Nausea and vomiting in pregnancy

Nausea and vomiting in pregnancy is nausea with or without vomiting that begins in early pregnancy, usually before 9 weeks, peaks at 8 to 12 weeks and resolves by 16 to 20 weeks in most women. Hyperemesis gravidarum is the severe form, with persistent vomiting, weight loss of 5% or more of pre pregnancy weight, ketonuria and electrolyte disturbance.

The main clinical point is to grade severity, treat early to prevent progression, exclude other causes of vomiting (especially when onset is late or atypical), and prevent complications such as dehydration, Wernicke encephalopathy and venous thromboembolism.

Clinical relevance. Nausea and vomiting affects most pregnancies, impairs work and quality of life, and is the leading reason for early pregnancy admission. Hyperemesis can cause nutritional deficiency, psychological distress and adverse maternal outcomes.

Mechanisms. The cause is multifactorial: rising human chorionic gonadotropin, oestrogen and progesterone, slowed gastric motility, thyroid stimulating effect of hCG, genetic susceptibility and Helicobacter pylori infection. Risk is higher in multiple pregnancy, trophoblastic disease, previous hyperemesis, family history, migraine and motion sickness.

Classification. By severity using the Pregnancy Unique Quantification of Emesis score (hours of nausea, vomiting episodes and retching episodes each scored 1 to 5, total 3 to 15): mild 6 or less, moderate 7 to 12, severe 13 or more. By diagnosis: nausea and vomiting of pregnancy (mild to moderate) and hyperemesis gravidarum (severe, with weight loss and ketonuria).

Temporal patterns. Onset after 10 weeks, a new onset in the second or third trimester, or persistence beyond 20 weeks suggests another cause. Vomiting with abdominal pain, fever, diarrhoea or neurological features needs investigation.

Key distinctions. Mild nausea and vomiting improves with dietary change and treatment of triggers. Hyperemesis causes ketonuria, weight loss and electrolyte disturbance and needs fluid replacement and antiemetics. Late onset, severe pain, jaundice or neurological signs suggest other disease.

History

• Onset (gestational age), pattern (morning or all day), vomiting frequency, ability to keep down fluids and food, weight loss, urine output, dizziness, ptyalism (excess saliva), triggers (smell, food, iron tablets, prenatal vitamins).
• Severity score (Pregnancy Unique Quantification of Emesis).
• Associated symptoms: abdominal pain, fever, dysuria, diarrhoea, constipation, jaundice, pruritus, headache, visual disturbance, neck stiffness, polyuria and polydipsia, palpitations, tremor, heat intolerance.
• Past: previous hyperemesis, motion sickness, migraine, peptic ulcer, gastro oesophageal reflux, gallstones, pancreatitis, hepatitis, diabetes, thyroid disease, adrenal disease, eating disorders, mental illness.
• Drugs: iron, prenatal vitamins, antibiotics, opioids, metformin, antiretrovirals, chemotherapy, cannabis (cannabinoid hyperemesis).
• Obstetric history: multiple pregnancy, trophoblastic disease, previous pregnancy complications, assisted conception.
• Psychological and social impact: work, family, depression, anxiety, suicidal thoughts, intimate partner violence, food insecurity.

Examination

• Vital signs: pulse, blood pressure (postural drop), temperature, respiratory rate, oxygen saturation.
• Weight and body mass index compared with pre pregnancy weight; capillary refill, skin turgor, mucous membranes, urine output.
• Abdomen: tenderness, guarding, distension, masses, bowel sounds; uterine size for dates.
• Neurological examination: gait, eye movements (nystagmus, ophthalmoplegia), confusion, ataxia, neck stiffness, papilloedema.
• Thyroid, signs of jaundice or liver disease, and breath odour of ketones.
• Calf swelling and tenderness (venous thromboembolism).
• Bedside tests: urine dipstick for ketones and infection, capillary glucose, point of care ultrasound for gestational age and viability.

