What is Hyperemesis Gravidarum
Hyperemesis gravidarum (HG) refers to an extreme form of vomiting during pregnancy that leads to weight loss and dehydration. It generally refers to the severe end of the spectrum regarding nausea and vomiting in pregnancy. It occurs in approximately two percent of all pregnancies and is unfortunately very challenging to treat.
Blood Testing for Hyperemesis Gravidarum
Our clinic can complete testing for common nutritional deficiencies that can worsen or aggravate the nausea and vomiting in HG. We can also provide a panel of testing to check for complications of HG. This allows complications to be diagnosed and addressed early.
Imbalances that may affecting nausea and vomiting include:
Electrolyte deficiencies
Kidney issues
Metabolic changes
Mineral deficiencies
Hormonal changes
Naturopathic Approach
Our clinic can help provide recommendations for:
Dietary therapies
Lifestyle changes
Supplementation
Herbal therapies and teas
Diagnostic testing and screening
Tips for Reducing Nausea and Vomiting
Eat before, or as soon as, you feel hungry to avoid an empty stomach, which can aggravate nausea
Snack before getting out of bed in the morning
Snack during the night before bathroom trips (eg. crackers with peanut butter or cheese)
Food journal - find best tolerated foods and consume those
Switching to a different toothpaste may help those for whom strongly flavored toothpaste is a trigger.
Fluids
Consume at least 30 minutes before or after solid food to lower sensation of stomach fullness
Consume in small amounts constantly
Use a straw or very small cup to slow down
Electrolyte-replacement sports drinks (if tolerated)
When To Go to Emergency Room
Symptoms of dehydration (extreme fatigue, postural dizziness, thirst, tachycardia)
Going 24 hours without having to urinate (pee)
Unable to keep food/fluids down for >12 hours
Environmental Triggers
Stuffy rooms
Odors (eg, perfume, chemicals, food, smoke)
Heat
Humidity
Noise
Visual or physical motion (eg, flickering lights, driving)
Quickly changing position
Lack of sleep
Extended food preparation time when making own meal
Lying down soon after eating and lying on the left side (slow emptying of stomach)
Food-Related Triggers | Food-Related Relievers |
Foods and food-habits that may worsen nausea:
| Foods and food-habits that may improve nausea:
|
When To Eat
When possible, it is often a good idea to wait 30 minutes until vomiting stops, then start by drinking clear liquids first (broth, juice, etc), then move to soups and cooked foods.
Ginger
Ginger may or may not work depending on the severity of HG. However, it is recommended by the American College of Obstetrics and Gynecology. It has been studied for nausea and vomiting for many decades and may provide additional benefits in the context of HG. H. pylori infections and slowed emptying of the stomach are both more common in HG, and studies suggest that ginger tends to help with both of these.
Intravenous Hydration and Nutrition
We may recommend regular intravenous (IV) water and nutrients if symptoms are severe and blood work shows many deficiencies. IVs can help prevent dehydration and malnutrition, both of which can worsen nausea and vomiting.
Risk factors for Hyperemesis Gravidarum
A 2011 study found the following risk factors for developing hyperemesis gravidarum:[1]
Total fat intake
Female pregnancy
Low protein intake
High saturated fat intake
Low vitamin intake
Family history
History of motion sickness
High beta-hcg hormone
H pylori infection
History of intolerance of oral contraceptives
Overactive immunity
High leptin levels
Depression
Outlook and Prognosis of Hyperemesis Gravidarum
Symptoms will often begin to improve 16 weeks into the pregnancy, but may last longer for a small portion of individuals.
Criteria for Hyperemesis Gravidarum
Some experts suggest hyperemesis gravidarum occurs when:
3-5% of body weight has been lost
3 or more vomiting episodes per day
What Causes Hyperemesis Gravidarum
There are many changes to the body that happen during pregnancy that can lead to increased nausea and vomiting. For example, progesterone can decrease smooth muscle contractility and thereby affect the emptying of the stomach. Slowed emptying of the stomach tends to make the stomach feel overfilled or backed up.
H. Pylori Screening
It is recommended to complete H. Pylori screening in patients who:
Have symptoms beyond the first trimester despite treatment
Who require multiple hospitalizations
Who have symptoms of acid reflux
This is because case reports have reported improvement in symptoms in patients with severe disease after treatment of H. pylori.
Medications
While medications are often limited in pregnancy, they may sometimes be used to prevent harm to the baby and mother in those with severe symptoms, such as excessive weight loss. Below are some of the common medications used and their associated risks.
