/20 6/69 (9%) 2/53 (4%) 4/16 (25%)

Current psychiatric

diagnosis

0/20 2/69 (3%) 1/53 (2%) 1/16 (6%)

Past psychiatric

diagnosis

8/20 (40%) 17/69 (25%) 13/53 (25%) 3/16 (19%)

Pregnancy desired –

proportion ‘very much

so’

7/20 (35%) 61/69 (88%) 49/53 (92%) 12/16 (75%)

3-month response rates:

Drop-out rate from 1 to

3 months

n/a 25/69 (36%) 20/53 (38%) 5/16 (31%)

Proportion of

respondents pregnant

at 3 month follow-up

n/a 6/44 (14%) 4/33 (12%) 2/11 (18%)

EPL - early pregnancy loss; IVF – In vitro fertilization

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STROBE 2007 (v4) Statement—Checklist of items that should be included in reports of cohort studies

Section/Topic Item

# Recommendation Reported on page #

Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the abstract 1

(b) Provide in the abstract an informative and balanced summary of what was done and what was found 3

Introduction

Background/rationale 2 Explain the scientific background and rationale for the investigation being reported 5

Objectives 3 State specific objectives, including any prespecified hypotheses 6

Methods

Study design 4 Present key elements of study design early in the paper 7

Setting 5 Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data

collection

8-9

Participants 6 (a) Give the eligibility criteria, and the sources and methods of selection of participants. Describe methods of follow-up 8

(b) For matched studies, give matching criteria and number of exposed and unexposed

Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria, if

applicable

10

Data sources/

measurement

8* For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe

comparability of assessment methods if there is more than one group

10

Bias 9 Describe any efforts to address potential sources of bias 16

Study size 10 Explain how the study size was arrived at 7

Quantitative variables 11 Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen and

why

10

Statistical methods 12 (a) Describe all statistical methods, including those used to control for confounding 11

(b) Describe any methods used to examine subgroups and interactions 11

(c) Explain how missing data were addressed 12, 14

(d) If applicable, explain how loss to follow-up was addressed n/a

(e) Describe any sensitivity analyses n/a

Results

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Participants 13* (a) Report numbers of individuals at each stage of study—eg numbers potentially eligible, examined for eligibility, confirmed

eligible, included in the study, completing follow-up, and analysed

flowchart

(b) Give reasons for non-participation at each stage flowchart

(c) Consider use of a flow diagram

Descriptive data 14* (a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential

confounders

Table 1,

supplementary table

(b) Indicate number of participants with missing data for each variable of interest flowchart

(c) Summarise follow-up time (eg, average and total amount) n/a

Outcome data 15* Report numbers of outcome events or summary measures over time flowchart

Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence

interval). Make clear which confounders were adjusted for and why they were included

13-15

(b) Report category boundaries when continuous variables were categorized 10

(c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period n/a

Other analyses 17 Report other analyses done—eg analyses of subgroups and interactions, and sensitivity analyses 13-15

Discussion

Key results 18 Summarise key results with reference to study objectives 16

Limitations

Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from

similar studies, and other relevant evidence

16-17

Generalisability 21 Discuss the generalisability (external validity) of the study results 17

Other information

Funding 22 Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on

which the present article is based

21

*Give information separately for cases and controls in case-control studies and, if applicable, for exposed and unexposed groups in cohort and cross-sectional studies.

Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and published examples of transparent reporting. The STROBE

checklist is best used in conjunction with this article (freely available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at

http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is available at www.strobe-statement.org.

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Post-traumatic stress, anxiety and depression following miscarriage or ectopic pregnancy: a prospective cohort

study

Journal: BMJ Open

Manuscript ID bmjopen-2016-011864.R1


Date Submitted by the Author: 04-Jun-2016





Mental health




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TITLE PAGE

Post-traumatic stress, anxiety and depression following


Jessica Farren clinical research fellow1, Maria Jalmbrant clinical psychologist2, Lieveke

Ameye medical statistician3, Karen Joash consultant gynaecologist1, Nicola Mitchell-

Jones clinical research fellow4, Sophie Tapp1 research assistant, Dirk Timmerman

professor of obstetrics and gynaecology3,5, Tom Bourne adjunct professor and


Corresponding author: Professor Tom Bourne, Tommy’s National Centre for Miscarriage Research, Imperial College, Queen Charlottes and Chelsea Hospital, Du Cane Road, London W12 0HS



1 Tommy’s National Centre for Miscarriage Research, Queen Charlottes and Chelsea Hospital,






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mailto:[email protected]




pregnancy


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ABSTRACT







after a diagnosis of EPL, and one month after the diagnosis of a viable ongoing pregnancy.









criteria for probable PTSD, 32% for anxiety, and 16% for depression at one month and 38%, 20%,

and 5% respectively at three months. In the control group, no women met criteria for PTSD and

10% met criteria for anxiety and depression. There was little difference in type or severity of

distress following ectopic pregnancy or miscarriage.


ectopic pregnancy fulfill the diagnostic criteria for probable PTSD. Many suffer from moderate

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to severe anxiety, and a lesser number depression. Psychological morbidity, and in particular

PTSD symptoms, persists at least three months following pregnancy loss.





- In addition to anxiety and depression we have tested for the probable presence or

absence of post-traumatic stress disorder





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INTRODUCTION


pregnant by the age of 39, constituting 12 to 20% of all pregnancies1. Ectopic pregnancy

(defined as the development of a pregnancy outside the uterine cavity, usually within the

fallopian tube) is less common, thought to occur in approximately 1% of pregnancies 2.









significant proportion of women meet the criteria for depression (27%) and anxiety (28-41%)3-5.


year6. In general, anxiety is more marked than depression7 8.






miscarriage. In one prospective study involving 113 women, 25% reported symptoms of PTSD at

one month and 7% four months following an EPL10. However this study included late pregnancy

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losses, so it is not possible to establish the prevalence of PTSD after a loss in early pregnancy

from these results.



ectopic pregnancies and suicide11. Ectopic pregnancy is a potentially life-threatening condition








the levels of PTSD, anxiety, and depression in women following EPL compared to a control group

of women with ongoing viable pregnancies. The secondary aim was to evaluate whether there

was any evidence to suggest different levels of PTSD, anxiety and depression in women who had

suffered a miscarriage compared to those with an ectopic pregnancy. A final aim was to explore

the feasibility and sample size required for a larger study to assess for risk factors, which could

be used to target screening or treatment of psychiatric morbidity in this context.

