folic acid in pregnancy 이민영 전임의
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folic acid in pregnancy 이민영 전임의



마더리스크라운드 발표자료

마더리스크라운드 발표자료



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folic acid in pregnancy 이민영 전임의 folic acid in pregnancy 이민영 전임의 Presentation Transcript

  • Folic acid in pregnancy 2013.9.3 주산기 전임의 이민영
  • Folic Acid Folic acid/ folate ?? INTRODUCTION Folic (Pteroyl-L-Glutamic) Acid Pteridine p-Aminobenzoic acid L-Glutamic acid Folate ; Polyglutamyl Tetrahydrofolates
  • Folic Acid INTRODUCTION Folate VS • Natural (complex) form  Foods such as dark- green leafy vegetables, broccoli, asparagus, lentils, beans, peanuts, strawberries, kiwi, orange juice, liver  Can be lost throught processing and cooking  Absorption : 50% • Synthetic (simple) form  Fully oxidized form, Pteroylmonoglutamic acid  Have only one glutamate molecule attached  Used in nutritional supplements and food fortification  Only form that can be transported across membranes  Absorption : ~93% Folic acid
  • Folic Acid INTRODUCTION Functions of folic acid  Amino acid/Nucleic acid metabolism – Essential for synthesis of serine, methionine, ATP, GTP, thymidylate  Cell growth and division  Formation of Red blood cells  Reduction blood homocystein level  Prevention of NTDs – All NTDs occur between 17th and 30th days following conception – Adequate folate should be obtained in the 1st trimester of pregnancy
  • Folic Acid Dietary Folate Feces PGn PG1 Pancreatic juice Bile Pool A (Plasma) Pool B (Tissues) Urine (Folates & Catabolites) METABOLISM Folate bioavailability
  • Folic Acid Drugs that interfere with folic acid  Alcohol ,Tabacco  Aspirin, ibuprofen, acetaminophen  Antacids & anti-ulcer medications ;  Cimetidine (Tagamet®)  Some antiseizure medications ;  Phenobarbital, Phenytoin,Primidone, Valproic acid  Some antibiotics/antibacterials;  Trimethoprim (Bactrim®), Sulfonamide (Septra®)  Oral hypoglycemic agents  HTN Tx. ;  ß-blocer, CCB, Triamterene (Dyrenium®)  Some anticancer drugs  MTX METABOLISM
  • Folic Acid METABOLISM Metabolic pathway SAM Demethylation MTHER. B12 MS,B12 CBS ,B6 Remethylation pathway Transsulfuration
  • Folic Acid Homocysteine (Hcy) • Sulfur-containing, highly reactive amino acid that is synthesized during protein catabolism by the conversion of methionine to cysteine • Homocysteine is metabolized by  Transsulfuration, depending on VitB6 and Remethylation, depending on folate & Vit B12 METABOLISM
  • Folic Acid What is homocysteine risks? METABOLISM  Atherosclerosis  CAD  MI  Stroke  Thromboembolism  Peripheral vascular disease Arterioscler Thromb Vasc Biol. 2001;21:1385–1386
  • Folic Acid Homocysteine and CAD METABOLISM
  • Folic Acid Causes of hyperhomocysteinemia • Genetic defects  Enzymes involved in homocysteine metabolism  CBS, MS deficiency  MTHFR deficiency • Nutritional deficiencies  Vitamin cofactors (folate, Vit B12, Vit B6) • Other factor  CKD, Hypothyroidism, Psoriasis, SLE, etc  Drugs: Methotraxate, Phenytoin, Theophylline, Niacin, Carbamazepine, Immumosuppressive agents , etc  Alcohol, Smoking, coffee METABOLISM
  • Folic Acid Homocysteine and other disease  Osteoporosis  Cognitive impairment  Alzheimer disease  Chronic kidney disease  Prenatal complications to women & Fetus  Preeclampia, placental abruption, pregnancy loss, IUGR  NTD METABOLISM Circulation. 2005;111:e289–e293
  • Folic Acid BIRTH DEFECT What are neural tube defects? • Neural tube defects (NTDs) are birth defects that occur early in pregnancy – 1 – 2 / 1,000 live births in the United States ~ 4,000 affected pregnancies per year – 2nd in the cause of infant mortaility (1st : Congenital heart defect) – Folds in on itself and forms a tube within first month of pregnancy – NTDs result when the neural tube doesn’t properly close.
  • Folic Acid BIRTH DEFECT Which NTDs are most common? Anterior neural pole Posterior Neural pole Failure to close =Anencephaly Failure to close =Spina bifida
  • Folic Acid BIRTH DEFECT Neural tube development
  • Folic Acid Etiology of NTDs • Multifactorial Inheritance  Single gene mutation  Meckel-Gruber syndrome • Aneuploidy  Trisomy 16, 18  Triploidy • Teratogenic Drugs  Accutane, Valproic acid, Carbamazepine • Hyperglycemia • Aberrations of folic acid intake / Metabolism BIRTH DEFECT
  • Folic Acid Who is at risk for NTDs? • All women capable of becoming pregnant • 95% of NTDs occur in women with no family history of NTDs BIRTH DEFECT
  • Folic Acid MRC Vitamin study --- in UK • International, multicenter, double blind randomized control trial  Recruit 1817 women who had a previous affected pregnancy • 4-Treated groups  A : Folic acid (4mg/day)  B : Folic acid + Multivitamins  C: Neither  D : Multivitamins • Evaluation of effects of folic acid or other vitamins – Comparison of groups A+B / C+D, groups B+D / A+C BIRTH DEFECT MRC Vitamin Study Research Group. Lancet 1991
