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 miscarriageFewer preterm deliveriesFewer stillbirthsFewer instances of low birth weight, growth restriction and mortality
Maternal Complications - Mechanical Stress of Vomiting ComplicationMallory–Weiss tear of the esophagusEsophageal rupturePneumomediastinumRetinal detachmentSplenic avulsion
Fetal ConsiderationsNVP: 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 measures Emotional support Acupressure Ginger Chiropractic
Combination of doxylamine/pyridoxineDelayed-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 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 releaseformulation of doxylaminesuccinate and pyridoxinehydrochloride is effective and welltolerated in treating nausea andvomiting 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, 2001A total of 123 women received standard doses (up to 4daily tablets of Diclectin®), and 102 women received ahigher than standard dose (“supradose”) of 5 to 12tablets/day.
ResultsThe incidence of sleepiness, tiredness, or drowsinesswas the same in patients who received the standarddose or the supradose.Birth weight, delivery weeks, major malformation: no increasedIf 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 Bendectinusage and birth defect rates. The population results of the ecological analyses complementthe person-specific results of the epidemiological analyses infinding no evidence of a teratogenic effect from the useof Bendectin.
Fetal Anomaly and Pregnancy Outcomes after Exposure to Doxylamine
Objectives To evaluate the safeness andpregnancy 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 variablesPregnancy 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)