What is hyperemesis gravidarum

Hyperemesis gravidarum is severe nausea and vomiting that occurs during pregnancy that may cause severe dehydration (not have enough water in your body) or result in the loss of more than 5 percent of your pre-pregnancy body weight. Hyperemesis gravidarum is much worse than morning sickness. If you’re being sick all the time and can’t keep food down, tell your midwife or doctor as soon as possible. Because hyperemesis gravidarum can cause dehydration, there’s also an increased risk of having deep vein thrombosis (a blood clot). Hyperemesis gravidarum may require hospitalization and treatment with intravenous (IV) fluids, medications and rarely a feeding tube. The International Statistical Classification of Disease and Related Health Problems, Tenth Revision, defines hyperemesis gravidarum (HG) as persistent and excessive vomiting starting before the end of the 22nd week of gestation and further subdivides the condition into mild and severe, with severe being associated with metabolic disturbances such as carbohydrate depletion, dehydration, or electrolyte imbalance ¹.

Less than 1-3 in 100 pregnant women experience hyperemesis gravidarum (depending on the literature source). Geographically, hyperemesis appears to be more common in western counties ². Pregnant women can become very ill, lose weight and become dehydrated, and may need to be admitted to hospital to receive fluid via a drip (known as intravenous fluid) and medication.

Bear in mind that hyperemesis gravidarum is much worse than regular pregnancy sickness. It is not the result of anything you have or haven’t done, and you do need treatment and support.

The best treatment at home for women suffering from hyperemesis gravidarum is to get plenty of rest and drink lots of fluid.

Hyperemesis gravidarum can start early in pregnancy and last throughout pregnancy. The average onset of hyperemesis gravidarum symptoms happens approximately 5 to 6 weeks into gestation ³. If you have hyperemesis gravidarum, you need treatment to help keep you and your baby safe. Hyperemesis gravidarum usually subsides by week 12-14 of pregnancy, although for some women it can last longer. Unlike regular pregnancy morning sickness, hyperemesis gravidarum may not get better by 14 weeks. Hyperemesis gravidarum may not clear up completely until the baby is born, although some symptoms may improve at around 20 weeks. However, with early diagnosis and treatment of hyperemesis gravidarum, there is no reason why you shouldn’t expect a healthy pregnancy.

See your doctor or midwife if you have severe nausea and vomiting, ideally before you start suffering from dehydration and weight loss. There are other conditions that can cause nausea and vomiting, and your doctor will need to rule these out first.

Mild cases of hyperemesis gravidarum may be controlled with a change in diet, rest and antacids. Severe cases may need specialist treatment, and you may need to be admitted to hospital so that doctors can assess your condition and give you the right treatment to protect the health of you and your baby. Your doctor may treat you with anti-sickness drugs via a vein or a muscle to help relieve your nausea and vomiting. You may need treatment in a hospital with intravenous (also called IV) fluids to treat the ketosis and treatment to stop the vomiting. IV fluids go through a needle into your vein. They help you stay hydrated and can give you nutrients that you usually get from food. If you continue to lose weight, you may need a feeding tube to make sure you’re getting enough nutrients for you and your baby.

There are medications that can be used in pregnancy, including the first 12 weeks, to help improve the symptoms of hyperemesis gravidarum. These include anti-sickness (anti-emetic) drugs, vitamins (B6 and B12) and steroids, or combinations of these. Daily intake of a multivitamin with folic acid at least one month prior to conception not only reduces the risk of congenital anomalies such as neural tube defects but has also been associated with reduced frequency and severity of nausea and vomiting in pregnancy ⁴.

Evidence suggests that the earlier you start treatment, the more effective it will be. You may need to try different types of medication until you find what works best for you. But don’t take medication for hyperemesis gravidarum without talking to your doctor first.

Will hyperemesis gravidarum harm my baby?

Hyperemesis gravidarum is unpleasant with dramatic symptoms, but the good news is it’s unlikely to harm your baby, if treated effectively.

However, if hyperemesis gravidarum causes you to lose weight during pregnancy, there is an increased risk that your baby may be born smaller than expected (have a low birth weight), preterm birth, and small-for-gestational age infants ⁵. A recent systematic review identified no association with Apgar scores, congenital anomalies, or perinatal death ⁵.

