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The windsor definition for hyperemesis gravidarum: A multistakeholder
international consensus definition
L.A.W. Jansen
a,b,
⇑
, M.H. Koot
a
, J. van’t Hooft
a
, C.R. Dean
c
, P.M.M. Bossuyt
d
, W. Ganzevoort
a
, N. Gauw
e
,
B.Y. Van der Goes
f
, J. Rodenburg
g
, T.J. Roseboom
a,d
, R.C. Painter
a
, I.J. Grooten
a
a
Department of Obstetrics and Gynaecology, Amsterdam UMC, University of Amsterdam, Amsterdam Reproduction and Development, the Netherlands
b
Department of Obstetrics and Gynaecology, Amphia Hospital, Breda, the Netherlands
c
Pregnancy Sickness Support, United Kingdom
d
Department of Epidemiology and Data Science, Amsterdam UMC, the Netherlands
e
Dutch Hyperemesis Gravidarum Patient Foundation (ZEHG), the Netherlands
f
Department of Obstetrics and Gynaecology, Leiden University Medical Centre, Leiden, the Netherlands
g
General Practice Czaar Peter Medical Center, Amsterdam, the Netherlands
article info
Article history:
Received 5 June 2021
Revised 30 August 2021
Accepted 7 September 2021
Keywords:
Definition
Delphi
Hyperemesis Gravidarum
Pregnancy
abstract
Objective: To develop an international definition for hyperemesis gravidarum to assist in clinical diagno-
sis and harmonize hyperemesis gravidarum definition for study populations.
Study design: A mixed-methods approach was used to identify potential hyperemesis gravidarum def-
inition criteria (i.e. systematic review, semi-structured interviews and closed group sessions with
patients and Project Steering Committee input). To reach consensus on the definition we used a web-
based Delphi survey with two rounds, followed by a face-to-face consensus development meeting, held
in Windsor UK, and a web-based consultation round, in which the provisional hyperemesis gravidarum
definition was fed back to the stakeholders. Four stakeholder groups were identified 1) researchers; 2)
women with lived experience of hyperemesis gravidarum and their families; 3) obstetric health profes-
sionals (obstetricians, gynecologists, midwives); and 4) other health professionals involved in care for
women with hyperemesis gravidarum (general practitioners, dieticians, nurses). To reflect the opinions
of the international community, stakeholders from countries in all global regions were invited to partic-
ipate.
Results: Twenty-one identified potential criteria entered the Delphi survey. Of the 277 stakeholders
invited, 178 completed round one, and 125 (70%) also completed round two. Twenty stakeholders
attended the consensus development meeting, representing all stakeholder groups. The consultation
round was completed by 96 (54%) stakeholders, of which 92% agreed with the definition as presented.
The consensus definition for hyperemesis gravidarum consisted of: start of symptoms in early pregnancy
(before 16 weeks gestational age); nausea and vomiting, at least one of which severe; inability to eat and/
or drink normally; strongly limits daily living activities. Signs of dehydration were deemed contributory
for the definition for hyperemesis gravidarum.
Conclusions: The proposed definition for hyperemesis gravidarum will help clinical studies to achieve
more uniformity, and ultimately increasing the value of evidence to inform patient care.
Ó2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license(http://
creativecommons.org/licenses/by/4.0/).
Introduction
Nausea and vomiting are common in early pregnancy (NVP);
approximately 80% of all pregnant women are affected to some
degree. [1] When NVP is severe or protracted, the condition is often
referred to as hyperemesis gravidarum (HG), affecting up to 3.6% of
pregnancies. [1–5] Women with HG may become dehydrated, lose
weight or require hospital admission. [6–7] After HG, women more
often report anxiety, depression and posttraumatic stress disorder,
reflecting the detrimental effect of HG on maternal wellbeing
and quality of life. [8–11] HG may increase the chance of preterm
birth and small for gestational age, and there is evidence suggest-
ing adverse long term outcomes among offspring and mothers.
