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Contents lists available at ScienceDirect

International Journal of Nursing Studies

journal homepage: www.elsevier.com/ijns

Holistic assessment of women with hyperemesis gravidarum:

A randomised controlled trial
S.J. Fletcher a, H. Waterman b, L. Nelson a, L.A. Carter c, L. Dwyer d, C. Roberts c,
D. Torgerson e, H. Kitchener a,*
a

Institute of Cancers Sciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK
School of Nursing, Midwifery and Social Work, University of Manchester, Oxford Road, Manchester M13 9PL, UK
Institute of Population Health, University of Manchester, Oxford Road, Manchester M13 9PL, UK
d
St Marys Hospital, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UK
e
Department of Health Sciences, University of York, Heslington, York YO10 5DD, UK
b
c

A R T I C L E I N F O

A B S T R A C T

Article history:
Received 19 March 2014
Received in revised form 12 June 2015
Accepted 16 June 2015

Background: Hyperemesis gravidarum or severe nausea and vomiting of pregnancy affects

womens physical, social and psychological wellbeing and often requires frequent hospital
admissions. Current standard care may be too medically focussed to meet all of womens
complex needs.
Aim: The aim of this study is to test where using a validated questionnaire, the
Hyperemesis Impact of Symptoms tool, delivered by a nurse to assess the overall effect of
hyperemesis on an individual womans life and to provide advice tailored to her specic
needs, will help her cope better with her symptoms and reduce admissions to hospital.
Design: This study was a two arm randomised controlled trial in which women with
hyperemesis from four hospitals were randomly allocated to one of two groups: (1) usual
care and (2) usual care plus assessment with the Hyperemesis Impact of Symptoms
questionnaire and a care plan tailored to their responses.
Participants and methods: Recruitment was from women who were admitted with
hyperemesis gravidarum; diabetic women or those over 14 weeks gestation were excluded.
Those who consented completed questionnaires to assess their quality of life and the severity
of symptoms at baseline and at three time points over the following 6 weeks.
Results: Womens average social functioning, Hyperemesis Impact of Symptom scores and
average number of admissions were not signicantly different between either group. The
average number of days in hospital for the questionnaire and tailored plan group was
signicantly lower, 4.97, compared with 6.14 in the usual care group. Using the
questionnaire to plan individualised care was not associated with signicant reduction in
health care costs.
Conclusion: Using the Hyperemesis Impact of Symptoms questionnaire to tailor a care
plan to address womens individual needs was not associated with any signicant
improvements in the quality of life. The cost effectiveness analysis did not indicate that the
questionnaire is cost saving. The Hyperemesis Impact of Symptoms questionnaire is a
practical tool for nurses and midwives to assess the overall impact of hyperemesis
gravidarum on the individual and could be useful for assessing symptoms and evaluating
physical, social and psychological changes following treatment in either clinical or
research settings.
2015 Elsevier Ltd. All rights reserved.

Keywords:
Hyperemesis gravidarum
Holistic assessment
Patient reported outcome measure

* Corresponding author. Tel.: +44 0161 701 6941; fax: +44 0161 701 6919.
E-mail address: Henry.kitchener@manchester.ac.uk (H. Kitchener).
http://dx.doi.org/10.1016/j.ijnurstu.2015.06.007
0020-7489/ 2015 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Fletcher, S.J., et al., Holistic assessment of women with hyperemesis gravidarum: A
randomised controlled trial. Int. J. Nurs. Stud. (2015), http://dx.doi.org/10.1016/j.ijnurstu.2015.06.007

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What is already known about the topic?

