Hyperemesis gravidarum

• Nausea and vomiting of pregnancy (NVP, often called "morning sickness") is very common, but hyperemesis gravidarum (HG) is a much smaller, severe form that stops a woman from eating and drinking normally, causes weight loss and dehydration and is the commonest reason for admission in early pregnancy.^[1][4]
• NVP is defined as nausea and/or vomiting with onset before 16 weeks of gestation and no other cause; HG is the severe end of that spectrum, not a separate disease.^[1][4]
• There is no single agreed test for HG; it is a clinical diagnosis by exclusion, usually supported by an inability to eat or drink, severe limitation of daily life and weight loss of at least 5% of pre-pregnancy weight.^[3][4]
• Ketonuria is not a measure of how dehydrated or how sick the woman is and should not be used to decide whether to admit her or how long to keep her in hospital (RCOG 2024; recent reviews agree).^[2][4]
• Treatment is stepwise: dietary advice and early antiemetics in the community first; then day-case or inpatient intravenous rehydration (normal saline with potassium chloride) and antiemetics by injection or suppository if she cannot keep tablets down; corticosteroids, enteral or parenteral nutrition and psychological support only if these fail.^[1][2][3][4]
• The one intervention that saves lives in HG is thiamine before any dextrose: thiamine is depleted within days of poor intake and deficiency causes Wernicke's encephalopathy.^[3][4]

By the end of this page you should be able to:

1. Distinguish NVP from HG, including the severity tools used.
2. Explain the risk factors and the current (GDF15-based) thinking on cause.
3. Assess a woman with vomiting in pregnancy, including red flags and the investigations that matter.
4. Diagnose and stage HG using current criteria and PUQE/HELP scores.
5. Run the treatment ladder: community, day case and inpatient, with drug, dose, route and duration.
6. Prevent and recognise the complications, including Wernicke's encephalopathy and refeeding syndrome.
7. Counsel about prognosis, recurrence and care in a future pregnancy.

The Royal College of Obstetricians and Gynaecologists (RCOG) defines NVP as the symptom of nausea and/or vomiting during pregnancy when onset is before 16 weeks of gestation and other causes have been excluded.^[1] It prefers the term "nausea and vomiting of pregnancy" to "morning sickness", which trivialises the condition because symptoms are not limited to the morning.^[1]

The Windsor definition, an international consensus definition, describes HG as nausea and vomiting, at least one of which is severe, starting before 16 weeks of gestation, causing an inability to eat and/or drink normally and strongly limiting daily living activities.^[2][4] This definition was created to make the diagnosis consistent between clinicians and researchers; there is still no single accepted definition in some guidelines, including ACOG's.^[3]

HG is therefore diagnosed by exclusion and by severity, not by a single laboratory threshold. ACOG lists four elements that support the diagnosis of HG when no alternative cause exists:

• persistent vomiting;
• signs of starvation such as ketonuria;
• weight loss of at least 5% of pre-pregnancy weight;
• electrolyte, thyroid or liver abnormalities.^[3]

The RCOG's (2016) diagnostic triad is similar: protracted NVP with weight loss of more than 5% of pre-pregnancy weight, dehydration and electrolyte imbalance.^[1][4] Either way, the presence of starvation signs, not of ketones alone, is what matters.

The Pregnancy-Unique Quantification of Emesis (PUQE) score is the most widely used validated tool. It asks about nausea hours, vomiting episodes and retching in the previous 24 hours and converts them into a score from 3 (no symptoms) to 15 (severe): mild 6 or less, moderate 7-12, severe 13-15.^[1][2][4] It is used to triage women to community, day-case or inpatient care, and to track response to treatment.^[1][4]

The HyperEmesis Level Prediction (HELP) score is a newer 12-question tool that also takes psychosocial impact into account, but it still needs fuller validation before it can replace PUQE in routine use.^[4]

• Typical NVP: starts around the time periods are missed, usually settles by 16-20 weeks.^[2]
• Persistent or refractory HG: symptoms continue into the second or third trimester and carry higher fetal-growth risk.
• Early-onset or severe HG: begins before the first antenatal visit and may already show starvation and electrolyte abnormalities.