[11–16]
https://doi.org/10.1016/j.ejogrb.2021.09.004
2215-1532/Ó2021 The Authors. Published by Elsevier B.V.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
⇑
Corresponding author.
E-mail address: l.a.w.jansen@amsterdamumc.com (L.A.W. Jansen).
European Journal of Obstetrics & Gynecology and Reproductive Biology 266 (2021) 15–22
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and
Reproductive Biology
journal homepage: www.elsevier.com/locate/euro
Recently there has been progress in understanding disease eti-
ology. The placenta and appetite hormone gene GDF15 has been
identified as the greatest genetic risk factor for HG. [17] The hor-
mone activates the vomiting center of the brain, causing nausea
and vomiting in animal models. [18] Higher circulating levels of
GDF15 are found in pregnant patients hospitalized with HG,
patients using antiemetics, patients with 2nd trimester vomiting,
and those carrying a female fetus. [19–20] More studies with a
clearly defined definition of HG are urgently needed to determine
whether GDF15 can be used as a biomarker for HG. Currently, there
are no biomarkers that can help diagnose or rule out HG. [21–22]
Therefore, HG has remained a clinical diagnosis, which can only
be made after other causes of nausea and vomiting have been ruled
out.
There is no international consensus on the definition for HG.
[23] A recent systematic review demonstrated that the definition
for HG used in trials varies widely. [24] The most recent guideline
on NVP and HG is the RCOG guideline which describes HG as pro-
tracted NVP with the triad of more than 5% pre pregnancy weight
loss, dehydration and electrolyte imbalance. [25]
The absence of a uniform definition has led to heterogeneity in
research populations on HG. This has further hampered the synthe-
sis of the already scant high-quality evidence on effective treat-
ment for HG, in meta-analyses. [26]
This study aimed to develop an international consensus defini-
tion for HG using robust consensus methods engaging all relevant
stakeholders. This will help clinical studies achieve more unifor-
mity in HG definition, and ultimately increasing the value of evi-
dence to inform patient care.
Material and methods
The study was prospectively registered on the COMET initiative
website (registration number 805) as part of the Definition and
Core Outcomes on HG (DCOHG) study. [27] The data collection
for the study was carried out between May 2016 and August 2018.
Project Steering Committee
To give guidance and feedback on the different phases of this
project a Project Steering Committee was established. The Project
Steering Committee consisted of three researchers (MHK, TJR,
IJG), two patient representatives (CRD, NG), two obstetricians
(WG, RCP), one research midwife (BYG), one general practitioner
(JR) and two methodologists (JvH, PMMB).
Recruitment of stakeholders
Four stakeholder groups were identified: 1) researchers; 2)
women with lived experience of HG and their families; 3) obstetric
health professionals (obstetricians, gynecologists, midwives); and
4) other health professionals involved in care for women with
HG (general practitioners, dieticians, nurses).
To reflect the opinions of the international community, stake-
holders from countries in all global regions were invited to partic-
ipate using different type of stakeholder platforms, see Table 1.
Participants were asked to provide basic demographic information,
for each question participants could choose from a list of options or
if they felt our options did not cover their background, to use the
option ‘other’.
Personal data were managed according to the General Data Pro-
tection Regulation.
Stakeholder panel size
There is no robust method for calculating the required sample
size of stakeholders in a Delphi survey. Our sample size was based
on 2 studies developing a definition using a Delphi method and on
4 studies in the field of obstetrics using a Delphi method for devel-
oping a core outcome set. [28–33] Based on previous literature a
drop-out rate of 15–21% could be expected. [28,34] We therefore
aimed to recruit 245 stakeholders. No minimum number of partic-
ipants per stakeholder group or per represented country was
defined.
Identification of potential criteria
A previously published systematic review on interventions for
HG was used to identify potential patient inclusion criteria used
for trial entry in published and ongoing randomized clinical trials.
[24] To identify additional HG definition criteria, semi-structured
patient interviews and closed group sessions through patient fora
were conducted and stakeholders were asked during the first Del-
phi round to list additional HG definition criteria (appendix A).
