The treatment of NVP depends on the severity and duration of the symptoms at the time of presentation. Treatment for common NVP can be divided into non-pharmacological and pharmacological treatments. Non-pharmacological therapies are most often recommended as first-line treatments out of concern for the developing fetus. If these methods fail, pharmacological options are considered.[2]American College of Obstetricians and Gynecologists. Practice bulletin no. 189: nausea and vomiting of pregnancy. Jan 2018 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/01/nausea-and-vomiting-of-pregnancy
In dehydrated patients, intravenous fluids should be utilised. In patients with hyperemesis gravidarum, hospitalisation and treatment with parenteral nutrition may be required.
Without volume depletion
Initial non-pharmacological therapy includes dietary modification. Patients often find that they can better tolerate smaller, more frequent meals.[2]American College of Obstetricians and Gynecologists. Practice bulletin no. 189: nausea and vomiting of pregnancy. Jan 2018 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/01/nausea-and-vomiting-of-pregnancy
Foods that taste bland and are low in fat and high in carbohydrates are often best tolerated. Women often report that they can tolerate salty foods early in the day. Tart or sour liquids (e.g., lemonade) may be better tolerated than water. Eliminating supplemental iron, and substituting folic acid for iron-containing antenatal vitamins, may improve symptoms of nausea.[2]American College of Obstetricians and Gynecologists. Practice bulletin no. 189: nausea and vomiting of pregnancy. Jan 2018 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/01/nausea-and-vomiting-of-pregnancy
If dietary modifications fail to improve symptoms, various alternative treatments (e.g., acupressure, acupuncture, ginger) have been evaluated in the treatment of NVP, and may be tried. Since there have been no head-to-head comparisons of the majority of these modalities, it is difficult to recommend a first-line treatment. Patients should be apprised of the various options and encouraged to try the one that they would prefer. Acupressure may improve symptoms.[2]American College of Obstetricians and Gynecologists. Practice bulletin no. 189: nausea and vomiting of pregnancy. Jan 2018 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/01/nausea-and-vomiting-of-pregnancy
[15]Matthews A, Haas DM, O'Mathúna DP, et al. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2015;(9):CD007575.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007575.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/26348534?tool=bestpractice.com
Acupressure may be applied to the P6 point (Neiguan point, located 3 finger-widths above the wrist on the volar surface). This may be applied using commercially available wrist bands. Ginger supplementation reduces symptoms of nausea.[2]American College of Obstetricians and Gynecologists. Practice bulletin no. 189: nausea and vomiting of pregnancy. Jan 2018 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/01/nausea-and-vomiting-of-pregnancy
[15]Matthews A, Haas DM, O'Mathúna DP, et al. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2015;(9):CD007575.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007575.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/26348534?tool=bestpractice.com
[16]McParlin C, O'Donnell A, Robson SC, et al. Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review. JAMA. 2016 Oct 4;316(13):1392-401.
http://www.ncbi.nlm.nih.gov/pubmed/27701665?tool=bestpractice.com
Ginger may be used alone or with acupressure, and is considered safe to use in all trimesters of pregnancy. It can be taken raw, as a tea, or in tablet/capsule form.[17]Ding M, Leach M, Bradley H. The effectiveness and safety of ginger for pregnancy-induced nausea and vomiting: a systematic review. Women Birth. 2013 Mar;26(1):e26-30.
http://www.ncbi.nlm.nih.gov/pubmed/22951628?tool=bestpractice.com
[18]Thomson M, Corbin R, Leung L. Effects of ginger for nausea and vomiting in early pregnancy: a meta-analysis. J Am Board Fam Med. 2014 Jan-Feb;27(1):115-22.
https://www.jabfm.org/content/27/1/115.long
http://www.ncbi.nlm.nih.gov/pubmed/24390893?tool=bestpractice.com
If non-pharmacological methods fail, drug therapy may be considered. First-line therapies include pyridoxine (vitamin B6) and/or doxylamine (an antihistamine).[2]American College of Obstetricians and Gynecologists. Practice bulletin no. 189: nausea and vomiting of pregnancy. Jan 2018 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/01/nausea-and-vomiting-of-pregnancy
One randomised controlled trial found that the combination was effective compared with placebo, but a re-analysis of the data queried the clinical significance of the findings.[19]Koren G, Clark S, Hankins GD, et al. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol. 2010 Dec;203(6):571.e1-7.
http://www.ncbi.nlm.nih.gov/pubmed/20843504?tool=bestpractice.com
[20]Persaud N, Meaney C, El-Emam K, et al. Doxylamine-pyridoxine for nausea and vomiting of pregnancy randomized placebo controlled trial: prespecified analyses and reanalysis. PLoS One. 2018 Jan 17;13(1):e0189978.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0189978
http://www.ncbi.nlm.nih.gov/pubmed/29342163?tool=bestpractice.com
The UK National Institute for Health and Care Excellence recommend doxylamine/pyridoxine in women with symptoms that have not responded to conservative management. However, there is no evidence to show how it compares with other first-line treatments.[21]National Institute for Health and Care Excellence. Doxylamine/pyridoxine (Xonvea) for treating nausea and vomiting of pregnancy. Jun 2019 [internet publication].
