Nutraceuticals in pregnancy 1


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  • 4th Report - The World Nutrition Situation: Nutrition throughout the Life Cycle (IFPRI - UNSSCN, 2000, 136 p.)
  • Slide 4: Maternal Malnutrition: A Life-Cycle Issue (one) Women are vulnerable to malnutrition throughout the life cycle for both biological and social reasons. Infancy and early childhood (0–24 months) . Most young girls living in poor environments are suboptimally breastfed in infancy and early childhood, receive infrequent and poor complementary foods (both in quantity and/or quality), and suffer frequent infections. Such nutritional neglect during the first two years of life has immediate and long-term negative consequences on women’s survival, growth, development, and productivity. Childhood (two to nine years) . At two years of age, many of the girls who survive under such nutritional stress are stunted with little chance of recovery. Moreover, in some parts of the world, girls are discriminated against in access to food, health care, and education throughout childhood .
  • Slide 5: Maternal Malnutrition: A Life-Cycle Issue (two) Adolescence (10–19 years). During adolescence, girls experience rapid physical growth and sexual maturation which significantly increases their needs for macronutrients and micronutrients (especially iron). Adolescent girls’ growth spurt occurs before menarche (first menstruation). Adolescent girls continue to grow in height long after menarche. Linear growth, particularly of the long bones, is not complete until the age of 18, and peak bone mass is not achieved until the age of 25. A malnourished adolescent girl whose menarche has been delayed may achieve full height as late as 23 years and will, therefore, be capable of conceiving before her body size is fully developed. Moreover, the development of the birth canal is slower than that of height and does not reach mature size until about two to three years after the growth in height has ceased. Pregnancy puts adolescent women at increased risk of malnutrition (diverting nutrients from the mother to the fetus), pregnancy complications, and poor pregnancy outcomes (including death). Early pregnancy contributes to the cycle of maternal malnutrition in two ways: Indirectly, through the premature cessation of the mother’s growth. Directly, through the increased risk of delivering a low birth weight baby. Pregnancy and lactation. In most developing countries, women spend a large proportion of their reproductive years pregnant, lactating or pregnant and lactating. McGuire and Popkin (1990) estimate that on average, African and Asian women between the ages of 15 and 45 are pregnant or lactating 30–48 percent of their time. The nutritional demands during pregnancy and lactation are multiple to support fetal growth and breastmilk production. These added nutritional requirements specific to pregnancy and lactation manifest themselves both at the macronutrient and the micronutrient level. More calories are needed to achieve adequate pregnancy weight gain and build stores for lactation. More iron is needed because of the growth of the fetus and placenta and the expansion of plasma volume. More vitamin A may be needed to ensure adequate vitamin A concentration in breastmilk. Closely spaced reproductive cycles, negative energy balance, and micronutrient deficiencies can lead to a condition known as “maternal depletion syndrome”. Nutritional stress is greatest when an adolescent woman is pregnant and lactating.
  • Slide 6: Maternal Malnutrition: a Life-Cycle Issue (three) Throughout life. Most women living in developing countries experience various biological and social stresses that increase the risk of malnutrition throughout life. These include: Food insecurity Inadequate diets Recurrent infections Frequent parasites Poor health care Heavy work burdens Gender inequities
  • Fetal growth has become fashionable because of the hypothesis of the fetal origins for adult disease which has been advocated by David Barker and his team. These two books summarize much of evidence which I will discuss at the end of the talk.
  • Let begin by addressing the definition of growth
  • Let begin by addressing the definition of growth
  • This baby has a growth disorder. It was born at term but starved in utero. It lacks sub-cutaneous tissue as can be seen by the prominent iliac wing and a thin leg (Pat insert arrows). So there is no question that intra-uterine starvation occurred.
  • More than a decade ago, we have proposed that preterm labor is a syndrome characterized by the presence of uterine contractions, cervical ripening and membrane/decidual activation caused by (click) infection/inflammation, which is the most common cause studied in the context of preterm labor and delivery. Our group and others have clearly demonstrated the importance of infection, the prevalence and the clinical significance of infection in preterm birth. The other potential causes are … (click) X 5
  • In contrast, intrauterine growth retardation is the failure to achieve an individual optimal growth potential Such a failure may occur even in the infants is above the 10 th percentile
  • Fetal growth has become fashionable because of the hypothesis of the fetal origins for adult disease which has been advocated by David Barker and his team. These two books summarize much of evidence which I will discuss at the end of the talk.
  • Some salts, bread and seafood have been supplemented with iodine. Iodine may be found in other locally available foods. The US recommended daily allowance is 150  g/day for adults, 175  g/day for pregnant women and 200  g/day for lactating women.
  • Therefore, both nutrients play important roles in immune function and the modulation of host resistance to infectious agents, reducing the risk, severity, and duration of infectious diseases
  • Classifications of anemia were taken from the World Health Organization (WHO). December 2000. Essential Care Practice Guide: Pregnancy, Childbirth and Newborn Care . Draft. Severe anemia is associated with a significantly increased risk of complications in pregnancy, specifically low birth weight newborns, premature birth, perinatal mortality, and increased maternal mortality and morbidity. This increase is due to low oxygen-carrying capacity for both fetus and mother.
  • Foods abundant in iron include: red meat (especially liver), poultry, fish, whole grains, dark green leafy vegetables, shellfish and dried fruit. Absorption is improved if taken with foods containing vitamin C. Adult females should get 30 mg/day, especially if they are pregnant.
