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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 : mnmhagra10@dataone.in / mnmhagra3@gmail.com
                                                      Website : www.malhotrahospitals.com
                                                          Apollo Pankaj Hospitals, Agra
                Consultant for IVF at jalandhar,ludhiana,ambala,bhiwani,gwalior,allahabad,gorakhpur,udaipur,bariely,jaipur,delhi
                                                               Neapal & Bangladesh
Nutrition during Pregnancy
Suppliment therapy in managing PIH & IUGR




    narendra malhotra
    jaideep malhotra
    drnarendra@malhotrahospitals.com
    jaideepmalhotraagra@gmail.com

    www.malhotrahospitals.com
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
Maternal Nutrition Issues



Effect of nutritional inadequacies at different
            points in the life cycle
    FROM INTRAUTERINE TO ADULTHOOD
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
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
Maternal Malnutrition: A Life-Cycle Issue
 Throughout life
   •   Food insecurity
   •   Inadequate diets
   •   Recurrent infections
   •   Frequent parasites
   •   Poor health care
   •   Heavy workloads
   •   Gender inequities
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)
Fetal Origins of Adult Disease
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
The nutritional status of pregnant women in
                    India




  60 plus years,India is still poor, pregnant and powerless
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
Average intake of nutrients




                       J Hum Ecol, 29(3): 165-170 (2010)
Study from Andhra Pradesh




               European Journal of Clinical Nutrition 2003; 57, 52–60
Study from northern India




                Maternal and Child Nutrition (2008), 4, pp. 86–94
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
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
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
Nutrient Intake of Lactating Mothers from Hisar
- Ind Jr Social Research 1998;39(2):91-99




Presentation Title   Company Confidential
Date                 © 200X Abbott
Women …. Pregnancy…. Baby
        Ultimate Desire
BUT IF
     IUGR                 AT RISK       PIH
Oligohydramnios                     Preeclampsia

POLYHYDRAMNIOS



PLACENTAL COMPLICATIONS
                                    Preterm labor


       Then it’s a matter of concern
As it leads to

                  Maternal Morbidity
                          &
                       Mortality



Fetal Morbidity
       &
   Mortality
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
Sadler TW Lagman’s Medical Embryology 1990

  Umbilical                                  Chorionic
   vessels         Chorionic                   plate                Amnion
                    vessels




              Normal Placental Development




                                                             Placental
                                            Spiral            septum
   Uteroplacental           Basal           artery
       veins                plate
From 9-12 weeks gestation the uterine spiral arteries are transformed from thick-
walled, muscular vessels, to more flaccid tubes to accommodate a 10-fold
increase in uterine blood flow to support the pregnancy.
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.
The Challenge of
   Obstetrics
Obstetrical Disease
     Obstetrical Disease
    The great obstetrical
    The great obstetrical
         syndrome
         syndrome
•    Preterm labor
•    Preterm Rupture of
     membranes
•    Pre-eclampsia
•    SGA/IUGR
•    Fetal Death
PRE ECLAMPSIA


Presentation Title   Company Confidential
Date                 © 200X Abbott
Preeclampsia
Patho-physiological Theories
 Abnormal trophoblastic invasion




 Prostanoid theory (imbalance between
  prostacyclin and thromboxane A2)




 Vascular endothelium dysfunction


               31
Preeclampsia
What happens to blood vessels?



                          Normal Levels of:
                          TxA2
                          Prostacyclin
                          Nitric Oxide
                          Free Radicals




                          Altered Levels of:
                          ↑ TxA2
                          ↓ Prostacyclin
                          ↓ Nitric Oxide
                          ↑ Free Radicals

     32
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.
Preeclampsia
Prostanoid - Theory




34
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
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
Decrease formation of NO
Increased production of
TxA2
Increased Free radicals


                    Increase blood pressure
                    Decrease Utero-Placental Blood
                    Flow
The Supply Line to the Human Fetus