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METHODS

Design

This was a prospective cohort study, with ethical approval of the study protocol granted by the

NRES committee of South-West Exeter, reference 11/SW/0052.

We recruited women presenting to the Early Pregnancy Assessment Unit (EPAU) at Queen

Charlottes and Chelsea hospital, which is a central London university teaching hospital. Women

attended the unit because of bleeding and/or pain, or for reassurance or dating. The data

represent a pilot to demonstrate the feasibility of, and provide data from which to derive the

sample size for, a larger study examining risk factors for the development of psychological

morbidity following EPL.













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Participants




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women were recruited (see Figure 1). Of those who declined to take part (12 cases), and

voluntarily provided a reason, the majority explained that they did not want to be reminded of

the event by the questionnaires. One woman explained that she had strong faith, and believed

that the loss was ‘in God’s hands’ – and explained that she felt participating and ‘questioning’

how she felt was against her faith. 11 women subsequently withdrew their consent by email.

None provided a reason for doing so. 11 women provided illegible or invalid email addresses.

















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Measures





presence of post-traumatic stress12. It has good psychometric properties across a range of

populations and has a sensitivity of 0.89 and specificity of 0.7513 It contains 17 items based on

the DSM-IV diagnostic criteria for PTSD and measures probable PTSD diagnosis and symptom

severity (a score out of 51, with >10 designating at least moderate severity). The respondents in

the EPL group were asked to rate their symptoms in relation to the pregnancy loss, whilst the

control group was asked to complete the questionnaire in the standard way, in relation to a self-

identified exposure to other trauma (if present).


item (seven questions related to each of anxiety and depression) questionnaire14. Each subscale


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symptoms). The HADS has good psychometric properties, and been used in a range of

populations; a review article identified 747 papers using HADS by May 200015 .


are the State Trait Anxiety Inventory (STAI), Norbeck Social Support Questionnaire (NSSQ), the

Rumination Response Scale (RRS) and Self-compassion scale – short form (SCS).







e-mailed). These results have therefore not been analysed for the pilot study, and this









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RESULTS










Response rates









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Respondents



history.


At one month, 19/69 (28% (95% CI 18%-39%)) women in the EPL group met the PDS criteria for

probable moderate or severe PTSD. In addition, 9/69 (13%) women met all criteria for probable

moderate or severe PTSD except the criterion requiring the symptoms they reported to have

been present for more than four weeks. At three months 17/44 (39% (26%-53%)) met the

criteria for probable moderate or severe PTSD. The mean severity score for all respondents with

EPL was 15.3 (SD 9.9) at one month, and 11.6 (SD 9.5) at three months.









had declined (50/69 (72% (61%-82%)) to 22/44 (50% (36%-64%)), p=0.07), and become the least

common. The reported impact of the endorsed symptoms on areas of respondents’ lives is

detailed in Table 2.

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with probable moderate-severe PTSD at one month (8/19 (42%)), than for those with no or mild

PTSD (16/49 (33%)).

In the control group, no women met the criteria for a diagnosis of probable PTSD for self-

reported traumatic life events (not specifically probing for previous EPLs).


At one month, 22/69 (32% (22%-44%)) of women in the EPL group met criteria for moderate-

severe anxiety, compared to 2/20 (10% (3%-30%)) in the control group (p=0.04) (Table 3 and

Figure 2). This declined over time in the EPL group to 9/44 (20% (11%-35%)) at 3 months. The

prevalence of moderate and severe depression symptoms was similar in both groups for all

time-points: 11/69 (16% (9%-26%)) for women with an EPL compared to 2/20 (10% (3%-30%))

for controls, dropping to lower than the control group (2/44 (5% (1%-15%))) at 3 months.









depression).

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experienced an ectopic pregnancy met criteria for probable PTSD (38% (18%-61%)), compared

to 13/53 (25% (15%-38%)) in the miscarriage group. 4/16 (25% (10-50%)) met the criteria for

moderate/severe anxiety symptoms, compared to 18/53 (34% (23%-47%)) in the miscarriage

group. 2/16 (13% (4%-36%)) met criteria for moderate/severe depression symptoms, compared

to 9/53 (17% (9%-29%)) in the miscarriage group. None of these differences reached statistical

significance.



pregnant. 9/22 (41% (23%-61%)) who were trying to conceive met criteria for probable PTSD,

compared to 2/6 (33% (10%-70%)) who were pregnant again, and 6/16 (38% (18%-61%)) who

had not tried to conceive. 5/22 (23% (10%-43%)) of those who were trying to conceive met the

criteria for moderate/severe anxiety, compared to none (0/6) of the group who were pregnant

again, and 4/16 (25% (10%-50%)) in the group who had not tried to conceive. For depression,

1/22 (5% (1%-22%)) who were trying to conceive, 1/6 (17% (3%-56%)) who were pregnant again,

and none (0/16) of the group who had not tried to conceive, met criteria.

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DISCUSSION

We have shown in our cohort of women attending an inner London EPAU that 39% of

participants three months after suffering an early pregnancy loss meet the criteria for probable

moderate to severe PTSD. Furthermore 20% meet the criteria for moderate to severe anxiety

compared to 10% in our control population. Levels of anxiety and depression dropped between

one and three months, but the symptoms associated with PTSD persisted. We also found that

women with ectopic pregnancy suffer from significant levels of emotional distress, with slightly

higher levels of PTSD symptoms compared to women who experience a miscarriage, but lower

levels of anxiety and depression.








themselves for involvement, with a high proportion (94%) of those approached providing

consent to take part. Knowledge of their clinical data and outcomes enabled us to send the

questionnaires at appropriate set time points after diagnosis. We also involved a relatively large

number of women compared to other studies of its type. A further strength is in the inclusion of

women with ectopic pregnancies, a group largely unreported in the literature to date.



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were more likely to respond, it is also likely that women with the greatest trauma avoid

engagement with a process that makes them confront the event. The observed selective drop

out of those with higher PTSD, anxiety and depression levels perhaps supports the view that

there may have been a group of women who did not want to be reminded of their feelings



colleagues’ study16. Finally, we recognise that this study relies on the use of self-report screening









early pregnancy loss if we were to rely on it as a normative baseline. Our control group is also

smaller than the EPL group, as a result of the recruitment methodology described, which has

implications for the power of the EPL versus control group calculations.