Hyperemesis gravidarum vs Morning sickness

Morning sickness is nausea and vomiting that occurs during pregnancy, especially during the first 3 months of pregnancy. And, despite its name, morning sickness can strike at any time of the day or night. The cause of morning sickness is not fully known but it may be related to pregnancy hormones. Morning sickness is normal, and there is no risk to a baby unless it is very severe.

Many pregnant women have morning sickness, especially during the first trimester. But some women have morning sickness throughout pregnancy. Management options include various home remedies, such as snacking throughout the day and sipping ginger ale or taking over-the-counter medications to help relieve nausea.

Rarely, morning sickness is so severe that it progresses to hyperemesis gravidarum. This is when someone with nausea and vomiting of pregnancy has severe symptoms that may cause severe dehydration or result in the loss of more than 5 percent of pre-pregnancy body weight. Hyperemesis gravidarum may require hospitalization and treatment with intravenous (IV) fluids, medications and rarely a feeding tube.

It is also important both you and your partner understand that during pregnancy you may not enjoy certain stimuli (visual, tastes, smells, touch and sexual experiences) that you used to. These changes may place a strain on your relationship.

Some key points to note about morning sickness:

• Up to 80% of pregnant women have some symptoms.
• Some may feel sick without vomiting.
• Even though it is called ‘morning’ sickness, you may feel sick and vomit at any time of the day or night.
• The severity of the morning sickness, and how long into the pregnancy it lasts, varies a great deal from one woman to another. It also can vary from one pregnancy to the next — you could have one pregnancy affected by morning sickness but feel fine the next time.
• It usually improves greatly by the end of the first 3 months, if not sooner, but for some women it lasts longer and sometimes until their baby is born.
• For some women it can be severe, causing them to lose weight and become dehydrated.

Managing morning sickness

In most cases no medical treatment is needed, but there are some things you can try that may make a difference.

Food: varying what and when you eat might help you to feel better. For example:

• Try eating cracker biscuits and sipping a cup of weak tea or a glass of water before you get out of bed in the morning. Many women find that it helps to keep a supply of cracker biscuits and a glass of water by their bed.
• Try eating smaller meals more often (rather than 3 large meals a day), and avoid fatty foods and coffee.
• Eat when you feel like eating rather than waiting for meal times.
• Try not to skip meals or go for long periods of time without eating.
• If possible, ask someone else to prepare meals.
• Have a range of foods on hand (for example, salty, sweet, crunchy) since your taste may change during the day.

Drinks: keeping up your fluid intake is important.

• Remember to drink plenty of water — 6 to 8 glasses a day is ideal. Sucking crushed ice may also be helpful. Small drinks often may be better than large drinks.
• If you can’t always manage to drink water, you may find dry ginger ale or flat lemonade better. Ginger tea may also be helpful.
• If you are vomiting a lot, you will need to take extra care to make sure you are drinking enough water.
• You may like to talk with your pharmacist about drinking an oral rehydration solution. These solutions replace the important electrolytes, as well as fluid, that your body loses when you are vomiting a lot.

These other options may also help to relieve nausea:

• acupressure wristbands worn to prevent travel sickness (available from pharmacies)
• chewing ginger pieces or mints
• taking ginger tablets or vitamin B6 (talk to a pharmacist about how much to take)

If your morning sickness is worrying you, talk to your doctor or midwife. There are prescription medicines that can be used to control severe morning sickness. These drugs have not been known to cause birth defects or have other harmful effects for unborn babies.

Hyperemesis gravidarum causes

It’s not known what causes hyperemesis gravidarum, or why some women get it and others don’t. Some experts believe it is linked to the changing hormones in your body that occur during pregnancy.

There is some evidence ⁶ that hyperemesis gravidarum runs in families, so if you have a mother or sister who has had hyperemesis gravidarum in a pregnancy, you may be more likely to get it yourself.

If you have had hyperemesis gravidarum in a previous pregnancy, you are more likely to get it in your next pregnancy than women who have never had it before, so it’s worth planning in advance.

There are several theories for what may contribute to the development of hyperemesis gravidarum process.