Cuningham FG, MacDonald PC, Leveno K, Gant NF, Gilstrap LC II Williams
                         Obstetrics 1993
Pro-oxidants:         Antioxidants:
 Homocysteine        • HDL
 LDL                 • transferrin,
 Hypertriglyceride     a blood
  mia                   protein
 Increased iron        which binds
                        with iron
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
Multisystemic, maternal
syndrome


                                Reduced
Reduced uterine
                                Placental
   blood flow
                                perfusion


                  Release of
                    Toxins-
                   Maternal
                  Endothelial
                   damage
Preeclampsia is a pregnancy complication
recognized by:


    New-onset gestational hypertension
  • systolic >140mm Hg
  • diastolic >90mm Hg
    Proteinuria (>300 mili grams in 24
    hours)
    Oedema feet
SGA-FGR
         SGA-FGR
            as a
            as a
“Great Obstetrical Syndrome”
“Great Obstetrical Syndrome”
“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
IUGR According to the
      Timing of the Insult

Type I     <28 weeks                Symmetric

Type II    30 weeks               Asymmetric

Type III   36 weeks                Postmature


                 Villar J and Belizan J. Obstet Gynecol Surv. 1982:37:499
IUGR According to the
      Timing of the Insult

Type I     <28 weeks   Symmetric

Type II    30 weeks    Asymmetric

Type III   36 weeks    Postmature
Asymmetric Growth Restriction
               38 weeks
               BW:2,200 grams (<10th)
               Length: 47 cm (>25th)
IUGR According to the
      Timing of the Insult

Type I     <28 weeks   Symmetric

Type II    30 weeks    Asymmetric

Type III   36 weeks    Postmature
Post-Maturity Syndrome



           42 weeks
           BW:2,600 grams (<10th)
           Length: 49 cm ( 50th)
Small for Gestational Age/FGR
          Environmental     Infection/
                          Inflammation


   Genetic                          Endocrine


                                         Maternal
 Nutritional


 Placental                               Unknown
Intrauterine Growth Restriction


   Failure to achieve its
 optimal growth potential
IUGR Morbidity
             IUGR Morbidity
• Perinatal hypoxia
• Meconium aspiration
• Fetal distress
• Hypothermia
• Hypoglycemia
• Polycythemia
• Impaired postnatal growth
• Neurodevelopmental handicap
Abnormal Uterine Artery
                 Doppler Velocimetry




Normal uterine artery Doppler   Abnormal uterine artery Doppler
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
Systolic



           Diastolic
Systolic               Systolic


                             Diastolic
           Diastolic
* *                     *
    *           *
                    **       *
*                            *
               *         *                *
                    *                *
                    *                    *
         *                       *
        * *                               *
MANAGEMENT OF GREAT OBSTETRICAL SYNDROMES




      Disease            Treatment
   Preterm labor          Tocolysis
                         Expectant
   Preterm PROM
                        management
                      Antihypertensive
   Pre-eclampsia
                           agents
       IUGR               Delivery
Fetal Life       Adult Life
             ?
Etiology of THE
    GREAT
    OBSTETRICAL
    SYNDROME
• Fetal
• Placental                 GENETIC
• Maternal                  ENVIORNMENTAL

There is considerable overlap
in these categories
Traditional View of Disease


             Genetic Component

             Environment Factors


© 2006 VR
Personalized Medicine Paradigm
Personalized Medicine Paradigm


    “It will be possible to ascertain the genetic
 predisposition to disease of a given individual or
population and then implement behavioral and/or
pharmacological interventions to delay or prevent
         disease or to improve treatment”



          Collins F and Guttmacheer AE. JAMA 2001;286:2332.
Fetal Origins of Adult Disease
Fetal Origins of Adult Disease
AIMS OF OBSTETRICAL CARE IS
so both are safe and Happy
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
Emerging Understandings about
Nutrition 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
Top Three “Best Practices” to
Improve Birth Outcomes & Reduce
High 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
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
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.
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.
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.
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.
Homocysteine


 Naturally occuring sulpher
  containing amino acid Results from
  the demethylation of the essential
  aminoacid methionine
Homocysteine metabolism