 That hyperemesis gravidarum is a debilitating condition
for women rendering them among other things: unable
to tolerate uids and diet, fatigued, unable to care for
the themselves and family, worried about the unborn
baby and unable to work.
 That there is no cure, and treatment, therefore, aims to
control symptoms and consists of rehydration and antiemetics.
 That women may benet from having a more holistic
assessment of their condition and an individualised plan
of care.
What this paper adds
 That the Hyperemesis Impact of Symptoms questionnaire and a tailored plan of care does not appear to have
any effect on womens social functioning nor vomiting
and nausea.
 That the questionnaire and tailored plan of care did not
reduce the cost of care.
 That the impact of hyperemesis gravidarum can be
measured by the Hyperemesis Impact of Symptoms
Score.
1. Introduction
Nausea and vomiting are common complaints of early
pregnancy, and for most these symptoms are mild and
while unpleasant are not clinically signicant. In 0.52%
of women the symptoms can be severe and lead to
dehydration, electrolyte disturbance and signicant
weight loss, a condition known as hyperemesis gravidarum (HG) (Bailit, 2005). Although a self limiting
condition, the majority beginning by ten weeks and
resolving by 20 weeks gestation, in more severe cases,
1045% of women, it does not resolve until after the birth
(Hizli et al., 2012; Kramer et al., 2013; Poursharif et al.,
2008; Rashid et al., 2012).
2. Background
The aetiology of HG is not well understood (Fell et al.,
2006; Verberg et al., 2005) but is probably multi-factorial
involving hormonal, immunological and psychosocial
factors (Bottomley and Bourne, 2009; Rashid et al.,
2012). Female foetus (Rashid et al., 2012; Veenendaal
et al., 2011), previous HG (Fejzo et al., 2011), and
immigrant populations (David et al., 2011) are some of
the many apparent risk factors for HG. Women with HG
may be at higher risk compared with those without of
pre-eclampsia, placental abruption (Bolin et al., 2013)
and spontaneous pre-term birth (McCarthy et al., 2011;
Veenendaal et al., 2011). In rare cases, Wernickes
encephalopathy has been identied as a serious complication of HG (Gangi et al., 2012). HG has also been found to be
associated with babies of low birth weight and who are
small for gestational age (Bolin et al., 2013; Veenendaal
et al., 2011). No high quality research has been conducted
to demonstrate whether or not there are long term effects

upon the child when the mother has had HG (Veenendaal

et al., 2011).
Treatment is empirical and standardised, and involves
antiemetic therapy and intravenous uids to relieve
nausea and vomiting and maintain hydration (American
College of Obstetricians and Gynecologists, ACOG, 2004).
However, the treatment is aimed at the symptoms of HG
and, hence, while recovery after rehydration is fairly swift
once the woman returns home, dehydration may recur
necessitating another hospital admission for further
rehydration. Thus HG is a common reason for multiple
admissions to hospital (Rashid et al., 2012) and, consequently, consumes signicant personal and health care
resources (Gazmararian et al., 2002).
Studies have indicated that women often feel that their
symptoms are dismissed and nihilistic attitudes of nurses
and doctors have a negative impact on patients experience
(Poursharif et al., 2008; Power et al., 2010). In one study
this was cited as one of the reasons women chose to
terminate their pregnancy (Poursharif et al., 2007). These
attitudes may arise from having no cure for the condition
leaving staff feeling powerless to help. The stigma
associated with the condition and lack of preventative
action in the community to reduce the impact of the
condition on the woman before HG requires hospital
admission (Power et al., 2010).
Several past studies show an association between HG
and high levels of depression and anxiety (Kramer et al.,
2013; McCormack et al., 2011; Munch et al., 2011; Power
et al., 2010). Most researchers conclude that the severe
mental distress exhibited by women is a sequelae of HG
and underlying psychological conditions are unlikely to be
the main cause (Power et al., 2010). Christodoulou-Smith
et al. (2011) report that the experience of HG may lead to
post-traumatic stress syndrome (PTSS) in 18% of women,
indicating that HG may have long term psychological
effects. The presence of PTSS was not related to a history of
anxiety and depression prior to pregnancy (ChristodoulouSmith et al., 2011). HG may also lead to loss of
employment, time off from work, avoidance of future
pregnancies and may lead to marital and nancial
problems (Poursharif et al., 2007). However, this study
was carried out in the United States and some of the
nancial issues arising from private health insurance may
not necessarily apply to publically funded health care.
Research from our unit indicated the day to day impact
of HG upon women. Common themes which emerged from
our previous qualitative research included inability to
tolerate diet and uids, fatigue, feelings of low mood,
defeat and hopelessness, worries about the unborn child,
ability to manage home and work life, feelings of being
disbelieved and difculties with self-care (Power et al.,
2010). These themes were used to develop a validated
questionnaire to be used as a clinical tool by nurses or
midwives for the holistic assessment of the impact of
symptoms of HG, the HIS questionnaire (Power et al., 2009).
3. Aim of the study
Our hypothesis for this study was that successful
management of HG needs to extend beyond rehydration