NVP of any severity affects up to 90% of pregnant people worldwide and is behind a large share of early-pregnancy health-service use.^[1][4] HG is much less common: RCOG quotes 0.3-3.6% of pregnancies^[1] and the 2025 review estimates around 1-3%.^[4] It is the most common reason for admission in early pregnancy and is second only to preterm labour as a cause of hospital admission in pregnancy overall.^[3][4]

Geographically, HG appears more prevalent in Western countries; registry data suggest better identification where antenatal care is highly organised.^[4] A British study estimated the NHS spends up to £62 million each year on NVP-related care, including admissions, GP visits and ambulance call-outs.^[4]

Collectively these figures frame the clinical problem: almost every pregnant woman will have some nausea, but the woman who cannot keep water down for more than a day, who is losing weight, or whose blood tests show electrolyte or thyroid abnormalities belongs in the HG pathway and needs same-week treatment, not reassurance alone.^[1][2][3][4]

No single cause is proven. The strongest candidate in recent evidence is Growth Differentiation Factor 15 (GDF15): a hormone produced by the placenta (trophoblast) during pregnancy. Higher maternal circulating levels are associated with more vomiting, and a woman's risk is shaped both by how much the placenta produces and by how sensitive she is to it; prior exposure to GDF15 (outside pregnancy) seems to reduce that sensitivity.^[4] Genetic variants in GDF15 and its receptor (GFRAL-RET) are associated with HG, which explains why this is, in part, heritable biology rather than behaviour.^[4]

Established risk factors include:

• a previous pregnancy with HG (the single largest risk factor) and a family history of HG in the mother or sister;^[4]
• multiple pregnancy, a female fetus, primiparity, younger maternal age and low or high pre-pregnancy body weight;^[4]
• a history of motion sickness, migraine or previous NVP;^[3]
• molar pregnancy or other increased placental mass;^[3]
• a history of nausea and vomiting outside pregnancy triggered by oestrogen-containing medicines.^[3]

Older theories (psychological causation, excessive human chorionic gonadotrophin) are not supported as sole explanations, and the "psychogenic" label has been discredited: it causes delay in treatment, trivialises suffering and worsens mental-health outcomes.^[4]

Why the woman presents the way she does follows from three mechanisms:

1. The trigger. The pregnant state (placental signals including GDF15, oestrogen/progesterone and hCG-related pathways) acts on the chemoreceptor trigger zone, the vestibular system and gastric motility. That produces nausea, vomiting and retching, and is why smells, heat and motion can provoke symptoms.^[3]
2. Starvation and dehydration. Inability to keep food or fluids down leads to ketosis, electrolyte loss (sodium, chloride, potassium), hemoconcentration and a rising urea and creatinine. Hyponatraemia, hypochloraemia and hypokalaemia are typical; rare extremes cause acute kidney injury or arrhythmia from severe hypokalaemia.^[4]
3. Micronutrient depletion. Thiamine (vitamin B1) is depleted within days of poor intake, particularly in pregnancy with its increased metabolic demand. Deficiency causes Wernicke's encephalopathy, which can progress to Korsakoff syndrome and is associated with a very high rate of fetal demise.^[4] Long before that, other deficits accumulate (folate, iron, riboflavin, calcium, zinc, vitamin C and others), which is why dietary assessment matters.^[4]

Refeeding is its own hazard. After prolonged starvation, rapid refeeding (and especially intravenous dextrose) can produce refeeding syndrome, a condition of hypophosphataemia, hypokalaemia and hypomagnesaemia. Intravenous dextrose can also worsen hypokalaemia and precipitate Wernicke's encephalopathy in a thiamine-deficient woman.^[4]

Women with HG may show transiently abnormal thyroid tests (gestational transient thyrotoxicosis) driven by the structural similarity between hCG and thyroid-stimulating hormone; this is managed supportively, not with antithyroid drugs.^[3] Liver enzymes can be mildly elevated in HG and usually improve as the HG settles.