 Fifty percent is re-methylated back into methionine

 Other fifty percent is transulfurated to
  cystathionine, a source of cysteine
Homocysteine conc regulated by
   Genetic factors
   Nutritional factors
   Age
   Pregnancy

Normal value – 5-15micromol/lit
MTHFR Deficiency - Hyperhomocystemia




 homocysteine            methionine
L
                                   IA
                                 EL
                               TH ION
                             DO CT
                           EN FUN
                             ENDOTHELIAL
                              FUNCTIO
                                     N
     VTE
     IUGR
                  E
Pre-ecl         VT
       ampsia
                           R      -
                         G
                      IU        re a
                             - P psi
                          H
                       PI lam
                          ec
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
Sample Collection
 Overnight fasting must
 Morning sample
 EDTA bulb
 To be centrifuged immediately
 Or kept on wet ice till
  centrifugation
Methods
 Chromatography

 Enzyme Immunoassay
 [used routinely]
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.
Presentation Title   Company Confidential
Date                 © 200X Abbott
BRAIN NUTRIENTS


 Presentation Title   Company Confidential
 Date                 © 200X Abbott
Brain Nutrients
DHA
 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
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
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.
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.
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
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
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.
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
FOLIC ACID
Important 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.
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
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.
Brain Nutrients
Folic 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
Brain Nutrients
Folic 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
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
VITAMIN B12
A 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.
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
Brain Nutrients
Iodine

• 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
Brain Nutrients
Iodine

  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
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.
Brain Nutrients
Folate, 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
Brain Nutrients
Choline

 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
Brain Nutrients
Choline

 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
GROWTH NUTRIENTS


Presentation Title   Company Confidential
Date                 © 200X Abbott
Growth Nutrients
Calcium
    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)
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 strength




Bucher et al 1996; Kulier et al 1998; Lopez-Jaramillo et al 1997.
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
Growth Nutrients
Vitamin 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
IMMUNE NUTRIENTS


Presentation Title   Company Confidential
Date                 © 200X Abbott
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.
Immune Nutrients
Vitamin 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
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
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
Zinc
supplementation 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;274:463–8

Prophylactic 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
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
L arginine
             Is an amino acid involved in
                  vascular regulation
                   immune activity
                  endocrine function
                  protein production
                    wound healing
                   erectile function
                        fertility
L- arginine to nitric oxide




                  Potent Vasodilator
L- arginine in pregnancy

                     L arginine

     Vascular                        Uterine
     Dilatation                     relaxation
                                        Inhibit
  Improved       antihypertensive     Preterm
 Fetoplacental    in gestational       Uterine
Circulation IUGR   hypertension
                                    contractions
Intra-Uterine Growth Retardation
Indian 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
Poverty


                      Ignorance


Inadequate diet      Poor utilization
     and                                  Poor environmental
                           And
  Manual labor                                 Hygiene
                  Lack of health facility




 Malnutrition                                Infection



                     IUGR
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
acceleration of fetal growth in
pregnancy 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.
Oligohydramnios
 Means less amniotic fluid

Amniotic 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
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)
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.
L arginine on neonatal outcome in pregnancy
complicated 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
Infant at delivery
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
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 effective




Human Reprod Update 1998;4:25-42.
J Perinat Med 1996;24:283-285.
DIGESTVE NUTRIENTS

Presentation Title   Company Confidential
Date                 © 200X Abbott
Digestive Health
FOS (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
Digestive Health
FOS
 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.
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.
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
nutraceuticals

 There is a lot of confusion regarding the terminologies like
  “nutraceuticals”
 “functional foods”
 “dietary supplements”
 “designer foods”
 “medical foods”
 “pharmafoods”
 “phytochemicals” etc.
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
 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
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.
Actions of nutraceuticals in PIH



 Antioxidant pathway
 Inflamatory pathway
 Immunomodulation
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
Nutritional Supplementation
and 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
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.
Some examples of nutrients and
       nutraceuticals