We were surprised by the prevalence of PTSD symptoms in our study. Even in women not

meeting the full criteria for PTSD, there was a significant endorsement of all symptom clusters

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by the majority of participants, along with impairment across social and occupational domains,

and in general satisfaction. This prevalence of probable PTSD is higher than previously reported

10. However, in the paper by Engelhard et al the participants were not limited to women with

losses in early pregnancy. Furthermore, the PDS scale was scored differently in our paper. We

scored according to Foa’s original recommendation – where a symptom was considered

endorsed if it occurs ‘once a week or less/once in a while’ – whereas Engelhard required a

symptom to occur ‘2-4 times a week/half the time’.

It will be noted that there is an apparent increase in probable PTSD between month one (28% of










after losing a pregnancy, and that this is more common than both anxiety and depression, is

important. In other contexts, we know that untreated PTSD has a significant impact on quality of

life, relationships, ability to work, suicide risk, and physical health17-19. PTSD also has implications

for future pregnancies, including poor health behaviour, reduced gestational length, and issues

with infant bonding20-22. The treatment for PTSD is specific and relies on trauma focused

cognitive behavioural therapy or eye movement desensitisation and reprocessing23. It is perhaps

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not surprising therefore that the outcome of a broad-brush approach of offering “counselling”

(in variable formats) to all women following miscarriage has been disappointing24. Given the

serious impact of untreated PTSD, screening women for the disorder following EPL may be a

more effective use of resources. Conversely, we have shown that there are a number of women

who do not suffer significant morbidity. These may not require any intervention following their

loss.



requirement for the trauma to result in fear, helplessness or horror was removed18. All of our







miscarriage or ectopic pregnancy fulfilling criteria for a ‘traumatic event’ according to DSM 5 18,









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study to demonstrate a 20% difference in prevalence between women with assisted

reproduction and those without (chosen as the least common potential risk factor of interest)

(power 0.80 and alpha 0.05). Accounting for rates of declined participation, withdrawal and non-

response, 811 women with EPL should be recruited.

Our findings are highly relevant to healthcare professionals who deal with early pregnancy loss.


the possible profound psychological sequelae. Given the high rates of PTSD symptomatology

found in this patient group, we believe that consideration should be given to screening all

women who have suffered an EPL for PTSD. There is also a need for tools to help predict those

women who are most at risk of serious psychological morbidity, in order to facilitate early


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ACKNOWLEDGEMENTS



CONTRIBUTORSHIP










explained.

COMPETING INTERESTS

None to declare

FUNDING



Imperial College Healthcare NHS Trust and Imperial College London. The early pregnancy unit at

Queen Charlottes and Chelsea Hospital is supported by the Tommy’s charity. The views

expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the

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Department of Health. DT is Senior Clinical Investigator of FWO (Research Foundation –

Flanders).



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REFERENCES

1. Blohm F, Friden B, Milsom I. A prospective longitudinal population-based study of clinical miscarriage in an urban Swedish population. BJOG 2008;115(2):176-82; discussion 83.

2. NICE. Ectopic pregnancy and miscarriage: diagnosis and initial management, 2012. 3. Lok IH, Yip AS, Lee DT, et al. A 1-year longitudinal study of psychological morbidity after

miscarriage. Fertil Steril 2010;93(6):1966-75. 4. Cumming GP, Klein S, Bolsover D, et al. The emotional burden of miscarriage for women and

their partners: trajectories of anxiety and depression over 13 months. BJOG 2007;114(9):1138-45.

5. Prettyman RJ, Cordle CJ, Cook GD. A three-month follow-up of psychological morbidity after early miscarriage. Br J Med Psychol 1993;66 ( Pt 4):363-72.

6. Janssen HJ, Cuisinier MC, Hoogduin KA, et al. Controlled prospective study on the mental health of women following pregnancy loss. Am J Psychiatry 1996;153(2):226-30.

7. 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(356):94-6.

8. Nikcevic AV, Tunkel SA, Nicolaides KH. Psychological outcomes following missed abortions and provision of follow-up care. Ultrasound Obstet Gynecol 1998;11(2):123-8.

9. Hamama L, Rauch SA, Sperlich M, et al. Previous experience of spontaneous or elective abortion and risk for posttraumatic stress and depression during subsequent pregnancy. Depress Anxiety 2010;27(8):699-707.

10. Engelhard IM, van den Hout MA, Arntz A. Posttraumatic stress disorder after pregnancy loss. Gen Hosp Psychiatry 2001;23(2):62-6.

11. Farhi J, Ben-Rafael Z, Dicker D. Suicide after ectopic pregnancy. N Engl J Med 1994;330(10):714.

12. Foa EB, Riggs DS, Dancu CV, et al. Reliability and validity of a brief instrument for assessing post-traumatic stress disorder. Journal of Traumatic Stress 1993;6(4):459-73.

13. Foa E, Cashman L, Jaycox L, et al. The validation of a self-report measure of posttraumatic stress disorder: The Posttraumatic Diagnostic Scale. Psychological Assessment 1997;9(4):445-51.

14. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta psychiatrica Scandinavica 1983;67(6):361-70.

15. Bjelland I, Dahl AA, Haug TT, et al. The validity of the Hospital Anxiety and Depression Scale: An updated literature review. Journal of Psychosomatic Research 2002;52(2):69-77.

16. Neugebauer R, Kline J, O'Connor P, et al. Depressive symptoms in women in the six months after miscarriage. Am J Obstet Gynecol 1992;166(1 Pt 1):104-9.

17. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry 2000;61 Suppl 5:4-12; discussion 13-4.

18. American Psychiatric A, American Psychiatric Association DSMTF. Diagnostic and statistical manual of mental disorders : DSM-5. Arlington, Va. ; London: American Psychiatric Association, 2013.

19. Rapaport MH, Clary C, Fayyad R, et al. Quality-of-life impairment in depressive and anxiety disorders. Am J Psychiatry 2005;162(6):1171-8.

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20. Rogal SS, Poschman K, Belanger K, et al. Effects of posttraumatic stress disorder on pregnancy outcomes. Journal of affective disorders 2007;102(1-3):137-43.

21. Dunkel Schetter C, Tanner L. Anxiety, depression and stress in pregnancy: implications for mothers, children, research, and practice. Current opinion in psychiatry 2012;25(2):141-8.

22. Klier CM, Geller PA, Ritsher JB. Affective disorders in the aftermath of miscarriage: a comprehensive review. Archives of women's mental health 2002;5(4):129-49.