https://www.nice.org.uk/advice/es20/chapter/Key-messages
Second-line therapies include alternative oral antihistamines (e.g., meclizine, dimenhydrinate, diphenhydramine) or antiemetics (e.g., chlorpromazine, prochlorperazine, metoclopramide, domperidone).[2]American College of Obstetricians and Gynecologists. Practice bulletin no. 189: nausea and vomiting of pregnancy. Jan 2018 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/01/nausea-and-vomiting-of-pregnancy
[22]Leathem A. Safety and efficacy of antiemetics used to treat nausea and vomiting in pregnancy. Clin Pharm. 1986 Aug;5(8):660-8.
http://www.ncbi.nlm.nih.gov/pubmed/2874910?tool=bestpractice.com
[23]Gill SK, O'Brien L, Koren G. The safety of histamine 2 (H2) blockers in pregnancy: a meta-analysis. Dig Dis Sci. 2009 Sep;54(9):1835-8.
http://www.ncbi.nlm.nih.gov/pubmed/19051023?tool=bestpractice.com
With volume depletion
Patients with NVP who are unable to keep down liquids despite treatment with conservative measures and drug therapies will often become dehydrated and require treatment with intravenous fluids. Ringer's lactate may be used; normal saline or 5% dextrose-saline are alternatives if Ringer's lactate is not available.[24]Herrell HE. Nausea and vomiting of pregnancy. Am Fam Physician. 2014 Jun 15;89(12):965-70.
https://www.aafp.org/afp/2014/0615/p965.html
http://www.ncbi.nlm.nih.gov/pubmed/25162163?tool=bestpractice.com
One randomised controlled trial has demonstrated similar outcomes in patients hydrated with either normal saline or 5% dextrose solution.[25]Tan PC, Norazilah MJ, Omar SZ. Dextrose saline compared with normal saline rehydration of hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2013 Feb;121(2 Pt 1):291-8.
https://journals.lww.com/greenjournal/Fulltext/2013/02000/Dextrose_Saline_Compared_With_Normal_Saline.13.aspx
http://www.ncbi.nlm.nih.gov/pubmed/23232754?tool=bestpractice.com
If solutions containing glucose are considered, some physicians suggest giving thiamine (vitamin B1) prior to administration in order to prevent Wernicke's encephalopathy.[1]Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol. 1998 Sep;41(3):597-605.
http://www.ncbi.nlm.nih.gov/pubmed/9742356?tool=bestpractice.com
[2]American College of Obstetricians and Gynecologists. Practice bulletin no. 189: nausea and vomiting of pregnancy. Jan 2018 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/01/nausea-and-vomiting-of-pregnancy
In patients with volume depletion, parenteral (or rectal) anti-emetic therapy may be necessary. Evidence suggests that ondansetron may be more effective at controlling severe vomiting than metoclopramide.[26]Kashifard M, Basirat Z, Kashifard M, et al. Ondansetrone or metoclopromide? Which is more effective in severe nausea and vomiting of pregnancy? A randomized trial double-blind study. Clin Exp Obstet Gynecol. 2013;40(1):127-30.
http://www.ncbi.nlm.nih.gov/pubmed/23724526?tool=bestpractice.com
[27]Slattery J, Quinten C, Candore G, et al. Ondansetron use in nausea and vomiting during pregnancy: a descriptive analysis of prescription patterns and patient characteristics in UK general practice. Br J Clin Pharmacol. 2022 Oct;88(10):4526-39.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545331
http://www.ncbi.nlm.nih.gov/pubmed/35483963?tool=bestpractice.com
However, in 2019 studies showed an increased risk of cleft palate following the use of ondansetron during the first trimester of pregnancy.[28]Huybrechts KF, Hernández-Díaz S, Straub L, et al. Association of maternal first-trimester ondansetron use with cardiac malformations and oral clefts in offspring. JAMA. 2018 Dec 18;320(23):2429-37.
https://jamanetwork.com/journals/jama/fullarticle/2718793
http://www.ncbi.nlm.nih.gov/pubmed/30561479?tool=bestpractice.com
The European Medicines Agency's (EMA's) pharmacovigilance risk assessment committee (PRAC) has recommended limiting the use of ondansetron during the first trimester of pregnancy.[29]European Medicines Agency. PRAC recommendations on signals: adopted at the 8-11 July 2019 PRAC meeting. Aug 2019 [internet publication].
https://www.ema.europa.eu/en/documents/prac-recommendation/prac-recommendations-signals-adopted-8-11-july-2019-prac-meeting_en.pdf
However, the UK Teratology Information Service (UKTIS), in collaboration with the European Network of Teratology Information Services (ENTIS), issued a joint statement in response to the recommendations from the EMA PRAC regarding the use of ondansetron in the first trimester of pregnancy. UKTIS and ENTIS suggest ondansetron should still be considered an option for patients with severe vomiting in pregnancy in whom first-line treatments have failed, noting in their statement that there is much more information available about safety during pregnancy for ondansetron than for other antiemetic drugs, with data now available from over 168,000 women treated during the first trimester.[30]UK Teratology Information Service. Ondansetron: official response statement to PRAC recommendations. Sep 2019 [internet publication].