Hormone Changes

• Levels of human chorionic gonadotropin (hCG) have been implicated. hCG (human chorionic gonadotropin) levels peak during the first trimester, corresponding to the typical onset of hyperemesis symptoms. Some studies show a correlation between higher hCG concentrations and hyperemesis ⁷. However, this data has not been consistent ⁸.
• Estrogen is also thought to contribute to nausea and vomiting in pregnancy. Estradiol levels increase early in pregnancy and decrease later, mirroring the typical course of nausea and vomiting in pregnancy. Additionally, nausea and vomiting are the known side effects of estrogen-containing medications. As the level of estrogen increases, so does the incidence of vomiting ⁹.

Changes in the Gastrointestinal System

It is well-known that the lower esophageal sphincter relaxes during pregnancy due to the elevations in estrogen and progesterone. This leads to an increased incidence of gastroesophageal reflux disease (GERD) symptoms in pregnancy, and one symptom of GERD is nausea ¹⁰. Studies examining the relationship between GERD (gastroesophageal reflux disease) and vomiting in pregnancy report conflicting results.

Genetics

• An increased risk of hyperemesis gravidarum has been demonstrated among women with family members who also experienced hyperemesis gravidarum ⁶.
• Two genes, GDF15 and IGFBP7, have been potentially linked to the development of hyperemesis gravidarum ¹¹.

Hyperemesis gravidarum risk factors

You may be at risk for hyperemesis gravidarum if you:

• Are pregnant for the first time
• Are pregnant with a girl
• Are pregnant with multiples (twins, triplets or more). Being pregnant with more than one baby may increase your risk for severe morning because you may have a large placenta and increased pregnancy hormones, like estrogen or human chorionic gonadotropin (also called HCG). The placenta grows in your uterus (womb) and supplies your babies with food and oxygen through the umbilical cord.
• Had mild or severe morning sickness in a previous pregnancy, or your mother or sister had severe morning sickness during pregnancy. Take your family health history to help you find out about health conditions that run in your family. This is a record of any health conditions and treatments that you, your partner and everyone in both of your families have had.
• Have motion sickness or migraines. A migraine is a severe headache that may make you sensitive to bright lights and sound.
• Are overweight
• Have trophoblastic disease, a condition that leads to abnormal cell growth in the uterus (womb)

Women who experience nausea and vomiting outside of pregnancy due to the consumption of estrogen-containing medications, exposure to motion, or have a history of migraines are at higher risk of experiencing nausea and vomiting during pregnancy ⁴.

Another pregnancy

If you have had hyperemesis gravidarum before, it’s likely you will get it again in another pregnancy.

If you decide on another pregnancy, it can help to plan ahead, such as arranging child care so you can get plenty of rest.

Think back to what helped you last time – for example, specific drinks – and make sure you implement these measures this time around.

Talk to your doctor about starting medication early.

Hyperemesis gravidarum signs and symptoms

Hyperemesis gravidarum in pregnancy is much worse than the nausea and vomiting of morning sickness. Symptoms usually start between 5 and 10 weeks of pregnancy and resolve by 20 weeks.

Signs and symptoms of hyperemesis gravidarum include:

• Prolonged and severe nausea and vomiting more than three to four times a day – some women report being sick up to 50 times a day
• Vomiting that makes you dizzy, lightheaded
• Vomiting that makes you dehydrated. Signs and symptoms of dehydration include feeling thirsty, having a dry mouth, having a fast heart beat or making little to no urine. If you’re drinking less than 500ml a day, you need to seek help.
• Weight loss – losing more than 10 pounds in pregnancy
• Ketosis — a serious condition that is caused by a raised number of ketones in the blood and urine (ketones are acidic chemicals that are produced when your body breaks down fat, rather than glucose, for energy)
• Low blood pressure (hypotension) when standing up
• Headaches, confusion, fainting and jaundice

The nausea and vomiting are usually so severe that it’s impossible to keep any fluids down, and this can cause dehydration and weight loss. Dehydration is when you don’t have enough fluids in your body.

Other symptoms you may experience:

• extremely heightened sense of smell
• excessive saliva production (ptyalism)
• headaches and constipation from dehydration
• pressure sores from long periods of time in bed
• episodes of urinary incontinence as a result of vomiting combined with the pregnancy hormone relaxin

If you experience these symptoms, you are not alone. Many women have them and although they can be distressing, they will go away when the hyperemesis gravidarum stops or the baby is born.