23. NICE. Post-traumatic stress disorder: management 2005. 24. Murphy FA, Lipp A, Powles DL. Follow-up for improving psychological well being for women


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TABLES Table 1. Demographic and background characteristics of the study sample


Number recruited

175 56

95 (including 13 resolved PUL)

24

Mean age (years)

33.8

34.1 33.0 34.9

Mean gestation at diagnosis (weeks)

9.2 10.3 9.1 7.1

IVF pregnancy (%)

10/175 (6%)

4/56 (7%)

6/95 (6%)

0/24 (0%)

First ultrasound inconclusive (%,)

76/175 (43%)

13/56 (23%)

57/95 (60%)

6/24 (25%,)

Final Management (%) None required/Expectant Medical management* Surgical management Lost to follow-up

N/A

35 (37%) 15 (16%,) 43** (45%) 2 (2%)

1 (4%) 2 (8%) 21*** (88%) 0 (0%)

*Medical management refers to the use of misoprostol to treat miscarriage, or the use of methotrexate to treat ectopic pregnancy ** including one molar pregnancy, and one PUL investigated with laparoscopy and suction evacuation, ultimately found to be intra-uterine *** including one cervical ectopic treated with suction evacuation PUL -Pregnancy of Unknown Location; IVF - In Vitro Fertilization

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Table 2. Proportion of respondents meeting criteria for post-traumatic stress disorder at 1 and 3 months (subdivided according to severity, including and excluding the duration criterion), individual symptom clusters within PDS endorsed, and areas of life symptoms reported to have impacted upon

One month

Three months

Including duration criterion**

Excluding duration criterion**

Total proportion meeting PDS criteria (%, 95% CI)

22/69 (32%, 22%-44%) 31/69 (45%, 34%-57%) 19/44 (43%, 30%-58%)

Mild 3/69 (4%, 1%-12%) 3/69 (4%, 1%-12%) 2/44 (5%, 1%-15%)

Moderate 6/69 (9%, 4%-18%) 11/69 (16%, 9%-26%) 9/44 (20%, 11%-35%)

Moderate-Severe 10/69 (14%, 8%-25%) 14/69 (20%, 12%-31%) 7/44 (16%, 8%-29%)

Severe 3/69 (4%, 1%-12%) 3/69 (4%, 1%-12%) 1/44 (2%, 0.4%-12%)

Symptom clusters endorsed* (%, 95% CI)

Re-experiencing 64/69 (93%, 84%-97%) 39/44 (89%, 76%-95%)

Avoidance 50/69 (72%, 61%-82%) 24/44 (55%, 40%-68%)

Hyper-arousal 39/69 (57%, 45%-68%) 27/44 (61%, 47%-74%)

Areas of life symptoms impacted on (%, 95% CI)

Work 36/69 (52%, 41%-64%) 13/44 (30%, 18%-44%)

Household chores 22/69 (32%, 22%-44%) 9/44 (20%, 11%-35%)

Relationships with family 28/69 (41%, 30%-52%) 16/44 (36%, 24%-51%)

Relationships with friends 34/69 (49%, 38%-61%) 17/44 (39%, 26%-53%)

Fun and leisure activities 38/69 (55%, 43%-66%) 21/44 (48%, 34%-62%)

Sex life 48/69 (70%, 58%-79%) 21/44 (48%, 34%-62%)

General satisfaction with life 48/69 (70%, 58%-79%) 26/44 (59%, 44%-72%)

Overall level of functioning 35/69 (51%, 39%-62%) 20/44 (45%, 32%-60%)

*endorsed so as to meet criteria i.e. Re-experiencing – one or more positive responses to 5 questions, Avoidance – three or more positive responses to 7 questions, Hyper-arousal – two or more positive responses to 5 questions ** the duration criterion requires a respondent to verify that the symptoms they are reporting have been present for “more than one month”. Where excluded, this requirement is disregarded PTSD - post traumatic stress disorder; PDS – Post-traumatic diagnostic scale

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Table 3. Proportion of respondents meeting criteria for post-traumatic stress disorder, anxiety and depression, according to PDS and HADS, and severity scores, for ectopic pregnancy, miscarriage and controls

Controls 1 month 3 months


Post-traumatic stress (moderate, moderate-severe, severe cases) (95% CI)

0/20 0% (0%-16%)

19/69 28% (18%-39%)

13/53 25% (15%-38%)

6/16 38% (18%-61%)

17/44 39% (26%-53%)

15/33 45% (30%-62%)

2/11 18% (5%-48%)

Mean PDS score (/51) (SD)

n/a 15.3 (9.9)

16.1 (9.9)

12.6 (9.7)

11.6 (9.5)

12.4 (9.2)

9.1 (10.2)

Anxiety (moderate & severe cases) (95% CI)

2/20 10% (3%-30%)

22/69 32% (22%-44%)

18/53 34% (23%-47%)

4/16 25% (10%-50%)

9/44 20% (11%-35%)

8/33 24% (13%-41%)

1/11 9% (2%-38%)

Mean anxiety score (/21) (SD)

6.6 (3.0)

7.8 (4.8)

8.1 (4.8)

6.9 (4.7)

6.8 (4.2)

7.2 (4.1)

5.6 (4.4)

Depression (moderate & severe cases) (95% CI)

2/20 10% (3%-30%)

11/69 16% (9%-26%)

9/53 17% (9%-29%)

2/16 13% (4%-36%)

2/44 5% (1%-15%)

1/33 3% (1%-15%)

1/11 9% (2%-38%)

Mean Depression score (/21) (SD)

3.9 (4.2)

5.7 (4.4)

6.0 (4.4)

4.9 (4.6)

4.2 (3.5)

4.3 (3.3)

3.7 (4.2)

PDS - Post-traumatic Diagnostic Scale; HADS – Hospital Anxiety and Depression Scale; EPL – early pregnancy loss; CI Confidence Interval; SD - Standard Deviation

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LEGENDS FOR FIGURES

Figure 1. Flowchart showing numbers invited to participate, reasons for withdrawal, and response rates to 1- and 3-month questionnaires


SUPPLEMENTARY FILE




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254x254mm (72 x 72 DPI)

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Supplementary table 1. A comparison of response rates, and reported demographic and background variables according to pregnancy outcome (viable pregnancy, early pregnancy loss (then subdivided into miscarriage and ectopic))

Viable pregnancy All EPL Miscarriage Ectopic Number recruited 58 128 104 24

Active withdrawal 2 9 9 0 Invalid email 6 5 5 0 Response rate 20/50 (40%) 69/114 (61%) 53/90 (59%) 16/24 (67%) Self-‐reported background characteristics: Length of time trying to conceive <3 months

9/20 (45%) 41/69 (59%) 32/53 (60%) 9/16 (65%)

