Journal of Obstetrics and Gynaecology

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Are early pregnancy complications more common

in women with hyperemesis gravidarum?

Sinead R. Morgan, Lisa Long, Jemma Johns, Chloe Angwin, Supriya Maitra &
Jackie A. Ross

To cite this article: Sinead R. Morgan, Lisa Long, Jemma Johns, Chloe Angwin, Supriya
Maitra & Jackie A. Ross (2017) Are early pregnancy complications more common in women
with hyperemesis gravidarum?, Journal of Obstetrics and Gynaecology, 37:3, 355-357, DOI:
10.1080/01443615.2016.1256955

To link to this article: http://dx.doi.org/10.1080/01443615.2016.1256955

Published online: 31 Jan 2017.

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JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 2017
VOL. 37, NO. 3, 355–357
http://dx.doi.org/10.1080/01443615.2016.1256955

ORIGINAL ARTICLE

Are early pregnancy complications more common in women with hyperemesis

gravidarum?
Sinead R. Morgan, Lisa Long, Jemma Johns, Chloe Angwin, Supriya Maitra and Jackie A. Ross
Early Pregnancy and Acute Gynaecology Assessment Unit, King’s College Hospital, London, UK

ABSTRACT KEYWORDS
Ultrasound evaluation is usually requested for women presenting with hyperemesis gravidarum (HG) in Hyperemesis gravidarum;
early pregnancy. This is to check viability as well as to diagnose multiple pregnancies and exclude ges- gestational trophoblastic
tational trophoblastic disease (GTD). The aim of this retrospective case control study was to evaluate disease; multiple pregnancy;
miscarriage; ultrasound
the early pregnancy outcomes in women with HG and to compare them with an asymptomatic control
group. 790 women referred with HG between 2002 and 2014 were matched for gestational age and
maternal age with an asymptomatic patient attending for a reassurance or dating scan. A higher pro-
portion of women with HG had ongoing pregnancies compared with controls and conversely, embry-
onic demise was less frequent in the HG group. The risk of twin pregnancy was doubled in the HG
group compared to controls. There was no evidence of an increase in the prevalence of GTD. There
appears to be a limited role for ultrasound in women who present with HG alone.

Introduction disease revealed an incidence of HG in 26% of women

Nausea and vomiting is the most common medical complaint
in early pregnancy and is thought to affect up to 70% of
pregnancies (Einarson et al. 2013). Hyperemesis gravidarum
(HG) describes the persistent vomiting experienced by
0.3–2% of pregnant women (Eliakim et al. 2000). The defin-
ition of what constitutes HG varies, but is widely thought to
consist of intractable vomiting, electrolyte disturbance, ketosis
and over 5% loss of pre-pregnancy body weight (Fairweather
1968).
The aetiology of hyperemesis gravidarum remains uncer-
tain but is thought to involve endocrine, vestibular, gastro-
intestinal, olfactory, and behavioural pathways (Goodwin
2002). The increased prevalence of nausea and vomiting in
the first trimester coincides with peak serum concentration of
oestradiol and human chorionic gonadotropin (hCG). It is this
combination of factors that have given rise to the supposition
that pregnancies associated with higher levels of hCG such as
multiple pregnancies or gestational trophoblastic disease
(GTD) are more likely to be complicated by HG.
The correlation between HG, multiple pregnancy and GTD
has been demonstrated in a number of epidemiological stud-
ies. An analysis of 3068 pregnancies affected by HG in
Sweden between 1973 and 1981 demonstrated a two-fold
increased incidence of twin pregnancy compared to the
expected background rate (Kallen 1987). A more recent case-
control study did not find an association between HG and
multiple pregnancy (Kirk et al. 2006). HG has also frequently
been described as a characteristic feature of GTD. A historical
review of notes from 306 cases of gestational trophoblastic
(Soto-Wright et al. 1995).
It is largely this concern regarding the possibility of gesta-
tional trophoblastic disease that has led to the recommenda-
tion that women with HG are offered an ultrasound scan in
early pregnancy (Niebyl 2010). The aim of this study was to
assess whether adverse early pregnancy outcomes were more
common in women with HG in the absence of other symp-
toms that would prompt ultrasound evaluation in modern
clinical practice such as abdominal pain or vaginal bleeding.
Materials and methods
This retrospective case-control study was based at the Early
Pregnancy Unit (EPU) in King’s College Hospital, London, UK.
A database search was undertaken to identify women
referred for an ultrasound scan due to HG between October
2002 and February 2014.
Women were referred from the emergency department,
their general practitioners or self-presented. They were identi-
fied as having HG if their sole reason for referral or presenta-
tion was vomiting, dehydration and ketosis. Women who
attended due to HG were matched for gestational age in
days and maternal age in years ±365 days with an asymp-
tomatic control attending for a dating or reassurance scan.
Patients with additional symptoms at the time of presenta-
tion such as pelvic pain or vaginal bleeding were excluded
from the analysis. Gestational age was calculated according
to the date of the last menstrual period. In cases where the
date of the last menstrual period was unknown, the preg-
nancy was dated according to the mean gestational sac

