see also:

• gynaecology;
• Obstetrics;
• pregnancy;
• anti-emetics
• WH Patient information Sheet (docx) - WH intranet only
• The Womens Hospital melbourne (RWH) clinical guideline on nausea and vomiting in pregnancy

• nausea and vomiting effect up to 85% of pregnant women
  • usually mild and self-limiting, frequently resolving before 14wks gestation
  • it is a sensitivity to the hormone GDF-15 and has been thought to be an evolutionary function to avoid eating foods which may be high risk to either the foetus (teratogenic or abortifacient such as plant toxins, alcohol, caffeine) or to the immunosuppressed mother who is at risk of food-borne pathogens which are more likely in meats, fish and eggs, while safer foods such as fruit, grains and sweets are craved ¹⁾
  • it tends to be associated with a positive pregnancy outcome (50-75% lower miscarriage rates)²⁾
• more severe cases with significant dehydration and ketonuria are a frequent presentation to ED
  • ~13% of these patients have symptoms beyond 20wks gestation ³⁾

• morning sickness and hyperemesis gravidarum are substantially caused by maternal sensitivity (resulting from low prenatal levels of GDF15) to the feto-placental production of the hormone growth differentiation factor 15 (GDF15) ⁴⁾
• the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit
• low levels of GDF15 in the non-pregnant state increase the risk of developing HG
• those with high levels of GDF15 in the non-pregnant state are at much very much lower risk of developing hyperemesis
  • eg. those with beta thallasaemia or on metformin
• GDF15 is a stress-regulated hormone that can be produced by almost any cell or tissue in the body and is produced at low levels by organs including the prostate, bladder and kidneys
• GDF15 can trigger nausea by binding to GFRAL receptors in the brainstem and is a potent anorectic factor
• “Under normal non-pregnant physiological conditions, circulating GDF15 levels are low, typically less than 1000 pg/ml, but are increased by a wide range of acute stressors such as sepsis and inflammation, and are characteristically persistently elevated in a number of chronic disease states, for example reaching levels of 10,000–100,000 pg/ml in patients with advanced cancers” ⁵⁾
• metformin elevates circulating GDF15 chronically in humans and the weight loss caused by this drug appears to be dependent on the rise in GDF15
• previously known as MIC1, NAG1, PLAB, or PTGFB, GDF15 was first identified in 1997 as one of the genes enriched in a model system of macrophage activation.

• hyperemesis gravidarum
  • transient hyperthyroidism of first trimester pregnancy
• gastroenteritis - in particular, suspect this if diarrhoea is present as well
• urinary tract infections (UTIs) / cystitis - UTI and persistent bacteriuria is a common problem in pregnancy due to ureteric stasis
• migraine

• molar pregnancy - hydatidiform mole - Dx on USS
• multiple pregnancy
• hyperthyroidism
• drug induced vomiting
• hepatitis
• surgical abdominal causes including biliary disease, pancreatitis, appendicitis and small bowel obstruction
• raised intracranial pressure eg. venous sinus thrombosis (mainly 2nd/3rd TM or post-partum)

• adrenocortical insufficiency
• diabetic ketoacidosis (DKA)
• incarcerated diaphragmatic hernia ⁶⁾

• these patients usually do well with iv rehydration Rx (eg. N Saline 1L over 2hrs then 1L over 2-4hrs then 3L/day of Hartmann's with 5% glucose - do not use 5% glucose alone!) + anti-emetics (see below)
• often these patients can be directly admitted from triage to a ED short stay observation unit using a care plan pathway
• send bloods for FBE, U&E, and, TSH if thyroid testing has not been done
• check urinalysis and send MSU m/c/s if suspicious of UTI
• exclude other conditions such as a surgical abdomen
• ensure an USS has be done or will be done within a week or so to exclude multiple pregnancies and molar pregnancy.
• repeated vomiting usually causes some oesophagitis and may even cause Mallory-Weiss tear resulting in small amounts of blood in vomit.
  • this does not usually need Ix but Mx with antacids or ranitidine may be useful.

• these patients can usually be managed as an outpatient
• check urine, USS as above
• non-pharmacologic measures
  • small frequent meals and snacks aiming for food/fluid every 1-2 hours
  • avoid foods that may trigger symptoms including spicy, odourous, very sweet or acidic foods
  • chew foods slowly
  • eliminate other non-dietary triggers
  • during the first trimester avoid multivitamins that contain high levels of iron (>27mg iron per tablet), re-start after 12wks
  • adequate sleep
  • sea-sickness P6 acupressure wristbands
  • ginger (orally as a tablet, syrup or as ginger tea) to a maximum of 1g daily but avoid ginger concentrates which may have potentially harmful contaminants and do not use if near labour or there is bleeding risk
  • treat gastro-oesophageal reflux
• oral agents to consider (as per WH guideline 2019):
  • first line:
    • pyridoxine (vitamin B6) 25mg o tds (this medication is optional as effectiveness is limited)
      • it seems that higher vitamin B6 levels (eg >=100mg/day supplements), may lead to the development of a predominantly, if not exclusively, sensory neuropathy of the axonal type however, data is inclonclusive due to small sample sizes. Some advisory bodies are recommending max daily intake of 50mg/day - average dietary intake is 5mg/day ⁷⁾ However TGA Australia anecdotal reports of a number of patients developing issues with under 50mg/d ⁸⁾ It appears the mechanism of pyridoxine induced peripheral neuropathy is necrosis of the dorsal root ganglion and is duration and dose dependent. ⁹⁾
  • second line:
    • add doxylamine (Restavit, a H1 antagonist) 12.5mg o nocte, increase to 25mg nocte, then add 12.5mg mane and afternoon if needed
  • third line, add either ONE of the following:
    • metoclopramide (Maxolon) (Maxolon, Pramin) 10mg o tds for maximum 5 days, or,
    • prochlorperazine (Stemetil) (Stemetil) 5-10mg o bd/tds, or 25mg PR once or twice daily
  • fourth line, add a sedating antihistamine:
    • promethazine 10-25mg tds/qid
  • fifth line if severe, persistent or resistant vomiting:
    • ondansetron (Zofran) 4-8mg o (tablet or wafer) bd/tds max 24mg/day
  • sixth line - consider parenteral administration of ONE of the following:
    • metoclopramide (Maxolon) 10mg iv/im 8hrly
    • prochlorperazine (Stemetil) 12.5mg im 8hrly
    • promethazine 12.5-25mg im 4-6hrly
    • ondansetron 4mg iv/im 8-12hrly
  • seventh line:
    • prednisolone 50mg o daily for 3 days, then 25mg o daily for 3 days, then reduce by 5mg as tolerated
      • may need initial IV hydrocortisone 100mg 12hrly un til oral pred is tolerated
      • monitor glucose levels and consider prophylactic ranitidine 300mg o nocte to prevent gastritis

• don't forget to remind patient to take folate supplements as well to reduce probability of neural tube defects
• patients with > 10% LOW with persistent symptoms or a pre-pregnancy BMI < 18 should be referred to dietitian