Please cite this article in press as: Fletcher, S.J., et al., Holistic assessment of women with hyperemesis gravidarum: A
randomised controlled trial. Int. J. Nurs. Stud. (2015), http://dx.doi.org/10.1016/j.ijnurstu.2015.06.007

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and anti-emetic therapy, in order to identify and address

an individuals concerns. Our objective was to use the HIS
questionnaire and manual (Power et al., 2009) so nurses
and midwives could achieve a more personalised approach
that validated womens experiences and provided targeted
reassurance as well as practical advice to support each
woman to develop strategies to manage symptoms
following discharge from hospital.
4. The study
A randomised controlled trial (RCT) to determine if
using the HIS score and manual to assess and tailor the care
and advice for women admitted to hospital with HG would
improve social functioning and reduce re-admissions and
days in hospital compared with usual care.
5. Methods
5.1. Participants
Between June 2008 and December 2010 women
admitted to one of four hospitals in Greater Manchester
with a diagnosis of HG were assessed for eligibility, HG
being dened as the need for admission with nausea and
vomiting in early pregnancy. Eligibility criteria included
admission within the previous 24 h, being aged 16 years or
over and able to give informed consent. Women were
excluded if nausea and vomiting in pregnancy had
commenced after 14 weeks gestation or if they were
diabetic. Hospital based interpreters were used when
required so that women whose rst language was not
English could be included.
5.2. Procedures
Two research nurses worked independently of each
other, one focused on accrual, and the other on obtaining
outcome data. Recruitment, informed consent and baseline
data collection was completed at the bedside. Randomisation took place after conrmation of eligibility. Participants were randomised remotely via telephone, through
the York Trials Unit, utilising computer generated simple
allocation.
5.3. The intervention
All recruited women received standard medical care
(intravenous rehydration and antiemetic therapy) according to each hospitals protocol. Women allocated to the
intervention group were also assessed using the HIS
questionnaire which has ten questions relating to the
aspects of a womans life where the symptoms of HG have
been found to have the most impact (Power et al., 2009).
Each question has four possible answers, scoring 03.
Answers scoring two or more indicate the need for advice
and support. Womens responses were used to tailor a care
package comprising practical and supportive care, including: dietary advice; practical advice regarding symptom
management and counselling regarding psychological
impact of symptoms. The woman was telephoned within

48 h of discharge, and was provided with contact details for

the research nurse in case telephone advice was required.
An appointment was arranged with the woman to contact
her by telephone following discharge in order to obtain
outcome measures at two weeks, four weeks and six weeks
post recruitment. The woman provided her telephone
number and home address, and consent was obtained to
send the questionnaire by post if all attempts to make
contact via telephone were not successful. To ensure
delity to the intervention the nurse was trained by the
originator of the HIS questionnaire and handbook and
observed in practice. The structured format of the HIS
and handbook means that care provided will be consistent
and systematic.
5.4. Demographic and outcome measures
At baseline, demographic data including age, marital
status, ethnicity and pregnancy data were collected. The
medical outcomes study 36-item short form health survey
(SF-36) was used to measure functional health status on
eight subscales that reect mental and physical components of health perceptions, role limitations due to health
problems, and other characteristics of functional status
(Ware et al., 1993). Raw scores were converted to 0100
with higher numbers reecting better functional status.
The EQ-5D instrument was used to measure womens
health status across ve dimensions: mobility; self care;
usual activities; pain/discomfort and anxiety/depression
(Williams, 1990). Women indicated whether they had no,
moderate or severe problems on each providing an index
score for each health state. The Pregnancy Unique
Quantication of Emesis (PUQE) score was used as it is
pregnancy specic (Koren et al., 2002) with three questions
relating to the main symptoms of nausea, vomiting and
retching in the previous 12 h. These questionnaires were
used at all three follow up time points (two, four and six
weeks) in conjunction with questions regarding work days
lost, additional childcare use and health care use (additional
visits to GP, midwife and admission to hospital). The Client
Satisfaction Questionnaire (CSQ) has been widely used to
assess satisfaction with health care (Larsen et al., 1979).
Women completed this at two and six weeks. Hospital
admission data (where available) were collected from
medical records following pregnancy completion; data
was not accessible for women who were admitted to
hospital outside of the study sites.
The primary outcome was social functioning at two
weeks follow-up, chosen as this has been reported to be
the parameter most adversely affected by HG (Power et al.,
2009). Social functioning, which comprises frequency and
duration of social contact in the previous week, is one of
the eight subscales of the SF-36. This was assessed using
questions 8 and 10 from the SF-36 (Ware et al., 1993).
Secondary outcomes included readmission rates, PUQE
scores, CSQ scores and EQ-5D scores.
5.5. Health economics
Secondary outcomes were cost effectiveness of experimental approach and readmission rate and length of stay.