Medication | Brand Name | Line | Strength | Adverse Effects | Malform-ation Risk |
Vitamin B6 | Eg. Natural Factors | First Line option | Mild | No major risks | None |
Doxylamine-Pyridoxine | Diclectin | Second line | Mild | Drowsiness | 5%↓ (decrease) |
Alternative antihist-amine (eg. Diphen-hydramine Dimen-hydrinate) | Eg. Gravol | Third line | Moderate | Drowsiness | 5-7%↑ NS |
Meto-clopramide | Reglan | Fourth line | Faster acting and stronger than diclectin and antihistamines | Tremors (rarely, may be irreversible) | 14%↑ NS 1 in 38 risk of birth defect with 1st trimester exposure (2021 study) |
Ondansetron | Zofran | Fifth line | Generally the strongest option | Fatigue, constipation, heart attack (mostly with IVs) | Cardiac defects in 1 in 256 births with first trimester use |
H2 Blockers (eg. ranitidine) | Zantac | First line for GERD | Eg. H2 Blockers; if GERD present | Rash, stomach pain | No increase found in study of 553 patients |
Proton Pump Inhibitor (eg. panto-prazole) | Protonix | Second line for GERD | If GERD present | Rare: headache, stomach pain, vitamin B12 deficiency | Less safety info available |
Acronyms: NS (Non-statistical significance: meaning technically there were more malformations in the treatment group; but the increase was not statistically significant due to small study size)
Research on Diclectin (Doxylamine-Pyridoxine)
As of August 2024, the world’s largest database (National Library of Medicine) has 6 studies evaluating the effectiveness of doxylamine for pregnancy as of 2024. Excluding 40+ year old studies, research on this medication has been done on 798 patients.
These studies all used the PUQE-symptoms score, a 15 point scale. For perspective, a 1 point decrease equates to about one less hour of nausea per day, or a reduction of two episodes of vomiting or two episodes of retching per day. Many of the studies enrolled those with severe symptoms, which means nausea around 5 hours/day, vomiting 5 times, and retching 5 times per day.
It’s important to use only placebo-controlled studies, because research has found nausea and vomiting symptoms decrease by nearly half in about 2 weeks with placebo alone.[12] The four highest quality placebo-controlled studies found a 7%, 4%, 9%, and 6% improvement in symptoms compared to placebo. That comes to an average of 6.5% improvement, or nearly a 1 point decrease on a 15-point scale.
To put this in perspective, a 2023 study on 128 patients found that adding watermelon to the diet led to a 1.5 point greater improvement in PUQE scores at week 1 and week 2 compared to placebo. Appetite and wellbeing improved in the watermelon group as well.[13] Body weight increased in the watermelon group, and decreased in the placebo group.
Studies on doxylamine + pyridoxine:
A 2023 study on 352 women found PUQE symptom scores decreased by (compared to placebo):[14]
0.7 points with acupuncture
1.0 point with doxylamine-pyridoxine
1.6 points with acupuncture plus doxylamine-pyridoxine
The patients in study had severe N&V (score of around 14). This means a 1 point decrease is equivalent to about a 7% improvement in symptoms.
A 2018 study on 256 women found (compared to placebo):[15]
0.38 to 0.73 point decline in PUQE (depending on statistical method used); approximately a 4% - 8% improvement in symptoms
A trend towards increased time lost from household tasks and employment
The study concluded there is a trend towards efficacy for nausea and vomiting symptoms with doxylamine-pyridoxine compared with placebo but the statistical significance disappears when using only patients with complete data available in the study and that the magnitude of the difference suggests that there is no clinically important benefit (the prespecified definition for determining benefit was a difference of 3 points).
A 2017 study reported information about an unpublished 1970s study on 2308 patients and found that when ignoring missing data and data integrity issues there was a:[16]
A 78% improvement with doxylamine + pyridoxine compared to a 57% improvement with placebo (21% absolute difference)
This study concluded: “The available information about this “8-way Bendectin” trial indicates it should not be used to support the efficacy of doxylamine, pyridoxine or dicyclomine for the treatment of nausea and vomiting during pregnancy because of a high risk of bias.”
A 2016 study on 256 patients found PUQE symptom scores decreased by (compared to placebo):[17]
0.9 points by day 15 (a 9% greater improvement). Around a 1 point improvement was seen on day 3, 4, and 5 as well.