•Vit c
•Vit e
•Zn
•Beta carotenes
•Carotenoids
•Glutathione
Flavonides        Selenium
                  Copper
                  Mangnese
                   Vit a
                   Lycopene
                   L arginine
Supplemental therapy proved of
benefits
           L arginine
           Folic acid
           Zinc
           Iron
           Calcium
           Omega 3 fatty
            acids
Herbs , flowers , ayurvedic medicinal plants
Fruits , legumes , vegetables




Tomatoes, oranges, apricots, garlic, brocolli,
      Fruit- juices, legumes, sprouts
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.
The evidences
A Peer-Reviewed Journal on Nutraceuticals and Nutrition
ISSN-1521-4524
The Role of Vascular Biology,
Nutrition and Nutraceuticals in the Prevention
and Treatment of Hypertension
Mark C. Houston,MD, SCH, FACP, FAHA



The Journal of the American Nutraceutical Association
Supplement No. 1 April 2002
 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."
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
Overall care during pregnancy and lactation
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
http://www.acog.org/publications/patient_education/bp056.cfm
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 labour


Dutta D.C. Text book of obs, 2004
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




http://www.acog.org/publications/patient_education/
bp001.cfm
Dutta D.C. Text book of obs, 2004
Planning healthy meals
 Include all food groups in
  diet
  •   Vegetables & fruits
  •   Milk and dairy foods
  •   Cereals & Grains
  •   Meat, beans, and eggs
  •   Fats and oils
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
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
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
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
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
Method to enhance active
components 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
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
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
“The doctor of the future will give no medicine, but will
interest his patient in the care of the human frame, in diet and
in the cause and prevention of disease” –

                 Thomas Edison.
And Finally… the goal is HEALTHY & SAFE
thank you
from a healty methyl folate baby
THANK YOU
THANK YOU FOR THIS OPPURTUNITY
AND FOR THE PATIENT HEARING




    WELCOME TO AGRA for SAFOG FEB 2013
Nutraceuticals in pregnancy 1
Nutraceuticals in pregnancy 1

