Hyperemesis of pregnancy

Vomiting is a normal feature of early pregnancy, especially between 7 and 12 weeks.

Severe vomiting may cause weight loss and electrolyte imbalance. In very rare instances jaundice may result - thought to be due to severe protein and vitamin malnutrition.

The cause of the vomiting is primarily physiological but psychological factors may affect the apparent severity.

Symptoms correlate with raised levels of Beta Human chorionic gonadotrophin (BHCG).

High levels of BHCG occur in:

• hydatidiform mole
• multiple pregnancy

Note that thyroid function should be assessed in all women with hyperemesis gravidarum. This is because hyperthyroidism may result from higher serum concentrations of BHCG, which has TSH-like activity. Generally, hyperthyroidism associated with increased levels of BHCG resolves spontaneously after the first trimester (1).

A combination of doxylamine and pyridoxine (vitamin B6) is licensed for the treatment of nausea and vomiting in pregnancy (NNVP) when conservative management has not worked

• the combination provides the action of two unrelated compounds
  • doxylamine succinate (an antihistamine) and pyridoxine hydrochloride (vitamin B6) provide anti-nauseant and antiemetic activity
  • doxylamine succinate, an ethanolamine, first-generation antihistamine crosses the blood-brain barrier and exerts an antiemetic action by selectively binding to H1 receptors in the brain
  • pyridoxine hydrochloride, a water-soluble vitamin, is converted to pyridoxal, pyridoxamine, pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate. Although pyridoxal 5'-phosphate is the main active antiemetic metabolite, the other metabolites also contribute to the biological activity
  • mechanism of action of the combination of doxylamine succinate and pyridoxine hydrochloride to treat nausea and vomiting of pregnancy has not been established (1)
    
    
• a clinical trial has demonstrated that the combination of doxylamine and pyridoxine produced small but statistically significant differences in symptoms and well-being compared with placebo (2)
  
  
• common or very common adverse effects include dizziness, drowsiness, dry mouth and fatigue (1)
  
  
• not aware of any high-quality evidence that shows that the combination of doxylamine and pyridoxine is more effective than other antiemetics (1)

Acupuncture and doxylamine/pyridoxine

• RCT (n=352 women in early pregnancy with mod-severe nausea and vomiting) found acupuncture (mean difference -0.7, 95% CI -1.3 to -0.1), doxylamine-pyridoxine (-1.0,-1.6 to -0.4) and the combination of both (-1.6, -2.2 to -0.9) had larger reduction in the Pregnancy-Unique Quantification of Emesis (PUQE) score vs placebo (3)
  • study authors concluded:
    • both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe nausea and vomiting of pregnancy (NVP)
      • however, the clinical importance of this effect is uncertain because of its modest magnitude
      • combination of acupuncture and doxylamin-pyridoxine may yield a potentially larger benefit than each treatment alone

Notes (4):

• rationale for the delayed-release characteristics of this combination is to allow women to take it before bedtime, when symptoms of NVP tend to be minimal, in order to counteract the increased symptoms more commonly experienced in the morning hours
• doxylamine succinate-pyridoxine hydrochloride delayed release combination is safe and well tolerated by pregnant women when used in the recommended dose of up to 4 tablets daily in treating nausea and vomiting of pregnancy (4)
• extensive data suggest that doxylamine/pyridoxine is safe for pregnant women to use, and that it is relatively well tolerated. The results of epidemiological studies designed to detect possible teratogenicity show no association with fetal abnormalities (5)

Reference:

1. Prescriber (2002), 13 (10), 50-68.
2. Drug Ther Bull. 2019 Jan 31.Doxylamine/pyridoxine for nausea and vomiting in pregnancy.
3. Xiao-Ke Wu, Jing-Shu Gao, Hong-Li Ma, et al. Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy: A Randomized, Controlled, 2 x 2 Factorial Trial. Ann Intern Med. [Epub 20 June 2023]. doi:10.7326/M22-2974
4. Korean G et al. Maternal safety of the delayed-release doxylamine and pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo controlled trial. BMC Pregnancy Childbirth. 2015; 15: 59.
5. NICE (June 2019). Doxylamine/pyridoxine (Xonvea) for treating nausea and vomiting of pregnancy