Red flags

• Confusion, ataxia, ophthalmoplegia or nystagmus (Wernicke encephalopathy).
• Weight loss of 5% or more, ketonuria 2+ or more, or inability to tolerate fluids.
• Haematemesis (Mallory Weiss tear, ulcer).
• Abdominal pain, fever, or guarding (appendicitis, cholecystitis, pancreatitis, pyelonephritis).
• Jaundice or pruritus (liver disease, intrahepatic cholestasis).
• Severe headache, neck stiffness, focal deficit, or papilloedema (central cause).
• Onset after 10 weeks, vomiting in the third trimester, or persisting beyond 20 weeks.
• Palpitations, tremor, goitre, tachycardia (thyrotoxicosis).
• Suicidal thoughts or severe depression.
• Diabetes with ketoacidosis.

Special groups. Multiple pregnancy and molar pregnancy: more severe symptoms. Adolescents: nutritional vulnerability. Women with diabetes: risk of ketoacidosis. Women with HIV on antiretroviral therapy: drug intolerance and absorption. Prior bariatric surgery: nutritional deficiency.

Organised by system. Each cause is common unless marked serious or uncommon. Pregnancy related

• Nausea and vomiting of pregnancy (the commonest cause).
• Hyperemesis gravidarum.
• Multiple pregnancy.
• Gestational trophoblastic disease.
• Serious: ectopic pregnancy (rarely presents as vomiting).
• Serious: acute fatty liver of pregnancy, pre eclampsia with HELLP syndrome, intrahepatic cholestasis of pregnancy (later pregnancy).
• Gestational transient thyrotoxicosis (hCG mediated).

Gastrointestinal

• Gastroenteritis, including viral and food borne.
• Gastro oesophageal reflux disease, peptic ulcer disease, Helicobacter pylori infection.
• Gastroparesis and cyclical vomiting.
• Serious: appendicitis, cholecystitis, biliary colic, acute pancreatitis, bowel obstruction.
• Viral hepatitis (A, B, E), hepatitis E in pregnancy (severe).
• Constipation.
• Inflammatory bowel disease.

Genitourinary

• Urinary tract infection and pyelonephritis.
• Ureteric colic, hydronephrosis.

Endocrine and metabolic

• Thyrotoxicosis (Graves disease).
• Serious: diabetic ketoacidosis.
• Serious: adrenal insufficiency, hypercalcaemia (hyperparathyroidism).
• Hyponatraemia, uraemia.

Neurological and psychiatric

• Migraine, idiopathic intracranial hypertension, vestibular disease.
• Serious: intracranial tumour, hydrocephalus, meningitis, encephalitis.
• Serious: Wernicke encephalopathy (complication).
• Anxiety, depression, eating disorder, rumination, bulimia.

Drugs and toxins

• Iron, vitamins, antibiotics (metronidazole, macrolides, nitrofurantoin), opioids, metformin, antiretrovirals, chemotherapy, theophylline, cannabinoid hyperemesis syndrome.
• Alcohol withdrawal and poisoning.

Infections

• Malaria, typhoid fever, tuberculous meningitis, HIV seroconversion, dengue.

Stepwise reasoning

1. Assess severity and hydration, weigh the woman, and check ketones and vital signs.
2. Check the pregnancy: viability, number of foetuses and exclude molar pregnancy.
3. Look for other causes if there is pain, fever, diarrhoea, late onset, or neurological or thyroid signs.
4. Decide between outpatient treatment, day case and admission.
5. Treat the cause of dehydration, correct electrolytes, and give thiamine before dextrose.

First line tests

• Urine dipstick for ketones, protein, nitrites and leucocytes; midstream urine culture.
• Capillary glucose.
• Urea, creatinine and electrolytes (sodium, potassium, chloride, bicarbonate): hypokalaemia, hyponatraemia, hypochloraemic metabolic alkalosis, raised urea, and raised haematocrit indicate severity.
• Liver function tests: modest rise in transaminases (usually under 300 IU/L) and bilirubin can occur in hyperemesis; higher values suggest hepatitis or another cause.
• Thyroid function: free thyroxine may be raised with suppressed thyroid stimulating hormone in hyperemesis (gestational transient thyrotoxicosis), generally resolves, with no antithyroid drugs unless Graves disease features are present (goitre, eye signs, antibodies).
• Full blood count; magnesium, calcium and phosphate (before feeding); amylase or lipase for pain.
• Ultrasound for viability, multiple pregnancy and trophoblastic disease.

