Hyperemesis gravidarum is a severe form of nausea and vomiting during pregnancy that can lead to dehydration, electrolyte imbalances, and nutritional deficiencies requiring hospitalization. While the exact causes are unknown, it is thought to be related to high levels of pregnancy hormones like HCG and estrogen. Treatment involves rehydration, antiemetics, nutritional support, and in severe cases corticosteroids. Monitoring for complications like Wernicke's encephalopathy is important given thiamine deficiencies from prolonged vomiting. A multidisciplinary team approach is needed for management.

1. HYPEREMESIS GRAVIDARUM
AN OBSTETRIC EMERGENCY
DR SUSANTA KUMAR BEHERA
ASSISTANT PROFESSOR

2. Introduction
 Up to 80% of all pregnant women experience
nausea and vomiting during their pregnancy
(NVP).
 Hyperemesis gravidarum is a clinical diagnosis;
most of physicians diagnose it by its typical
presentation and exclusion of other causes of
nausea and vomiting in the pregnant woman.
 It is a common experience affecting 50% to 90%
of all women.

3.  It typically occurs between the 4th and the
10th week of gestation and peaks by 12
weeks, with resolution by 20 weeks of
gestation.
 Estimates of the incidence of HG vary from 0.3
to 1.5% of all live births, with most authors
reporting an incidence of 0.5%.
 Most common indication for hospitalization
during the first half of pregnancy.

4.  Usually limited to first trimester but 20% of
women continue throughout pregnancy.
 Protracted cases of HG refractory to
pharmacological therapy : Nasogastric feeding
or total parenteral nutrition has been used to
maintain adequate maternal nutrition and well
being.

5.  Sometimes all forms of conventional treatment
fail or the maternal condition becomes life
threatening and termination of pregnancy is
required.
 Elective termination of approximately 2% of
pregnancies complicated by HG has been
reported.
 Not only can HG be a life-threatening illness for
the mother, adverse pregnancy outcomes such
as lower birth weight, preterm delivery and foetal
malformation is seen in the offspring of HG
patients.

6. Definition
Hyperemesis gravidarum is the most severe
form of nausea and vomiting during pregnancy
and is characterized by intractable nausea and
vomiting that leads to dehydration, electrolyte
and metabolic disturbances, and nutritional
deficiency that may require hospitalization.

7. Aetiology
 Morning sickness protects the embryo by causing
pregnant women to physically vomit and
subsequently avoid foods that contain teratogenic
and abortifacient chemicals, especially toxic
chemicals in strong-tasting vegetables,
caffeinated beverages and alcohol.
 HG is most prevalent during first trimester of
pregnancy when both the placenta and the
corpus luteum are producing hormones and the
body is adapting to the pregnant state.

8.  Other pathogenic mechanisms and causes
have been hypothesized but not confirmed
 Until the discovery of the aetiology and
pathogenesis of HG, treatment and patient
care will remain empirical and therefore
suboptimal.

9.  Theories on how pregnancy hormones could
cause HG assert that patients who develop HG
may be exposed to higher levels of hormones
during early pregnancy.
 Alternatively HG patients might be more
vulnerable to their effects.
 Because HG is most prevalent in weeks when
both the placenta and the corpus luteum
produce hormones, progesterone and HCG in
particular are thought to be associated with HG.

10. HCG
 HCG is often stated as the most likely cause of HG,
as because the highest incidences of HG occur at the
time HCG has its peak level and because HG has a
higher incidence in conditions said to be associated
with elevated HCG levels, namely twin and molar
pregnancies, pregnancies of female foetuses and
those with down syndrome.
 Mechanisms : stimulating effect on the secretory
processes in the upper gastrointestinal tract (GIT) or
by stimulation of thyroid function because of its
structural similarity to thyroid stimulating hormone
(TSH).

11.  Other conditions associated with high HCG levels,
such as choriocarcinoma, do not typically result in
nausea and vomiting, and many pregnant women
with high HCG levels do not suffer from HG.
 Substantial proportion of patients with HG in which
symptoms continue beyond the first trimester when
HCG levels are falling, mitigate against the
hypothesis of HCG as the sole factor in the
aetiology of HG.

12. Progesterone
Pregnancies with iatrogenic elevated
progesterone levels, such as pregnancies with
multiple corpus luteum caused by controlled ovarian
stimulation (COS), or pregnancies in which
progesterone is administered for luteal phase
support do not exhibit an increased incidence of
HG, suggesting that high progesterone levels
(endogenous or exogenous) alone do not cause
HG.

