Nausea and vomiting of pregnancy

1. NAUSEA AND VOMITING OF PREGNANCY
제일병원 주산기 전임의 안계형

2. Nausea and vomiting of pregnancy (NVP)
M/C medical complication in pregnancy.
Affect 80% of pregnant women.
Usually, starting at 4~9 GA wks.
Peak :7~12 GA wks.
Resolved by 16 GA wks.
20-30% of pregnant women experience beyond 20 GA
wks.

3. Hyperemesis gravidarum (HG)
Persistent nausea and vomiting of pregnancy.
dehydration, ketonuria, Electrolyte disturbance.
Weight loss greater than 5% of prepregnancy weight.
Less than 2% of women with NVP->hyperemesis
gravidarum.
Approximately 10% of HG patients-> persisting Sx.
throughtout pregnancy.

4. Several Theories of NVP
Psychological factors?
Elevated progesterone level?
HCG and estrogen?
H.pylori involvement?
Gastric Motility?
Exact cause remains unclear

5. Benefits?
Women with uncomplicated “ morning sickness” have
been noted to have improved pregnancy outcomes.
Fewer miscarriage
Fewer preterm deliveries
Fewer stillbirths
Fewer instances of low birth weight, growth restriction and
mortality

6. Maternal Complications
- Metabolic Nutritional Complication
Wernicke’s encephalophathy (B1 deficiency)
Beriberi (B1 deficiency)
Central pontine myelinolysis
Hepatic insufficiency
Acute tubular necrosis
Peripheral neuropathy (B6, B12 deficiencies)

7. Maternal Complications
- Mechanical Stress of Vomiting Complication
Mallory–Weiss tear of the esophagus
Esophageal rupture
Pneumomediastinum
Retinal detachment
Splenic avulsion

8. Fetal Considerations
NVP: no association with adverse fetal outcomes
Hyperemesis
: women who gain < 7kg have increased risk
– 5-minute APGAR <7
– Low birth weight (12.5% vs 4.2% of controls)
– SGA
– Preterm birth (13.9% vs 4.9% of controls)
• Obstet Gynecol 2006; 107, 285-292)

9. Nonphamacologic Treatment
Dietary measures
Emotional support
Acupressure
Ginger
Chiropractic

10. Phamacologic treatment
• Pyridoxine (Vitamin B6) • Dicyclomine (spatomin)
• Doxylamine ®and scopolamine
• Dopamine antagonists
(buscopan)
• Corticosteroids
• Phenothiazine
• Proton pump inhibitors (PPI)
• Metochopramide
• Thiamine
• Domperidone/Dropeidol
• H.pylori Tx. : Antibiotic
• Serotonin 5-HT3
Antagonist therapy
• Anticholinergics

11. Combination of doxylamine/pyridoxine
Delayed-release combination of doxylamine
succinate(10mg) and pyridoxine hydrochloride(10mg)
Half life
- Doxylamine (H1 antagonist): 11.7hours
- Pyridoxine (vitamin B6): 56hours
-> metabolized mainly in the liver.
Standard dose: 4 tablets per day.
2T at bedtime/ 1T in the morning/ 1T in the afternoon.
Full effect: takes several days.

12. Combination of doxylamine/pyridoxine
• Bendectin in US. (1958-1983)
• Diclectin in Canada. (1979)
• Only one approved by FDA.
• Voluntary removal from
market in 1983 after a large
series of lawsuits alleging an
excess of birth defects.
• hospitalizations of pregnant
women for severe form of
NVP, hyperemesis
gravidarum : increased two
fold.

13. • A randomized, double-blind, multicenter placebo controlled
trial study
• Diclectin (n=131) or placebo (n=125) for 14 days.
• Nausea and vomiting of pregnancy symptoms were evaluated
daily using the pregnancy unique quantification of emesis scale.

15. Diclectin delayed release
formulation of doxylamine
succinate and pyridoxine
hydrochloride is effective and well
tolerated in treating nausea and
vomiting of pregnancy.

16. • NVP has an enhancing effect on later child outcome. Diclectin
does not appear to adversely affect fetal brain development
and can be used to control NVP when clinically indicated. (J
Pediatr 2009;155:45-50).

17. Journal of Clinical Pharmacology, 2001
A total of 123 women received standard doses (up to 4
daily tablets of Diclectin®), and 102 women received a
higher than standard dose (“supradose”) of 5 to 12
tablets/day.

18. Results
The incidence of sleepiness, tiredness, or drowsiness
was the same in patients who received the standard
dose or the supradose.
Birth weight, delivery weeks, major malformation: no
increased
If needed, Diclectin® can be given at doses higher than 4
tablets/day to normalize for body weight or optimize
efficacy.

19. To assess the temporal relationship between Bendectin
usage and birth defect rates.
The population results of the ecological analyses complement
the person-specific results of the epidemiological analyses in
finding no evidence of a teratogenic effect from the use
of Bendectin.

21. Fetal Anomaly and Pregnancy Outcomes after
Exposure to Doxylamine

22. Objectives
To evaluate the safeness and
pregnancy outcomes after use of
doxylamine succinate

23. Materials & Methods
• 2006~2011
• Delivery at Cheil General Hospital
• Diagnosed with hyperemesis
• Use of doxylamine(n): 800
• Not use of doxylamine(n): 1600
• Review medical records
• Retrosprctive observational study
Doxylamine 25mg : 2T #2
Pyridoxine 50mg : 2T # 2

24. Clinical variables
Pregnancy outcomes
 Delivery weeks
 Apgar score
 Birth weight
 Spontaneous abortion
 Intrauterine fetal death
 Major malformation
 NICU admission
 Hospital days in NICU

25. Clinical variables
• Exposure weeks
• Dose of drug
• Duration of exposure
• Maternal age
• Gravidity
• Re-admission
• Exposure to the heat, alcohol, radiation, cigarrete
somking (exposure weeks, dose)

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