CONTACT Sinead Morgan sineadmorgan@nhs.net Early Pregnancy and Acute Gynaecology Assessment Unit, King’s College Hospital, London, SE5 9RS, UK
ß 2017 Informa UK Limited, trading as Taylor & Francis Group
356 S. R. MORGAN ET AL.

diameter or crown rump length. Ultrasound scans were per- the four cases of early embryonic demise in the HG group
formed transvaginally and/or transabdominally by and 16 of the 34 cases in the control group, the rest chose
Gynaecologists working in the EPU. non-surgical management of their miscarriages. No additional
The primary outcome measure was the ultrasound diagno- cases of GTD were identified in either group.
sis at the index assessment. The possible diagnoses were
ongoing intrauterine pregnancy, early intrauterine pregnancy,
Discussion
ectopic pregnancy, pregnancy of unknown location, early
embryonic demise and suspected GTD. The diagnosis of early Traditionally, women with HG have been offered an ultra-
intrauterine pregnancy encompassed intrauterine pregnancies sound to exclude GTD. This recommendation is largely based
of uncertain viability due to the gestation being too early to on retrospective reviews of the clinical presentation of known
visualise an embryo, and also those pregnancies that had cases of GTD. A review of the clinical presentation of GTD
failed but were too small for the diagnosis of early embryonic found that the traditional clinical signs of GTD such as hyper-
demise to be made at the index scan. It was also noted emesis, pre-eclampsia and excessive uterine size are less
whether the pregnancy was multiple in cases where more prevalent in modern clinical practice, with the vast majority
than one gestational sac and/or embryo was visualised. of GTD patients presenting early with vaginal bleeding alone
Categorical data were compared with McNemar’s Chi square (Soto-Wright et al. 1995; Hou et al. 2008). This study aimed to
test (v2). Non-parametric data were compared using the assess early pregnancy complications in a cohort of women
Mann–Whitney U-test. with HG in the absence of other symptoms. We identified
one case of GTD in the HG group with no cases amongst the
controls, this is consistent with the reported 1/714 back-
Results ground incidence of GTD in the United Kingdom (Tham et al.
Totally 790 women were referred for a scan where the only 2003). Although a history of vaginal bleeding was not elicited
indication was HG during the study period. All women were at the time of the ultrasound assessment, a detailed review
of the case notes revealed a history of vaginal bleeding ear-
matched with an asymptomatic control. The demographic
lier in the pregnancy for which the patient had not presented
and clinical histories of the cases and controls are illustrated
to hospital. The index scan in this case was performed during
in Table 1. A higher proportion of women with HG had
an admission for symptomatic thyrotoxicosis and these symp-
ongoing pregnancies compared with controls and conversely,
toms would have formed a sufficient basis for an early ultra-
the incidence of early embryonic demise was significantly
sound assessment to check for a miscarriage or GTD.
lower in the HG group (Table 2). The prevalence of a non-
Our study identified an increased prevalence of multiple
viable pregnancy or a scan where viability could not be
pregnancy in those diagnosed with HG. This supports the
ascertained was almost five times lower in the HG group
findings of an epidemiological study that also identified a
(3.2% vs. 15.1%, relative risk 0.21, 95% CI 0.14 to 0.32,
two-fold increased prevalence of multiple pregnancy in 6227
p < .001). The prevalence of multiple pregnancy was double women hospitalised with HG (Basso and Olsen 2001).
that of the control group (relative risk ¼2.08, 95%CI Although the aetiology of HG remains unclear, the link
