Pregnancy is a wonderful time in a woman’s life-a time filled with hope, joy and the expectation of bringing new life into the world.
Everything good in life, however, comes with a price, and pregnancy is no exception. Pregnant women know to expect the weight gain, stretch marks, urinary frequency, hemorrhoids and varicose veins. Nausea and vomiting is also known to be characteristic of early pregnancy, and is extremely common.
As a matter of fact, any woman of childbearing age who has complaints of nausea and vomiting, will raise suspicion in both the physician and the lay person, of pregnancy. The majority of pregnant women will have mild and tolerable nausea in the first trimester that is not accompanied by vomiting. It is usually self limited and terminates around the twelfth week of pregnancy and non pharmacologic interventions are often sufficient to ameliorate the symptoms and allow the pregnant woman to continue with her work and home life.
A smaller percentage of women have more significant symptoms and are plagued by vomiting along with nausea which interferes with their ability to take care of daily work and home tasks.
This subgroup of women is considered to have hyperemesis gravidarum, which is a problematic malady of persistent and unremitting nausea and vomiting of pregnancy that significantly interferes with function. These women can also become dehydrated and develop electrolye abnormalities due to persistent nausea and vomiting. It is this group of women that requires pharmacologic agents so as to exist.
One study showed that 69% of pregnant women had nausea with or without vomiting in pregnancy, and another 15% required medication. (reference 1- ObGyn Management Feb 2015, vol 27, no 2, page 8. Editorial by Robert Barbieri MD).
As Obstetricians, we try to limit the administration of medication to pregnant women, but in cases of hyperemesis, medication is often required. Everything in life involves a risk/benefit ratio, and medication in pregnancy falls into that category. Using the most efficacious, safest medication for the shortest duration of time is the goal, and this article will serve as a review of the spectrum of nausea and vomiting in pregnancy, along with the pharmacologic and non- pharmacologic therapies available, along with their safety profiles.
WHAT CAUSES THE NAUSEA AND VOMITING OF PREGNANCY, AND WHEN DOES IT USUALLY HAPPEN?
Nausea and vomiting in pregnancy begins between 6 and 8 weeks of gestation (6-8 weeks from the last menstrual period) and usually ceases between 12 and 14 weeks. It is caused by the exponential increase in the HCG hormone that circulates in the blood of pregnant women. HCG secretion begins when the embryo implants into the lining of the uterus. The HCG level doubles approximately every 48 hours in early pregnancy, and it is this rapid increase in HCG levels that is thought to cause nausea and vomiting.
By 10-12 weeks the HCG level tends to stop rising so abruptly and exponentially, and instead tends to plateau. The relief from nausea usually coincides with the plateau in HCG level. This will happen at different times in different women, but in general relief occurs by 12-14 weeks.
There is a wide range of symptomatology with regards to nausea and vomiting in pregnancy, with some women experiencing absolutely no symptoms, while others are plagued with devastating and unremitting nausea and vomiting. The first trimester is when all of the vital organs of the baby are developing and where the fetus is most susceptible to teratogens (medications or exposures that can cause birth defects), but this is also the time frame when the most significant nausea and vomiting occur, so this causes a “catch 22”.
WHAT IS “MORNING SICKNESS?"
The lay terminology for nausea and vomiting in pregnancy is “morning sickness”. It is common for pregnant women to wake up in the morning with nausea, but the majority of women complain not just of sickness in the morning, but more like 'all day sickness'. Once the pregnant woman has something to eat after she arises, the nausea usually subsides, but again, a significant subgroup of women will experience symptoms throughout the day and not just in the morning.
WHAT IS PTYALISM?
Ptyalism is excessive salivation that is a manifestation of hyperemesis of pregnancy. It involves the release of copious amounts of saliva and many women who have this need to carry around a cup to spit into all day due to the excessive release of saliva.
ARE THERE CERTAIN GROUPS OF WOMEN WHO HAVE WORSE MORNING SICKNESS?
Women who have multiple gestations such as twins and triplets have a higher chance of nausea and vomiting and particularly hyperemesis due to the particularly high levels of HCG in their bloodstream. Women who have abnormal molar pregnancies also experience more nausea and vomiting. Pregnant women who had hyperemesis in prior pregnancies are also more predisposed to having this condition in subsequent pregnancies.
ANY NON PRESCRIPTION HOME REMEDIES THAT REALLY WORK FOR NAUSEA AND VOMITING OF PREGNANCY?
A variety of over the counter preparations work well and are safe in pregnancy.
1- Acupressure wrist bands. These elastic bands are sold over the counter in the drug store and are inexpensive and very effective. They are traditionally used for people who experience motion sickness (long car rides, boats, airplanes). They are placed 3 finger breaths above the wrist crease and have a small plastic knob that exerts pressure in the midline. They can be worn 24 hours a day and have no untoward side effects for mother and fetus.