  • Folic Acid MRC Vitamin study --- in UK BIRTH DEFECT MRC Vitamin Study Research Group. Lancet 1991
  • Folic Acid MRC Vitamin study --- in UK • Folic acid supplementation reduces the risk of an NTD in pregnancy • Women who had at least on previous pregnancy with a NTD – 4mg folic acid/day before pregnancy and thoroughout the first trimester – 71% protective effects BIRTH DEFECT MRC Vitamin Study Research Group. Lancet 1991
  • Folic Acid Other benefits of folic acid • Additional birth defect – Orofacial cleft – Congenital heart disease – Urinary tract anomaly – Limb defect • May prevent – Cardiovascular disease – Cancer; Colorectal cancer, Colorectal adenoma – Alzheimer disease BIRTH DEFECT Hernandez-Diaz S, et al. NEJM 2000 Centers for Disease Control and Prevention and March of Dimes T. Bottiglieri and L. Wallock.
  • Folic Acid CURRENT Folic acid behavior March of Dimes Folic Acid Survey conducted by The Gallup Organization, August 2003 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Aware of folic acid Know it prevents birth defects Know to take it before pregnancy 79% 10% 21% 2003 Folic acid knowledge (All women 18-45)
  • Folic Acid Folic acid knowledge of women March of Dimes Folic Acid Survey conducted by The Gallup Organization, August 2003 24% 25% 26% 27% 28% 29% 30% 31% 32% 33% 34% 1997 1998 2000 2001 2002 2003 30% 30% 27% 2003 Daily use of Vit containg Folic acid 29% 32% 31% CURRENT
  • Folic Acid The challenge • NTDs happen in the first month of pregnancy---- Before most women know they are pregnant !!! • Half of all pregnancies in the US are not planned !! Be prepared! CURRENT
  • Folic Acid PREVENTION CDC recommends for US women • How much? – 400㎍/day; All women in childbearing age low risk women – 1 mg/day ;Pregnant women – 4 mg/day ; Women with history of neural tube defect deliveries take folic acid 1 month prior to conception and during first trimester • When ? – 1~3 months before and continuing through the first months of pregnancy Nutrition and Micronutrients in Pregnancy - Prof.S.N.Panda
  • Folic Acid PREVENTION Recommends • High risk for NTD recurrence – Daily 4.0mg of folic acid – At least 50~72% ↓ • Low risk pregnancy – Daily 0.4mg of folic acid – The incideince rates of NTDs by 40~60% ↓ Maternal-Fetal Toxicology. 2001
  • Folic Acid Who is at high risk for NTDs? • Women who…  Have a previous pregnancy affected by an NTD  Have a family history of NTDs  Use certain anti-seizure medication  Have insulin-dependent diabetes  Been diagnosed as clinically obese  Abuse alcohol PREVENTION FDA 1996
  • Folic Acid • Folic acid is added to some grains as:  Pasta  Breads  Cereals  Rice • Folate is naturally found in:  Leafy green vegetables  Cooked dry edible beans  Broccoli  Peanuts  Citrus fruits What foods contain folate/folic acid? RECOMMEND
  • Folic Acid RECOMMEND Best sources of folate  1/4 cup peanuts: 207 mcg  3 oz. beef liver: 185 mcg  1/2 cup garbanzo beans: 134 mcg  1 cup navy beans: 129 mcg  1/2 cup pinto beans: 117 mcg  1/2 cup lentils, split peas, black beans, or kidney beans: 114 mcg  1/2 cup black-eyed peas: 105 mcg  1/2 cup cooked spinach: 100 mcg  1/2 cup corn: 88 mcg  4 spears of asparagus: 85 mcg
  • Folic Acid • Look for “Folic Acid” or “Folate” in the left column • Check value in the right column – this number is the percent of your recommended daily value 100% = 400 mcg Sample food label RECOMMEND
  • Folic Acid RECOMMEND Fortified foods? • The FDA ruled that starting January 1, 1998, all cereal grain products labeled “ Enriched” must be fortified with folic acid.  140 mcg FA per 100 gram of flour  Observed NTD redution :18% National Center for Health Statistics. Trends in spinal bifida and anencephalus in the United States 1991-1999
  • Folic Acid RECOMMEND How much is “too much”? • 1000mcg is the upper limit for folic acid • Too much folic acid may hide Vitamin B12 deficiency – Do not correct the changes in the nervous system that result from Vit B12 deficiency – Nerve damage could theoretically occur due to such masking
  • Folic Acid RECOMMEND Take home message • More than 4,000 babies in the United States are born each year with Neural Tube Defects (NTDs). • Taking folic acid at least one month before and during the first trimester of pregnancy can help prevent NTDs. • Women of child bearing age with no history of NTDs should take 400mcg of Folic acid daily. • Women of child bearing age with a personal or family history of NTDs should take 4,000mcg of Folic Acid