IVF pregnancy 2/20 (10%) 5/69 (7%) 3/53 (6%) 0/16 (0%)

Existing children 5/20 (25%) 26/69 (38%) 22/53 (42%) 4/16 (25%) Previous miscarriage 9/20 (45%) 27/69 (39%) 22/53 (42%) 5/16 (31%) Previous ectopic 0/20 6/69 (9%) 2/53 (4%) 4/16 (25%) Current psychiatric diagnosis

0/20 2/69 (3%) 1/53 (2%) 1/16 (6%)

Past psychiatric diagnosis

8/20 (40%) 17/69 (25%) 13/53 (25%) 3/16 (19%)

Pregnancy desired – proportion ‘very much so’

7/20 (35%) 61/69 (88%) 49/53 (92%) 12/16 (75%)

3-‐month response rates: Drop-‐out rate from 1 to 3 months

n/a 25/69 (36%) 20/53 (38%) 5/16 (31%)

Proportion of respondents pregnant at 3 month follow-‐up

n/a 6/44 (14%) 4/33 (12%) 2/11 (18%)

EPL -‐ early pregnancy loss; IVF – In vitro fertilization

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Section/Topic Item




Introduction



Methods



collection

8-9




applicable

10

Data sources/

measurement



10




why

10






Results

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flowchart




confounders

Table 1,

supplementary table






13-15




Discussion


Limitations



16-17


Other information



21





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Post-traumatic stress, anxiety and depression following miscarriage or ectopic pregnancy: a prospective cohort

study

Journal: BMJ Open

Manuscript ID bmjopen-2016-011864.R2


Date Submitted by the Author: 11-Aug-2016





Mental health




BMJ Open on F


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TITLE PAGE

Post-traumatic stress, anxiety and depression following


Jessica Farren clinical research fellow1, Maria Jalmbrant clinical psychologist

2, Lieveke

Ameye medical statistician3, Karen Joash consultant gynaecologist

1, Nicola Mitchell-

Jones clinical research fellow4, Sophie Tapp

1 research assistant, Dirk Timmerman

professor of obstetrics and gynaecology3,5

, Tom Bourne adjunct professor and


Corresponding author: Professor Tom Bourne, Tommy’s National Centre for Miscarriage

Research, Imperial College, Queen Charlottes and Chelsea Hospital, Du Cane Road, London W12

0HS



1 Tommy’s National Centre for Miscarriage Research, Queen Charlottes and Chelsea Hospital,






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pregnancy


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ABSTRACT







after a diagnosis of EPL, and one month after the diagnosis of a viable ongoing pregnancy.









criteria for probable PTSD, 32% for anxiety, and 16% for depression at one month and 38%, 20%,

and 5% respectively at three months. In the control group, no women met criteria for PTSD and

10% met criteria for anxiety and depression. There was little difference in type or severity of

distress following ectopic pregnancy or miscarriage.


ectopic pregnancy fulfill the diagnostic criteria for probable PTSD. Many suffer from moderate

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to severe anxiety, and a lesser number depression. Psychological morbidity, and in particular

PTSD symptoms, persists at least three months following pregnancy loss.





- In addition to anxiety and depression we have tested for the probable presence or

absence of post-traumatic stress disorder





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INTRODUCTION


pregnant by the age of 39, constituting 12 to 20% of all pregnancies1. Ectopic pregnancy

(defined as the development of a pregnancy outside the uterine cavity, usually within the

fallopian tube) is less common, thought to occur in approximately 1% of pregnancies 2.









significant proportion of women meet the criteria for depression (27%) and anxiety (28-41%)3-5

.


year6. In general, anxiety is more marked than depression

7 8.






miscarriage. In one prospective study involving 113 women, 25% met criteria according to the

self-report symptom scale for PTSD at one month, and 7% four months following an EPL10

.

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However this study included late pregnancy losses, so it is not possible to establish the

prevalence of PTSD after a loss in early pregnancy from these results.



ectopic pregnancies and suicide11

. Ectopic pregnancy is a potentially life-threatening condition








the symptoms of PTSD, anxiety, and depression in women following EPL compared to a control

group of women with ongoing viable pregnancies. The secondary aim was to evaluate whether

there was any evidence to suggest different levels of PTSD, anxiety and depression

symptomatology in women who had suffered a miscarriage compared to those with an ectopic

pregnancy. A final aim was to explore the feasibility and sample size required for a larger study

to assess for risk factors, which could be used to target screening or treatment of psychiatric

morbidity in this context.

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METHODS

Design

This was a prospective cohort study, with ethical approval of the study protocol granted by the

NRES committee of South-West Exeter, reference 11/SW/0052.

We recruited women presenting to the Early Pregnancy Assessment Unit (EPAU) at Queen

Charlottes and Chelsea hospital, which is a central London university teaching hospital. Women

attended the unit because of bleeding and/or pain, or for reassurance or dating. The data

represent a pilot to demonstrate the feasibility of, and provide data from which to derive the

sample size for, a larger study examining risk factors for the development of psychological

morbidity following EPL.













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Participants




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women were recruited (see Figure 1). Of those who declined to take part (12 cases), and

voluntarily provided a reason, the majority explained that they did not want to be reminded of

the event by the questionnaires. One woman explained that she had strong faith, and believed

that the loss was ‘in God’s hands’ – and explained that she felt participating and ‘questioning’

how she felt was against her faith. 11 women subsequently withdrew their consent by email.

None provided a reason for doing so. 11 women provided illegible or invalid email addresses.

















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Measures





presence of post-traumatic stress12

. It contains 17 items based on the DSM-IV diagnostic criteria

for PTSD and measures probable PTSD diagnosis and symptom severity (a score out of 51, with

>10 designating at least moderate severity). It has good psychometric properties across a range

of populations, with a sensitivity of 0.89 and specificity of 0.75, and a Cronbach’s alpha

coefficient of internal consistency of 0.92 for total symptom severity13

. The respondents in the

EPL group were asked to rate their symptoms in relation to the pregnancy loss, whilst the

control group was asked to complete the questionnaire in the standard way, in relation to a self-

identified exposure to other trauma (if present).


item (seven questions related to each of anxiety and depression) questionnaire14

. Each subscale


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symptoms). The HADS has good psychometric properties, with Cronbach’s alpha coefficient of

internal consistency a mean of 0.83 for anxiety, and 0.82 for depression, and has been used in a

range of populations; a review article identified 747 papers using HADS by May 200015

.


are the State Trait Anxiety Inventory (STAI), Norbeck Social Support Questionnaire (NSSQ), the

Rumination Response Scale (RRS) and Self-compassion scale – short form (SCS).







e-mailed). These results have therefore not been analysed for the pilot study, and this









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RESULTS










Response rates









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Respondents



history.