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Nutraceuticals in pregnancy 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 : mnmhagra10@dataone.in / mnmhagra3@gmail.com Website : www.malhotrahospitals.com Apollo Pankaj Hospitals, Agra Consultant for IVF at jalandhar,ludhiana,ambala,bhiwani,gwalior,allahabad,gorakhpur,udaipur,bariely,jaipur,delhi Neapal & Bangladesh
  • 2. Nutrition during Pregnancy Suppliment therapy in managing PIH & IUGR narendra malhotra jaideep malhotra drnarendra@malhotrahospitals.com jaideepmalhotraagra@gmail.com www.malhotrahospitals.com
  • 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. Maternal Nutrition Issues Effect of nutritional inadequacies at different points in the life cycle FROM INTRAUTERINE TO ADULTHOOD
  • 5.
  • 6. 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
  • 7. 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
  • 8. Maternal Malnutrition: A Life-Cycle Issue  Throughout life • Food insecurity • Inadequate diets • Recurrent infections • Frequent parasites • Poor health care • Heavy workloads • Gender inequities
  • 9. 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)
  • 10. Fetal Origins of Adult Disease
  • 11. 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
  • 12. The nutritional status of pregnant women in India 60 plus years,India is still poor, pregnant and powerless
  • 13. 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
  • 14. Average intake of nutrients J Hum Ecol, 29(3): 165-170 (2010)
  • 15. Study from Andhra Pradesh European Journal of Clinical Nutrition 2003; 57, 52–60
  • 16. Study from northern India Maternal and Child Nutrition (2008), 4, pp. 86–94
  • 17. 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
  • 18. 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
  • 19. 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
  • 20. Nutrient Intake of Lactating Mothers from Hisar - Ind Jr Social Research 1998;39(2):91-99 Presentation Title Company Confidential Date © 200X Abbott
  • 21. Women …. Pregnancy…. Baby Ultimate Desire
  • 22. BUT IF IUGR AT RISK PIH Oligohydramnios Preeclampsia POLYHYDRAMNIOS PLACENTAL COMPLICATIONS Preterm labor Then it’s a matter of concern
  • 23. As it leads to Maternal Morbidity & Mortality Fetal Morbidity & Mortality
  • 24.
  • 25. 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
  • 26. Sadler TW Lagman’s Medical Embryology 1990 Umbilical Chorionic vessels Chorionic plate Amnion vessels Normal Placental Development Placental Spiral septum Uteroplacental Basal artery veins plate From 9-12 weeks gestation the uterine spiral arteries are transformed from thick- walled, muscular vessels, to more flaccid tubes to accommodate a 10-fold increase in uterine blood flow to support the pregnancy.
  • 27. 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.
  • 28. The Challenge of Obstetrics
  • 29. Obstetrical Disease Obstetrical Disease The great obstetrical The great obstetrical syndrome syndrome • Preterm labor • Preterm Rupture of membranes • Pre-eclampsia • SGA/IUGR • Fetal Death
  • 30. PRE ECLAMPSIA Presentation Title Company Confidential Date © 200X Abbott
  • 31. Preeclampsia Patho-physiological Theories  Abnormal trophoblastic invasion  Prostanoid theory (imbalance between prostacyclin and thromboxane A2)  Vascular endothelium dysfunction 31
  • 32. Preeclampsia What happens to blood vessels? Normal Levels of: TxA2 Prostacyclin Nitric Oxide Free Radicals Altered Levels of: ↑ TxA2 ↓ Prostacyclin ↓ Nitric Oxide ↑ Free Radicals 32
  • 33. 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.
  • 35. 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
  • 36. 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
  • 37. Decrease formation of NO Increased production of TxA2 Increased Free radicals Increase blood pressure Decrease Utero-Placental Blood Flow
  • 38. The Supply Line to the Human Fetus Cuningham FG, MacDonald PC, Leveno K, Gant NF, Gilstrap LC II Williams Obstetrics 1993
  • 39. Pro-oxidants: Antioxidants:  Homocysteine • HDL  LDL • transferrin,  Hypertriglyceride a blood mia protein  Increased iron which binds with iron
  • 40. 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
  • 41. Multisystemic, maternal syndrome Reduced Reduced uterine Placental blood flow perfusion Release of Toxins- Maternal Endothelial damage
  • 42. Preeclampsia is a pregnancy complication recognized by: New-onset gestational hypertension • systolic >140mm Hg • diastolic >90mm Hg Proteinuria (>300 mili grams in 24 hours) Oedema feet
  • 43. SGA-FGR SGA-FGR as a as a “Great Obstetrical Syndrome” “Great Obstetrical Syndrome”
  • 44. “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
  • 45. IUGR According to the Timing of the Insult Type I <28 weeks Symmetric Type II 30 weeks Asymmetric Type III 36 weeks Postmature Villar J and Belizan J. Obstet Gynecol Surv. 1982:37:499
  • 46. IUGR According to the Timing of the Insult Type I <28 weeks Symmetric Type II 30 weeks Asymmetric Type III 36 weeks Postmature
  • 47. Asymmetric Growth Restriction 38 weeks BW:2,200 grams (<10th) Length: 47 cm (>25th)
  • 48. IUGR According to the Timing of the Insult Type I <28 weeks Symmetric Type II 30 weeks Asymmetric Type III 36 weeks Postmature
  • 49. Post-Maturity Syndrome 42 weeks BW:2,600 grams (<10th) Length: 49 cm ( 50th)
  • 50. Small for Gestational Age/FGR Environmental Infection/ Inflammation Genetic Endocrine Maternal Nutritional Placental Unknown
  • 51. Intrauterine Growth Restriction Failure to achieve its optimal growth potential
  • 52. IUGR Morbidity IUGR Morbidity • Perinatal hypoxia • Meconium aspiration • Fetal distress • Hypothermia • Hypoglycemia • Polycythemia • Impaired postnatal growth • Neurodevelopmental handicap
