Nausea and vomiting of pregnancy (NVP) is a common event that affects 70-85% of pregnant women.  Approximately 35% of pregnant women consider their symptoms severe enough to limit their activities of daily living which extends to loss of time at work.  While a single etiology of NVP has not been identified, elevated levels of estrogen and human chorionic gonadotropin (hCG) have been shown to be associated with it in a dose-dependent fashion. (Olson, 2010) Risk factors include an increased placental mass as seen with molar gestation or multiple gestations, a personal or family  history of hyperemesis gravidarum (HG), a history of motion sickness or migraines. NVP is often associated with biochemical hyperthyroidism due to the action of human chorionic gonadotropin (HCG) on the thyroid-stimulating hormone (TSH) receptor. NVP does not cause true hyperthyroidism and routine thyroid function tests are not indicated. TSH is often suppressed to undetectable levels but as long as the patient does not have overt signs of hyperthyroidism with elevated Free T4 after volume repletion, antithyroid medications should not be started.
Hyperemesis gravidarum (HG) represents the extreme spectrum of NVP; it occurs in approximately 0.5-2% of pregnancies, and includes symptoms such as persistent vomiting, dehydration, acid-base disturbance, weight loss of at least 5% of prepregnancy weight, ketonuria, and electrolyte disturbances.  HG is the most common reason for admission to the hospital during the first half of pregnancy.

Clinical Course

The mean gestational age at onset is 5-6 weeks from the last menstrual period. Severity and frequency peak at ~9 weeks and then begin to subside. Symptoms persist beyond 16 weeks in only 10 to 15% of women. When NVP persists in the second and third trimesters, the intensity usually remains fairly consistent and does not lessen.

Diagnostic Approach

NVP is a diagnosis of exclusion.  Physical exam findings not characteristic of NVP include:
•    Abdominal pain (other than musculoskeletal due to retching)
•    Abdominal tenderness other than mild epigastric discomfort
•    Fever
•    Headache
•    Abnormal neurologic exam (suggestive of a primary neurological disorder)
•    Goiter (suggestive of primary thyroid disease)
The presence of these findings should lead to consideration of other serious medical conditions such as pyelonephritis and appendicitis. An ultrasound should be performed (if not already done) to rule out predisposing factors such as multiple gestation or molar pregnancy.

Classification

After a thorough evaluation, patients with NVP can be classified according to the following criteria:

Category Symptoms Impact on ADL
Mild Nausea <1 hr during the day Little to none
Moderate Nausea and vomiting up to 2 times/day Moderate
Severe Persistent symptoms for ≥6 hrs with ≥5 episodes of vomiting or retching/day Significant: requires hospitalization for IV hydration

Management

If symptoms of NVP are impacting the patient’s activities of daily living, some form of management should be initiated to prevent the progression to HG. Medications should be administered on a scheduled basis with doses titrated to individual patient needs. Patients with severe NVP or HG require urgent medical care due to dehydration and malnutrition.  Enteral tube feeding has been found to be well tolerated during pregnancy and can be used in severe forms of HG. All other therapies should be considered and tried before initiating enteral tube feeding. Total Parental Nutrition (TPN) is not recommended.
Common recommendations to alleviate symptoms:
•    Rest
•    Avoidance of sensory stimuli
•    Frequent, small meals
•    Bland, dry diet high in protein; decrease fat and spicy foods
•    Crackers in the morning before arising
•    Ginger capsules, 250 mg 4 times per day
•    Pressure (acupressure technique) or electrical stimulation at the Neiguan point on the inside of the wrist (conflicting results)

Pharmacologic Therapies
Drug Dosage Route
start with: Vitamin 6 25-50mg 3-4 time/day Oral
If no improvement

add:

Doxylamine

(Unisom)

12.6mg 3-4 time/day Oral or

Rectal

If no improvement

add:

Promethazine

(Phenergan)

OR

Dimenhydrinate

(Dramamine*)

12.5-25mg every 4 hrs

 

 

50-100mg every 4-6 hrs

Oral or

Rectal

 If no improvement

and no dehydration

add:

 Metoclopramide

(Reglan)

OR

Promethazine

(Phenergan)

OR

Trimethobenzamide

(Tebamide or Tigan)

 5-10mg every 8 hrs

 

 

12.5-25mg every 4 hrs

 

 

200mg every 6-8 hrs

 

 IM or oral

IM, oral

or rectal

Rectal

 If no improvement

and dehydration

add:

 IV fluids

AND

 

Dimenhydrinate

(Dramamine*)

OR

Metoclopramide

(Reglan)

OR

Promethazine

(Phenergan)

 0.9%Saline

OR

5% dextrose-0.9% saline

 

50-100mg every 4-6 hrs

 

 

5-10mg every 8 hrs

 

 

12.5-25mg every 4 hrs

 

IV 

 

 

 

 If no improvement

add:

 Ondansetron

(Zofran)

 8mg IV over 15 min

every 12 hrs

IV
 If still

no improvement

Consult with MFM

and consider transfer

NVP Classification

Category Symptoms Impact on ADL
Mild Nausea <1 hr during the day Little to none
Moderate Nausea and vomiting up to 2 times/day Moderate
Severe Persistent symptoms for ≥6 hrs with ≥5 episodes of vomiting or retching/day Significant: requires hospitalization for IV hydration

Management

If NVP is impacting the patient’s activities, some form of management should be initiated to prevent progression to HG.

  • Administer medications on a scheduled basis with doses titrated to individual patient needs.
  • Patients with severe NVP or HG require urgent medical care due to dehydration and malnutrition.
  • After all other therapies have been considered and tried, enteral tube feeding and can be used in severe forms of HG.
  • Total Parental Nutrition (TPN) is not recommended.
  • A commercially fixed dose combination of doxylamine (antihistamine) and pyridoxine hydrochloride (Vitamin B6) is available for the treatment of nausea and vomiting of pregnancy. While the dosage is lower than non-fixed regimens, it may be more convenient for patient use. Medicaid preauthorization is required.
Drug
Vitamin B6
Dosage
25-50mg 3-4 time/day
Route
Oral
Drug
Doxylamine (Unisom)
Dosage
12.6mg 3-4 time/day
Route
Oral or Rectal

Drug
Promethazine (Phenergan)
Dosage
12.5-25mg every 4 hours
Route
Oral or Rectal
 
OR
 
Drug
Dimenhydrinate (Dramamine*)
Dosage
50-100mg every 4-6 hours
Route
Oral or Rectal

Drug
Metoclopramide (Reglan)
Dosage
5-10mg every 8 hours
Route
IM or Oral
 
OR
 
Drug
Promethazine (Phenergan)
Dosage
12.5-25mg every 4 hours
Route
IM, Oral or Rectal
 
OR
 
Drug
Trimethobenzamide (Tebamide or Tigan)
Dosage
200mg every 6-8 hours
Route
Rectal

Drug
IV fluids
Dosage
0.9% Saline OR 5% dextrose -0.9% saline
Route
IV
 
AND
 
Drug
Dimenhydrinate (Dramamine*)
Dosage
50-100mg every 4-6 hours
Route
IV
 
OR
 
Drug
Promethazine (Phenergan)
Dosage
12.5-25mg every 4 hours
Route
IV

Drug
Ondansetron (Zofran)
Dosage
8mg IV over 15 minutes every 12 hrs
Route
IV

Drug
Consult with MFM and consider transfer