At one month, 19/69 (28% [95% CI 18%-39%]) women in the EPL group met the PDS criteria for

probable moderate or severe PTSD. In addition, 9/69 (13%) women met all criteria for probable

moderate or severe PTSD except the criterion requiring the symptoms they reported to have

been present for more than four weeks. At three months 17/44 (39% [26%-53%]) met the

criteria for probable moderate or severe PTSD. The mean severity score for all respondents with

EPL was 15.3 (SD 9.9) at one month, and 11.6 (SD 9.5) at three months.









had declined (50/69 (72% [61%-82%]) to 22/44 (50% [36%-64%]), p=0.07), and become the least

common. The reported impact of the endorsed symptoms on areas of respondents’ lives is

detailed in Table 2.

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with probable moderate-severe PTSD at one month (8/19 (42%)), than for those with no or mild

PTSD (16/49 (33%)).

In the control group, no women met the criteria for a diagnosis of probable PTSD for self-

reported traumatic life events (not specifically probing for previous EPLs).


At one month, 22/69 (32% [22%-44%]) of women in the EPL group met criteria for moderate-

severe anxiety, compared to 2/20 (10% [3%-30%]) in the control group (p=0.04) (Table 3 and

Figure 2). This declined over time in the EPL group to 9/44 (20% [11%-35%]) at 3 months. The

prevalence of moderate and severe depression symptoms was similar in both groups for all

time-points: 11/69 (16% [9%-26%]) for women with an EPL compared to 2/20 (10% [3%-30%])

for controls, dropping to lower than the control group (2/44 [5% (1%-15%]) at 3 months.









depression).

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experienced an ectopic pregnancy met criteria for probable PTSD (38% [18%-61%]), compared

to 13/53 (25% [15%-38%]) in the miscarriage group. 4/16 (25% [10-50%]) met the criteria for

moderate/severe anxiety symptoms, compared to 18/53 (34% [23%-47%]) in the miscarriage

group. 2/16 (13% [4%-36%]) met criteria for moderate/severe depression symptoms, compared

to 9/53 (17% [9%-29%]) in the miscarriage group. None of these differences reached statistical

significance.



pregnant. 9/22 (41% [23%-61%]) who were trying to conceive met criteria for probable PTSD,

compared to 2/6 (33% [10%-70%]) who were pregnant again, and 6/16 (38% [18%-61%]) who

had not tried to conceive. 5/22 (23% [10%-43%]) of those who were trying to conceive met the

criteria for moderate/severe anxiety, compared to none (0/6) of the group who were pregnant

again, and 4/16 (25% [10%-50%]) in the group who had not tried to conceive. For depression,

1/22 (5% [1%-22%]) who were trying to conceive, 1/6 (17% [3%-56%]) who were pregnant again,

and none (0/16) of the group who had not tried to conceive, met criteria.

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DISCUSSION

We have shown in our cohort of women attending an inner London EPAU that 39% of

participants three months after suffering an early pregnancy loss meet the criteria for probable

moderate to severe PTSD. Furthermore 20% meet the criteria for moderate to severe anxiety

compared to 10% in our control population. Levels of anxiety and depression dropped between

one and three months, but the symptoms associated with PTSD persisted. We also found that

women with ectopic pregnancy suffer from significant levels of emotional distress, with slightly

higher levels of PTSD symptoms compared to women who experience a miscarriage, but lower

levels of anxiety and depression.








themselves for involvement, with a high proportion (94%) of those approached providing

consent to take part. Knowledge of their clinical data and outcomes enabled us to send the

questionnaires at appropriate set time points after diagnosis. We also involved a relatively large

number of women compared to other studies of its type. A further strength is in the inclusion of

women with ectopic pregnancies, a group largely unreported in the literature to date.



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were more likely to respond, it is also likely that women with the greatest trauma avoid

engagement with a process that makes them confront the event. The observed selective drop

out of those with higher PTSD, anxiety and depression levels perhaps supports the view that

there may have been a group of women who did not want to be reminded of their feelings



colleagues’ study16

. Finally, we recognise that this study relies on the use of self-report screening









early pregnancy loss if we were to rely on it as a normative baseline. Our control group is also

smaller than the EPL group, as a result of the recruitment methodology described, which has

implications for the power of the EPL versus control group calculations.

We were surprised by the prevalence of PTSD symptoms in our study. Even in women not

meeting the full criteria for PTSD, there was a significant endorsement of all symptom clusters

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by the majority of participants, along with impairment across social and occupational domains,

and in general satisfaction. This prevalence of probable PTSD is higher than previously reported

10. However, in the paper by Engelhard et al the participants were not limited to women with

losses in early pregnancy. Furthermore, the PDS scale was scored differently in our paper. We

scored according to Foa’s original recommendation – where a symptom was considered

endorsed if it occurs ‘once a week or less/once in a while’ – whereas Engelhard required a

symptom to occur ‘2-4 times a week/half the time’.

It will be noted that there is an apparent increase in probable PTSD between month one (28% of










after losing a pregnancy, and that this is more common than both anxiety and depression, is

potentially important. In other contexts, we know that untreated PTSD has a significant impact

on quality of life, relationships, ability to work, suicide risk, and physical health17-19

. PTSD also

has implications for future pregnancies, including poor health behaviour, reduced gestational

length, and issues with infant bonding20-22

. The treatment for PTSD is specific and relies on

trauma focused cognitive behavioural therapy or eye movement desensitisation and

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reprocessing23

. It is perhaps not surprising therefore that the outcome of a broad-brush

approach of offering “counselling” (in variable formats) to all women following miscarriage has

been disappointing24

. Given the serious impact of untreated PTSD, screening women for the

disorder following EPL may be a more effective use of resources. Conversely, we have shown

that there are a number of women who do not suffer significant morbidity. These may not

require any intervention following their loss.



requirement for the trauma to result in fear, helplessness or horror was removed18

. All of our







miscarriage or ectopic pregnancy fulfilling criteria for a ‘traumatic event’ according to DSM 5 18

,









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study to demonstrate a 20% difference in prevalence between women with assisted

reproduction and those without (chosen as the least common potential risk factor of interest)

(power 0.80 and alpha 0.05). Accounting for rates of declined participation, withdrawal and non-

response, 811 women with EPL should be recruited.