  • Slide 40: Improving Maternal Weight Increases in weight can be achieved within a woman’s reproductive life by: Increasing caloric intake and/or by Reducing energy expenditure and/or by Reducing caloric depletion (delaying the first pregnancy and increasing birth intervals)
  • Nutraceuticals in pregnancy 1

    1. 1. NARENDRA MALHOTRA M.D., F.I.C.O.G., F.I.C.M.C.H President FOGSI (2008) Dean of I.C.M.U. (2008) Director Ian Donald School of Ultrasound National Tech. Advisor for FOGSI-G.O.I.—Mc Arthur Foundation EOC Course Hon Prof Ob Gyn at DMIMS,Sawangi,Advisor ART unit at MAMC & SMS Jaipur Practicing Obstetrician Gynecologist at Agra. Special Interest in High Risk Obs., Ultrasound, Laparoscopy and Infertility, ART & Genetics Member and Fellow of many Indian and international organisations FOGSI Imaging Science Chairman (1996-2000) Awarded best paper and best poster at FOGSI : 5 times, Ethicon fellowship, AOFOG young gyn. award, Corion award, Man of the year award, Best Citizens of India award Over 30 published and 100 presented papers Over 50 guest lectures given in India & Abroad.Presented 10 orations. Organised many workshops, training programmes, travel seminars and conferences Editor 8 books, many chapters, on editorial board of many journals Editor of series of STEP by STEP books Revising editor for Jeatcoate’s Textbook of Gynaecology (2007) Very active Sports man, Rotarian and Social worker MALHOTRA HOSPITALS 84, M.G. Road, Agra-282 010 Phone : (O) 0562-2260275/2260276/2260277, (R) 0562-2260279, (M) 98370-33335; Fax : 0562-2265194 E-mail : / Website : Apollo Pankaj Hospitals, Agra Consultant for IVF at jalandhar,ludhiana,ambala,bhiwani,gwalior,allahabad,gorakhpur,udaipur,bariely,jaipur,delhi Neapal & Bangladesh
    2. 2. Nutrition during PregnancySuppliment therapy in managing PIH & IUGR narendra malhotra jaideep malhotra
    3. 3. Maternal Nutrition Overview  At no other time in woman’s life is nutrition so important as before, during and after pregnancy • Preconception nutrient needs • Pregnancy increased nutrient demands • Lactation nutrient needs
    4. 4. Maternal Nutrition IssuesEffect of nutritional inadequacies at different points in the life cycle FROM INTRAUTERINE TO ADULTHOOD
    5. 5. Maternal Malnutrition: A Life-Cycle Issue Infancy and early childhood (0-24 months) • Suboptimal breastfeeding practices • Inadequate complementary foods • Infrequent feeding • Frequent infections Childhood (2-9 years) • Poor diets • Poor health care • Poor education
    6. 6. Maternal Malnutrition: A Life-Cycle Issue  Adolescence (10-19 years) • Increased nutritional demands • Greater iron needs • Early pregnancies  Pregnancy and lactation • Higher nutritional requirements • Increased micronutrient needs • Closely-spaced reproductive cycles
    7. 7. Maternal Malnutrition: A Life-Cycle Issue Throughout life • Food insecurity • Inadequate diets • Recurrent infections • Frequent parasites • Poor health care • Heavy workloads • Gender inequities
    8. 8. Fetal origin of adult diseases It is now widely accepted that the risks of a number of chronic diseases in adulthood such as diabetes mellitus, hypertension and coronary heart disease may have their origins before birth(NUTRITION AND GENES)JK Science, Dep of obs & gyn, Indraprastha hospital, 2007, 9(4)
    9. 9. Fetal Origins of Adult Disease
    10. 10. Maternal nutrition A healthy, balanced diet that contains adequate amounts of nutrients is essential for the development of a baby During pregnancy and after delivery, a mother’s body goes through many physiological changes, including a need for increased nutrients and energy
    11. 11. The nutritional status of pregnant women in India 60 plus years,India is still poor, pregnant and powerless
    12. 12. Current scenario in India Pregnant women with the calorie consumption of less than 50% of the recommended had a lower serum zinc level compared to the women who had a higher calorie intake Asia Pac J Clin Nutr 2008;17 (2):276-279 Results on dietary intake showed that 18%, 34%, 85% and 57% of the pregnant women were consuming less than 50% of calories, proteins, iron and b-carotene, respectively as compared to their RDA
    13. 13. Average intake of nutrients J Hum Ecol, 29(3): 165-170 (2010)
    14. 14. Study from Andhra Pradesh European Journal of Clinical Nutrition 2003; 57, 52–60
    15. 15. Study from northern India Maternal and Child Nutrition (2008), 4, pp. 86–94
    16. 16. Calcium Status in India Indian RDA for non-pregnant women has been increased from 400 mg/day to 600 mg/day. Over 50% of women, are not meeting this number There is evidence of calcium depletion, measured by bone mineral density, particularly in women after repeated pregnancy and lactation
    17. 17. Vitamin D status in India Rickets has become rare, but recent studies from North and South India show that vitamin D deficiency exists in adultsbased on serum levels of 25- hydroxy vitamin D2
    18. 18. Vitamin D status in India (Review article)– Summary of Indian studies All studies uniformly point to low 25(OH)D levels in the populations studies despite abundant sunshine in our country All studies have uniformly documented low dietary calcium intake compared to Recommended Daily/Dietary Allowances (RDA) by Indian Council of Medical Research (ICMR) Vit D status of children - very low in both urban and rural populations Pregnant women and their new born had low vitamin D status Dietary calcium supplementation had positive effect on 25(OH)D levels JAPI, 2009; (57):40-48
    19. 19. Nutrient Intake of Lactating Mothers from Hisar- Ind Jr Social Research 1998;39(2):91-99Presentation Title Company ConfidentialDate © 200X Abbott
    20. 20. Women …. Pregnancy…. Baby Ultimate Desire
    21. 21. BUT IF IUGR AT RISK PIHOligohydramnios PreeclampsiaPOLYHYDRAMNIOSPLACENTAL COMPLICATIONS Preterm labor Then it’s a matter of concern
    22. 22. As it leads to Maternal Morbidity & MortalityFetal Morbidity & Mortality
    23. 23. Normal Placental Development Uterine spiral artery remodeling takes place by the invasion of trophoblast cells into the uterine lining. These trophoblasts enter the arterial walls and replace parts of the vascular endothelium so that smooth muscle is lost and the artery dilates. Poor placentation and preeclampsia
    24. 24. Sadler TW Lagman’s Medical Embryology 1990 Umbilical Chorionic vessels Chorionic plate Amnion vessels Normal Placental Development Placental Spiral septum Uteroplacental Basal artery veins plateFrom 9-12 weeks gestation the uterine spiral arteries are transformed from thick-walled, muscular vessels, to more flaccid tubes to accommodate a 10-foldincrease in uterine blood flow to support the pregnancy.
    25. 25. An immune response facilitates normal placental development: In the uterine decidua, maternal lymphocytes and macrophages assist the trophoblasts to invade into the uterine myometrium and the spiral arteries.