Targeted tests

• Arterial or venous blood gas with ketones for suspected acidosis or diabetic ketoacidosis.
• Blood cultures if febrile; malaria rapid test or film in endemic regions; hepatitis serology; HIV test.
• Helicobacter pylori testing if persistent and not improving (stool antigen; treat after the first trimester if needed).
• Abdominal ultrasound for suspected cholecystitis or appendicitis; MRI for appendicitis if ultrasound is inconclusive.
• Cranial imaging and ophthalmology review for neurological features; thiamine level (red cell transketolase) not required before treatment.

Limitations. Severity scores are subjective. Electrolyte abnormalities may be absent in early dehydration. Liver and thyroid abnormalities are common in hyperemesis and rarely need treatment. Normal ketones do not exclude a serious cause.

Immediate steps. Assess hydration and vital signs. For women unable to tolerate oral fluids, begin intravenous fluids and antiemetics. Give thiamine before any dextrose. Exclude Wernicke encephalopathy and treat promptly if suspected.

General measures. Rest, small frequent meals (every 2 to 3 hours), dry carbohydrate snacks, cold or ginger containing drinks, avoiding triggers, separate fluid and food intake, avoid iron tablets and prenatal vitamins during the worst symptoms (use folic acid alone), acupressure wristbands (limited evidence), and psychological support. Treat constipation and reflux. Ginger 1 g daily in divided doses can be tried (evidence limited).

Mild to moderate symptoms (score 12 or less), oral therapy

• Pyridoxine (vitamin B6) 10 to 25 mg orally three to four times daily (maximum 100 mg daily), alone or with doxylamine 10 to 25 mg at night.
• Doxylamine with pyridoxine as a combination tablet 10 mg and 10 mg: two tablets at bedtime, increased to a maximum of four tablets daily (one in the morning, one in the afternoon and two at bedtime).
• Adverse effects: drowsiness, dry mouth. Take care with driving, glaucoma and urinary retention.
• Cyclizine 50 mg orally three times daily (maximum 150 mg daily); avoid in severe heart failure; drowsiness.
• Prochlorperazine 5 to 10 mg orally two to three times daily, or 12.5 mg intramuscularly or intravenously, maximum 40 mg daily; monitor for dystonia, sedation and QT prolongation.
• Promethazine 12.5 to 25 mg orally every 4 to 6 hours, maximum 100 mg daily; sedation.
• Metoclopramide 10 mg orally, intramuscularly or intravenously three times daily, maximum 30 mg daily, for no more than 5 days (risk of extrapyramidal reactions, especially in women under 20; reduce the dose in renal impairment, creatinine clearance under 60 mL/min).
• Ondansetron 4 mg orally every 8 hours, or 4 mg intravenously (maximum 16 mg daily). It is second line after other drugs fail.
• A small increase in oral cleft risk in the first trimester is reported, so discuss with the woman. Check the QT interval and avoid with long QT syndrome. It may cause constipation.
• Corticosteroids (specialist): after other drugs fail, give hydrocortisone 100 mg intravenously twice daily, then convert to oral prednisolone 40 to 50 mg daily with slow reduction by half every 3 days to the lowest effective dose.
• Avoid before 10 weeks if possible (oral cleft risk). Monitor glucose, blood pressure and mood. Short courses only.
• Vitamin B1 (thiamine) 100 mg orally daily with persistent vomiting.