A 2015 study on 160 patients found a 0.5 point decline (6% greater improvement) in PUQE scores compared to placebo.[18] In those with more severe symptoms, a 2.2 point decline was seen compared to B6 alone.
A 2014 study on 30 patients found that there more than double the patients using ondansetron that had a clinically meaningful improvement compared to the doxylamine-pyridoxine group.[19] There was no placebo group in the trial, however the percentage change in symptoms using doxylamine-pyridoxine were less than the placebo group at day 5 from the 2016 study above.
Conclusion
HG is a debilitating condition affecting a significant portion of pregnant individuals, causing severe nausea and vomiting that can lead to dehydration and malnutrition. While the exact causes are complex and multifactorial, our understanding of the contributing factors has advanced, allowing for a more comprehensive approach to managing HG.
We recognize the importance of addressing underlying imbalances, including electrolyte deficiencies, nutrient deficiencies, and hormonal changes. This necessitates thorough diagnostic testing to identify and address potential complications. Our clinic offers a comprehensive approach, integrating personalized plans that include dietary therapies, lifestyle changes, supplementation, and herbal remedies tailored to individual needs.
While non-pharmacological strategies are often helpful, we also recognize the need for medications in severe cases. It is important to consider the benefits and risks of various medications.
Ultimately, navigating HG requires a multi-faceted approach, encompassing early detection, individualized treatment plans, and ongoing support for both the pregnant individual and their family. We encourage open communication with healthcare professionals to optimize management strategies and achieve positive outcomes for both mother and child.
References
[1] Lee NM, Saha S. Nausea and vomiting of pregnancy. Gastroenterol Clin North Am. 2011 Jun;40(2):309-34, vii. doi: 10.1016/j.gtc.2011.03.009. PMID: 21601782; PMCID: PMC3676933.
[2] Keating A, Chez RA. Ginger syrup as an antiemetic in early pregnancy. Altern Ther Health Med. 2002 Sep-Oct;8(5):89-91. PMID: 12233808.
[3] Haji Seid Javadi E, Salehi F, Mashrabi O. Comparing the effectiveness of vitamin b6 and ginger in treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol Int. 2013;2013:927834. doi: 10.1155/2013/927834. Epub 2013 Oct 22. PMID: 24250336; PMCID: PMC3819920.
[4] Koren G, Clark S, Hankins GD, Caritis SN, Umans JG, Miodovnik M, Mattison DR, Matok I. Demonstration of early efficacy results of the delayed-release combination of doxylamine-pyridoxine for the treatment of nausea and vomiting of pregnancy. BMC Pregnancy Childbirth. 2016 Nov 24;16(1):371. doi: 10.1186/s12884-016-1172-9. PMID: 27881103; PMCID: PMC5122025.
[5] Carlsson CP, Axemo P, Bodin A, Carstensen H, Ehrenroth B, Madegård-Lind I, Navander C. Manual acupuncture reduces hyperemesis gravidarum: a placebo-controlled, randomized, single-blind, crossover study. J Pain Symptom Manage. 2000 Oct;20(4):273-9. doi: 10.1016/s0885-3924(00)00185-8. PMID: 11027909.
[6] Gill SK, Maltepe C, Koren G. The effectiveness of discontinuing iron-containing prenatal multivitamins on reducing the severity of nausea and vomiting of pregnancy. J Obstet Gynaecol. 2009 Jan;29(1):13-6. doi: 10.1080/01443610802628528. PMID: 19280488.
[8] Sharifzadeh F, Kashanian M, Koohpayehzadeh J, Rezaian F, Sheikhansari N, Eshraghi N. A comparison between the effects of ginger, pyridoxine (vitamin B6) and placebo for the treatment of the first trimester nausea and vomiting of pregnancy (NVP). J Matern Fetal Neonatal Med. 2018 Oct;31(19):2509-2514. doi: 10.1080/14767058.2017.1344965. Epub 2017 Jul 7. PMID: 28629250.
[9] Royal College of Obstetricians and Gynaecologists. https://www.rcog.org.uk/media/y3fen1x1/gtg69-hyperemesis.pdf
[10] Tan PC, Ramasandran G, Sethi N, Razali N, Hamdan M, Kamarudin M. Watermelon and dietary advice compared to dietary advice alone following hospitalization for hyperemesis gravidarum: a randomized controlled trial. BMC Pregnancy Childbirth. 2023 Jun 17;23(1):450. doi: 10.1186/s12884-023-05771-7. PMID: 37330467; PMCID: PMC10276427.