• Onset is in the first trimester; RCOG defines NVP as beginning before 16 weeks with no other cause, and women typically describe symptoms starting with the first missed period.^[1]
• Continuous nausea, retching and vomiting through the day, not just "morning".
• Inability to keep water, food or oral medicines down; vomiting may be triggered by smells, heat, motion or brushing the teeth.
• Weight loss, weakness, lightheadedness on standing, syncope, reduced urine.
• Hypersalivation; food aversions; severe quality-of-life impairment and work absence.
• Mental-health symptoms: anxiety, low mood, despair; suicidal thoughts occur in a significant minority and must be asked about directly.^[4]

These should be sought at every contact, because HG is a diagnosis of exclusion:

• onset after 9-10 weeks' gestation;^[3]
• abdominal pain unrelated to vomiting, fever, diarrhoea, urinary symptoms;^[3]
• severe headache, visual disturbance, right upper-quadrant pain, breathlessness on exertion, or jaundice;^[3]
• neurologic abnormalities or goitre;^[3]
• known (or suspected) multiple or molar pregnancy.^[3]

• Weight (compare with the booking and pre-pregnancy weight) and general appearance.
• Signs of dehydration: dry mucous membranes, reduced skin turgor, sunken eyes, tachycardia, orthostatic hypotension, reduced urine output.
• Abdominal and pelvic examination as guided by symptoms (tenderness, palpable masses, adnexal pain).
• Thyroid (goitre), and a full neurologic examination when indicated.
• Fetal heart rate, depending on gestational age.
• Mental-health assessment and risk of self-harm.

A woman who cannot tolerate oral fluids, who has lost weight, or whose vital signs or mental status have changed needs hospital-level assessment, whatever her PUQE score says.^[2][3][4]

NVP is usually obvious from the history. The diagnostic work is to exclude the other causes of nausea and vomiting in a pregnant woman: gastrointestinal, metabolic, renal, hepatic, neurologic, reproductive, and obstetric conditions.

There is no positive test for HG. Investigations are used to exclude other causes, assess severity and guide treatment.

A practical synthesis of the Windsor and ACOG/RCOG/NICE positions is:

1. Timing: symptoms start before 16 weeks of gestation.^[1]
2. Exclusion of other causes by history, examination and the tests above.
3. Severity: at least one of weight loss of 5% or more of pre-pregnancy weight, an inability to eat or drink normally with severe limitation of daily life, dehydration, or electrolyte abnormality.^[3][4]
4. Severity score (PUQE-24): mild 6 or less (community), moderate 7-12, severe 13-15 (day case or inpatient).^[1][4]

Ketonuria alone is not one of these criteria. Ketones reflect a starvation state that can arise in any pregnant woman who is not eating, and they are not associated with HG severity; using them as admission or discharge criteria has been abandoned in the 2024 RCOG/NICE guidance.^[2][4]

The aim is symptom control, hydration and nutrition while avoiding harm (extrapyramidal effects, QT prolongation, teratogenic exposure, thrombosis and Wernicke's encephalopathy). Treatment intensity is matched to severity, and drugs from different classes are added rather than swapped, because different classes can act synergistically and many women need three or more.^[2][4]

• Reassurance that mild to moderate nausea usually settles by 16-20 weeks.^[2]
• Dietary and lifestyle measures: small dry meals every 1-2 hours, bland foods, protein with each meal, avoid fatty/spicy foods, keep ginger-containing foods/drinks, folic acid supplementation, rest, fresh air, avoid smells and heat, do not lie flat after eating; stop iron supplements if they worsen symptoms.^[2][3]
• Ginger is a reasonable non-pharmacological option when preferred (NICE).^[2]
• WHO's 2016 antenatal care guideline also covers interventions for common physiological symptoms in pregnancy.^[5]
• Antiemetic by mouth, chosen from the first-line options below, with review after 24-72 hours.^[2]
• Pyridoxine (vitamin B6) alone or with doxylamine is ACOG's recommended first-line pharmacological treatment; combined pyridoxine/doxylamine is the only licensed treatment for NVP in the UK.^[3][4]
• Take multivitamins for a month before pregnancy where possible to reduce the incidence and severity of NVP.^[3]
• Consider H2 blockade or a proton-pump inhibitor if reflux/oesophagitis/gastritis develops, and treat constipation.^[1]