¼1.08–4.00, p ¼ .03). between HG and elevated hCG is well documented (Derbent
There was one case of suspected GTD in the HG group, et al. 2011), suggesting the increased incidence of HG in
which was subsequently diagnosed as a complete mole on multiple pregnancies may be linked to the higher serum
histological examination. Histology was available for three of concentration of hCG found in twin pregnancy (Steier et al.
1989).
Previous studies have revealed a reduction in the early
Table 1. Demographic and clinical history of study and control groups. pregnancy loss rate in women with HG (Kirk et al. 2006).
Controls Our study confirmed this observation, demonstrating an
Parameter HG (n ¼ 790) (n ¼ 790) p
eight-fold reduction in the incidence of early embryonic
Maternal age (years)a 27.0 (15–45) 27.0 (15–44) .95
Gestational age (days)a 58.0 (27–120) 58.0 (27–120) 1.0 demise in women with HG. It is not unreasonable to assume
Graviditya 2 (1–12) 2 (1–11) .02 that the control group consisting of women attending for
Paritya 1 (0–8) 1 (0–7) .03 reassurance scans or dating scans could have an increased
History of miscarriage, n (%) 174 (22.0) 170 (21.5) .81
History of multiple miscarriages, n (%) 49 (6.2) 41 (5.2) .39 prevalence of early pregnancy loss. However, we did not
a
Median (range). find any difference in the prevalence of a previous miscar-
riage between cases and controls that could account for a
Table 2. Early pregnancy outcome between HG and controls. higher incidence of miscarriage in the control group.
Control
Maternal age remains the most important predictor for foe-
Ultrasound diagnosis HG (n ¼ 790) (n ¼ 790) p tal loss (Nybo Andersen et al. 2000), hence the two groups
Ongoing intrauterine pregnancy, n (%) 765 (96.8) 671 (84.9) <.0001 were matched for this variable. They were also matched for
Early intrauterine pregnancy, n (%) 19 (2.4) 80 (10.1) <.0001 gestational age to allow for the difference in incidence of
Early embryonic demise, n (%) 4 (0.5) 34 (4.3) <.0001
Gestational trophoblastic disease, n (%) 1 (0.1) 0 1.0000
miscarriage at progressive gestations in early pregnancy
Tubal ectopic pregnancy, n (%) 0 3 (0.4) .08 (Simpson et al. 1987).
Pregnancy of unknown location, n (%) 1 (0.1) 2 (0.3) .56 A limitation of this study is the lack of standardisation
Multiple pregnancy, n (%) 27 (3.4) 13 (1.6) .03
with regard to the diagnostic criteria for HG. The HG group

consisted of a spectrum of disease severity including those
hospitalised with the condition, as well as those with milder
symptoms managed as outpatients in whom a diagnosis of
nausea and vomiting in early pregnancy may have been
more appropriate. Despite this, the results of this study sug-
gest that HG or vomiting in early pregnancy are associated
with a reduced risk of early pregnancy loss, an increased inci-
dence of twins and in the absence of vaginal bleeding, no
greater risk of GTD above background risk.
This study would suggest that there appears to be a lim-
ited role for ultrasound assessment in cases of HG in the
absence of any other symptoms. A diagnosis of multiple
pregnancy does not alter care in early pregnancy and will be
identified on the routine first trimester dating scan offered in
the UK to all women. Nausea and vomiting is viewed by
many women as an inevitable part of early pregnancy
(Locock et al. 2008), raising the question as to whether
women with these symptoms need to be referred for an early
scan and should be reassured on clinical grounds alone.
Future studies could assess the role of ultrasound in the psy-
chological support of women with HG, as this would appear
to be the only potential clinical benefit.
Disclosure statement
The authors report no conflict of interest
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