Hyperemesis gravidarum is very unpleasant with dramatic symptoms, but the good news is it’s unlikely to harm your baby. However, if it causes you to lose weight during pregnancy there is an increased risk that your baby may be born smaller than expected.

How you might feel

The nausea and vomiting of hyperemesis gravidarum can have a huge impact on your life at a time when you were expecting to be enjoying pregnancy and looking forward to the birth of your baby.

It can affect you both emotionally and physically. The symptoms not only make your life a misery, but may lead to further health complications, such as depression or tears in your esophagus.

Severe sickness can be exhausting and stop you doing everyday tasks, such as going to work or even getting out of bed.

In addition to feeling very unwell and tired, you might also feel:

• anxious about going out or being too far from home in case you need to vomit
• isolated because you don’t know anyone who understands what it’s like to have hyperemesis gravidarum
• confused as to why this is happening to you
• unsure whether you can cope with the rest of the pregnancy if you continue to feel very ill

If you feel any of these, don’t keep it to yourself. Talk to your midwife or doctor, and explain the impact hyperemesis gravidarum is having on your life and how it is making you feel. You could also talk to your partner, family and friends if you want to.

Hyperemesis gravidarum complications

As hyperemesis gravidarum involves 2 patients, both must be considered when discussing complications.

Maternal Complications

In severe cases of hyperemesis, complications include vitamin deficiency, dehydration, and malnutrition, if not treated appropriately. Wernicke’s encephalopathy, caused by vitamin-B1 deficiency, can lead to death and permanent disability if it goes untreated ¹². Additionally, there have been case reports of injuries secondary to forceful and frequent vomiting, including esophageal rupture and pneumothorax ¹³. Electrolyte abnormalities such as hypokalemia can also cause significant morbidity and mortality ¹⁴. Additionally, patients with hyperemesis may have higher rates of depression and anxiety during pregnancy ¹⁵.

Fetal Complications

Studies report conflicting information regarding the incidence of low birthweight and premature infants in the setting of nausea and vomiting in pregnancy ¹⁶. However, studies have not shown an association between hyperemesis and perinatal or neonatal morality ¹⁶. The frequency of congenital anomalies does not appear to increase in patients with hyperemesis ¹⁷.

Hyperemesis gravidarum diagnosis

There is no single accepted definition for hyperemesis gravidarum ⁴. However, hyperemesis gravidarum generally refers to the extreme cases of nausea and vomiting during pregnancy. Hyperemesis Gravidarum is a clinical diagnosis. The criteria for diagnosis include vomiting that causes significant dehydration (as evidenced by ketonuria or electrolyte abnormalities) and weight loss (the most commonly cited marker for this is the loss of at least five percent of the patient’s pre-pregnancy weight) in the setting of pregnancy without any other underlying pathological cause for vomiting. Significant abdominal tenderness, pelvic tenderness, or vaginal bleeding should prompt workup for alternative diagnoses.

The evaluation should include urinalysis to check for ketonuria and specific gravity, in addition to a complete blood count and electrolyte evaluation. An elevation in hemoglobin or hematocrit may be due to hemoconcentration in the setting of dehydration. Significant dehydration may result in acute kidney injury as evidenced by an elevation in serum creatinine, blood urea nitrogen, and a reduced glomerular filtration. Potassium, calcium, magnesium, sodium, and bicarbonate may be affected by prolonged bouts of vomiting and reduced oral intake of fluids. Thyroid tests, lipase, and liver function testing may also be completed to evaluate for alternate diagnoses.

Radiographic studies may be appropriate to rule out alternate diagnoses. Obstetrical ultrasounds may be considered to rule out multiple gestations, ectopic pregnancy, and gestational trophoblastic disease depending on the patient’s history and prior obstetrical evaluations. Magnetic resonance imaging (MRI) may be used to assess alternative diagnoses, such as appendicitis.

Hyperemesis gravidarum treatment

Treatment should be guided by the American College of Obstetrics and Gynecology (ACOG) Nausea and Vomiting in Pregnancy guidelines. Initial treatment should begin with non-pharmacologic interventions such as switching the patient’s prenatal vitamins to folic acid supplementation only, using ginger supplementation (250 mg orally 4 times daily) as needed, and by applying acupressure wristbands ¹⁸.