Please cite this article in press as: Fletcher, S.J., et al., Holistic assessment of women with hyperemesis gravidarum: A
randomised controlled trial. Int. J. Nurs. Stud. (2015), http://dx.doi.org/10.1016/j.ijnurstu.2015.06.007

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Table 1
Data sources and unit costs used in costing trial for hyperemesis gravidarum.
Item

Unit cost ()

Source

Note

Intervention
Nurse consultation

23.5

Curtis (2013)

30 min per consultation (with qualication cost)

NHS setting
GP
Other healthcare professionals
Hospital admission

53
45
667

Curtis (2013)
Department of Health (2013)
Department of Health (2013)

17.2 min per consultation (with qualication cost)

Assumed the cost of midwife visit
Ante-natal or Post-natal Investigation age between
16 and 40 years with length of stay 1 day or more

Others
Days off work

99.8/day

Ofce for National Statistics (2011)

Partner or helpers days off work

99.8/day

Ofce for National Statistics (2011)

Child care
Child care (unpaid)

28.16/day
28.16/day

Daycare Trust (2010)

Daycare Trust (2010)

April 2010 median grossly week earning for full time

employees 499
April 2010 median grossly week earning for full time
employees 499
Assume 8 h per day
Give a shadow price as above

Health economic analysis was carried out to look at both an

NHS and societal perspective. The data collection period was
6 weeks after recruitment. Therefore, neither cost nor
outcome was discounted in the analysis. The main outcome
measure was quality adjusted life year (QALY), weighted by
EQ-5D. The year of pricing was chosen as year 2010. The data
input for cost included the number of hospital admissions,
frequency of visiting GP, other health care professional, as
well as time off work and partner/helpers work day lost,
paid child care (days) and unpaid child care (days, Table 1).
The number of hospital admissions was extracted from
patients medical charts; the rest of the information was
self-reported by patients through a phone interview.
More than 70% of the data were missing, hence these
estimates are based on the complete data set; missing
data was imputed at random and analyses were
repeated, adjusted for age, gestation, PUQE scores and
previous HG.
5.6. Sample size and power calculation
In our previous research the mean social functioning
score (SF36) for women with HG was 29, compared to 41 for
pregnant women not suffering with HG, a mean difference of
12 (SD 14.2, Power et al., 2009). An effective intervention
was unlikely, in our view, to lead to an improvement of
12 points between women with HG and those without.
Consequently, we felt that a 5 point difference would be a
more realistic difference between the treatment groups (i.e.,
approximately 1/3rd of a standard deviation). Therefore a
5 point increase in the mean social functioning score at
two weeks compared with the control group was required
to demonstrate improvement. Allowing for 20% attrition,
accrual of 240 women (with 192 achieving the primary
endpoint) would have 80% power to detect a clinically
meaningful change in social functioning.
5.7. Statistical methods
Statistical analysis of the treatment effect was based on
intention-to-treat subject to the availability of data.
Preliminary analysis examined the pattern of missing

data by comparing the baseline characteristics of participants with and without follow-up data.
We consider an analysis adjusted in this way superior to
an analysis without adjustment for several reasons. First,
the estimate of the treatment effect in an adjusted analysis
can be expected to have greater precision than an
unadjusted analysis. Secondly, adjustment will remove
any chance bias due to imbalance of these covariates.
Thirdly, it makes the assumption of missing at random
more plausible, as these covariates are potential predictors
of loss to follow-up, whereas an unadjusted analysis would
require the stronger assumption that missing data are
missing completely at random. It can be argued that
adjusting analyses conditions on what is known and
making more complete use of available information are
therefore more valid (Senn, 2012).
Following the procedure suggested by Roberts and
Torgerson (1999), baseline covariates that are potential
predictors of outcome were identied using prior knowledge and opinion. This was done prior to the statistical
analysis of outcome data as part of preparation of the
statistical analysis plan. We identied maternal age,
previous HG, gestational age and PUQE score covariates
and social function as potential predictors and these
covariates were incorporated in the statistical analysis
plan. They were included as covariates in a linear model
analysis to estimate the mean effect of the intervention on
the primary and secondary outcomes measures. To prevent
analysis bias, caused by multiple analyses being conducted
but then the most favourable being presented, the prespecied analysis was implemented and no variable
selection was carried out. The pre-selection of covariates
based on the prognostic values is preferable to selecting
baseline covariates based on statistical testing or inspection of baseline imbalance; as the latter can cause bias
(Roberts and Torgerson, 1999). For a small number of
women the baseline covariates were missing and so the
baseline values were imputed using a procedure suggested
by White and Thompson (2005). We have been asked to
provide the unadjusted analysis. This analysis, which was
not in the statistical analysis plan, has been added to the
results table.