RCOG and NICE favour outpatient or day-case management where possible: it is as effective as inpatient care for many women and cheaper.^[1][2][4] Indications include persistent vomiting despite oral antiemetics, inability to tolerate oral medication, or the need for IV rehydration, provided the woman can go home afterwards.^[1][4] Criteria from the clinical summaries include vomiting for more than 24 hours with inability to maintain oral hydration for 12 hours or more, or severe clinical dehydration.^[1]

Admit or manage as an inpatient when any of the following applies:

• continued nausea and vomiting with inability to keep down oral antiemetics;^[1]
• continued nausea and vomiting with weight loss greater than 5% of body weight, dehydration and/or electrolyte imbalance despite oral antiemetics;^{[1] [4]}
• suspected or confirmed comorbidity where HG prevents taking oral medication (for example UTI unable to tolerate oral antibiotics);^[1][4]
• comorbidities such as epilepsy, HIV, type 1 diabetes or serious psychiatric illness, where delayed intake of essential medicines is dangerous;^[4]
• signs changing in vital status, renal impairment, arrhythmia or mental-status change.^[3][4]

Normal saline (0.9% NaCl) with added potassium chloride, guided by daily monitoring of electrolytes, is the most appropriate intravenous fluid.^[1][4] A commonly used inpatient regimen is:

• 1 L over 1 hour, then 1 L over 2-3 hours;
• add potassium chloride (for example 20 mmol in the second bag) according to the serum potassium level and local protocol;
• adapt further fluids to the electrolyte results and weight losses; if more than 3 L or abnormal U&E are needed, admit and recheck after about 6 hours;^[4]
• a practical total of 3 L of 0.9% NaCl with 20 mmol potassium chloride per litre over 4 hours appears in current reviews (about 60 mmol of potassium daily, added to each bag).^[4]

Dextrose-containing fluids are avoided unless serum sodium is normal and thiamine has been given, because they can precipitate Wernicke's encephalopathy in thiamine-deficient women and can precipitate or worsen hypokalaemia.^[1][4] Thiamine (100 mg orally three times a day, or intravenous as part of vitamin B complex/Pabrinex) should be given to every woman admitted with vomiting or with markedly reduced intake, before any dextrose or parenteral nutrition.^[1][4]

Other points:

• Monitor U&E and renal function daily during IV fluids; check urine output (review if less than 0.5 mL/kg/h), weight weekly, urine dipstick daily.^[1][4]
• If enteral nutrition is being re-introduced after a long fast, do it slowly, with electrolyte monitoring, to avoid refeeding syndrome.^[4]
• Seek dietitian input for weight loss, suspected malnutrition or persistent symptoms; optimise folate and thiamine at minimum.^[4]
• Withhold non-essential drugs that provoke nausea, such as iron, and give essential ones by alternative routes (buccal, rectal, transdermal, subcutaneous).^[1][4]

The drugs below are the shared RCOG/ACOG/NICE set used in practice; the doses and regimens are drawn from current open-access reviews. Use drugs from different classes rather than repeats if one class is ineffective, and add rather than replace where possible.

Important cautions:

• Metoclopramide is second-line because of extrapyramidal symptoms and oculogyric crises; give IV doses slowly (at least 3 minutes) to reduce dystonic reactions, stop the drug and give procyclidine if they occur.^[1][4]
• Ondansetron is safe and effective as second-line; women can be reassured that its association with orofacial clefting is a very small absolute increase (about 14 per 10,000 births compared with about 11.4 per 10,000) and should be weighed against the risks of poorly managed HG. Avoid concomitant QT-prolonging drugs.^[3][4]
• Corticosteroids should be reserved for refractory cases; avoid before 10 weeks because of a possible small increase in orofacial clefting; do not use for more than 6 weeks; monitor blood pressure and screen for gestational diabetes; consider fetal-growth monitoring.^[3]
• Combining dopamine antagonists (metoclopramide with promethazine/prochlorperazine/chlorpromazine) increases the risk of extrapyramidal effects and neuroleptic malignant syndrome; combining ondansetron with phenothiazines can prolong the QT interval.^{[3] [4]}
• Route matters: patients who cannot keep tablets down do better with buccal, rectal, IM or IV formulations than with the same drug by mouth.^[4]