    26. 26. The Challenge of Obstetrics
    27. 27. Obstetrical Disease Obstetrical Disease The great obstetrical The great obstetrical syndrome syndrome• Preterm labor• Preterm Rupture of membranes• Pre-eclampsia• SGA/IUGR• Fetal Death
    28. 28. PRE ECLAMPSIAPresentation Title Company ConfidentialDate © 200X Abbott
    29. 29. PreeclampsiaPatho-physiological Theories Abnormal trophoblastic invasion Prostanoid theory (imbalance between prostacyclin and thromboxane A2) Vascular endothelium dysfunction 31
    30. 30. PreeclampsiaWhat happens to blood vessels? Normal Levels of: TxA2 Prostacyclin Nitric Oxide Free Radicals Altered Levels of: ↑ TxA2 ↓ Prostacyclin ↓ Nitric Oxide ↑ Free Radicals 32
    31. 31. Normal function of endothelial cells THE RESULT: Line all blood vessels providing vessel wall integrity Prevent intravascular coagulation Regulate smooth muscle contractility Mediate immune and inflammatory responses VASCULAR ENDOTHELIAL DYSFUNCTION Poor placentation, or a decreased capacity of the uteroplacental circulation. This causes placental hypoxia, resulting in oxidative stress. • Pathophysiology is generally established before 20 weeks.
    32. 32. PreeclampsiaProstanoid - Theory34
    33. 33. Vascular Endothelial Dysfunction Normal function of endothelial cells Line all blood vessels providing vessel wall integrity Prevent intravascular coagulation Regulate smooth muscle contractility Mediate immune and inflammatory responses
    34. 34. Preeclampsia What is NO Nitric oxide, also known as EDRF,( endothelium- derived relaxation factor) Important mediator of vasodilatation NO is formed from L-arginine L-arginine levels are depleted in preeclampsia pts 36
    35. 35. Decrease formation of NOIncreased production ofTxA2Increased Free radicals Increase blood pressure Decrease Utero-Placental Blood Flow
    36. 36. The Supply Line to the Human FetusCuningham FG, MacDonald PC, Leveno K, Gant NF, Gilstrap LC II Williams Obstetrics 1993
    37. 37. Pro-oxidants: Antioxidants: Homocysteine • HDL LDL • transferrin, Hypertriglyceride a blood mia protein Increased iron which binds with iron
    38. 38. Oxidative stress may be the mechanism causing endothelial dysfunction: leads to the formation of oxygen free radicals and lipid peroxides free radicals are highly reactive, interacting with and damaging molecules within the cells lipid peroxides and free radicals are both directly toxic to endothelial cells
    39. 39. Multisystemic, maternalsyndrome ReducedReduced uterine Placental blood flow perfusion Release of Toxins- Maternal Endothelial damage
    40. 40. Preeclampsia is a pregnancy complicationrecognized by: New-onset gestational hypertension • systolic >140mm Hg • diastolic >90mm Hg Proteinuria (>300 mili grams in 24 hours) Oedema feet
    41. 41. SGA-FGR SGA-FGR as a as a“Great Obstetrical Syndrome”“Great Obstetrical Syndrome”
    42. 42. “Great Obstetrical Syndromes” “Great Obstetrical Syndromes”• Multiple etiologies• Long pre-clinical phase• Fetal diseases• Clinical manifestations are adaptive• Symptomatic treatment is ineffective• Genetic/environmental factors
    43. 43. IUGR According to the Timing of the InsultType I <28 weeks SymmetricType II 30 weeks AsymmetricType III 36 weeks Postmature Villar J and Belizan J. Obstet Gynecol Surv. 1982:37:499
    44. 44. IUGR According to the Timing of the InsultType I <28 weeks SymmetricType II 30 weeks AsymmetricType III 36 weeks Postmature
    45. 45. Asymmetric Growth Restriction 38 weeks BW:2,200 grams (<10th) Length: 47 cm (>25th)
    46. 46. IUGR According to the Timing of the InsultType I <28 weeks SymmetricType II 30 weeks AsymmetricType III 36 weeks Postmature
    47. 47. Post-Maturity Syndrome 42 weeks BW:2,600 grams (<10th) Length: 49 cm ( 50th)
    48. 48. Small for Gestational Age/FGR Environmental Infection/ Inflammation Genetic Endocrine Maternal Nutritional Placental Unknown
    49. 49. Intrauterine Growth Restriction Failure to achieve its optimal growth potential
    50. 50. IUGR Morbidity IUGR Morbidity• Perinatal hypoxia• Meconium aspiration• Fetal distress• Hypothermia• Hypoglycemia• Polycythemia• Impaired postnatal growth• Neurodevelopmental handicap
    51. 51. Abnormal Uterine Artery Doppler VelocimetryNormal uterine artery Doppler Abnormal uterine artery Doppler
    52. 52. Study of the Arterial Cerebral Circulation Middle cerebral artery (MCA) Anterior cerebral artery (ACA) Pericallosal artery Posterior cerebral artery (PCA) Figueroa-Diesel H , Hernandez-Andrade E, Acosta-Rojas R, Cabero L, Gratacos E. Ultrasound Obstet Gynecol 2007;30:297-302
    53. 53. Systolic Diastolic
    54. 54. Systolic Systolic Diastolic Diastolic
    55. 55. * * * * * ** ** * * * * * * * * * * * * *
    56. 56. MANAGEMENT OF GREAT OBSTETRICAL SYNDROMES Disease Treatment Preterm labor Tocolysis Expectant Preterm PROM management Antihypertensive Pre-eclampsia agents IUGR Delivery
    57. 57. Fetal Life Adult Life ?
    58. 58. Etiology of THE GREAT OBSTETRICAL SYNDROME• Fetal• Placental GENETIC• Maternal ENVIORNMENTALThere is considerable overlapin these categories
    59. 59. Traditional View of Disease  Genetic Component  Environment Factors© 2006 VR
    60. 60. Personalized Medicine ParadigmPersonalized Medicine Paradigm “It will be possible to ascertain the genetic predisposition to disease of a given individual orpopulation and then implement behavioral and/orpharmacological interventions to delay or prevent disease or to improve treatment” Collins F and Guttmacheer AE. JAMA 2001;286:2332.