The Project Steering Committee discussed all potential HG crite-
ria, duplicates were excluded and overarching domains were
established through interactive discussion using the thematic clus-
tering of a previously published systematic review. [24]
Consensus process
A 9-point Likert scale, grade 1 to 9, was used to score each cri-
terion. Grade 1 to 3 was defined as of limited importance, grade 4
to 6 as important but not critical, and grade 7 to 9 as critical crite-
rion to include in the HG definition. To be included in the defini-
tion, at least 70% of each stakeholder group had to score a
criterion as ‘critical’ and fewer than 15% of stakeholders in each
stakeholder group had to score the criterion of ‘limited impor-
Table 1
Invited stakeholders.
Invited stakeholders
Speakers at the first World Colloquium on Hyperemesis Gravidarum
(NoHype, Bergen, Norway 2015)
Speakers at the hyperemesis gravidarum Associations Satellite meeting of
the European Board & College of Obstetrics and Gynaecology (EBCOG)
conference (Glasgow, Scotland, 2014)
Speakers at the three Pregnancy Sickness Support (PSS) Conferences (UK,
2013, 2014, 2015)
All corresponding authors of studies referenced in the Cochrane
systematic review on treatment of HG
All members of the core outcomes in women’s health and newborn health
(CROWN) initiative
1
All members of the Cochrane Pregnancy and Childbirth Group and the
Global Obstetrics Network (GONet)
Obstetricians, midwives, general practitioners, dieticians and nurses were
invited through (inter-)national professional organisations among
others:*The Australian College of Midwives (AUS)*The European
Federation of the Associations of Dietitians (EU)*The College of Family
Physicians of Canada (CA)_*Dutch General Practitioner Network
(Netherlands)*The Royal Australian College of General Practitioners
(AUS)*Obstetric health professionals associated with the nationwide
Dutch Consortium for Healthcare Evaluation and Research in Obstetrics
and Gynaecology (Netherlands)
Identification of patient representatives took place by approaching
national and international patient organisations who used their social
media:* Pregnancy Sickness Support (PSS) (UK)* Hyperemesis
Education & Research foundation (HER) (USA)*
Zwangerschapsmisselijkheid en Hyperemesis Gravidarum (ZEHG)
(Netherlands)
Stakeholders that responded to our initial invitation were also encouraged
to forward their invitation to others who might be willing to
participate in developing a definition for HG
L.A.W. Jansen, M.H. Koot, J. van’t Hooft et al. European Journal of Obstetrics & Gynecology and Reproductive Biology 266 (2021) 15–22
16
tance’). To be excluded from the definition, fewer than 70% of each
stakeholder group had to score a criterion as ‘critical’ after round
two. In case one or more, but not all stakeholder groups, scored a
criterion as ‘critical’ in the second Delphi round, the criterion
was listed as ‘undecided’ (Table 2). These cut-offs were prespeci-
fied and are commonly used in previous published work on the
consensus process in women and newborn health research.
[28,35–36]
Modified Delphi procedure
A two-round modified Delphi survey was performed followed
by a consensus meeting and a consultation round. A Delphi proce-
dure is an iterative process with anonymous consultation and with
controlled feedback and quantified analysis of the responses. [37]
Stakeholders received an invitation email containing a link to the
web-based survey (LimeSurvey GmbH, Hamburg, Germany) for
each Delphi round. [38] After accepting the invitation a unique
identification code was generated, this identifier ensured future
responses to be both linked and anonymous. Weekly reminders
were sent to non-responders and after four weeks the survey
was closed. Those who had not responded or had stated they were
not willing to participate further were not invited to subsequent
rounds.
In each round, criteria were presented per domain accompanied
by a brief explanation for each criterion. Stakeholders were able to
indicate if they felt they were unable to judge a criterion. Prior to
rescoring the criteria, scores from round one were presented per
criterion in percentages per stakeholder group. On the criteria,
for which consensus to include had been reached after the first
Delphi round, participants were asked in round two to agree or dis-
agree with inclusion of these criteria in the definition. If consensus
to exclude had been reached, or if no consensus was reached in
round one, stakeholders were asked to re-score these criteria using
a 3-point Likert scale; limited importance, important but not crit-
ical and critical.