• Dietitian review, optimisation of food and fluid intake, oral nutritional supplements; if intake remains inadequate after rehydration and antiemetics, consider enteral (nasogastric or nasoduodenal) tube feeding first.^[4]
• Total parenteral nutrition carries a high complication rate and is reserved for women losing weight who are unresponsive to enteral feeding.^[3][4]
• Avoid prolonged fasting and repeated unsupported intravenous access; peripherally inserted central catheters have a high complication rate and are a last resort.^[3]

• Acupressure or acupuncture (P6 point) may improve NVP and is safe; NICE and ACOG accept that evidence for acupressure as an adjunct is limited, and it should be used as an addition rather than a substitute for antiemetics in HG.^[2][3]
• H2-receptor antagonists or proton-pump inhibitors for reflux, oesophagitis or gastritis; laxatives for constipation (common with ondansetron).^[1][3]
• Intravenous hydration at home or in the community is an option where services exist and has high patient satisfaction.^[4]
• Thromboprophylaxis: women admitted with HG have an increased risk of venous thromboembolism, so risk should be assessed and prophylaxis given according to the local maternity VTE guideline. Anti-embolism measures should also be used in hospital.^[2][4]
• Psychological support should be part of routine care: assess mental health, refer early, warn about the risk of depression, anxiety, post-traumatic stress and suicidal thoughts, and signpost to patient support groups.^[4]
• For severe or persistent symptoms, draw on a multidisciplinary team: midwife, nurse, dietitian, pharmacist, endocrinology, gastroenterology and mental-health professionals.^[1][4]

All therapeutic measures should be tried before considering ending a wanted pregnancy. Up to 10% of women with HG report terminating a wanted pregnancy, and not offering full treatment is a recognised contributor, so termination must only be considered after the whole ladder above, including corticosteroids, enteral nutrition and psychological support, has been used.^[4]

Maternal complications of HG:

• Dehydration with hyponatraemia, hypochloraemia and hypokalaemia; acute kidney injury; arrhythmia from severe hypokalaemia.^[4]
• Wernicke's encephalopathy, and its progression to Korsakoff syndrome, from thiamine deficiency.^[4]
• Vitamin K deficiency, causing coagulopathy-related bleeding, embryopathy or neonatal intracranial haemorrhage, in rare cases.^[4]
• Refeeding syndrome after rapid reintroduction of nutrition.^[4]
• Venous thromboembolism antenatally, at delivery and postpartum in women admitted with HG.^[2][4]
• Increased risk of placental abruption and pre-eclampsia if HG persists into the second trimester.^[4]
• Depression, anxiety, post-traumatic stress disorder and suicidal thoughts, in many cases beyond the pregnancy.^[4]
• Repeat admissions, occurring in 28-60% of women.^[4]

Offspring consequences:

• Low birth weight, preterm birth, neonatal intensive care admission.^[4]
• Long-term associations with anxiety disorders and sleep problems have been reported.^[4]
• HG is associated with reductions in macrosomia and stillbirth in some data.^[4]

For most women NVP clears by 16-20 weeks, and by about 90% before 20 weeks.^[1][2] HG is more variable: hospitalisation is common, recurrence is high (registry studies quote around 15%, cohort studies up to 89% in a later pregnancy) and the psychological and economic burden can outlast the pregnancy.^[4] Women should be counselled that:

• an adequate response usually follows the full treatment ladder, but several drugs and routes are often needed together;^[2][4]
• if symptoms persist into the late second or third trimester, serial scans to monitor fetal growth are recommended;^[1][4]
• antiemetics should be continued after discharge, then tapered as symptoms settle; stopping too early often causes relapse and unplanned admission.^[2]

No test predicts HG with certainty, but several measures reduce its likelihood or severity:

• Multivitamins for a month before pregnancy reduce the incidence and severity of NVP (ACOG).^[3]
• Starting antiemetic treatment before symptoms appear, in women with previous HG, may reduce severity.^[3]
• Ginger (NICE) and dietary measures (small frequent bland meals, avoidance of triggers, resting, fresh air).^[2][3]
• WHO's guideline for antenatal care likewise addresses common physiological symptoms of pregnancy.^[5]
• Avoid iron-containing preparations if they exacerbate symptoms; separate antacids from iron/folate by two hours to avoid reduced absorption.^[1]
• Early identification of high-risk women (previous HG, motion sickness, migraine, multiple pregnancy) so they have a treatment plan and access to first-line drugs from the first missed period.^[3][4]
• Pre-conception counselling in someone who has had HG: recurrence risk, a pre-emptive plan (use whichever drugs worked before), mental-health support and dietitian contact before pregnancy.^[4]

