Nausea & Vomiting in Pregnancy / Hyperemesis Gravidarum

Nausea & Vomiting in Pregnancy /

Hyperemesis Gravidarum

Professor Cathy Nelson-Piercy

Consultant Obstetric Physician

KCL Division of Women’s Health

Nausea & Vomiting in Pregnancy (NVP)

• Affects 50-85% of pregnancies1.

• Symptoms usually start between 6-8 weeks of gestation

• Rise to a peak before the end of the first trimester, and in the majority of

women, resolve by 20 weeks2.

• Most women (65-70%) do not seek medical advice but attempt to manage

their symptoms with avoidance of dietary triggers and oral hydration2.

1. Niebyl JR. Clinical practice. Nausea and vomiting in pregnancy. N Engl J Med. Oct 14

2010;363(16):1544-1550.

2. Jarvis S, Nelson-Piercy C. Management of nausea and vomiting in pregnancy. BMJ. 2011;342:d3606.

1

Hyperemesis Gravidarum (HG)

• 0.3-1% of pregnancies1

• Peak occurrence 8-12 weeks gestation

• Severe end of NVP spectrum2

• intractable nausea, vomiting, dehydration

• ketosis, electrolyte imbalance

• weight loss (> 5% of body weight)

1. Niebyl JR. Clinical practice. Nausea and vomiting in pregnancy. N Engl J

Med. Oct 14 2010;363(16):1544-1550.

2. Jarvis S, Nelson-Piercy C. Management of nausea and vomiting in

pregnancy. BMJ. 2011;342:d3606.

Page 3

Nausea Vomiting in pregnancy: prevalence 80%

Hyperemesis gravidarum: prevalence 1.5%

Fiaschi, Nelson-Piercy, Tata. Human Reproduction, May,2016Page 4

Page 5

HG admission and readmission (surrogate for severity) higher risk if :

• younger (<30)

• more socioeconomically deprived status

• Asian or Black ethnicity,

• carrying a female fetus

• multiple pregnancy

Page 6Fiaschi, Nelson-Piercy, Tata. Human Reproduction, May,2016

Comorbidities most strongly associated with HG were:

• parathyroid dysfunction (aOR 3.83, 95% CI 2.28–6.44),

• Hypercholesterolemia (aOR 2.54, 1.88–3.44),

• Type 1 diabetes (aOR 1.95, 1.82–2.09),

• thyroid dysfunction (aOR 1.85, 1.74–1.96).

History of HG was the strongest independent risk factor (aOR . 4.74, 4.46–5.05).

Women with higher parity had a lower risk of HG compared with

nulliparous women (aOR . 0.90, 0.89–0.91), which was not explained by

women with HG curtailing further pregnancies

Page 7Fiaschi, Nelson-Piercy, Tata. Human Reproduction, May,2016

Clinical Features

Nausea

Vomiting

Ptyalism

Dehydration

Weight Loss

Protein-calorie

malnutrition

Ketonuria

Hyponatraemia

Hypokalaemia

Low urea

Hypochloraemic alkylosis

Vitamin deficiency

Pathophysiology

• Genetic

• Increased risk in daughters of sufferers1

• Endocrine

• Higher levels of human chorionic gonadotrophin, (hCG) have been associated

with more severe forms of NVP/HG2

• Gastrointestinal factors

• Delayed gastric emptying

• H pylori infection3

1. Vikanes AV, et al. Recurrence of hyperemesis gravidarum across generations: population based cohort

study. BMJ. 2010;340(c2050).

2. Derbent AU, et al. First trimester maternal serum PAPP-A and free beta-HCG levels in hyperemesis

gravidarum. Prenatal Diagnosis. 2011;31:450-453.

3. Sandven I, et al. Helicobacter pylori infection and hyperemesis gravidarum: a systematic review and

meta-analysis of case-control studies. Acta Obstet Gynecol Scand. 2009;88 :1190-1200.

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Diagnosis

• Likely if previous history of HG

• Higher risk in the second pregnancy of women with a previous history of

HG1

• Unlikely if onset after 10-12 weeks

1. Trogstad LIS, et al. Recurrence risk in hyperemesis gravidarum. BJOG 2005;112:1641-

1645.

Diagnosis of exclusion

• Infection eg. UTI

• Endocrine eg.