Please cite this article in press as: Fletcher, S.J., et al., Holistic assessment of women with hyperemesis gravidarum: A
randomised controlled trial. Int. J. Nurs. Stud. (2015), http://dx.doi.org/10.1016/j.ijnurstu.2015.06.007

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As scales were non-normally distributed being

bounded by maximum and minimum values, the condence intervals for the treatment effect were calculated
using a non-parametric bootstrap with 2000 repetitions.
All statistical analyses were carried out using Stata 11
(2011).

6. Results
Between June 2008 and December 2010, 273 women
were randomised; 131 into the intervention group and
142 into the control group (Fig. 1). The gestational age at
recruitment ranged from 3 to 20 weeks; mean 9.18 and
9.2 in the intervention and control groups respectively
(Table 2). The ethnicity of the sample was representative
of the Greater Manchester wider population. Baseline
PUQE scores ranged from 3 to 15 with no signicant
difference in mean scores between the arms; 8.4 (SD 3.1)
and 9.1 (SD 3.0) between the intervention and control
groups respectively, indicating that the nausea and
vomiting was moderate at accrual. Loss to follow up at
two weeks was 27.5% (N = 67), which increased after the
rst follow up point. Reasons for attrition included
feeling too unwell or too busy when telephoned, no
response to telephone or postal contacts. The numbers
lost to follow up did not differ signicantly between
groups (Fig. 1).

6.1. Primary outcome

The primary outcome was social functioning at two
weeks follow up. Mean scores increased over time as
would be expected with a self limiting condition. At two
weeks the intervention group mean score was 34.7 (SD
30.8) and although this was higher than the control group
(32.7, SD 31.6), the difference between the means when
adjusted for baseline values was not statistically signicant (adj. mean difference 4.95, 95% CI ( 3.51, 13.30),
P = 0.254, Table 3).
6.2. Secondary outcomes
There was no signicant difference between mean
scores for the intervention and control groups at any time
point, for PUQE and CSQ. 119 women were known to have
been readmitted; generating a total of 243 readmissions
indicating that some women were readmitted more than
once (range 117 readmissions). The utility score as
measured by the EQ-5D demonstrated the same results
as the primary outcome SF36 Social Functioning scale;
both arms showed an improved trend over time with no
difference between arms at any time point (Table 3).
Analysis using Spearmans correlation coefcient
suggested that there was a signicant relationship
between the HIS and the following SF36 subscales: Social
Functioning, Role Functioning, Role Physical, Mental

Assessed for eligibility

(n=503)
Not meeng inclusion criteria
(n=93)

Enrollment

Refused to parcipate (n=126)

No interpreter = 9
Other = 2

Randomised = 273

Control arm (n=142)

2 week data (n=108)

4 week data (n=63)
6 week data (n=69)
Complete data (n=46)

Allocaon

Follow-Up

Intervenon (n=131)

2 week data (n=98)

4 week data (n=68)
6 week data (n=54)
Complete data (n=38)
Complete loss (n=27)

Complete loss (n=30)

Analysed (n=112)
Excluded (n= 0)

Analysis

Analysed (n=104)
Excluded (n= 0)

Fig. 1. Consort diagram.