Consensus development meeting
After the second Delphi round, a consensus development meet-
ing was held during the second International Colloquium on HG
(ICHG) conference, in Windsor in October 2017, using a modified
nominal group technique. [39] Invitations to participate were sent
to all participants of the second Delphi round and the ICHG confer-
ence. Results of prior rounds were presented during this face-to-
face meeting during a plenary introduction, after which small
groups were formed to discuss criteria listed as undecided after
the second Delphi round. Stakeholders voted anonymously,
through a mobile phone based electronic voting system, to include
or exclude criteria listed as undecided after the second Delphi
round, after which a provisional definition was formulated.
Consultation round
A web-based consultation round was held among participants
who completed the second round, the purpose was to verify
whether participants of the second Delphi round agreed with the
provisional definition resulting from the consensus development
meeting, which was named as a limitation by another Delphi pro-
cedure. [28] The provisional definition was presented and stake-
holders were asked to agree or disagree with this definition. In
case more than 80% of stakeholders agreed with the provisional
definition, we considered the decisions made by stakeholders of
the consensus development meeting supported by the participants
of the second Delphi round. In case less than 80% agreed with the
provisional definition a new Delphi round would take place. In case
of disagreement, participants were encouraged to comment in a
free text response. These comments were discussed in the Project
Steering Committee meeting before a final definition on HG was
formulated. This consultation round complements the existing
COMET guidelines. [40]
Theory
HG is a clinical diagnosis, which can only be made after other
causes of nausea and vomiting have been ruled out. [23] The fact
that there is no international consensus on the definition for HG
has resulted in heterogeneity in research populations and hampers
aggregation of evidence, with only a minority of existing papers
using overlapping criteria for trial inclusion. [26]
Results
Identification of criteria
The findings from the systematic review describing variation in
HG definition and outcome reporting in randomized clinical trials
have been previously published. [24] Briefly, the systematic review
yielded thirty-one published trials, reporting data from 2511
women, and three ongoing trials, with a planned total sample size
of 360 participants. 15 criteria were identified through the system-
atic review (appendix B).
Through semi-structured interviews and closed group discus-
sions on patient fora, five additional criteria were added by seven
women with lived experience of HG. One criterion was added by
the Project Steering Committee. Therefore, 21 criteria were identi-
fied, clustered in five overarching domains by the Project Steering
Committee, before they entered the Delphi process (Fig. 1).
Modified Delphi survey
Upon the initial invitation, 277 potential participants expressed
their willingness to participate in the survey; they received an invi-
tation for round 1 (appendix C). 178 (64%) responded, with respon-
dents from 22 different countries (appendix D and E).
Characteristics of participants are shown in Table 3. In the first sur-
vey round, consensus on inclusion was reached on four criteria (ap-
pendix F). Stakeholders suggested 20 additional criteria in round 1
of the survey. The Project Steering Committee discussed all sug-
gested criteria but decided none of the suggestions were suitable
for uptake in the list of definition criteria for round 2. The majority
of suggested criteria were in fact examples of criteria that had
Table 2
Cut off values.
Limited importance Grade 1 to 3
Important but not critical Grade 4 to 6
Critical Grade 7 to 9
Include At least 70% of each stakeholder
group had to score a criterion as
‘critical’ and fewer than 15% of
stakeholders in each stakeholder
group had to score the criterion
of ‘limited importance’
Exclude Fewer than 70% of each
stakeholder group had to score a
criterion as ‘critical’ after round
two
Undecided In case at least 70% of one or
more, but not all stakeholder
groups, scored a criterion as
‘critical’
L.A.W. Jansen, M.H. Koot, J. van’t Hooft et al. European Journal of Obstetrics & Gynecology and Reproductive Biology 266 (2021) 15–22
17
already been included in round one or concerned risk factors for
HG rather than new definition criteria (appendix G). Five respon-
dents expressed they were not willing to participate further, with-
out stating their reason.