[11] Mohammadbeigi R, Shahgeibi S, Soufizadeh N, Rezaiie M, Farhadifar F. Comparing the effects of ginger and metoclopramide on the treatment of pregnancy nausea. Pak J Biol Sci. 2011 Aug 15;14(16):817-20. doi: 10.3923/pjbs.2011.817.820. PMID: 22545357.
[12] Koren G, Clark S, Hankins GD, Caritis SN, Umans JG, Miodovnik M, Mattison DR, Matok I. Demonstration of early efficacy results of the delayed-release combination of doxylamine-pyridoxine for the treatment of nausea and vomiting of pregnancy. BMC Pregnancy Childbirth. 2016 Nov 24;16(1):371. doi: 10.1186/s12884-016-1172-9. PMID: 27881103; PMCID: PMC5122025.
[13] Tan PC, Ramasandran G, Sethi N, Razali N, Hamdan M, Kamarudin M. Watermelon and dietary advice compared to dietary advice alone following hospitalization for hyperemesis gravidarum: a randomized controlled trial. BMC Pregnancy Childbirth. 2023 Jun 17;23(1):450. doi: 10.1186/s12884-023-05771-7. PMID: 37330467; PMCID: PMC10276427.
[14] Wu XK, Gao JS, Ma HL, Wang Y, Zhang B, Liu ZL, Li J, Cong J, Qin HC, Yang XM, Wu Q, Chen XY, Lu ZL, Feng YH, Qi X, Wang YX, Yu L, Cui YM, An CM, Zhou LL, Hu YH, Li L, Cao YJ, Yan Y, Liu L, Liu YX, Liu ZS, Painter RC, Ng EHY, Liu JP, Mol BWJ, Wang CC. Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial. Ann Intern Med. 2023 Jul;176(7):922-933. doi: 10.7326/M22-2974. Epub 2023 Jun 20. PMID: 37335994.
[15] Persaud N, Meaney C, El-Emam K, Moineddin R, Thorpe K. Doxylamine-pyridoxine for nausea and vomiting of pregnancy randomized placebo controlled trial: Prespecified analyses and reanalysis. PLoS One. 2018 Jan 17;13(1):e0189978. doi: 10.1371/journal.pone.0189978. PMID: 29342163; PMCID: PMC5771578.
[16] Zhang R, Persaud N. 8-Way Randomized Controlled Trial of Doxylamine, Pyridoxine and Dicyclomine for Nausea and Vomiting during Pregnancy: Restoration of Unpublished Information. PLoS One. 2017 Jan 4;12(1):e0167609. doi: 10.1371/journal.pone.0167609. PMID: 28052111; PMCID: PMC5215753.
[17] Koren G, Clark S, Hankins GD, Caritis SN, Umans JG, Miodovnik M, Mattison DR, Matok I. Demonstration of early efficacy results of the delayed-release combination of doxylamine-pyridoxine for the treatment of nausea and vomiting of pregnancy. BMC Pregnancy Childbirth. 2016 Nov 24;16(1):371. doi: 10.1186/s12884-016-1172-9. PMID: 27881103; PMCID: PMC5122025.
[18] Pope E, Maltepe C, Koren G. Comparing pyridoxine and doxylamine succinate-pyridoxine HCl for nausea and vomiting of pregnancy: A matched, controlled cohort study. J Clin Pharmacol. 2015 Jul;55(7):809-14. doi: 10.1002/jcph.480. Epub 2015 Mar 27. PMID: 25663469.
[19] Oliveira LG, Capp SM, You WB, Riffenburgh RH, Carstairs SD. Ondansetron compared with doxylamine and pyridoxine for treatment of nausea in pregnancy: a randomized controlled trial. Obstet Gynecol. 2014 Oct;124(4):735-742. doi: 10.1097/AOG.0000000000000479. PMID: 25198265.
[20] Wu XK, Gao JS, Ma HL, Wang Y, Zhang B, Liu ZL, Li J, Cong J, Qin HC, Yang XM, Wu Q, Chen XY, Lu ZL, Feng YH, Qi X, Wang YX, Yu L, Cui YM, An CM, Zhou LL, Hu YH, Li L, Cao YJ, Yan Y, Liu L, Liu YX, Liu ZS, Painter RC, Ng EHY, Liu JP, Mol BWJ, Wang CC. Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial. Ann Intern Med. 2023 Jul;176(7):922-933. doi: 10.7326/M22-2974. Epub 2023 Jun 20. PMID: 37335994.