    61. 61. Fetal Origins of Adult DiseaseFetal Origins of Adult Disease
    62. 62. AIMS OF OBSTETRICAL CARE ISso both are safe and Happy
    63. 63. Pregnancy – importance of nutrients There are periods before and during pregnancy in which specific nutrients are required for optimal development. There is growing evidence that optimal dietary intake of important nutrients, like iodine, docosahexaenoic acid (DHA), choline, and folate, is necessary during pregnancy and lactation Am J Clin Nutr 2009;89(suppl):685S–7S
    64. 64. Emerging Understandings aboutNutrition in PregnancyFetal nutritional status is affected by the intrauterine and childhood nutritional experiences of the motherMaternal nutritional status at time of conception is an important determinant of outcomesIntrauterine nutritional environment affects health and development of the fetus throughout life
    65. 65. Top Three “Best Practices” toImprove Birth Outcomes & ReduceHigh Risk Births(NGA, June 2004)  Improve access to medical care and health care services  Encourage good nutrition and healthy lifestyles • Eating healthy foods • Taking folic acid (Methylating agents)  Reduce use of harmful substances
    66. 66. Nine Months of pregnancy …….Nine Challenges NTDs Spontaneous miscarriage Recurrent abortion IUGR Pre-eclampsia Placental abruption Intrauterine fetal death Pre-term labour Other Congenital defects Confidential © 2011 Abbott Nutrition
    67. 67. Hyperhomocystenemia as a risk factor____ Women who develop severe preeclampsia have higher plasma homocysteine levels in early pregnancy than women who remain normotensive throughout pregnancy. [threefold risk ] --- Cotter AM, Molloy AMet al, Am J Obstet Gynecol. 2002 May;186(5):1107; Am J Obstet Gynecol. 2001 Oct;185(4):781-5.
    68. 68. Hyperhomocystenemia as a risk factor____ Pregnant women with hyperhomocysteinemia have a 7.7-fold risk for preeclampsia – López-Quesada E, Vilaseca MA, Lailla JM. Eur J Obstet Gynecol Reprod Biol. 2003 May 1;108(1):45-9.
    69. 69. Hyperhomocystenemia as a risk factor____ Hyperhomocysteinemia is associated with pre- eclampsia as well as eclampsia, but in eclampsia the severity of homocysteine elevation is more compared to that in pre-eclampsia. ___ Hoque MM, Bulbul T, Mahal M, Islam NA, Bangladesh Med Res Counc Bull. 2008 Apr;34(1):16-20.
    70. 70. Hyperhomocystenemia as a risk factor____ Both maternal and umbilical cord plasma homocysteine concentrations were elevated in pregnancies complicated by pre-eclampsia compared to normotensive controls. Aust N Z J Obstet Gynaecol. 2008 Jun;48(3):261-5.
    71. 71. Homocysteine Naturally occuring sulpher containing amino acid Results from the demethylation of the essential aminoacid methionine
    72. 72. Homocysteine metabolism Fifty percent is re-methylated back into methionine Other fifty percent is transulfurated to cystathionine, a source of cysteine
    73. 73. Homocysteine conc regulated by Genetic factors Nutritional factors Age PregnancyNormal value – 5-15micromol/lit
    74. 74. MTHFR Deficiency - Hyperhomocystemia homocysteine methionine
    75. 75. L IA EL TH ION DO CT EN FUN ENDOTHELIAL FUNCTIO N VTE IUGR EPre-ecl VT ampsia R - G IU re a - P psi H PI lam ec
    76. 76. When to screen? Values in early pregnancy are more reliable Second-trimester plasma homocysteine concentrations do not predict the subsequent development of pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction.Hogg BB, Tamura T, Johnston KE, Dubard MB, Goldenberg RL. Am J Obstet Gynecol. 2000 Oct;183(4):805-9.Zeeman GG, Alexander JM, McIntire DD, Devaraj S, Leveno KJ. Am J Obstet Gynecol. 2003 Aug;189(2):574-6
    77. 77. Sample Collection Overnight fasting must Morning sample EDTA bulb To be centrifuged immediately Or kept on wet ice till centrifugation
    78. 78. Methods Chromatography Enzyme Immunoassay [used routinely]
    79. 79. Why to treat ? Perinatal outcome in patients with a history of preeclampsia or fetal growth restriction and hyperhomocysteinemia who are teated appears to be favorable. Leeda M, Riyazi .Am J Obstet Gynecol. 1998 Jul;179(1):135-9.
    80. 80. Presentation Title Company ConfidentialDate © 200X Abbott
    81. 81. BRAIN NUTRIENTS Presentation Title Company Confidential Date © 200X Abbott
    82. 82. Brain NutrientsDHA Docosahexaenoic acid (DHA, 22:6n23)- limited capacity for synthesis inside body, hence conditionally required in diet Major omega-3 fatty acid needed to build fetal brain Critical period during which dietary DHA may be needed to optimize brain development extends from mid-pregnancy into the first year of life DHA accumulation in fetal brain is most rapid during the last intrauterine trimester & first year of life Am J Clin Nutr 2009;89(suppl):685S–7S
    83. 83. Omega fatty acids Essential Dietary source: sea food India standard of 2 servings/week: Inadequate critical for fetal neurodevelopment and may be important for the timing of gestation and birth weight as well – DHA fetal development of brain & retina during 3 rd trimester and up to 18 months of life. – EPA play role in DHA transplacental transport & intracellular absorption. Rev Obstet Gynecol. 2008;1(4):162-169
    84. 84. Omega 3 – fatty acids Fatty acids of the omega-3 series (n-3 fatty acids) present in fish are well established dietary components affecting plasma lipids and the major cardiovascular disorders, such as arrhythmias.
    85. 85. Role of DHA DHA is an omega-3-fatty acid and is derived from alpha-linolenic acid. It accounts for about 40% of poly- unsaturated fatty acids in the brain and 60% in the retina.