• Pre-existing disease. Women with epilepsy, HIV, type 1 diabetes or serious psychiatric illness are vulnerable because HG can prevent timely intake of essential medicines; they need earlier, more intense management and multidisciplinary care.^[4]
• Multiple pregnancy or molar pregnancy raises risk through increased placental mass and is ruled out by ultrasound.^[3]
• Women with recurrent disease may want to defer or modify future pregnancies; counselling and continuity of care reduce the burden.^[4]
• Pregnant people of any gender identity. The recommendations apply to all pregnant people; services should use respectful, inclusive language. (ACOG notes the same.)^[3]
• Children, younger adolescents and older adults are not normally the patient in this condition; the relevant "special group" concept is children of highly affected mothers (nutritional follow-up) and anyone in whom HG conceals another disease.

• A history, weight, vital signs and a pregnancy test already separate most women; in remote settings these, plus an inexpensive blood panel (U&E, creatinine), are more informative than ketone dipsticks. Ketonuria should not drive admission.^[2][4]
• Do not wait for ultrasound before rehydrating a woman who is clinically dehydrated; confirm pregnancy and scan as soon as possible to exclude molar or multiple pregnancy.^[3]
• Rehydrate with available crystalloid fluids; give thiamine wherever dextrose is used. Injectable antiemetics such as promethazine or metoclopramide are used where available, dosed according to local protocol.
• Give magnesium and other electrolytes according to what is available; avoid dextrose without thiamine; monitor urine output.
• Refer early to the nearest centre that can provide IV therapy, enteral feeding and LMWH; arrange transport before the woman deteriorates.
• Provide clear written take-home advice and a follow-up contact, and ask about suicidal thoughts even in very short consultations.

• Nausea and vomiting of pregnancy is very common (up to 90%); hyperemesis gravidarum affects about 0.3-3.6% and is the commonest reason for admission in early pregnancy.^[1][4]
• NVP and HG are the same condition at different severities; onset is before 16 weeks and other causes must be excluded.^[1]
• The Windsor definition of HG is severe nausea/vomiting starting before 16 weeks that prevents normal eating/drinking and strongly limits daily life.^[4]
• Ketonuria is not a measure of severity or dehydration and should not determine admission or length of stay.^[2][4]
• Hyperthyroid and liver abnormalities are usually mild and transient; treat thyroid supportively.^[3]
• Risk factors include previous HG, multiple pregnancy, female fetus, younger age and low/high body weight; the strongest modern mechanism is GDF15 from the placenta and individual sensitivity to it.^{[4] [3]}
• Treatment runs in steps: dietary and ginger, then first-line antiemetics, then day-case/inpatient IV rehydration with normal saline plus KCl, then second-line drugs, then corticosteroids, then enteral and lastly parenteral nutrition.^[1][2][3][4]
• Add drugs from different classes rather than replacing; many women need three or more antiemetics together.^[2][4]
• Give thiamine before any dextrose in any woman admitted with vomiting, to prevent Wernicke's encephalopathy.^[3][4]
• Corticosteroids are reserved for refractory HG; avoid before 10 weeks, limit to 6 weeks, monitor blood pressure and glucose.^[3]
• Women admitted with HG are at increased risk of venous thromboembolism, so VTE risk should be assessed and managed with the local maternity VTE guideline.^[2][4]
• Offer pyridoxine vitamin B6 first pharmacologically; ondansetron's orofacial-cleft signal is very small and should not stop its use if first-line drugs fail.^[3][4]
• Recovery is usually good, but recurrence is common; women with persistent symptoms need serial growth scans and pre-conception counselling.^[1][4]

These related MedGrasp topics are listed as plain text until they are published: diagnosis of pregnancy and normal physiology of pregnancy; gestational diabetes mellitus; diabetes in pregnancy; vitamin deficiencies (especially thiamine); acid-base disorders; venous thromboembolism; hypertensive disorders of pregnancy; mental health in pregnancy.