The second round of the Delphi survey was completed by 125
(72%) of 173 invited stakeholders. Consensus on inclusion was con-
firmed on all four criteria, which reached ‘consensus in’ in round 1
(appendix H). ‘Consensus out’ was reached on twelve criteria. On
the five remaining criteria no consensus was reached.
Consensus development meeting
Twenty stakeholders attended the consensus development
meeting, representing all stakeholder groups. The five criteria that
were undecided after the second Delphi round were discussed and
individual voting on the in- or exclusion of these criteria was per-
formed. Three additional criteria were included in the definition
and the phrasing of one criteria was changed after discussion (ap-
pendix I).
Fig. 1. Flowchart of identification and selection of criteria.
L.A.W. Jansen, M.H. Koot, J. van’t Hooft et al. European Journal of Obstetrics & Gynecology and Reproductive Biology 266 (2021) 15–22
18
Consultation round
Of the 125 invited stakeholders that completed round 2, 96
(77%) responded in the consultation round, of whom 92% agreed
with the preliminary definition as presented (Table 4). Those
who did not agree with the preliminary definition were asked to
provide arguments for their disagreement, these were discussed
in the Project Steering Committee (appendix J).
Final definition
Each of the following criteria are required for the definition for
HG:
Symptoms starts in early pregnancy, before a gestational age of
16 weeks. More than 70% of stakeholders agreed symptoms had
to start before a gestational age of 16 weeks (appendix K)
Characterized by severe nausea and/or vomiting
Inability to eat and/or drink normally
Strongly limits daily activities
Signs of dehydration were deemed contributory but not manda-
tory for the definition for HG (Appendix L).
Discussion
Principal findings
Through an international consensus process including all rele-
vant stakeholders we present the first international definition for
HG. The Windsor definition for HG can be used to decide on eligi-
bility for patients in studies and as a guideline for clinicians diag-
nosing HG.
Strengths and limitations
Our study has several strengths. First, an important strength of
this study lies in its design: a modified Delphi method, combined
with a face-to-face consensus meeting and a consultation round.
Our methods enabled many geographically distant participants to
participate with an equal voice in the consensus process. Face-to-
face consensus meetings are known to potentially contribute to
underrepresentation of certain stakeholder groups, [28,41] which
we tackled by introducing a consultation round. Second, people
with lived experience of HG were extensively involved in forming
the HG definition which is unique and should be considered
another strength of our study [42,43].
Some limitations should be noted. The attrition rate could pre-
sent a limitation. Our sample size was lower and our drop-out rate
was higher than anticipated (36, 28 and 23% for round 1, round 2
and the consultation round respectively) but comparable to other
Delphi studies. [36,44] Compared to panel sizes described in other
studies on disease definition using the Delphi technique published
in the last five years, our study’s panel size of 96 participants in the
final round was among the largest of its kind, although this fully
cannot rule out possible lack of robustness of findings if an even
larger panel size had been employed. [29,45–48] Furthermore,
there were no differences between those participants that com-
pleted all rounds, and those who dropped out, leading us to believe
that attrition bias was not a major issue (appendix M). Second, the
majority of participants had a high level of education (88%), 92%
had a white background, and low- and middle-income countries
Table 3
Number and Baseline Characteristics of Participants in the Delphi survey and Consensus Meeting for HG definition.