13. Estrogen
 HG is more prevalent in a number of conditions that
are associated with high estrogens levels, such as a
higher body mass index, first pregnancy .
 Higher incidence of testicular carcinoma has been
observed in the offspring of mothers who suffered
from HG during pregnancy
 These findings, coupled with the fact that nausea is
a common side effect of estrogen treatment, support
the hypothesis that estrogen may be causally
related to HG.

14.  High estrogen levels cause slower intestinal
transit time and gastric emptying, and result in an
increased accumulation of fluid caused by
elevated steroid hormones.
 A shift in pH in the GIT could lead to the
manifestation of a subclinical Helicobacter pylori
infection, which could be related to gastrointestinal
symptoms.
 Pregnancies induced by COS in assisted
reproduction techniques (ART) when circulating
estrogen levels are very high is not associated
with a higher incidence of HG makes it less likely
that HG is simply caused by high estrogen levels

15. Thyroid hormones
 Thyroid gland is physiologically stimulated
during early pregnancy.
 Thyroid hormone values will deviate from the
normal range sometimes, leading to a state
which is referred to as gestational transient
thyrotoxicosis (GTT).
 GTT has been observed in up to two thirds of
women suffering from HG.

16.  Under the influence of estrogens, the
production of thyroid-binding globulin increases
and T4 metabolism is slowed, causing a
transient decrease in free T4 level.
 Higher renal iodine clearance causes
stimulation of the thyroid to compensate for a
relative iodine deficiency.
 Because of its structural similarity to TSH,
increased HCG levels can cause excessive
stimulation of the thyroid gland.

17.  Other causes of hyperthyroidism like Graves’
disease do not cause HG-like symptoms.
 Hyperthyroidism is more prevalent but not
exclusive to HG patients, and many HG patients
do not suffer from hyperthyroidism.

18. Leptin
 Leptin is a circulating hormone which acts as an
afferent satiety signal to regulate body weight and
has a structure similar to that of cytokines.
 A relationship between leptin and HG was
originally based on the notion that leptin was
exclusively expressed in white adipose tissue and
its main function was to play a crucial role in
reducing appetite.

19. Adrenal cortex
 Overactivity of the hypothalamic-pituitary-adrenal
axis appears to be associated with HG, but it is not
clear whether it is actually involved in the
pathogenesis.
 Increased ACTH and cortisol levels have also
been observed in women with starvation, anorexia
and bulimia nervosa, this being interpreted as a
protective mechanism to conserve energy in
starvation.

20. Immunology
 During pregnancy, changes in the humoral and
cell-mediated immune systems occur. Probably
the most important aspect of these changes is to
protect the foetus and decidua from disruption
by the maternal immune system.
 Changes of the physiological immune response
to pregnancy cause pregnancy-related
disorders.

21.  HG has been regarded as the result of an over
activated immune system, which could in part be
related to pregnancy hormone synthesis.
 Starvation normally causes suppression of immune
functions, but these findings rather support an
activated immune system in HG. It cannot be
concluded from these preliminary findings whether
the immune response is a cause or a reaction to
HG.

22. Helicobacter pylori
 H. pylori infection in pregnant caused by changes in
the gastric pH or pregnancy-related changes in the
immune system.
 A manifestation of subclinical H. Pylori infection
could be the result of a change in gastric pH
because of an increased accumulation of fluid
caused by elevated steroid hormones in pregnant
women.
 Changes in humoral and CMI during pregnancy
could cause an increased susceptibility to H. pylori
infection in pregnancy(more pronounced in HG
patients)

23.  Although H. pylori infection has been observed
more often in patients with HG, most pregnant
women with H. pylori infection remain
asymptomatic.
 Susceptibility to H. pylori is secondary to
steroid levels or changes in the immune
system does not provide a satisfactory
explanation.
 Damage to the upper GIT due to excessive
vomiting increases susceptibility to subclinical
H. pylori infection.

24. Gastric and intestinal motility
During pregnancy, sex steroids
cause abnormal activity in gastric
and colonic smooth muscle,
leading to slower small intestinal
and colonic transit times and slow
gastric emptying that may cause
nausea.

25. Lower oesophageal sphincter
pressure
 Many women have symptoms of GERD
during their pregnancy, could be the result of
progressive decrease in lower oesophageal
sphincter pressure.
 HG is most pronounced during the first
trimester of pregnancy, and the decrease in
LESP is more severe in the end of pregnancy,
thus mitigating against this hypothesis.

26. Psychological causes
 Nausea was the result of resentment against
pregnancy or ambivalence of women ill-prepared
for motherhood due to immaturity of personality,
strong mother dependence, and anxiety and
tension related to pregnancy.
 Other hypotheses state that HG is a sexual disorder
resulting from sexuality aversion.
 HG has also been described as a conversion
symptom, or a symptom of hysteria, neurosis or
depression, and HG could be resulting from
psychosocial stresses, poverty and marital conflicts.

