NAUSEA AND VOMITING OF PREGNANCY

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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 miscarriageFewer preterm deliveriesFewer stillbirthsFewer instances of low birth weight, growth restriction and

mortality

Maternal Complications - Metabolic Nutritional Complication

Wernicke’s encephalophathy (B1 deficiency)Beriberi (B1 deficiency)Central pontine myelinolysisHepatic insufficiencyAcute tubular necrosisPeripheral neuropathy (B6, B12 deficiencies)

Maternal Complications - Mechanical Stress of Vomiting Complication

Mallory–Weiss tear of the esophagusEsophageal rupturePneumomediastinumRetinal detachmentSplenic avulsion

Fetal Considerations

NVP: no association with adverse fetal outcomesHyperemesis : 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)

Nonphamacologic Treatment

Dietary measuresEmotional support

AcupressureGinger

Chiropractic

Phamacologic treatment• Pyridoxine (Vitamin B6)• Doxylamine• Dopamine antagonists• Phenothiazine • Metochopramide• Domperidone/Dropeidol• Serotonin 5-HT3 Antagonist• Anticholinergics

• Dicyclomine (spatomin) ®and scopolamine (busco-pan)

• 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. (1958-1983)• Diclectin in Canada. (1979) • Only one approved by FDA.• Voluntary removal from mar-

ket 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 : in-creased 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 formula-tion of doxylamine succinate and pyridoxine hydrochloride is effec-tive 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 drowsinesswas the same in patients who received the standarddose or the supradose.

Birth weight, delivery weeks, major malformation: no in-creased

If needed, Diclectin® can be given at doses higher than 4 tablets/day to normalize for body weight or optimize effi-cacy.

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 useof Bendectin.

To assess the temporal relationship between Bendectinusage 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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