Hyperemesis gravidarum medication

If you continues to experience significant symptoms, the first-line pharmacologic therapy should include a combination of vitamin B6 (pyridoxine) and doxylamine ⁴. Three dosing regiments are endorsed by the American College of Obstetrics and Gynecology, including pyridoxine 10 to 25 mg orally with 12.5 mg of doxylamine 3 or 4 times per day, 10 mg of pyridoxine and 10 mg of doxylamine up to 4 times per day, or 20 mg of pyridoxine and 20 mg of doxylamine up to 2 times per day ⁴. As demonstrated in multi-center randomized controlled trials, these first-line medications demonstrate efficacy in the treatment of nausea and vomiting, preserved good fetal and maternal safety profiles and are listed as one of the few FDA pregnancy category A medications ¹⁹.

Second-line medications include antihistamines and dopamine antagonists such as dimenhydrinate 25 to 50 mg every 4 to 6 hours orally, diphenhydramine 25 to 50 mg every 4 to 6 hours orally, prochlorperazine 25 mg every 12 hours rectally, or promethazine 12.5 to 25 mg every 4 to 6 hours orally or rectally. If the patient continues to experience significant symptoms without exhibiting signs of dehydration, metoclopramide, ondansetron, or promethazine may be given orally. In the case of dehydration, intravenous fluid boluses or continuous infusions of normal saline should be given in addition to intravenous metoclopramide, ondansetron, or promethazine. Electrolytes should be replaced as needed. Severe refractory cases of hyperemesis gravidarum may respond to intravenous or intramuscular chlorpromazine 25 to 50 mg or methylprednisolone 16 mg every 8 hours, orally or intravenously ²⁰.

Hyperemesis gravidarum treatment at home

To help manage symptoms at home, try these tips.

Avoid triggers. You may notice that certain things can trigger nausea and vomiting. These may include:

• Certain noises and sounds, even the radio or TV
• Bright or blinking lights
• Toothpaste
• Smells such as perfume and scented bathing and grooming products
• Pressure on your stomach (wear loose-fitting clothes)
• Riding in a car
• Taking showers

Eat and drink when you are able. Take advantage of the times you feel better to eat and drink. Eat small, frequent meals. Try dry, bland foods such as crackers or potatoes. Try eating any foods that appeal to you. See if you can tolerate nutritious smoothies with fruits or vegetables.

Increase fluids during times of the day when you feel least nauseated. Seltzer, ginger ale, or other sparkling drinks may help. You can also try using low-dose ginger supplements or acupressure wrist bands to ease symptoms.

Vitamin B6 (no more than 100 mg daily) has been shown to decrease nausea in early pregnancy. Ask your provider if this vitamin might help you. Another medicine called doxylamine (Unisom) has been shown to be very effective and safe when combined with Vitamin B6 for nausea in pregnancy. You can buy this medicine without a prescription.

Hyperemesis gravidarum prognosis

Nausea and vomiting in pregnancy is common. Symptoms usually begin prior to 9 weeks gestation and the majority of cases are resolved by week 20 of gestation. A minority of patients, approximately 3%, will continue to experience vomiting during the third trimester. Approximately 10% of patients with hyperemesis gravidarum will be affected throughout the pregnancy ²¹.

