NAUSEA AND VOMITING OF PREGNANCY 제일병원 주산기 전임의 안계형

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.

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.

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

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

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)

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

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, )

Nonphamacologic Treatment Dietary measures Emotional support Acupressure Ginger Chiropractic

Phamacologic treatment 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

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.

Combination of doxylamine/pyridoxine Bendectin in US. ( ) 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.

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.

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 assess the temporal relationship between Bendectin usage and birth defect rates.

Fetal Anomaly and Pregnancy Outcomes after Exposure to Doxylamine

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

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

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

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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