• Addison’s

• Thyrotoxicosis

• Hypercalcaemia

• Pancreatitis, Cholecystitis

• Peptic ulceration, gastritis

• ENT eg. labyrinthitis

• Drugs eg. iron

NVP: Potential risks

• emotional and psychological distress1,2

• reduced quality of life1,2

1. Mazzotta P, Maltepe C, Navioz Y, Magee LA, Koren G. Attitudes, management and

consequences of nausea and vomiting of pregnancy in the United States and Canada. Int

J Gynaecol Obstet. Sep 2000;70(3):359-365.

2. Smith C, Crowther C, Beilby J, Dandeaux J. The impact of nausea and vomiting on

women: a burden of early pregnancy. Aust N Z J Obstet Gynaecol. 2000;40:397-401.

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HG: Potential Risks

Maternal

Dehydration / Malnutrition / Metabolic

Wernicke’s encephalopathy

Central Pontine Myelinolysis

Psychiatric

Venous thrombosis

Fetal

FGR

Preterm delivery

IUD

Psychological factors

• Anxiety and depression present in 57% (consequence)

• Affected women do not have antecedent psychological illness and do not

take up offer of a psychiatry appointment for assessment.

• Women with HG consider HG to have a biologic basis.

• Psychological consequences can be profound

• No quality data to support a primary psychological basis for HG.

Tan & Omar. Current Opinion in Obstetrics and Gynecology 2011, 23:87–93

Qualitative research

Highlights debilitating effects and burden of HG on patients and lack of

appreciation and interest by care providers as perceived by patients.

• Patients felt unpopular with healthcare professionals who may be

skeptical about symptom severity.

• Women left with perception they are time wasters or somebody else’s

responsibility.

• For women most severely affected, it appears that primary care support

is often lacking.

Power Z, Thomson AM, Waterman H. Understanding the stigma of

hyperemesis gravidarum: qualitative findings from an action research study.

Birth 2010; 37:237–244.

Validated measures of severity

• The Rhodes Index

• Pregnancy-Unique Quantification of Emesis/Nausea (PUQE) index.

• 3 questions, correlate with Rhodes

• Moderate – severe NVP = PUQE ≥ 7

PUQE: Validated Scoring System for NVP

Question Point Value Enter

1) In the last 24 hours for how long

have you felt nauseated or sick

to your stomach?

Not at all

(1)

1 hour or

less

(2)

2-3 hours

(3)

4-6 hours

(4)

More

than 6

hour

(5)

2) In the last 24 hours have you

vomited or thrown up?

7 or more

times

(5)

5-6

times

(4)

3-4

times

(3)

1-2

times

(2)

I did not

throw up

(1)

3) In the last 24 hours how many

times have you had retching or

dry heaves without bringing

anything up?

No time

(1)

1-2 times

(2)

3-4

times

(3)

5-6

times

(4)

7 or more

times

(5)

Sum point values for the 3 questions to find the PUQE Score PUQE Score

PUQE-24 Score ≤6 7-12 13-15

NVP Severity Mild Moderate Severe

Hospital Management

• Intravenous fluid and electrolytes

• Emotional support

• Nutritional support - Thiamine

• Antiemetic therapy

• Thromboprophylaxis

Intravenous fluids – in-patients

N Saline

KCL

Hartmanns/plasmalyte

Dextrose Saline

5% Dextrose

2 N Saline

1/5 N Saline

N Saline 1 litre + 40 mmol KCL – 3 litres /day

Check U + E daily

Problems with In-patient Mx

Costly

Disruptive to patient / work / family life

Problems with gynae elective beds

Pressures on length of stay result in premature discharge and recurrent admissions

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Safety Data

Cochrane review

Systematic review and metaanalyses1,2

Registry data

Sweden3

metoclopramide, (884)

prochlorperazine (145)

promethazine (4740)

cyclizine (1221)

Danish4

Ondansetron (2000)

1. Magee LA, Mazzotta P, Koren G. Am J Obst Gyn 2002;186(5 Suppl 2):S256–61.

2. Gill & Einarson. Expert Opin Drug Safety 2007; 6:685-694

3. Asker et al. Eur J Clin Pharmacol 2005; 61: 899-906

4. NEJM 2013; 368:814-23.

• Review by the European Medicines Agency’s Committee for Medicinal

Products for Human Use, confirmed risks of short-term extrapyramidal

disorders and tardive dyskinesia, particularly in young people.