Please cite this article in press as: Fletcher, S.J., et al., Holistic assessment of women with hyperemesis gravidarum: A
randomised controlled trial. Int. J. Nurs. Stud. (2015), http://dx.doi.org/10.1016/j.ijnurstu.2015.06.007

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Table 2
Baseline demographics of the sample by group.
Variable

Category

Intervention (n = 131)

Age

<20
2024
2530
3034
35+

14
38
41
25
13

10.7
29.0
31.3
19.1
9.9

12
49
47
23
11

8.5
34.5
33.1
16.2
7.8

Previous HG

Yes
No
n/a
Missing

49
32
47
3

37.4
24.4
35.9
2.3

59
40
42
1

41.6
28.2
29.6
0.7

Marital status

Single (partner absent)

Single (partner living separate)
Married/living together
Missing

14
8
109
0

10.7
6.1
83.2
0.0

14
22
105
1

9.9
15.5
73.9
0.7

Ethnic group

White British
White European
Bangladeshi
Indian
Pakistani
Black African
Black Caribbean
Middle Eastern
Other
Missing

76
2
2
11
17
11
3
1
4
4

58
1.5
1.5
8.4
13
8.4
2.3
0.8
3.1
3

84
3
7
13
15
7
1
2
4
6

59
2.1
4.9
9.2
10.6
4.9
0.8
1.4
2.8
4.2

Employment status

Full time
Part-time
Unemployed
Full time parent
Student

50
28
13
30
10

38.2
21.4
9.9
22.9
7.6

57
32
11
32
10

40.1
22.5
7.8
22.5
7.0

Variable

Gestation on admission
Age
Parity
Gravida
BMI
PUQE

Control (n = 142)

Intervention (n = 131)

Control (n = 142)

Mean

SD

Min

Max

Mean

SD

Min

Max

9.2
26.5
0.9
2.3
24.0
8.4

2.6
5.6
1.2
1.7
5.5
3.1

3
16
0
1
15.8
3

17
39
6
10
39.5
15

131
131
131
131
76
131

9.2
25.8
1.0
2.4
24.3
9.1

2.6
4.9
1.4
1.8
5.8
3.0

5
17
0
1
14.9
3

20
39
10
15
47.6
15

142
142
142
142
76
142

Health and Vitality, as each had a negative relationship

with the HIS score (Table 4). The coefcients varied in
strength, Social Functioning having the strongest correlation coefcient of 0.44.
6.3. Cost effectiveness
Health care use did not differ signicantly between trial
arms, except that the number of other healthcare contacts
at 2 week follow up was signicantly higher in the
intervention group (0.21, SD 0.69 vs. 0.07, SD 0.32). There
was no statistical difference in the number of hospital
admissions 1.70 and 1.75 in the intervention and control
groups respectively, although length of stay (days)
4.97 and 6.14 was signicantly shorter in the intervention
group (P = 0.05). The total NHS cost (including hospital
admissions, GP and other health care professional visits)
was higher in the control arm (1360.50) than for the
intervention arm (1185.90). However, the intervention
arm was associated with more days lost from work costed
at 1930.50 vs. 1468.80. There was no signicant

difference between groups on child care costs. As a result

the intervention had a higher societal cost than the control
arm (3174.90 vs. 2977.50).
EQ5D index scores in both arms demonstrate a trend for
improved scores over time, as observed in all other
outcome measures indicating symptom improvement
with time, which would be expected in a self limiting
condition. Differences between EQ5D scores were not
signicant at any time point. The QALY estimates were
0.063 and 0.066 in intervention and control arm, respectively (unadjusted, not imputed). As expected, the QALY
difference between two arms was relatively small.
Base case analyses (with imputation) suggested that in
both perspectives the intervention was associated with
both higher benets and higher costs. From an NHS
perspective, patients who received the intervention
treatment for their HG gained 0.0009 (95% CI: 0.0061
to 0.0078) more QALYs than those treated with usual care
alone, at an increased cost of around 12.4 (95% CI: 158.7
to 183.4) per patient, yielding an incremental cost
effectiveness ratio of 13,751 per QALY. Whilst from the

Please cite this article in press as: Fletcher, S.J., et al., Holistic assessment of women with hyperemesis gravidarum: A
randomised controlled trial. Int. J. Nurs. Stud. (2015), http://dx.doi.org/10.1016/j.ijnurstu.2015.06.007

Intervention

Adjusted* mean
difference+

Control

Mean

(SD)

Mean

(SD)

Baseline

19.4

(22.0)

130

22.7

(25.6)

142

2 weeks
4 weeks
6 weeks

34.7
50.0
59.8

(30.8)
(35.8)
(32.6)