https://www.medicinesresources.nhs.uk/en/Medicines-Awareness/Safety-Alerts/Safety-alerts/Ondansetron-in-pregnancy--updated-UK-Teratology-Information-Service-UKTIS-healthcare-professional-monograph-and-patient-information-leaflet
The UK Medicines and Healthcare products Regulatory Agency also issued a drug safety update for ondansetron that provides similar advice.[31]Medicines and Healthcare products Regulatory Agency. Drug safety update. Ondansetron: small increased risk of oral clefts following use in the first 12 weeks of pregnancy. Jan 2020 [internet publication].
https://www.gov.uk/drug-safety-update/ondansetron-small-increased-risk-of-oral-clefts-following-use-in-the-first-12-weeks-of-pregnancy
Ondansetron should therefore be reserved as a second-line agent for the treatment of NVP.[32]Royal College of Obstetricians and Gynaecologists. Green-top guideline no. 69: the management of nausea and vomiting in pregnancy and hyperemesis gravidarum. Feb 2024 [internet publication].
https://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.17739
Patients must be adequately counselled about the benefits of ondansetron, as well as the small increase in the risk of cleft palate that may exist.
Proton-pump inhibitors (PPIs) may be used as an alternative treatment option to parenteral or rectal anti-emetics, or in combination with them.[33]Einarson A, Maltepe C, Boskovic R, et al. Treatment of nausea and vomiting in pregnancy: an updated algorithm. Can Fam Physician. 2007 Dec;53(12):2109-11.
https://www.cfp.ca/content/53/12/2109.full
http://www.ncbi.nlm.nih.gov/pubmed/18077743?tool=bestpractice.com
Data have demonstrated that PPIs are safe in pregnancy and are not associated with a significant increase in birth defects.[34]Pasternak B, Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects. N Engl J Med. 2010 Nov 25;363(22):2114-23.
http://www.ncbi.nlm.nih.gov/pubmed/21105793?tool=bestpractice.com
However, analysis of data derived from observational studies suggests that PPI use during pregnancy may be associated with a modest increased risk of asthma during childhood.[35]Lai T, Wu M, Liu J, et al. Acid-suppressive drug use during pregnancy and the risk of childhood asthma: a meta-analysis. Pediatrics. 2018 Feb;141(2):e20170889.
http://www.ncbi.nlm.nih.gov/pubmed/29326337?tool=bestpractice.com
Hyperemesis gravidarum is defined as persistent vomiting, volume depletion and electrolyte imbalance, ketosis, and >5% weight loss.[1]Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol. 1998 Sep;41(3):597-605.
http://www.ncbi.nlm.nih.gov/pubmed/9742356?tool=bestpractice.com
These patients will frequently require hospitalisation. For patients who have failed initial therapies, corticosteroids can be considered after the first trimester (their use has been associated with cleft palate in fetuses exposed in the first trimester).[2]American College of Obstetricians and Gynecologists. Practice bulletin no. 189: nausea and vomiting of pregnancy. Jan 2018 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2018/01/nausea-and-vomiting-of-pregnancy
[36]Park-Wyllie L, Mazzotta P, Pastuszak A, et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology. 2000 Dec;62(6):385-92.
http://www.ncbi.nlm.nih.gov/pubmed/11091360?tool=bestpractice.com
A randomised, double-blind, controlled study has demonstrated improvement in symptoms.[37]Safari HR, Fassett MJ, Souter IC, et al. The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: a randomized, double-blind, controlled study. Am J Obstet Gynecol. 1998 Oct;179(4):921-4.
http://www.ncbi.nlm.nih.gov/pubmed/9790371?tool=bestpractice.com
In extreme cases, patients may require enteral feeding or total parenteral nutrition to provide calories and replace electrolytes and nutrients. Enteral feeding has been shown to be effective in one small study utilising a nasogastric tube with infusion rates up to 100 mL/hour.[38]Hsu JJ, Clark-Glena R, Nelson DK, et al. Nasogastric enteral feeding in the management of hyperemesis gravidarum. Obstet Gynecol. 1996 Sep;88(3):343-6.
http://www.ncbi.nlm.nih.gov/pubmed/8752236?tool=bestpractice.com
Helicobacter pylori-positive patients
In severe cases, patients who test positive for Helicobacter pylori may be treated with appropriate eradication regimens.[7]Goldberg D, Szilagyi A, Graves L. Hyperemesis gravidarum and Helicobacter pylori infection: a systematic review. Obstet Gynecol. 2007 Sep;110(3):695-703.
http://www.ncbi.nlm.nih.gov/pubmed/17766620?tool=bestpractice.com