Round 1 Round 2 Consensus Meeting Consultation round
n=178 n=125 n=20 n=96
(%) (%) (%) (%)
Stakeholder group
Researchers 21 (12) 14(11) 9 (45) 11 (11)
Women or families with lived experience 56 (31) 35(28) 5 (25) 27 (28)
Obstetric health professionals 62 (35) 50(40) 3 (15) 44 (46)
Other health care professionals 39 (22) 26(21) 3 (15) 14 (15)
2nd stakeholder group 43 (24) 34 (27) 8 (40) 27 (28)
Researchers 16 (9) 12 (10) 3 (15) 10 (10)
Women or families with lived experience 13 (7) 10 (8) 2 (10) 7 (7)
Obstetric health professionals 9 (5) 7 (6) 3 (15) 6 (6)
Other health care professionals 5 (3) 5 (4) 0 (0) 4 (4)
Health care professionals involved in research 97 (54) 72 (58) 15 (71) 59 (61)
Members of CROWN 7 (4) 4 (3) 0 (0) 4 (4)
Part of Cochrane Collaboration 15 (8) 12 (10) 0 (0) 9 (9)
Involved in (inter)national guideline development 45 (25) 35 (28) 10 (48) 32 (33)
Role in allocation of healthcare budgets 10 (6) 7 (6) 1 (5) 6 (6)
Sex
Male 32 (18) 22 (18) 2 (10) 17 (18)
Female 146 (82) 103 (82) 18 (90) 79 (82)
Personal experience with HG 77 (43) 49 (39) 10 (48) 36 (38)
Patients who participated in a study 14 (8) 10 (8) 3 (14) 8 (8)
Education level
High 158 (89) 115 (92) 15 (75) 87 (91)
Middle 16 (9) 8 (6) 2 (10) 7 (7)
Low 4 (2) 2 (2) 1 (5) 2 (2)
Missing 0 (0) 0 (0) 2 (10) 0 (0)
Ethnic background
Asian 8 (4) 5 (4) 2 (10) 5 (5)
Black 2 (1) 2 (2) 0 (0) 1 (1)
Mixed 2 (1) 2 (2) 0 (0) 2 (2)
White 164 (92) 114 (91) 15 (75) 88 (92)
Other 1 (1) 1 (1) 1 (5) 0 (0)
Missing 1 (1) 1 (1) 2 (10) 0 (0)
No. Of countries represented* 22 20 6 18
L.A.W. Jansen, M.H. Koot, J. van’t Hooft et al. European Journal of Obstetrics & Gynecology and Reproductive Biology 266 (2021) 15–22
19
were poorly represented, each of which may have reduced the
external validity although it is difficult to hypothesise how this
could have affected our conclusions.
Interpretation
Developing a definition for a disease has several consequences.
In our case there have been concerns, among health care providers
and patients alike, that the introduction of an internationally rec-
ognized definition for HG could exert harmful side effects on
patient care. By delineating HG from non-HG, the definition may
lead to a group of pregnant women with some, but not all, hall-
marks of HG, who do not meet the criteria for HG and could there-
fore be denied treatment. However, this is already the case for HG
at present: many clinicians consider ketonuria an essential defin-
ing attribute to HG, while in fact the evidence underpinning its
utility is weak. [23,49–50] The use of ketonuria in delineating HG
from non-HG has led to groups of patients being denied HG care,
when they would have met the current Windsor definition. [49]
Other definitions used in obstetrics, including those for preeclamp-
sia [51] and gestational diabetes [52], have in common with the
current Windsor HG definition, that the underlying conditions dis-
play signs and symptoms across a spectrum between physiology
and disease states. This can frustrate health care professionals
who wish to avoid missing a diagnosis when applying stricter diag-
nostic criteria. In conclusion, the Windsor definition is not
intended to be used to include or exclude patients from treatment
or, for example, for health insurers to reimburse. As a consequence,
the current Windsor definition for HG is broad and therefore may
bias future studies toward a less severely affected study population
and dilute conclusions. Therefore, identification of women with HG
with factors indicating a poor prognosis, e.g. prolonged illness or
more severe weight loss, would be of great value. Unfortunately,
such factors are yet unknown, but could be uncovered in future
research, in which case updating the HG definition should be per-
formed, by adding categories to the definition for severity based on
prognosis.
The Windsor definition for HG consists of subjective criteria.