27. Other causes
a) Growth hormone and prolactin.
b) Placental serum markers like SP1 and
pregnancy specific beta-1 glyco-protein.
c) Fluid secretion in GIT.
d) Elevated serum amylase.
e) Deficiency of vitamins like thiamine and
Vit.K.
f) Trace element like elevated plasma zinc
level.

28. Diagnosis
 NVP should only be diagnosed when onset is
in the first trimester of pregnancy and other
causes of nausea and vomiting have been
excluded.
 HG can be diagnosed when there is
protracted NVP with the triad of more than
5% prepregnancy weight loss, dehydration
and electrolyte imbalance.

29. Severity of NVP
An objective and validated index of
nausea and vomiting such as the
Pregnancy-Unique Quantification of Emesis
(PUQE) score can be used to classify the
severity of NVP.

31. Life threatening complications
a. Acute kidney injury
b. Severe depression
c. Diaphragmatic rupture
d. Esophageal rupture i.e. Boerhaave
syndrome
e. Hypoprothrombinemia due to Vit K
deficiency
f. Hyper alimentation complications
g. Mallory-Weiss tears
h. Wernicke encephalopathy

32. Initial clinical assessment

34. D/D
 Peptic ulcers, cholecystitis, gastroenteritis,
hepatitis, pancreatitis, genitourinary
conditions such as urinary tract infection or
pyelonephritis, metabolic conditions,
neurological conditions and drug-induced
nausea and vomiting.
 Chronic infection with Helicobacter pylori can
be associated with NVP and HG and testing
for H. pylori antibodies is considered.

35. What is the initial management of NVP
and HG?
 Women with mild NVP should be managed in
the community with antiemetic.
 Ambulatory daycare management should be
used for suitable patients when
community/primary care measures have failed
and where the PUQE score is less than 13.

36. Inpatient management should be
considered if there is at least one of the
following:
a) Continued nausea and vomiting and inability to
keep down oral antiemetic.
b) Continued nausea and vomiting associated with
ketonuria and/or weight loss (greater than 5% of
body weight), despite oral antiemetic.
c) Confirmed or suspected co morbidity (such as
urinary tract infection and inability to tolerate oral
antibiotics).

37. What therapeutic options are available ?
 Safety and efficacy data for first-line antiemetics
such as antihistamines (H1 receptor antagonists)
and phenothiazines and they should be prescribed
when required for NVP and HG.
 Combinations of different drugs should be used in
women who do not respond to a single antiemetic.
 For women with persistent or severe HG, the
parenteral or rectal route may be necessary and
more effective than an oral regimen.

38.  Clinicians should use antiemetics with which
they are familiar and should use drugs from
different classes if the first drug is not
effective.
 Metoclopramide is safe and effective, but
because of the risk of extrapyramidal effects it
should be used as second-line therapy.
 Ondansetron is safe and effective, but
because data are limited it should be used as
second-line therapy.

40. Pyridoxine
Pyridoxine is not recommended for NVP and HG.
Diazepam
 Diazepam is not recommended for the management of
NVP or HG.
 While the addition of diazepam to the treatment regimen
reduced nausea, there was no difference in vomiting
between those treated with or without diazepam.

41. Corticosteroids
 Corticosteroids should not be used until
conventional treatment with intravenous fluid
replacement and regular antiemetic has failed.
 IV hydrocortisone 100 mg twice daily, and once
clinical improvement occurs convert to oral
prednisolone 40–50 mg daily, with the dose
gradually tapered
 In most cases prednisolone needs to be continued
until the gestational age at which HG would have
typically resolved

42. Rehydration
 Normal saline with additional potassium
chloride in each bag, with administration
guided by daily monitoring of electrolytes, is
the most appropriate intravenous hydration.
 Dextrose infusions are not appropriate
unless the serum sodium levels are normal
and thiamine has been administered.

43.  Most important intervention is likely to be
appropriate intravenous fluid and electrolyte
replacement.
 Dextrose-containing solutions can precipitate
Wernicke’s encephalopathy in thiamine-deficient
states; hence, each day intravenous dextrose is
administered, high (e.g. 100 mg) doses of
parenteral thiamine should be given to prevent
Wernicke’s encephalopathy.

44. Complementary therapies
Ginger
Ginger may be used by women wishing to avoid
antiemetic therapies in mild to moderate NVP.
Acustimulations
Women may be reassured that acupressure and
acupuncture are safe in pregnancy. Acupressure
may improve NVP.