2- Acupuncture- Safe and effective for women who experience nausea and vomiting in pregnancy.
3- Ginger 250mg 4 times a day in capsules or syrup
5- Watermelon juice
6- Vitamin B6
7- Avoidance of heavy, spicy meals.
8- Eating small frequent meals instead of 3 large meals per day is important because the gastric emptying time in the pregnant woman is significantly delayed. Eating 6 small meals instead of 3 big meals makes a big difference.
9- Take the prenatal vitamin at night right after dinner and before bedtime instead of at other times during the day. If the vitamin is contributing to the nausea and vomiting and changing the timing doesn’t work, you should consider changing vitamins or discontinuing the vitamin all together and instead take a tablet of 1000 micrograms of folic acid daily to support the growing neural tube and decrease the chances of a spinal birth defect like spina bifida.
WHO SHOULD CONSIDER MEDICATION?
Those patients who either have severe unremitting hyperemesis that has either interfered with work/home life that is not responsive to conservative measures or if she becomes dehydrated or can’t hold anything down should consider pharmacologic intervention.
Diclegis is an excellent medication that is extremely safe in pregnancy and is the only Category A medication in pregnancy for nausea and vomiting.
Category A medications are those that have been extensively studied in human subjects and have been found not to cause any birth defects or fetal issues. It is FDA approved and is recommended as first line for nausea and vomiting in pregnancy by
the American College of OB/GYN (ACOG).
It is a combination of vitamin B6 (pyridoxine) and an antihistamine (doxylamine). Decades ago this was marketed as Benedictin which was taken off of the market due to conjecture regarding birth defects (this was never proven but was pulled from the market because of litigation issues). 2 tablets of Diclegis are taken at night before bedtime. If that works it is continued until the end of the first trimester. If nausea and vomiting continue despite the 2 tablets of Diclegis, a third tablet of Diclegis is added in the morning, and if this still doesn’t work, a fourth tablet of Diclegis can be added in the afternoon. Diclegis is given on an empty stomach.
Diclegis can be expensive, and may not be covered by all insurance plans. In that case, some advocate using vitamin B6 (25mg 2-3 times per day) and over the counter Unisom- this is 25mg of doxylamine which is an antihistamine (one half tablet 2-3 times per day) .
Reglan is considered second line treatment for hyperemesis of pregnancy when Diclegis fails.
Reglan increases gastric motility and gastric emptying and is a Category B medication, with animal studies showing no risk or adverse fetal effects, and in humans it is not known to cause birth defects (A study in Denmark showed no increased risk of birth defects in over 28,000 infants whose mothers took reglan in the first trimester- reference 1).
10mg of reglan is given 3 times a day.
There is an unusual side effect called tardive dyskinesia that can occur with the use of reglan. It is a movement disorder that may be irreversible and increases with total duration and total cumulative dose of the drug, and if these symptoms occur, the medication should be discontinued immediately, and neurology consultation is recommended. This medication should not be used for longer than 12 weeks.
Zofran has been used extensively for nausea and vomiting associated with chemotherapy and also in post operative care. Over the last decade, it became a prominent and successful drug for the treatment of hyperemesis. Original studies showed it to be a safe and very efficacious drug.
Recently, there have been small studies (2 studies- one from Sweden with over 1300 patients and one from Denmark with over 1200 infants) that showed a significant increase in cardiac abnormalities in babies born to women who used zofran. One study from the US showed an increased risk of cleft palate. The studies are few and small, but do show significance, and many newer references plan to categorize Zofran as a category C instead of the previous Category B medication.
Therefore, Zofran is now considered a third line choice for hyperemesis in pregnancy. There is still a significant number of patients who fail all other therapies and will need to be offered and take zofran in pregnancy. These patients should be counseled extensively regarding the risks, benefits and alternatives to the medication.
Nausea and vomiting in pregnancy is a significant affliction that affects the majority of pregnant women. Using conservative measures such as acupressure wrist bands, acupuncture, ginger, and altering the amount and frequency of meals and the timing or type of prenatal vitamin often helps significantly.
In those 15% of pregnant women who are recalcitrant to conservative measures, and the symptoms interfere with work and home life, pharmacologic treatment is recommended. Using medications that are known to be safe in pregnancy, especially in the all important first trimester of pregnancy where all of the vital organ systems of the baby are forming and are vulnerable to birth defects is of paramount importance.
First line therapy is Diclegis, second line is reglan and third line is Zofran. If conservative measures don’t work for you, talk to your doctor to go over the options in detail to see what is best for you.
THINKING ABOUT GETTING PREGNANT OR HAVE QUESTIONS ABOUT YOUR PREGNANCY?
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