    86. 86. Benefits of DHA Various studies have shown that a higher maternal DHA status/cord blood DHA was associated with: Longer gestation Higher visual acuity Better cognitive development in infants Studies have also shown that women with lower omega-3- fatty acids were 6 times more likely to get depressed during the antenatal period. A daily intake of DHA in pregnant and lactating women is recommended to be 200 mg
    87. 87. Benefits of DHA Various studies have shown that a higher maternal DHA status/cord blood DHA was associated with: Longer gestation Higher visual acuity Better cognitive development in infants Studies have also shown that women with lower omega-3- fatty acids were 6 times more likely to get depressed during the antenatal period. A daily intake of DHA in pregnant and lactating women is recommended to be 200 mg
    88. 88. Folate Folate deficiency has been reported in parts of India, West Africa, and Burma It is due to inadequate dietary intakes, cooking habits that exacerbate losses, food taboos Deficiency is associated with megaloblastic anemia, low birth weight, and potential fetal anomaly Murphy et al have reported that mothers with Hyperhomocysteinemia at 8 wk of pregnancy had nearly four times the odds of giving birth to LBW neonate Murphy MM. Clin Chem 2004; 50 : 1406-12.
    89. 89. Treatment Dietary modification Folate supplementation Methylcobalamin supplementation particulary for indian population due to high prevalance of vegeterian diet Supplementation of pyridoxine[B6] Anticagulation if history of thrombosis
    90. 90. FOLIC ACIDImportant cofactor in the Remethylation of Homocysteine  Adequate intake minimizes DNA uracil and plasma Hcy accumulation, resulting in reduced risk of chromosome breaks.  Folic acid-vitamin B supplementation significantly reduce tHcy levels (Bostom et al, 2002).  Low conc associated with risk of preterm delivery, Low birth weight infants and FGR AJCN. 2000; 71: 1295S-1303S, Am J Obstet Gynecol. 2004 Dec;191(6):1851-7.
    91. 91. L methyl Folate ..(Natures Folate) L-methylfolate is the primary biologically active form of folate1 and the primary form of folate in circulation. Folic acid, the synthetic form of folate, must undergo enzymatic reduction by methylenetetrahydrofolate reductase (MTHFR) to become biologically active
    92. 92. The Active Folate L-methylfolate is a substantially pure source of L-methylfolate containing not more than 1% D-methylfolate. D-methylfolate is not metabolized by the body and inhibits regulatory enzymes related to folate and homocysteine metabolism and reduces the bioavailability of L-methylfolate.
    93. 93. Brain NutrientsFolic acid Neural Tube Defects (NTDs) are common (the most common malformations of the central nervous system and probably second only to cardiac defects) among major congenital anomalies Maternal folic acid supplementation prevents a substantial proportion of NTDs American College of Obstetricians and Gynecologists & American Academy of Pediatrics, Food and Nutrition Board of the Institute of Medicine also recommended that all women capable of becoming pregnant should consume 0.4 mg of folate daily from supplements or fortified foods or a combination of the 2 in addition to consuming folate from a varied diet Am J Clin Nutr 2007;85(suppl):285S– 8S
    94. 94. Brain NutrientsFolic acid Plays important role in nucleic acid synthesis Marginal folate intake during gestation can impair cellular growth & replication in the fetus or placenta Sustained intake after complete closure of the neural tube to decrease the risk of other poor pregnancy outcomes During pregnancy, low concentrations of dietary and circulating folate are associated with increased risks of preterm delivery, infant low birth weight, and fetal growth retardation Am J Clin Nutr 2000;71(suppl):1295S–303S
    95. 95. Folic acid In Females : • Folic acid plays imp role in oocyte quality and maturation, implantation, fetal growth and organ development In Male : • Folic Acid plays an important role in DNA synthesis and in spermatogenesis • Folic acid proves to increase sperm count, enhance sperm motility and reduces immature cells in semen
    96. 96. VITAMIN B12A cofactor, Methionine Synthetase (MS) in methylation Enzyme, catalyses the transfer of CH3 group from MethylTetrahydrofolate Homocysteine In Vit. B12 def, folate is trapped as unusable MTHF, causing functional folate deficiency. Thus plays a key role in the remethylation of Homocysteine to Methionine.
    97. 97. VITAMIN B6 A cofactor, Pyridoxal Phosphate in methylation Reduces the level of homocysteine by the process of transulphuration to cysteine & hence related pregnancy complications are reduced. Vitamin B6 levels of mothers at the onset of pregnancy have a positive correlation with birth weight of newborns (Int J Vitam Nutr Res. 1978;48(4):341-7) Needed for CNS formation of fetus
    98. 98. Brain NutrientsIodine• Providing adequate iodine in mid-to- late pregnancy improves infant cognitive development, there are greater benefits when iodine is given before or early in pregnancy Am J Clin Nutr 2009;89(suppl):685S–7S
    99. 99. Brain NutrientsIodine WHO increased their recommended iodine intake during pregnancy from 200 to 250 mcg/d & suggested a median urinary iodine (UI) concentration of 150– 249 lg/L indicates adequate iodine intake in pregnant women Cross-sectional studies - reported impaired intellectual function & motor skills in children from iodine-deficient areas An adequate iodine supply should continue after child birth Iodine requirement of women who is fully breastfeeding her infant is even higher than that during pregnancy
    100. 100. Iodine Supplementation  Iodine deficiency is a preventable cause of mental impairment  Supplementation may be effective at preconception up to mid-pregnancy period  Form of iodine supplementation (iodinating food or oral/injectable iodine) depend on: – Severity of iodine deficiency – Cost – Availability of different preparation Enkin et al 2000; Mahomed and Gülmezoglu 2000.