Hyperemesis and dehydration (admit or day case)

• Intravenous fluid: sodium chloride 0.9% with potassium chloride 20 mmol/L (adjust to serum potassium) 1 L over 2 to 4 hours, then 1 L every 6 to 8 hours as needed.
• Avoid dextrose containing fluids until thiamine is given. Correct hyponatraemia slowly (maximum rise 10 mmol/L in 24 hours) to avoid osmotic demyelination. Monitor potassium, magnesium and phosphate.
• Intravenous thiamine 100 mg daily for all women admitted with persistent vomiting, and oral thiamine 100 mg daily on discharge until vomiting stops.
• Antiemetic combination: cyclizine 50 mg intravenously three times daily plus metoclopramide 10 mg intravenously three times daily or ondansetron 4 mg intravenously every 8 hours, then prochlorperazine 12.5 mg intravenously; regular rather than as needed dosing.
• Thromboprophylaxis: enoxaparin 40 mg subcutaneously once daily for admitted women (20 mg once daily under 50 kg; 60 mg once daily for 91 to 130 kg).
• Adjust for creatinine clearance under 30 mL/min to 20 mg or 30 mg. Continue while dehydrated and immobile, and review risk factors.
• Nutrition: oral intake as tolerated; enteral feeding (nasogastric or nasojejunal) or parenteral nutrition for refractory cases lasting more than 7 days with ongoing weight loss, with careful refeeding monitoring; thiamine before feeding.
• Treat reflux: omeprazole 20 mg orally once daily; antacid (magnesium trisilicate) as needed.
• Treat constipation with macrogol 3350 with electrolytes 1 to 3 sachets daily.

Wernicke encephalopathy. Medical emergency. Thiamine 200 to 500 mg intravenously three times daily for 2 to 3 days, then 250 mg intravenously or intramuscularly once daily for 3 to 5 days or until improvement, then oral thiamine 100 mg daily; give before glucose; correct magnesium; monitor for anaphylaxis (rare).

Other causes. Treat gastroenteritis supportively; pyelonephritis with ceftriaxone 1 to 2 g intravenously once daily; Graves disease with propylthiouracil in the first trimester; appendicitis and cholecystitis by surgery; diabetic ketoacidosis with fluids, insulin and potassium in high dependency.

Gestational trophoblastic disease. Evacuation and monitoring.

Psychological care. Screen for depression and anxiety. Provide peer and psychological support.

Counsel on partner and family support. Consider termination only when symptoms are intractable despite full treatment and the woman wants it.

Special groups. Multiple pregnancy: expect more severe symptoms and treat early. Women with HIV: continue antiretroviral therapy, splitting doses with food, and use intravenous therapy if needed. Women with diabetes: monitor glucose and ketones, and adjust insulin. Women with previous hyperemesis: start pyridoxine with doxylamine before symptoms are expected (at 4 to 6 weeks) and treat early.

Monitoring. Daily weight, urine ketones, input and output, and electrolytes while admitted. Review after discharge in 3 to 7 days, then weekly while symptoms persist. Check thyroid function again at 20 weeks if abnormal initially.

Referral and escalation. Refer to the obstetric team for persistent symptoms despite two antiemetics, weight loss of 5% or more, ketonuria, and electrolyte disturbance. Refer to endocrinology for thyrotoxicosis with features of Graves disease. Refer to gastroenterology and surgery for hepatic or surgical causes. Refer to dietetics and mental health services as needed.

Admission criteria. Inability to tolerate oral fluids, ketonuria 2+ or more with persistent vomiting, weight loss of 5% or more, abnormal electrolytes, confusion or neurological signs, other illness (such as pyelonephritis), failed outpatient management, and unsafe home environment.

Discharge and follow up. Discharge when the woman tolerates oral fluids, ketones are clearing and symptoms are controlled on oral antiemetics. Provide a written plan for medication and a contact for early review.

Safety netting. Return for inability to keep fluids down for 24 hours, reduced urine output, dizziness, weight loss, confusion, double vision, unsteady walking, abdominal pain, fever, jaundice, haematemesis, or low mood with thoughts of self harm.