제일병원 주산기 전임의 안계형


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.


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.

Psychological factors?
Elevated progesterone level?
HCG and estrogen?
H.pylori involvement?
Gastric Motility?
Exact cause remains unclear


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

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

Mechanical Stress of Vomiting Complication

Mallory–Weiss tear of the esophagus

Esophageal rupture

Pneumomediastinum

Retinal detachment

Splenic avulsion


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)

Dietary measures
Emotional support
Acupressure
Ginger
Chiropractic

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


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.

•
•
•
•
•
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.

•
•
•
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.

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

•
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).

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.


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.

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.

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

•
•
•
•
•
•
•
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

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

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