• should only be prescribed for short-term use (maximum dose of 30 mg in 24

hours and maximum duration of 5 days)

• intravenous doses should be administered by slow bolus injection over at least

3 minutes to help minimise these risks.

• Dystonic reactions have been shown to be significantly less common in non

pregnant patients receiving a slow infusion as opposed to a bolus injection of

10 mg of metoclopramide.

Metoclopramide – second line therapy Page 29

Studies on the safety of ondansetron are mixed.

• Large retrospective analysis of data from the Danish birth registry of 608 385

pregnancies found no increased risk of major birth defect, stillbirth, preterm

labour or small-for-gestational age.

• Case–control study with 4524 cases and 5859 controls found a two-fold

increased risk of cleft palate (adjusted OR 2.37, 95% CI 1.18–4.76)

• Data from the Swedish Medical and Birth Register demonstrated a small

increased risk of cardiovascular defects and cardiac septal defects (OR 1.62,

95% CI 1.04–2.14, and risk ratio 2.05, 95% CI 1.19–3.28, respectively).

Ondansetron – second line therapy Page 30

Reproductive toxicology 2016; 62: 87-91 Page 31

Ondansetron

1070

HG / No

ondansetron

771

No HG / No

ondansetron

1555

Malformations 3.47% 3.4%

VSD 2/952 0 4/1286

Cleft palate 1/952 0 2/1286

Terminations 2.52% 8.69%

Page 32

Hviid A, Molgaard-Nielsen D. CMAJ 2011;183(7):796-804.

• Cohort study of all live births in Denmark 1996 to 2008.

• 832 636 live births

• 51 973 exposures to corticosteroids during the first trimester

• 1232 isolated orofacial clefts (i.e., cleft lip, cleft palate, or cleft lip

and cleft palate) diagnosed within first year of life

84 in which the infant had been exposed to corticosteroids

during the first trimester

Hviid A, Molgaard-Nielsen D. Corticosteroid use during pregnancy and risk of orofacialclefts. CMAJ 2011;183(7):796-804.

Iron supplements

Two-thirds of 97 women who discontinued iron supplements reported

improvement in their severe NVP in a Canadian prospective cohort

study.

Gill SK, Maltepe C, Koren G.

The effectiveness of discontinuing iron-containing prenatal

multivitamins on reducing the severity of nausea and vomiting

of pregnancy. J Obs Gyn 2009; 29: 13-16.

Page 36

Pre-emptive treatment

Canadian study comparing women with NVP [PUQE ≥ 13] who took pre-

emptive antiemetics before pregnancy or before the onset of symptoms

with those who did not

• lower recurrence rate of HG

• significant improvement in the PUQE score of NVP severity compared

to the previous pregnancy in the pre-emptive group.

• Women who have experienced severe NVP in a previous pregnancy

may benefit from taking antiemetics before or immediately at the start

of symptoms in a subsequent pregnancy.

Koren G, Maltepe C. Pre-emptive therapy for severe nausea and

vomiting of pregnancy and hyperemesis gravidarum. J Obstet Gynaecol

2004;24:530–3. 37

Jarvis & Nelson-Piercy. BMJ 2011;342

Jarvis & Nelson-Piercy. BMJ 2011;342

Page 40

I visited my GP who said he would prescribe the ondansetron on repeat only

because you had authorised it 'because GPs aren't allowed to prescribe

high risk medications during pregnancy.'

I politely mentioned that the UK guidelines recommend ondansetron for HG.

He was of the view that NVP is very normal so I should 'keep eating and

keep vomiting' because something will stay down eventually!

Thank you once again for seeing me at short notice and for making the

nausea and vomiting bearable!

I feel so much better and it's all thanks to you! I have been able to eat small

meals after weeks of surviving on 2 crackers a day.

Of course you could use my GPs quote - whatever it takes to get GPs to

understand that HG is more than a touch of morning sickness!

• Pre-eclampsia

• Acute fatty liver of pregnancy

Not specific to pregnancy:

• UTI

• Gastoenteritis

• Cholecystitis

• Appendicitis

• Pancreatitis

• Metabolic / Endocrine – DKA, hyperparathyroidism

Other pregnancy causes of nausea and vomiting Page 41

H2 blockers

Proton pump inhibitors

H pylori eradication therapy

OGD / endoscopy

ARE ALL SAFE IN PREGNANCY !!

Drugs Page 42