Journal Health of Woman. 2024. 3(172): 72-81. doi: 10.15574/HW.2024.172.72
Petrenko Ye. V., Bondarenko L. A.
Dnipro State Medical University, Ukraine

For citation: Petrenko YeV, Bondarenko LA. (2024). Nausea and vomiting of pregnancy: a review of modern opportunities. Ukrainian Journal Health of Woman. 3(172): 72-81. doi: 10.15574/HW.2024.172.72.
Article received: Mar 16, 2024. Accepted for publication: Jun 15, 2024.

Nausea and vomiting of pregnancy (NVP) are the most frequent and characteristic symptoms of pregnancy for the first trimester that potentially may cause substantial negative consequences for the physical and emotional health of a woman. According to various studies, from 50 to 90% of women suffer from NVP. Usually, the symptoms of NVP begin at 5-6 weeks after the last menstrual period and disappear in most cases by the 16th-20th week of pregnancy, but sometimes they persist and may be observed until the third trimester, and in rare cases – even until childbirth. The doctor's main task in providing assistance to a pregnant woman with NVP is the timely application of an adequate treatment strategy, both effective and safe for a mother and a fetus, as well as ensuring the highest achievable life quality for a woman.
The aim of this article is to analyze modern management opportunities for pregnant women with NVP, including an assessment of the advantages and disadvantages of different treatment strategies, for a comprehensive understanding of the NVP problem and the main principles and ways for solving it.
This review is based on national guidelines (updated Royal College of Obstetricians and Gynecologists (RCOG) Green-top clinical guideline 2024, Society of Obstetricians and Gynecologists of Canada (SOGC) Guideline 2016), the results of various studies, and review articles (database of the Cochrane Library, UpToDate, EMBASE, MEDLINE).
Conclusion: a combination of pyridoxine and doxylamine can be prescribed for the prevention of NVP since the diagnosis of pregnancy in a high-risk group of women. In case of already existing symptoms of NVP, the objective assessment of complaints, as well as a response to the prescribed therapy, are facilitated by the unified scales. In most cases, lifestyle modification and first-line drug therapy effectively reduce the severity of NVP symptoms and improve a woman's quality of life. In case of insufficient response, other drugs are added to the treatment regimen, including second and third-line drugs, with a consideration of possible drug interactions. Some patients might need admission, and in addition to antiemetic therapy, they might need intravenous rehydration, electrolyte balance restoration, and thromboprophylaxis.
The authors declare that there is no conflict of interest.
Keywords: pregnancy, nausea and vomiting of pregnancy, hyperemesis gravidarum, Pregnancy-Unique Quantification of Emesis (PUQE).

REFERENCES

1. Abas MN, Tan PC, Azmi N, Omar SZ. (2014). Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 123(6): 1272-1279. https://doi.org/10.1097/AOG.0000000000000242; PMid:24807340

2. Boelig RC, Barton SJ, Saccone G, Kelly AJ, Edwards SJ, Berghella V. (2016). Interventions for treating hyperemesis gravidarum. Cochrane Database Syst Rev. 2016(5): CD010607. https://doi.org/10.1002/14651858.CD010607.pub2; PMid:27168518 PMCid:PMC10421833

3. Campbell K, Rowe H, Azzam H, Lane CA. (2016). The Management of Nausea and Vomiting of Pregnancy. J Obstet Gynaecol Can. 38(12): 1127-1137. https://doi.org/10.1016/j.jogc.2016.08.009; PMid:27986189

4. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. (2007). Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai. 90(1): 15-20.

5. Committee on Practice Bulletins-Obstetrics. (2018). ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 131(1): 15-30. https://doi.org/10.1097/AOG.0000000000002456; PMid:29266076

6. Danielsson B, Wikner BN, Källén B. (2014). Use of ondansetron during pregnancy and congenital malformations in the infant. Reprod Toxicol. 50: 134-7. https://doi.org/10.1016/j.reprotox.2014.10.017; PMid:25450422

7. Derzhavnyi reiestr likarskykh zasobiv Ukrainy. URL: http://www.drlz.com.ua/ibp/ddsite.nsf/all/shlist?opendocument.

8. Eliakim R, Abulafia O, Sherer DM. (2000). Hyperemesis gravidarum: a current review. Am J Perinatol. 17(4): 207-18. https://doi.org/10.1055/s-2000-9424; PMid:11041443