93
66
55

32.7
46.3
60.5

(31.6)
(36.6)
(32.3)

105
64
69

4.95
5.25
2.35

95% Bootstrap CI

P-value

( 3.50, 13.30)
( 6.16, 17.19)
( 12.98, 9.02)

0.254
0.386
0.685

95% Bootstrap CI

P-value

( 0.83, 0.97)
( 1.18, 0.62)
( 0.50, 1.23)

0.923
0.614
0.312

95% Bootstrap CI

P-value

( 2.05, 0.78)
( 1.71, 2.12)

0.374
0.866

Un-adjusted
mean difference+

1.94
3.71
0.73

95% Bootstrap CI

P-Value

( 6.86, 10.59)
( 8.66, 15.27)
( 11.77, 10.72)

0.663
0.560
0.900

95% Bootstrap CI

P-Value

( 1.10, 0.75)
( 1.26, 0.56)
( 0.51, 1.22)

0.673
0.425
0.378

95% Bootstrap CI

P-Value

( 1.83, 0.97)
( 2.14, 1.55)

0.538
0.807

PUQE
Intervention

Adjusted* mean
difference+

Control

Mean

(SD)

Mean

(SD)

Baseline

8.4

(3.1)

131

9.1

(3.0)

142

2 weeks
4 weeks
6 weeks

7.6
6.2
5.6

(3.20)
(2.5)
(2.5)

93
64
54

7.8
6.6
5.3

(3.3)
(2.7)
(2.2)

107
63
67

0.04
0.24
0.43

Un-adjusted
mean difference+

0.19
0.37
0.38

Client Satisfaction Questionnaire

Intervention

2 weeks
6 weeks

Adjusted* mean
difference+

Control

Mean

(SD)

Mean

(SD)

25.3
26.2

(4.9)
(5.20)

88
54

25.8
26.4

(4.9)
(5.0)

101
65

0.65
0.16

Un-adjusted
mean difference+

0.44
0.23

Intervention control.
* Adjusted for age, previous hyperemesis, gestational age, PUQE score and baseline value of social functioning.

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Social functioning

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Please cite this article in press as: Fletcher, S.J., et al., Holistic assessment of women with hyperemesis gravidarum: A
randomised controlled trial. Int. J. Nurs. Stud. (2015), http://dx.doi.org/10.1016/j.ijnurstu.2015.06.007

Table 3
Primary and secondary outcomes: Social functioning, vomiting and client satisfaction.

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Table 4
Spearmans rank correlation coefcient between HIS and SF-36 summary
scores.
SF-36 summary score
Social functioning
Physical function
Role physical
Role mental
Mental health
Vitality
Pain
General
Change

Spearmans Rho
0.44
0.25
0.37
0.17
0.28
0.29
0.08
0.06
0.17

p-Value
<0.001
0.004
0.000
0.056
0.001
0.001
0.372
0.492
0.056

societal perspective an individual who receives the

intervention has 0.0009 (95% CI: 0.0060 to 0.0079) more
QALYs at 13.3 (95% CI: 516.1 to 542.7) higher cost,
yielding an incremental cost effectiveness ratio of 14,499
per QALY. However, in both perspectives, none of the
differences in costs and benets between these alternative
treatments were statistically signicant indicating a high
level of uncertainty associated with the results.
Analysis of completed cases produced different results.
Completed cases analyses from an NHS perspective
suggested that the intervention was less benecial
( 0.0025 QALYs, CIs: 0.0136 to 0.0085), but cost saving
(76.5 per patient, 433.8 to 280.9). From a societal
perspective the intervention was a dominated treatment
having 0.0004 less QALYs ( 0.0128 to 0.0120) at a higher
cost of 215.5 ( 622.6 to 1053.6).

supportive, non-pharmacological measures. The second

reason is that the screening process using the HIS
questionnaire was insensitive, which we do not believe
is the case. The third reason could be that the supportive
measures indicated by the screening questionnaire could
not be delivered, but this was not the case in this study.
Further research is required to investigate how best to
palliate the symptoms of hyperemesis.
7.1. Nursing and midwifery implications
The HIS did not appear to work as an intervention to
improve the womens health outcomes and, as a consequence, it would be easy for nurses and midwives to
dismiss the tool. However, it can be argued that since it
has been validated through this and previous research
(Power et al., 2010), it will help nurses and midwives to
understand how women are individually affected by HG so
that they can respond appropriately to their needs. Also, in
the very act of using the HIS, they will be behaving
positively towards women with HG and, as a result, will
also validate womens experiences of this debilitating
condition (Poursharif et al., 2007; Power et al., 2010).
Importantly, the HIS will be useful to practitioners as a
bench mark of how well pharmacological treatment effects
outcomes identied as important by women. Future
research could evaluate whether the HIS is suitable to
be a patient reported outcome measure in assessing the
effectiveness of new treatments.
8. Limitations