1. World Health Organization . International Statistical Classification of Diseases and Related Health Problems. 10th Rev. World Health Organization; 2007. http://apps.who.int/classifications/apps/icd/icd10online2007/[↩]
2. Lacasse A, Rey E, Ferreira E, Morin C, Bérard A. Epidemiology of nausea and vomiting of pregnancy: prevalence, severity, determinants, and the importance of race/ethnicity. BMC Pregnancy Childbirth. 2009 Jul 02;9:26.[↩]
3. Gadsby R, Barnie-Adshead AM, Jagger C. A prospective study of nausea and vomiting during pregnancy. Br J Gen Pract. 1993 Jun;43(371):245-8.[↩]
4. Jennings LK, Krywko DM. Pregnancy, Hyperemesis Gravidarum. [Updated 2018 Oct 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532917[↩][↩][↩][↩][↩]
5. Consequences of hyperemesis gravidarum for offspring: a systematic review and meta-analysis. Veenendaal MV, van Abeelen AF, Painter RC, van der Post JA, Roseboom TJ. BJOG. 2011 Oct; 118(11):1302-13. https://www.ncbi.nlm.nih.gov/pubmed/21749625/[↩][↩]
6. Fejzo MS, Ingles SA, Wilson M, Wang W, MacGibbon K, Romero R, Goodwin TM. High prevalence of severe nausea and vomiting of pregnancy and hyperemesis gravidarum among relatives of affected individuals. Eur. J. Obstet. Gynecol. Reprod. Biol. 2008 Nov;141(1):13-7.[↩][↩]
7. Kimura M, Amino N, Tamaki H, Ito E, Mitsuda N, Miyai K, Tanizawa O. Gestational thyrotoxicosis and hyperemesis gravidarum: possible role of hCG with higher stimulating activity. Clin. Endocrinol. (Oxf). 1993 Apr;38(4):345-50.[↩]
8. Soules MR, Hughes CL, Garcia JA, Livengood CH, Prystowsky MR, Alexander E. Nausea and vomiting of pregnancy: role of human chorionic gonadotropin and 17-hydroxyprogesterone. Obstet Gynecol. 1980 Jun;55(6):696-700.[↩]
9. Goldzieher JW, Moses LE, Averkin E, Scheel C, Taber BZ. A placebo-controlled double-blind crossover investigation of the side effects attributed to oral contraceptives. Fertil. Steril. 1971 Sep;22(9):609-23.[↩]
10. Brzana RJ, Koch KL. Gastroesophageal reflux disease presenting with intractable nausea. Ann. Intern. Med. 1997 May 01;126(9):704-7.[↩]
11. Fejzo MS, Sazonova OV, Sathirapongsasuti JF, Hallgrímsdóttir IB, Vacic V, MacGibbon KW, Schoenberg FP, Mancuso N, Slamon DJ, Mullin PM., 23andMe Research Team. Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum. Nat Commun. 2018 Mar 21;9(1):1178[↩]
12. Spruill SC, Kuller JA. Hyperemesis gravidarum complicated by Wernicke’s encephalopathy. Obstet Gynecol. 2002 May;99(5 Pt 2):875-7.[↩]
13. Garg R, Sanjay, Das V, Usman K, Rungta S, Prasad R. Spontaneous pneumothorax: an unusual complication of pregnancy–a case report and review of literature. Ann Thorac Med. 2008 Jul;3(3):104-5.[↩]
14. Walch A, Duke M, Auty T, Wong A. Profound Hypokalaemia Resulting in Maternal Cardiac Arrest: A Catastrophic Complication of Hyperemesis Gravidarum? Case Rep Obstet Gynecol. 2018;2018:4687587.[↩]
15. Mitchell-Jones N, Gallos I, Farren J, Tobias A, Bottomley C, Bourne T. Psychological morbidity associated with hyperemesis gravidarum: a systematic review and meta-analysis. BJOG. 2017 Jan;124(1):20-30.[↩]
16. Vandraas KF, Vikanes AV, Vangen S, Magnus P, Støer NC, Grjibovski AM. Hyperemesis gravidarum and birth outcomes-a population-based cohort study of 2.2 million births in the Norwegian Birth Registry. BJOG. 2013 Dec;120(13):1654-60.[↩][↩]
17. Veenendaal MV, van Abeelen AF, Painter RC, van der Post JA, Roseboom TJ. Consequences of hyperemesis gravidarum for offspring: a systematic review and meta-analysis. BJOG. 2011 Oct;118(11):1302-13.[↩]
18. Madjunkova S, Maltepe C, Koren G. The delayed-release combination of doxylamine and pyridoxine (Diclegis®/Diclectin ®) for the treatment of nausea and vomiting of pregnancy. Paediatr Drugs. 2014 Jun;16(3):199-211.[↩]
19. McParlin C, O’Donnell A, Robson SC, Beyer F, Moloney E, Bryant A, Bradley J, Muirhead CR, Nelson-Piercy C, Newbury-Birch D, Norman J, Shaw C, Simpson E, Swallow B, Yates L, Vale L. Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy: A Systematic Review. JAMA. 2016 Oct 04;316(13):1392-1401[↩]
20. Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol. 1998 Sep;41(3):597-605.[↩]
21. Goodwin TM. Hyperemesis gravidarum. Obstet. Gynecol. Clin. North Am. 2008 Sep;35(3):401-17, viii.[↩]