    101. 101. Brain NutrientsFolate, Choline Folate is an essential vitamin, whereas choline is class of nutrients for which there is limited capacity for synthesis inside body, & therefore conditionally required in the diet Choline is required for membrane synthesis, methylation reactions, and for neurotransmitter synthesis Maternal dietary deficiency of either choline or folic acid diminishes new nerve formation (neurogenesis) and increases neural cell death in the fetal brain Am J Clin Nutr 2009;89(suppl):685S–7S
    102. 102. Brain NutrientsCholine Choline status during pregnancy influences brain development in fetus Transport of choline from mother to fetus depletes maternal plasma choline Demand for choline is so high that stores are depleted Hence supply of choline is critical during pregnancy Because milk contains a great deal of choline, lactation further increases maternal demand for choline, resulting in further depletion of tissue stores
    103. 103. Brain NutrientsCholine During pregnancy and lactation - maternal reserves depleted At the same time, the availability of choline for normal development of brain is critical Lack of choline in a mother’s diet during pregnancy and lactation may have life-long adverse effects on their child The Institute of Medicine (IOM) of the National Academy of Sciences set an adequate intake (AI) level for choline of 550 mg/day for men and 425 mg/day for women Journal of the American College of Nutrition, 2004; 23 (6), 621S–626S
    104. 104. GROWTH NUTRIENTSPresentation Title Company ConfidentialDate © 200X Abbott
    105. 105. Growth NutrientsCalcium Developing fetal skeleton accumulates about 30 g of calcium by term, about 80% of it during the third trimester Women lose 300 to 400mg of calcium daily through breast milk, this calcium demand is met by a 5–10% loss of skeletal mineral content during 6 months of exclusive lactation Women nursing twins, Ca losses may be as great as 1000 mg or more Limited maternal intake of Ca & other minerals may adversely affect fetal skeletal development, or perhaps lead to severe losses of maternal bone mineral content during pregnancy Low calcium intake might adversely affect fetal development, and is important to recommend calcium supplementation during pregnancy Journal of Mammary Gland Biology and Neoplasia,2005,10(2)
    106. 106. Calcium Recommend increase in calcium intake through diet in women at risk of hypertension or low calcium areas Reduction of incidence of PIH Calcium decreases risk pre-eclampsia, low birth weight, and chronic hypertension in children Maintain bone strengthBucher et al 1996; Kulier et al 1998; Lopez-Jaramillo et al 1997.
    107. 107. Growth Nutrients Vitamin D Maternal vit D deficiency during pregnancy was reported about 18% in UK, 25% in the UAE, 80% in Iran, 42% in northern India, 61% in New Zealand and 60–84% of pregnant non-Western women in the Netherlands, have been shown serum concentrations of 25(OH)D [25 Hydroxy vitamin D3] <25 nmol/l Studies show that infants are entering the world with a vitamin D deficit that begins in utero (within womb of mother) Concern is based on the strong relationship between maternal and fetal (cord blood) circulating 25(OH)D levels, studies from many countries, have demonstrated a high prevalence of vitamin D deficiency in mother-infant pairs at birth Significance of maternal deficiency during pregnancy - fetus developing in a state of hypovitaminosis D, which likely has significant effects on fetal and childhood bone development Am J Clin Nutr 2009;89(suppl):685S–7S
    108. 108. Growth NutrientsVitamin D Risk of osteoporotic fracture in adulthood could be determined partly by environmental factors during fetal life and early infancy In a longitudinal study, 198 children born were followed up for 9 years of age. Body builds, nutrition, and vit D status of mothers recorded during pregnancy Children were followed up at age 9 yrs to relate these maternal characteristics to their body size and bone mass Reduced concentration of 25(OH)-vitamin D in mothers during late pregnancy was associated with reduced whole-body and lumbar-spine bone-mineral content in children at age 9 years Reduced concentration of umbilical-venous calcium also predicted reduced childhood bone mass Vitamin D supplementation of pregnant women, could lead to reductions in the risk of osteoporotic fracture in their offspring Lancet 2006; 367: 36–43
    109. 109. IMMUNE NUTRIENTSPresentation Title Company ConfidentialDate © 200X Abbott
    110. 110. ANTIOXIDANTSSelenium..a trace element which has antioxidant & anticancer propertiesVitamin E …A powerful antioxidant…protects against damaging effect of free radicals Combats oxidative stress….which is an important factor in IUGR, NTD, PLACENTAL ABRUPTIONVitamin C……Antioxidant & has a role in immune system.
    111. 111. Immune NutrientsVitamin C, Zinc Vitamin C concentrations in the plasma and white blood cells (leukocytes) rapidly decline during infections and stress Supplementation of vitamin C was found to improve components of the human immune system such as antimicrobial and natural killer cell activities, lymphocyte proliferation and other immune reactions Vitamin C contributes to maintain integrity of cells and thereby protects them against reactive oxygen species generated during the metabolic reactions and the inflammatory response Zinc under-nutrition or deficiency was shown to impair cellular intermediates of innate immunity such as phagocytosis ,natural killer cell activity, and other immune mechanisms Ann Nutr Metab 2006;50:85–94
    112. 112. ZINC Zinc is an essential trace element for all forms of life. Numerous aspects of cellular metabolism are zinc- dependent. Zinc plays important roles in growth and development, the immune response, neurological function, and reproduction RDA – 12 to 15 mg/d
    113. 113. Zinc In Female : • Enhances maternal and fetal immunity • Improves the fertility outcome • Promotes bone growth and metabolism • Shows positive impact on maternal and fetal immunity In Male : • Zinc helps in elevating sperm count
    114. 114. Zincsupplementation in High risk pts.. In women at high risk of having LBW infants, supplementation with 25 mg Zn/d, beginning at an average of 19 wk gestation was evaluated There was greater fetal growth (including head circumference) that was independent of gestational age Goldberg RL. JAMA 1995;274:463–8Prophylactic doses of 20-25 mg of elemental zinc/day have been used in developing countries with WHO setting the upper limit at 35 mg/d Ladipo OA Am J Clin Nutr 2000;72 [Suppl]:280S-90S
    115. 115. Immune Nutrients Vitamin E Vitamin E is nature’s most effective lipid- soluble, chain-breaking antioxidant, protecting cell membranes from peroxidative damage Research evidence suggests that an adequate intake of vitamin E and the other antioxidants can provide protection from the increasingly high free-radical concentrations caused by air pollutants and current lifestyle patterns
    116. 116. L arginine Is an amino acid involved in  vascular regulation  immune activity  endocrine function  protein production  wound healing  erectile function  fertility
    117. 117. L- arginine to nitric oxide Potent Vasodilator
    118. 118. L- arginine in pregnancy L arginine Vascular Uterine Dilatation relaxation Inhibit Improved antihypertensive Preterm Fetoplacental in gestational UterineCirculation IUGR hypertension contractions
    119. 119. Intra-Uterine Growth RetardationIndian Scenario In India, the majority of LBW infants because of IUGR are born small [<2500g] even at full-term [>37 wks of gestation] In a prospective population study, 4307 pregnant women were identified and followed to delivery IUGR was widely prevalent – IUGR (% < 10th percentile) – 54.2% – IUGR (LBW) – 24.8% UNDERNUTRITION Muthayya S. Indian J Med Res 130, November 2009, pp 600-608
    120. 120. Poverty IgnoranceInadequate diet Poor utilization and Poor environmental And Manual labor Hygiene Lack of health facility Malnutrition Infection IUGR
    121. 121. L arginine in IUGR 43 pregnant women with IUGR received from the 30th week of gestation L-arginine 6 g per os/day Results • 32 patients improved the clinical course of pregnancy • 19 recovered the whole retardation L-arginine is the precursor for nitric oxide (NO) NO improves uteroplacental blood circulation Increase oxygen delivery to fetus Reverse IUGR Lampariello C. Minerva Ginecol. 1997 Dec;49(12):577-81
    122. 122. acceleration of fetal growth inpregnancy complicated by IUGR L-arginine 3 gm/day orally accelerated fetal growth. with mean value of 2526 g Neonates delivered in L-arginine group revealed higher Apgar score, better umbilical cord acid-base status. Lower incidence of RDS and admission to NICU.