7. Discussion
The results of this trial indicate that the holistic
assessment using the HIS and accompanying handbook
to provide additional support, did not improve womens
outcomes (social functioning, vomiting, nor rate of
admission) compared with standard medical management. Nor was there any evidence of a health economic
benet.
The published literature and our previous research
(Power et al., 2009, 2010) supported the investigation of
a more holistic approach to the management of HG.
Background research was carried out in an attempt to
develop carefully a robust and effective intervention as the
guidance from the MRC recommends on the development
and evaluation of complex interventions (Craig et al.,
2008). A pragmatic RCT however, affords rigorous assessment in a real world setting. It could have been that the
care regime on the wards undermined some aspects of the
HIS care plan, for example careful attention to dietary
intake. All women in the RCT received rehydration and
were offered anti-emetics and may also have been given
advice by ward nurses about how to cope with HG at home,
some of which, may have been contradictory to the advice
given by the research nurses, although, this would not have
been based on any structured or standardised assessment.
Unfortunately, we have no information on whether this
was the case. There are several reasons why hyperemesis
may be unaffected by a planned intervention. The rst
is that the nausea and vomiting are simply not amenable to

The trial was powered to obtain a reliable assessment of

the intervention for the primary outcome measure of social
functioning at 2 weeks, and the number required for the
primary endpoint was met. Serial follow-up was more
difcult which meant that missing data was a key issue in
the economic analysis. This has implications for future
trials in HG and though failure by some women to adhere
to the follow up protocol is inevitable, improving compliance with follow up will be important. Results differed
between the completed and imputed data sets, which
imposed uncertainty and meant a reliable conclusion could
not be arrived at with respect to the cost effectiveness of
the intervention.
9. Conclusion
In conclusion, this trial failed to demonstrate any value
in providing a holistic plan of care arrived at by using the
HIS and manual to help women control the impact of HG.
Maximum effort should continue to be concentrated on
symptomatic relief of the condition at home and in
hospital. Ambulatory care is an increasingly popular
option, which affords women the exibility of receiving
symptomatic relief not available in primary care, without
the social difculties that overnight hospital care can
entail. There is no doubt that the management of HG is
suboptimal, with high rates of readmission and women
experiencing a poor quality of life. Palliation by antiemetic
measures and rehydration are directed at the symptoms

Please cite this article in press as: Fletcher, S.J., et al., Holistic assessment of women with hyperemesis gravidarum: A
randomised controlled trial. Int. J. Nurs. Stud. (2015), http://dx.doi.org/10.1016/j.ijnurstu.2015.06.007

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S.J. Fletcher et al. / International Journal of Nursing Studies xxx (2015) xxxxxx

and not the cause. A lack of understanding of the cause of

the condition is the major barrier to improving outcomes.
Our attempt to mitigate the impact of the condition
through a supportive approach was unsuccessful. It is clear
that a more determined effort to achieve research led
improvements in care is required for this somewhat
neglected condition.
Acknowledgements
We wish to thank all the women who so generously
gave up their time to participate in the study. We also wish
to thank the hospital staff who kindly supported the study.
Conict of interest. None declared.
Funding. The article represents independent research
commissioned by the National Institute for Health Research
(NIHR) under the Research for Patient Benet Programme
(RfPB). The views expressed in this publication are those of
the author(s) and not necessarily those of the NHS, the NIHR
or the Department of Health.
Ethical approval. The ethics approval was given by NRES
Committee North West Greater Manchester West, reference number: 07/H1009/88.
The trial reference number: ISRCTN 01121147.
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Please cite this article in press as: Fletcher, S.J., et al., Holistic assessment of women with hyperemesis gravidarum: A
randomised controlled trial. Int. J. Nurs. Stud. (2015), http://dx.doi.org/10.1016/j.ijnurstu.2015.06.007