Such subjective symptoms could be further quantified using vali-
dated scoring systems, e.g. Pregnancy-Unique Quantification of
Emesis (PUQE) scoring system [53], or MOS-36 item short form
health survey to quantify impact on daily living. [54] However,
these questionnaires are likely to present a further burden on clin-
icians, as they are not part of routine clinical history, and are there-
fore unlikely to provide benefit in implementation of the Windsor
definition. Furthermore, the Windsor definition may prove difficult
to ascertain in retrospective or registry studies, as it relies on
patient reported measures, which are usually not collected in reg-
istries. Such studies are likely to maintain their reliance on ICD-
codes, hospital admission, prescription and birth registry data.
We recommend the criteria in de Windsor definition be ascer-
tained using routine clinical history and primarily in prospective
cohorts and trials.
Conclusions
We propose to define HG as a condition that starts early in preg-
nancy, before a gestational age of 16 weeks, and is characterized by
severe nausea and/or vomiting, inability to eat and/or drink nor-
mally and strongly limits daily activities. This Windsor definition
for HG can help to standardise inclusion in HG research. When
more insight is gained on predicting disease prognosis, this defini-
tion needs to be reviewed.
Contribution of authorship
RCP and IJG conceived the idea. The protocol was developed by
IJG with help from Jv’tH and MHK. Input for the development of the
protocol came from BYG, CD, JMND, JR, NG, RCP, TJR and WG. IJG,
LAWJ and MHK executed the project. Expert input at various stages
Table 4
Presented definition in the consultation round, results of the consultation round and the final definition.
Definition criteria
Nausea
Vomiting
Severe nausea and/or vomiting
Signs of dehydration
Inability to drink and/or eat normally
Strongly affects daily living activities
Gestational age at beginning of symptoms
HG definition
Who? Pregnant woman
Other causes of nausea and vomiting have been excluded
When? Beginning of symptoms in early pregnancy
Symptoms? Nausea and vomiting. At least one of these should be severe
Inability to eat and/or drink normally
Strong effect on daily living activities
Signs of dehydration contribute to the diagnosis
Results consultation round:
Stakeholder groups
Agree/disagree with the presented definition Total Researchers Patients and carers Obstetric health professionals Other health professionals
(n = 96) (n = 11) (n = 27) (n = 44) (n = 14)
Agree 92% 91% 92% 89% 100%
Disagree 7% 0% 8% 11% 0%
Unable to score 1% 9% 0% 0% 0%
Final definition HG:
Mandatory Contributory
Nausea and vomiting, one of these has to be severe Signs of dehydration
Inability to drink and/or eat normally
Strongly affects daily living activities
Beginning of symptoms in early pregnancy
L.A.W. Jansen, M.H. Koot, J. van’t Hooft et al. European Journal of Obstetrics & Gynecology and Reproductive Biology 266 (2021) 15–22
20
of the project came from BYG, CD, JR, Jv’tH, NG, PMMB, RCP, TJR
and WG. Data were analysed by LAWJ with input from IJG and
RCP. LAWJ drafted the manuscript with input from all co-authors.
Details of ethics approval
The ethics board of the Academic Medical Center Amsterdam
reviewed the study protocol and provided a waiver for formal eth-
ical approval (dated 11th May 2016, reference number E2-172).
Funding
This study did not receive any funding.
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledgements
We would like to acknowledge (1) stakeholders of the Delphi
survey; and (2) stakeholders of the consensus meeting. Further-
more, we would like to acknowledge JMN Duffy, expert on core
outcome set development, for his advice during the DCOHG
project.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.ejogrb.2021.09.004.
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Vitae Larissa Jansen: Larissa Jansen is a 30 year old
resident in obstetrics and gynecology in the Netherlands
and a pHd student on hyperemesis gravidarum. Toge-
ther with a team, including Dr. Painter, Dr. Roseboom
and Dr. Grooten she already developed a core outcome
set for hyperemesis gravidarum. Currently she is also
working on systematic reviews on perinatal and long
term health outcomes of offspring after pregnancies
complicated by hyperemesis gravidarum.
L.A.W. Jansen, M.H. Koot, J. van’t Hooft et al. European Journal of Obstetrics & Gynecology and Reproductive Biology 266 (2021) 15–22
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