    123. 123. Oligohydramnios Means less amniotic fluidAmniotic fluid volume predictive of IUGR Second trimester amniotic fluid levels of NO in women who subsequently developed IUGR have been shown to be lower than in controls. NO could play an important role in the prevention and treatment of IUGR as it can improve uteroplacental circulation increasing fetal blood supply
    124. 124. NO in PIH and Pre-eclampsia Preeclampsia is associated with decreased endothelial nitric oxide synthase expression, which increases cell permeability (Wang, 2004) Nitric oxide maintains the normal low-pressure vasodilated state characteristic of fetoplacental perfusion (Myatt, 1992)
    125. 125. L-arginine in Pregnancy induced HT Rytlewski et al. • L-arginine orally in dose 6 g/day in gestation complicated by pregnancy-induced hypertension • They found a normalization of blood pressure • increased nitrite/nitrate levels that usually are decreased in preeclamptic patients.Rytlewski K., Olszanecki R., Zdebski Z. (2001) 308-330.
    126. 126. L arginine on neonatal outcome in pregnancycomplicated by IUGR & gestational hypertension Pregnant women with gestational HT and IUGR • n= 42 received L arginine 3 g/day • n= 27 placebo L-arginine grp showed significantly higher birth weight at delivery, gestational age, and higher Apgar score Significantly lower number of cesarean sections in L-arginine grp than in placebo
    127. 127. Infant at delivery
    128. 128. Prolonged oral treatment with L-arginine in preeclampsia pregnancy Rytlewski et al. – Preeclamptic women at 29.2+3.4 weeks of gestation, – a prolonged supplementation with L- arginine (3 g for 3 weeks) – Significantly decreased blood pressure promoting endothelial synthesis and/or bioavailability of NO
    129. 129. NO donor in Preterm Labor NO to promote relaxation of smooth muscle, so NO donors have been employed as tocolytics. Maintain uterine quiescence during pregnancy. IV arginine infusion (30 g over 30 min) in women with premature uterine contractions transiently reduced uterine contractility. Oral arginine 7-15 gm /day may be effectiveHuman Reprod Update 1998;4:25-42.J Perinat Med 1996;24:283-285.
    130. 130. DIGESTVE NUTRIENTSPresentation Title Company ConfidentialDate © 200X Abbott
    131. 131. Digestive HealthFOS (Fructo-oligo saccharides) Stimulate the growth of beneficial bacteria present in colon Growth of beneficial bacteria helps in keeping healthy and strong large intestine. Prebiotics keep • Beneficial bacteria healthy • Have lipid reducing activity, • Boost the immune system • Help in improving mineral absorption and balance, • Clear the gut of harmful microorganisms, • Help in prevention of constipation and diarrhea Pharma Times - Vol 40 - No. 9 - September 2008
    132. 132. Digestive HealthFOS Human gut micro-flora can play a major role in host health. Prebiotics are nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of beneficial bacterial species already resident in the colon, and thus help to improve host health. Intake of prebiotics can significantly modulate the colonic micro-flora by increasing the number of beneficial bacteria and thus changing the composition of the micro-flora.
    133. 133. Dietary fiber Dietary fiber preparation from defatted rice bran has laxative and cholesterol-lowering ability with attendant benefits towards prevention or alleviation of cardiovascular disease, diabetes, diverticulosis and colon cancer.
    134. 134. Nutraceuticals "Nutraceutical" is a made-up word combining the words nutrition and pharmaceuticals, creating the concept that extracts from food can be used as drugs, i.e. food supplements Nutraceuticals (often referred to as phytochemicals or functional foods) are natural, bioactive chemical compounds that have health promoting, disease preventing or medicinal properties
    135. 135. nutraceuticals There is a lot of confusion regarding the terminologies like “nutraceuticals” “functional foods” “dietary supplements” “designer foods” “medical foods” “pharmafoods” “phytochemicals” etc.
    136. 136. Actions of nutraceuticals Inhibits the production of proinflammatory cytokines in vascular intima tissue. Reverses impaired NO production . Positive impact on platelet aggregation, triglycerides and LDL
    137. 137.  Nutraceuticals have been claimed to have a physiological benefit or provide protection against the following diseases (and/or found to act as) Cardiovascular agents Antiobese agents Antidiabetics Anticancer agents Immune boosters Chronic inflammatory disorders Degenerative diseases
    138. 138. nutraceuticals (mechanism of action) Nutrients and nutraceuticals with calcium channel blocking activity (thus antihypertensive activity) include α-Lipoic acid, magnesium, Vitamin B6 (pyridoxine), Vitamin C, N acetyl cysteine, Hawthorne, Celery, ω-3 fatty acids etc12.
    139. 139. Actions of nutraceuticals in PIH Antioxidant pathway Inflamatory pathway Immunomodulation
    140. 140. Phytochemicals A phytochemical is a chemical that acts as nutraceutical or dietary supplement that comes from plants • Isoflavones from soy • Antioxidants from vegetables • Lycopene from tomatoes
    141. 141. Nutritional Supplementationand Anemia WHO definition of severe anemia: Hemoglobin < 7 g/dL Level of risk • Moderate anemia (Hgb 7–11 g/dL): Not increased • Severe anemia: Significant risk Severe anemia associated with: • Low birth weight newborns • Premature newborns • Perinatal mortality • Increased maternal mortality and morbidity
    142. 142. Iron Supplementation  Iron requirements: • Average non-pregnant adult: – 800 µg iron lost/day – + 500 µg iron lost/day during menses • Pregnant woman: Increased need  Routine vs. selective iron supplementation: • Prevalence of nutritional anemia • Routine iron and folate supplementation where nutritional anemia is prevalent • Recommended dose: 60 mg elemental iron + 5 µg folic acid Mahomed 2000b; WHO 1994.