45. Monitoring
 Urea and serum electrolyte levels should be
checked daily in women requiring intravenous
fluids.
 Histamine H2 receptor antagonists or proton
pump inhibitors may be used for women
developing gastro-oesophageal reflux disease,
oesophagitis or gastritis.
 Thiamine supplementation (either oral or
intravenous) should be given to all women
admitted with prolonged vomiting, especially
before administration of dextrose or parenteral
nutrition.

46.  Women admitted with HG should be offered
thromboprophylaxis with low-molecular-weight
heparin unless there are specific
contraindications such as active bleeding.
 Women with previous or current NVP or HG
should consider avoiding iron-containing
preparations if these exacerbate the
symptoms.

47. Wernicke’s encephalopathy
 Due to vitamin B1 (thiamine) deficiency
classically presents with blurred vision,
unsteadiness and confusion/memory
problems/drowsiness.
 Usually nystagmus, ophthalmoplegia,
hyporeflexia or areflexia, gait and/or finger–
nose ataxia.
 In HG, Wernicke’s encephalopathy is a
potentially fatal but reversible medical
emergency.

48.  Overall pregnancy loss rate including
intrauterine deaths and terminations
was 48%.
 So thiamine supplementation is
recommended for all women with
protracted vomiting.

49. What is the role of the multidisciplinary team?
 Severe HG : input required from other professionals,
such as dieticians, pharmacists, endocrinologists,
nutritionists and gastroenterologists, and a mental health
team, including a psychiatrist.
 Involvement of a mental health team in the woman’s care
may improve quality of life and the ability to cope with
pregnancy.
 Emotional support and psychological or psychiatric care
may be required with targeted interventions

50. When should enteral and parenteral
nutrition be considered ?
 No defined criteria for parenteral or enteral feeding.
 They can be successful and are often employed as
a last resort when all other medical therapy has
failed and the only other practical option is
termination of the pregnancy.
 Close monitoring of metabolic and electrolyte
balance, related complications and nutritional
requirements are needed

51.  Enteral feeding include nasogastric,
nasoduodenal or nasojejunal tubes, or
percutaneous endoscopic gastrostomy or
jejunostomy feeding.
 Parenteral feeding with a peripherally inserted
central catheter (PICC line) is often better
tolerated than enteral feeding.

52.  TPN is a complex high-risk intervention(may be
useful in refractory cases)
 Only be used as a last resort when all other
treatments have failed as it is inconvenient,
expensive and can be associated with serious
complications such as thrombosis, metabolic
disturbances and infection.
 A strict protocol with careful monitoring is
essential when undertaking total parenteral
nutrition.

53. When should termination of pregnancy
be considered?
 Treatment options of antiemetics, corticosteroids,
enteral and parenteral feeding, and correction of
electrolyte or metabolic disturbances should be
considered before deciding termination.
 A psychiatric opinion should also be sought, and the
decision for termination needs to be multidisciplinary,
with documentation of therapeutic failure, if this is the
reason for the termination.
 Women should be offered counselling before and after
a decision of pregnancy termination is made.

54. Discharge and follow-up
 Essential advise to continue with their
antiemetics where appropriate.
 Earlier treatment may reduce the need for
hospital admission.
 Rehydration and a review of antiemetic
treatment should ideally be undertaken in an
ambulatory day-care setting.

55.  Checking for ketonuria may identify a problem
before vomiting is severe, allowing earlier access
for rehydration.
 Women with HG and low pregnancy weight gain
(less than 7 kg during pregnancy) are at an
increased risk of preterm delivery and low birth
weight (less than 2500 g).
 Women with severe NVP or HG who have
continued symptoms into the late second or the
third trimester should be offered serial scans to
monitor fetal growth.

56. Advise about future pregnancies
 Women with previous HG should be advised that
there is a risk of recurrence in future
pregnancies.
 Early use of lifestyle/dietary modifications and
antiemetics that were found to be useful in the
index pregnancy is advisable to reduce the risk
of NVP and HG in the current pregnancy.
 HG recurrence rates :15% to 80%

57. What is the effect of NVP and HG on
quality of life?
 A woman’s quality of life can be adversely affected by
NVP and HG and practitioners should address the
severity of a woman’s symptoms in relation to her
quality of life and social situation.
 One should assess a woman’s mental health status
during the pregnancy and postnatally and refer for
psychological support if necessary.

58.  Women should be referred to sources of
psychosocial support.
 Practitioners should validate the woman’s
physical symptoms and psychological distress.
 Women should be advised to rest as required
to alleviate symptoms.

59. Thank u