Our findings are relevant to healthcare professionals who deal with early pregnancy loss.


the possible profound psychological sequelae. The data presented is in the context of a pilot

study, however if our findings are supported by further large prospective studies, we believe

that consideration should be given to screening all women who have suffered an EPL for PTSD.

There is also a need to assess how to predict those women who are most at risk of serious

psychological morbidity, in order to better direct limited resources, and to facilitate early


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ACKNOWLEDGEMENTS



CONTRIBUTORSHIP










explained.

COMPETING INTERESTS

None to declare

FUNDING



Imperial College Healthcare NHS Trust and Imperial College London. The early pregnancy unit at

Queen Charlottes and Chelsea Hospital is supported by the Tommy’s charity. The views

expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the

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Department of Health. DT is Senior Clinical Investigator of FWO (Research Foundation –

Flanders).



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REFERENCES

1. Blohm F, Friden B, Milsom I. A prospective longitudinal population-based study of clinical

miscarriage in an urban Swedish population. BJOG 2008;115(2):176-82; discussion 83.

2. NICE. Ectopic pregnancy and miscarriage: diagnosis and initial management, 2012.

3. Lok IH, Yip AS, Lee DT, et al. A 1-year longitudinal study of psychological morbidity after

miscarriage. Fertil Steril 2010;93(6):1966-75.

4. Cumming GP, Klein S, Bolsover D, et al. The emotional burden of miscarriage for women and

their partners: trajectories of anxiety and depression over 13 months. BJOG

2007;114(9):1138-45.

5. Prettyman RJ, Cordle CJ, Cook GD. A three-month follow-up of psychological morbidity after

early miscarriage. Br J Med Psychol 1993;66 ( Pt 4):363-72.

6. Janssen HJ, Cuisinier MC, Hoogduin KA, et al. Controlled prospective study on the mental

health of women following pregnancy loss. Am J Psychiatry 1996;153(2):226-30.

7. 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(356):94-6.

8. Nikcevic AV, Tunkel SA, Nicolaides KH. Psychological outcomes following missed abortions and

provision of follow-up care. Ultrasound Obstet Gynecol 1998;11(2):123-8.

9. Hamama L, Rauch SA, Sperlich M, et al. Previous experience of spontaneous or elective

abortion and risk for posttraumatic stress and depression during subsequent pregnancy.

Depress Anxiety 2010;27(8):699-707.

10. Engelhard IM, van den Hout MA, Arntz A. Posttraumatic stress disorder after pregnancy loss.

Gen Hosp Psychiatry 2001;23(2):62-6.

11. Farhi J, Ben-Rafael Z, Dicker D. Suicide after ectopic pregnancy. N Engl J Med

1994;330(10):714.

12. Foa EB, Riggs DS, Dancu CV, et al. Reliability and validity of a brief instrument for assessing

post-traumatic stress disorder. Journal of Traumatic Stress 1993;6(4):459-73.

13. Foa E, Cashman L, Jaycox L, et al. The validation of a self-report measure of posttraumatic

stress disorder: The Posttraumatic Diagnostic Scale. Psychological Assessment

1997;9(4):445-51.

14. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta psychiatrica

Scandinavica 1983;67(6):361-70.

15. Bjelland I, Dahl AA, Haug TT, et al. The validity of the Hospital Anxiety and Depression Scale:

An updated literature review. Journal of Psychosomatic Research 2002;52(2):69-77.

16. Neugebauer R, Kline J, O'Connor P, et al. Depressive symptoms in women in the six months

after miscarriage. Am J Obstet Gynecol 1992;166(1 Pt 1):104-9.

17. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin

Psychiatry 2000;61 Suppl 5:4-12; discussion 13-4.

18. American Psychiatric A, American Psychiatric Association DSMTF. Diagnostic and statistical

manual of mental disorders : DSM-5. Arlington, Va. ; London: American Psychiatric

Association, 2013.

19. Rapaport MH, Clary C, Fayyad R, et al. Quality-of-life impairment in depressive and anxiety

disorders. Am J Psychiatry 2005;162(6):1171-8.

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20. Rogal SS, Poschman K, Belanger K, et al. Effects of posttraumatic stress disorder on

pregnancy outcomes. Journal of affective disorders 2007;102(1-3):137-43.

21. Dunkel Schetter C, Tanner L. Anxiety, depression and stress in pregnancy: implications for

mothers, children, research, and practice. Current opinion in psychiatry 2012;25(2):141-

8.

22. Klier CM, Geller PA, Ritsher JB. Affective disorders in the aftermath of miscarriage: a

comprehensive review. Archives of women's mental health 2002;5(4):129-49.

23. NICE. Post-traumatic stress disorder: management 2005.

24. Murphy FA, Lipp A, Powles DL. Follow-up for improving psychological well being for women


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TABLES

Table 1. Demographic and background characteristics of the study sample


Number recruited

175 56

95

(including 13 resolved

PUL)

24

Mean age

(years)

33.8

34.1 33.0 34.9

Mean gestation at diagnosis

(weeks)

9.2 10.3 9.1 7.1

IVF pregnancy

(%)

10/175

(6%)

4/56

(7%)

6/95

(6%)

0/24

(0%)

First ultrasound inconclusive

(%,)

76/175

(43%)

13/56

(23%)

57/95

(60%)

6/24

(25%,)

Final Management (%)

None required/Expectant

Medical management*

Surgical management

Lost to follow-up

N/A

35 (37%)

15 (16%,)

43** (45%)

2 (2%)

1 (4%)

2 (8%)

21*** (88%)

0 (0%)

*Medical management refers to the use of misoprostol to treat miscarriage, or the use of methotrexate to treat

ectopic pregnancy

** including one molar pregnancy, and one PUL investigated with laparoscopy and suction evacuation, ultimately

found to be intra-uterine

*** including one cervical ectopic treated with suction evacuation

PUL -Pregnancy of Unknown Location; IVF - In Vitro Fertilization

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Table 2. Proportion of respondents meeting criteria for post-traumatic stress disorder at 1 and 3

months (subdivided according to severity, including and excluding the duration criterion),

individual symptom clusters within PDS endorsed, and areas of life symptoms reported to have

impacted upon

One month

Three months

Including duration

criterion**

Excluding duration

criterion**

Total proportion meeting PDS

criteria (% [95% CI])

22/69 (32% [22%-44%]) 31/69 (45% [34%-57%]) 19/44 (43% [30%-58%])