9. Fejzo MS, Ingles SA, Wilson M, Wang W, MacGibbon K, Romero R, Goodwin TM. (2008). High prevalence of severe nausea and vomiting of pregnancy and hyperemesis gravidarum among relatives of affected individuals. Eur J Obstet Gynecol Reprod Biol. 141(1): 13-17. https://doi.org/10.1016/j.ejogrb.2008.07.003; PMid:18752885 PMCid:PMC2660884

10. Fejzo MS, Sazonova OV, Sathirapongsasuti JF, Hallgrímsdóttir IB, Vacic V, MacGibbon KW et al. (2018). Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum. Nature Communications. 9(1): 1-9. https://doi.org/10.1038/s41467-018-03258-0; PMid:29563502 PMCid:PMC5862842

11. Fejzo M, Rocha N, Cimino I, Lockhart SM, Petry CJ, Kay RG et al. (2023). GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Nature. 625(7996): 760-767. https://doi.org/10.1038/s41586-023-06921-9; PMid:38092039 PMCid:PMC10808057

12. Fischer-Rasmussen W, Kjaer SK, Dahl C, Asping U. (1991). Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol. 4; 38(1): 19-24. https://doi.org/10.1016/0028-2243(91)90202-V; PMid:1988321

13. Gadsby R, Barnie-Adshead AM, Jagger C. (1993). A prospective study of nausea and vomiting during pregnancy. Br J Gen Pract. 43(371): 245-248.

14. Hammond N, Wang Y, Dimachkie MM, Barohn RJ. (2013). Nutritional neuropathies. Neurol Clin. 31(2): 477-489. https://doi.org/10.1016/j.ncl.2013.02.002; PMid:23642720 PMCid:PMC4199287

15. Hishinuma K, Yamane R, Yokoo I, Arimoto T, Takahashi K, Goto M et al. (2021). Pregnancy outcome after first trimester exposure to domperidone – an observational cohort study. Journal of Obstetrics and Gynaecology Research. 47(5): 1704-1710. https://doi.org/10.1111/jog.14709; PMid:33631840 PMCid:PMC8248151

16. Hughes AE, Freathy RM. (2023). Nausea and vomiting in pregnancy linked to hormone from fetus. Nature. 625(7996): 670-671. https://doi.org/10.1038/d41586-023-03940-4; PMid:38093044

17. Jarvis S, Nelson-Piercy C. (2011). Management of nausea and vomiting in pregnancy. BMJ. 342: d3606. https://doi.org/10.1136/bmj.d3606; PMid:21685438

18. Jennings LK, Mahdy H. (2023). Hyperemesis Gravidarum. StatPearls. URL: https://www.ncbi.nlm.nih.gov/books.

19. Koch KL, Frissora CL. (2003). Nausea and vomiting during pregnancy. Gastroenterology Clinics of North America. 32(1): 201-234. https://doi.org/10.1016/S0889-8553(02)00070-5; PMid:12635417

20. Koch KL. (2002). Gastrointestinal factors in nausea and vomiting of pregnancy. Am J Obstet Gynecol. 186(5): S198-203. https://doi.org/10.1067/mob.2002.122598; PMid:12011886

21. Koren G, Boskovic R, Hard M, Maltepe C, Navioz Y, Einarson A. (2002). Motherisk-PUQE (pregnancy-unique quantification of emesis and nausea) scoring system for nausea and vomiting of pregnancy. Am J Obstet Gynecol. 186(5): S228-231. https://doi.org/10.1067/mob.2002.123054; PMid:12011891

22. Koren G, Clark S, Hankins GD, Caritis SN, Umans JG, Miodovnik M et al. (2015). Maternal safety of the delayed-release doxylamine and pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo-controlled trial. BMC Pregnancy Childbirth. 18(15): 59. https://doi.org/10.1186/s12884-015-0488-1; PMid:25884778 PMCid:PMC4391332