    143. 143. Some examples of nutrients and nutraceuticals•Vit c•Vit e•Zn•Beta carotenes•Carotenoids•GlutathioneFlavonides Selenium Copper Mangnese Vit a Lycopene L arginine
    144. 144. Supplemental therapy proved ofbenefits  L arginine  Folic acid  Zinc  Iron  Calcium  Omega 3 fatty acids
    145. 145. Herbs , flowers , ayurvedic medicinal plants
    146. 146. Fruits , legumes , vegetablesTomatoes, oranges, apricots, garlic, brocolli, Fruit- juices, legumes, sprouts
    147. 147. Flavonoids Flavonoids are widely distributed in onion, endives,cruciferous vegetables, black grapes, red wine,grapefruits, apples, cherries and berries13 Flavonoids block the angiotensin-converting enzyme (ACE) that raises blood pressure; by blocking the "suicide" enzyme cyclooxygenase that breaks down prostaglandins, they prevent platelet stickiness and hence platelet aggregation.
    148. 148. The evidencesA Peer-Reviewed Journal on Nutraceuticals and NutritionISSN-1521-4524The Role of Vascular Biology,Nutrition and Nutraceuticals in the Preventionand Treatment of HypertensionMark C. Houston,MD, SCH, FACP, FAHAThe Journal of the American Nutraceutical AssociationSupplement No. 1 April 2002
    149. 149.  Accordingly, Houston suggests that "there is a role for the selected use of single and component nutraceuticals, vitamins, antioxidants, and minerals in the treatment of hypertension based on scientifically controlled studies as a complement to optimal nutritional, dietary, and other lifestyle modifications."
    150. 150. conclusion Nutraceuticals have a direct role in PIH May have a role in prevention, arrest of progression of the disease. Further research is needed in this field
    151. 151. Overall care during pregnancy and lactation
    152. 152. Intervention - Preconception Visit to doctor Change in lifestyle Diet and nutrition • Weight control • Use of vitamins or other supplements • Eating habits, such as a vegetarian diet or fasting Keeping fit Medical conditions
    153. 153. Principles – Antenatal advice  Regular health check up  Maintain or improve health status to optimum status till delivery by judicious advice regarding diet, drugs and hygiene  Improve and tone up psychology by explaining principal changes & events likely to occur during pregnancy and labourDutta D.C. Text book of obs, 2004
    154. 154. Diet  Starting a healthy diet before pregnancy  Diet - Quantity and quality  Basic and extra nutrients for • Maintenance of maternal health • Needs of growing fetus • Strength and vitality required during labour • Successful lactation  Special concerns D.C. Text book of obs, 2004
    155. 155. Planning healthy meals Include all food groups in diet • Vegetables & fruits • Milk and dairy foods • Cereals & Grains • Meat, beans, and eggs • Fats and oils
    156. 156. Special concerns Caffeine • Limited intake during pregnancy • Excess caffeine can interfere with sleep and contribute to nausea and light- headedness • Can increase urination and lead to dehydration Vegetarian diets – low intake of iron, vitamin B12, vitamin D Pica • Strong urge to eat nonfood items such as clay, ice, laundry starch, or cornstarch • May affect intake of nutrients and can lead to constipation and anemia
    157. 157. Supplementary nutrition Personal food preferences, lifestyle habits and special needs may affect the intake of nutrients Essential vitamins lacking in diet or destroyed during cooking Nutritional supplements are one of the ways to fill the nutritional gap that may be arising due to improper diet It fills the gap by providing the vitamins, minerals, and other substances that may be missing out
    158. 158. Vital nutrients in breast milk Breast milk provides all the nutrients a baby needs to grow well for the first six months of life. The key nutrients in breast milk support the optimal growth and development of the baby and all organs and systems. Breast milk contains: • DHA and AA - building blocks of brain & eye development • Taurine & choline - support overall mental development & functioning. • Calcium and vitamin D for bone development • Many protective factors that protect the infant from infections • Fat, protein and carbohydrate, which are easily digested and absorbed
    159. 159. Mother’s nutrition influences the composition and quality of breast milk The nutritional needs of a breastfeeding mother is high - increased demand for Energy, Vitamins C, B12 • Nutrients consumed by mother is transferred to the growing baby to support its growth and development. • Nutritional deficiencies may develop during this period and affect both mothers and infants Maintaining a diet of fruits, vegetables, whole grains, lean meats, and dairy products regularly will help to meet nutritional needs Company Conf
    160. 160. Nutrition during lactation Human milk feeding is adequate as the sole source of nutrition for up to age 6 month providing that the maternal diet and reserves are adequate and a sufficient quantity is transferred to the infant Milk secreted in 4 months represents an amount of energy roughly equivalent to the total energy cost of pregnancy As with energy, recommended intakes for several vitamins and minerals are higher in lactation than in pregnancy Maternal nutritional adequacy does influence performance indexes both in pregnancy and lactation
    161. 161. Method to enhance activecomponents in food  Manipulating the diet to get maximum level of active components  Combination of food ingredients rich in nutraceuticals  Fortifying food with active ingredients  By fermentation of food products  Changing food habits to natural type of diet
    162. 162. Summary Evidence of nutritional intervention effectiveness • Balanced energy/protein supplementation • Zinc • Periconceptional folic acid intake • Iron supplementation • Calcium • Omega fatty acids • Iodine use • L -arginine
    163. 163. CONCLUSION Nutraceuticals are present in most of the food ingredients with varying concentration Concentration, time and duration of supply of nutraceuticals influence human health Manipulating the foods, the concentration of active ingredients can be increased Diet rich in nutraceuticals along with regular exercise, stress reduction and maintenance of healthy body weight will maximise health and reduce disease risk
    164. 164. “The doctor of the future will give no medicine, but willinterest his patient in the care of the human frame, in diet andin the cause and prevention of disease” – Thomas Edison.
    165. 165. And Finally… the goal is HEALTHY & SAFE
    166. 166. thank youfrom a healty methyl folate baby
    167. 167. THANK YOU