Mild 3/69 (4% [1%-12%]) 3/69 (4% [1%-12%]) 2/44 (5%,[1%-15%])

Moderate 6/69 (9% [4%-18%]) 11/69 (16% [9%-26%]) 9/44 (20% [11%-35%])

Moderate-Severe 10/69 (14% [8%-25%]) 14/69 (20% [12%-31%]) 7/44 (16% [8%-29%])

Severe 3/69 (4% [1%-12%]) 3/69 (4% [1%-12%]) 1/44 (2% [0.4%-12%])

Symptom clusters endorsed* (%, 95% CI)

Re-experiencing 64/69 (93% [84%-97%]) 39/44 (89% [76%-95%])

Avoidance 50/69 (72%,[61%-82%]) 24/44 (55% [40%-68%])

Hyper-arousal 39/69 (57% [45%-68%]) 27/44 (61% [47%-74%])

Areas of life symptoms impacted on (%, 95% CI)

Work 36/69 (52% [41%-64%]) 13/44 (30% [18%-44%])

Household chores 22/69 (32% [22%-44%]) 9/44 (20% [11%-35%])

Relationships with family 28/69 (41% [30%-52%]) 16/44 (36% [24%-51%])

Relationships with friends 34/69 (49% [38%-61%]) 17/44 (39% [26%-53%])

Fun and leisure activities 38/69 (55% [43%-66%]) 21/44 (48% [34%-62%])

Sex life 48/69 (70% [58%-79%]) 21/44 (48% [34%-62%])

General satisfaction with life 48/69 (70% [58%-79%]) 26/44 (59% [44%-72%])

Overall level of functioning 35/69 (51% [39%-62%]) 20/44 (45% [32%-60%])

*endorsed so as to meet criteria i.e. Re-experiencing – one or more positive responses to 5 questions, Avoidance –

three or more positive responses to 7 questions, Hyper-arousal – two or more positive responses to 5 questions

** the duration criterion requires a respondent to verify that the symptoms they are reporting have been present for

“more than one month”. Where excluded, this requirement is disregarded

PTSD - post traumatic stress disorder; PDS – Post-traumatic diagnostic scale

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Table 3. Proportion of respondents meeting criteria for post-traumatic stress disorder, anxiety

and depression, according to PDS and HADS, and severity scores, for ectopic pregnancy,

miscarriage and controls

Controls 1 month 3 months


Post-traumatic stress

(moderate, moderate-severe, severe cases)

[95% CI]

0/20

0%

[0%-16%]

19/69

28%

[18%-39%]

13/53

25%

[15%-38%]

6/16

38%

[18%-61%]

17/44

39%

[26%-53%]

15/33

45%

[30%-62%]

2/11

18%

[5%-48%]

Mean PDS score (/51)

(SD)

n/a 15.3

(9.9)

16.1

(9.9)

12.6

(9.7)

11.6

(9.5)

12.4

(9.2)

9.1

(10.2)

Anxiety


[95% CI]

2/20

10%

[3%-30%]

22/69

32%

[22%-44%]

18/53

34%

[23%-47%]

4/16

25%

[10%-50%]

9/44

20%

[11%-35%]

8/33

24%

[13%-41%]

1/11

9%

[2%-38%]

Mean anxiety score (/21)

(SD)

6.6

(3.0)

7.8

(4.8)

8.1

(4.8)

6.9

(4.7)

6.8

(4.2)

7.2

(4.1)

5.6

(4.4)

Depression


[95% CI]

2/20

10%

[3%-30%]

11/69

16%

[9%-26%]

9/53

17%

[9%-29%]

2/16

13%

[4%-36%]

2/44

5%

[1%-15%]

1/33

3%

[1%-15%]

1/11

9%

[2%-38%]

Mean Depression score (/21)

(SD)

3.9

(4.2)

5.7

(4.4)

6.0

(4.4)

4.9

(4.6)

4.2

(3.5)

4.3

(3.3)

3.7

(4.2)

PDS - Post-traumatic Diagnostic Scale; HADS – Hospital Anxiety and Depression Scale; EPL – early pregnancy loss; CI

Confidence Interval; SD - Standard Deviation

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LEGENDS FOR FIGURES

Figure 1. Flowchart showing numbers invited to participate, reasons for withdrawal, and

response rates to 1- and 3-month questionnaires

Figure 2. Bar chart illustrating proportion of women meeting criteria for moderate or severe

anxiety/depression, according to HADS, with 95% confidence limits

SUPPLEMENTARY FILE




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254x254mm (72 x 72 DPI)

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Supplementary table 1. A comparison of response rates, and reported demographic and background variables according to pregnancy outcome (viable pregnancy, early pregnancy loss (then subdivided into miscarriage and ectopic))

Viable pregnancy All EPL Miscarriage Ectopic Number recruited 58 128 104 24

Active withdrawal 2 9 9 0 Invalid email 6 5 5 0 Response rate 20/50 (40%) 69/114 (61%) 53/90 (59%) 16/24 (67%) Self-‐reported background characteristics: Length of time trying to conceive <3 months

9/20 (45%) 41/69 (59%) 32/53 (60%) 9/16 (65%)

IVF pregnancy 2/20 (10%) 5/69 (7%) 3/53 (6%) 0/16 (0%)

Existing children 5/20 (25%) 26/69 (38%) 22/53 (42%) 4/16 (25%) Previous miscarriage 9/20 (45%) 27/69 (39%) 22/53 (42%) 5/16 (31%) Previous ectopic 0/20 6/69 (9%) 2/53 (4%) 4/16 (25%) Current psychiatric diagnosis

0/20 2/69 (3%) 1/53 (2%) 1/16 (6%)

Past psychiatric diagnosis

8/20 (40%) 17/69 (25%) 13/53 (25%) 3/16 (19%)

Pregnancy desired – proportion ‘very much so’

7/20 (35%) 61/69 (88%) 49/53 (92%) 12/16 (75%)

3-‐month response rates: Drop-‐out rate from 1 to 3 months

n/a 25/69 (36%) 20/53 (38%) 5/16 (31%)

Proportion of respondents pregnant at 3 month follow-‐up

n/a 6/44 (14%) 4/33 (12%) 2/11 (18%)

EPL -‐ early pregnancy loss; IVF – In vitro fertilization

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Section/Topic Item




Introduction



Methods



collection

8-9




applicable

10

Data sources/

measurement



10




why

10






Results

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flowchart




confounders

Table 1,

supplementary table






13-15




Discussion


Limitations



16-17


Other information



21





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