23. Koren G, Piwko C, Ahn E, Boskovic R, Maltepe C, Einarson A et al. Navioz Y, Ungar WJ. (2005). Validation studies of the Pregnancy Unique-Quantification of Emesis (PUQE) scores. J Obstet Gynaecol. 25(3): 241-244. https://doi.org/10.1080/01443610500060651; PMid:16147725

24. Lacasse A, Rey E, Ferreira E, Morin C, Bérard A. (2008). Validity of a modified Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) scoring index to assess severity of nausea and vomiting of pregnancy. Am J Obstet Gynecol. 198(1): 71.e1-7. https://doi.org/10.1016/j.ajog.2007.05.051; PMid:18166311

25. Lacroix R, Eason E, Melzack R. (2000). Nausea and vomiting during pregnancy: A prospective study of its frequency, intensity, and patterns of change. Am J Obstet Gynecol. 182(4): 931-937. https://doi.org/10.1016/S0002-9378(00)70349-8; PMid:10764476

26. Li L, Li L, Zhou X, Xiao S, Gu H, Zhang G. (2015) Helicobacter pylori Infection Is Associated with an Increased Risk of Hyperemesis Gravidarum: A Meta-Analysis. Gastroenterol Res Pract. 2015: 278905. https://doi.org/10.1155/2015/278905; PMid:25861257 PMCid:PMC4378596

27. Li Q, Mitchell AA, Werler MM, Yau WP, Hernández-Díaz S. (2013). Assessment of antihistamine use in early pregnancy and birth defects. J Allergy Clin Immunol Pract. 1(6): 666-74.e1. https://doi.org/10.1016/j.jaip.2013.07.008; PMid:24565715 PMCid:PMC4140658

28. MacGibbon KW, Kim S, Mullin PM, Fejzo MS. (2021). HyperEmesis Level Prediction (HELP Score) Identifies Patients with Indicators of Severe Disease: a Validation Study. Geburtshilfe Frauenheilkd. 81(1): 90-98. https://doi.org/10.1055/a-1309-1997; PMid:33487669 PMCid:PMC7815331

29. Maltepe C, Koren G. (2013). Preemptive treatment of nausea and vomiting of pregnancy: results of a randomized controlled trial. Obstet Gynecol Int. 2013: 809787. https://doi.org/10.1155/2013/809787; PMid:23476657 PMCid:PMC3588181

30. Mazzotta P, Magee LA. (2000). A risk-benefit assessment of pharmacological and nonpharmacological treatments for nausea and vomiting of pregnancy. Drugs. 59(4): 781-800. https://doi.org/10.2165/00003495-200059040-00005; PMid:10804035

31. McKeigue PM, Lamm SH, Linn S, Kutcher JS. (1994). Bendectin and birth defects: I. A meta-analysis of the epidemiologic studies. Teratology. 50(1): 27-37. https://doi.org/10.1002/tera.1420500105; PMid:7974252

32. Miller AD. (1999). Central mechanisms of vomiting. Dig Dis Sci. 44(8): 39S-43S.

33. Mohd Nafiah NA, Chieng WK, Zainuddin AA, Chew KT, Kalok A, Abu MA et al. (2022). Effect of Acupressure at P6 on Nausea and Vomiting in Women with Hyperemesis Gravidarum: A Randomized Controlled Trial. Int J Environ Res Public Health. 1; 19(17): 10886. https://doi.org/10.3390/ijerph191710886; PMid:36078602 PMCid:PMC9518577

34. Nelson-Piercy C, Dean C, Shehmar M, Gadsby R, O'Hara M, Hodson K et al. (2024). The Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum (Green-top Guideline No. 69). BJOG. 00: 1-30. https://doi.org/10.1111/1471-0528.17739; PMid:38311315

35. Niebyl JR. (2010). Clinical practice. Nausea and vomiting in pregnancy. N Engl J Med. 14; 363(16): 1544-1550. https://doi.org/10.1056/NEJMcp1003896; PMid:20942670

36. Oliveira LG, Capp SM, You WB, Riffenburgh RH, Carstairs SD. (2014). Ondansetron compared with doxylamine and pyridoxine for treatment of nausea in pregnancy: a randomized controlled trial. Obstet Gynecol. 124(4): 735-742. https://doi.org/10.1097/AOG.0000000000000479; PMid:25198265

37. Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L, Hunnisett L et al. (2000). Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology. 62(6): 385-392. https://doi.org/10.1002/1096-9926(200012)62:6<385::AID-TERA5>3.0.CO;2-Z; PMid:11091360

38. Pasternak B, Svanström H, Hviid A. (2013). Ondansetron in pregnancy and risk of adverse fetal outcomes. N Engl J Med. 28; 368(9): 814-823. https://doi.org/10.1056/NEJMoa1211035; PMid:23445092

39. Petry CJ, Ong KK, Beardsall K et al. (2018). Vomiting in pregnancy is associated with a higher risk of low birth weight: a cohort study. BMC Pregnancy Childbirth. 18(133). https://doi.org/10.1186/s12884-018-1786-1; PMid:29728080 PMCid:PMC5935997

40. Pope E, Maltepe C, Koren G. (2015). Comparing pyridoxine and doxylamine succinate-pyridoxine HCl for nausea and vomiting of pregnancy: A matched, controlled cohort study. J Clin Pharmacol. 55(7): 809-814. https://doi.org/10.1002/jcph.480; PMid:25663469

41. Pradat P, Robert-Gnansia E, Di Tanna GL, Rosano A, Lisi A, Mastroiacovo P. (2003). Contributors to the MADRE database. First trimester exposure to corticosteroids and oral clefts. Birth Defects Res A Clin Mol Teratol. 67(12): 968-970. https://doi.org/10.1002/bdra.10134; PMid:14745915

42. Rotman P, Hassin D, Mouallem M, Barkai G, Farfel Z. (1994). Wernicke's encephalopathy in hyperemesis gravidarum: association with abnormal liver function. Isr J Med Sci. 30(3): 225-228.

43. Sahakian V, Rouse D, Sipes S, Rose N, Niebyl J. (1991). Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind placebo-controlled study. Obstet Gynecol. 78(1): 33-36.

44. Shaban MM, Kandil HO, Elshafei AH. (2014). Helicobacter pylori seropositivity in patients with hyperemesis gravidarum. The American Journal of the Medical Sciences. 347(2): 101-105. https://doi.org/10.1097/MAJ.0b013e31827bef91; PMid:23459164

45. Shapiro S, Kaufman DW, Rosenberg L, Slone D, Monson RR, Siskind V, Heinonen OP. (1978) Meclizine in pregnancy in relation to congenital malformations. Br Med J. 1(6111): 483. https://doi.org/10.1136/bmj.1.6111.483; PMid:626846 PMCid:PMC1603111

46. Sun L, Xi Y, Wen X, Zou W. (2021). Use of metoclopramide in the first trimester and risk of major congenital malformations: A systematic review and meta-analysis. PLoS ONE. 16(9): e0257584. https://doi.org/10.1371/journal.pone.0257584; PMid:34543335 PMCid:PMC8452057

47. Vutyavanich T, Wongtra-ngan S, Ruangsri R. (1995). Pyridoxine for nausea and vomiting of pregnancy: A randomized, double-blind, placebo-controlled trial. American Journal of Obstetrics and Gynecology. 173(3): 881-884. https://doi.org/10.1016/0002-9378(95)90359-3; PMid:7573262

48. Weigel MM, Weigel RM. (1989). Nausea and vomiting of early pregnancy and pregnancy outcome. An epidemiological study. Br J Obstet Gynaecol. 96(11): 1304-1311. https://doi.org/10.1111/j.1471-0528.1989.tb03228.x; PMid:2611169

49. Yost NP, McIntire DD, Wians FH Jr, Ramin SM, Balko JA, Leveno KJ. (2003). A randomized, placebo-controlled trial of corticosteroids for hyperemesis due to pregnancy. Obstet Gynecol. 102(6): 1250-1254. https://doi.org/10.1016/j.obstetgynecol.2003.08.013; PMid:14662211

50. Zhang Y, Cantor RM, MacGibbon K, Romero R, Goodwin TM, Mullin PM, Fejzo MS. (2011). Familial aggregation of hyperemesis gravidarum. Am J Obstet Gynecol. 204(3): 230.1-7. https://doi.org/10.1016/j.ajog.2010.09.018; PMid:20974461 PMCid:PMC3030697