  • 53. Abnormal Uterine Artery Doppler Velocimetry Normal uterine artery Doppler Abnormal uterine artery Doppler
  • 54. 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
  • 55. Systolic Diastolic
  • 56. Systolic Systolic Diastolic Diastolic
  • 57. * * * * * ** * * * * * * * * * * * * * * *
  • 58. MANAGEMENT OF GREAT OBSTETRICAL SYNDROMES Disease Treatment Preterm labor Tocolysis Expectant Preterm PROM management Antihypertensive Pre-eclampsia agents IUGR Delivery
  • 59. Fetal Life Adult Life ?
  • 60. Etiology of THE GREAT OBSTETRICAL SYNDROME • Fetal • Placental GENETIC • Maternal ENVIORNMENTAL There is considerable overlap in these categories
  • 61. Traditional View of Disease  Genetic Component  Environment Factors © 2006 VR
  • 62.
  • 63.
  • 64.
  • 65.
  • 66. Personalized Medicine Paradigm Personalized Medicine Paradigm “It will be possible to ascertain the genetic predisposition to disease of a given individual or population and then implement behavioral and/or pharmacological interventions to delay or prevent disease or to improve treatment” Collins F and Guttmacheer AE. JAMA 2001;286:2332.
  • 67.
  • 68. Fetal Origins of Adult Disease Fetal Origins of Adult Disease
  • 69. AIMS OF OBSTETRICAL CARE IS so both are safe and Happy
  • 70. 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
  • 71. Emerging Understandings about Nutrition 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
  • 72. Top Three “Best Practices” to Improve Birth Outcomes & Reduce High 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
  • 73. 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
  • 74. 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.
  • 75. 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.
  • 76. 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.
  • 77. 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.
  • 78. Homocysteine  Naturally occuring sulpher containing amino acid Results from the demethylation of the essential aminoacid methionine
  • 79. Homocysteine metabolism  Fifty percent is re-methylated back into methionine  Other fifty percent is transulfurated to cystathionine, a source of cysteine
  • 80.
  • 81. Homocysteine conc regulated by  Genetic factors  Nutritional factors  Age  Pregnancy Normal value – 5-15micromol/lit
  • 82. MTHFR Deficiency - Hyperhomocystemia homocysteine methionine
  • 83. L IA EL TH ION DO CT EN FUN ENDOTHELIAL FUNCTIO N VTE IUGR E Pre-ecl VT ampsia R - G IU re a - P psi H PI lam ec
  • 84. 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
  • 85. Sample Collection  Overnight fasting must  Morning sample  EDTA bulb  To be centrifuged immediately  Or kept on wet ice till centrifugation
  • 86. Methods  Chromatography  Enzyme Immunoassay [used routinely]
  • 87. 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.
  • 88. Presentation Title Company Confidential Date © 200X Abbott
  • 89. BRAIN NUTRIENTS Presentation Title Company Confidential Date © 200X Abbott
  • 90. Brain Nutrients DHA  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
  • 91. 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
  • 92. 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.
  • 93. 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.
  • 94. 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
  • 95. 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
  • 96. 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.
  • 97. 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
  • 98. FOLIC ACID Important 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.
  • 99. 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
  • 100. 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.
  • 101. Brain Nutrients Folic 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
  • 102. Brain Nutrients Folic 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
  • 103. 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
  • 104. VITAMIN B12 A 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.
  • 105. 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
  • 106. Brain Nutrients Iodine • 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
  • 107. Brain Nutrients Iodine  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
  • 108. 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.
  • 109. Brain Nutrients Folate, 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
  • 110. Brain Nutrients Choline  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
  • 111. Brain Nutrients Choline  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
  • 112. GROWTH NUTRIENTS Presentation Title Company Confidential Date © 200X Abbott
  • 113. Growth Nutrients Calcium  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)
  • 114. 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 strength Bucher et al 1996; Kulier et al 1998; Lopez-Jaramillo et al 1997.
  • 115. 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
  • 116. Growth Nutrients Vitamin 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
  • 117. IMMUNE NUTRIENTS Presentation Title Company Confidential Date © 200X Abbott
  • 118. 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.
  • 119. Immune Nutrients Vitamin 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
  • 120. 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
  • 121. 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
  • 122. Zinc supplementation 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;274:463–8 Prophylactic 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
  • 123. 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
  • 124. L arginine Is an amino acid involved in  vascular regulation  immune activity  endocrine function  protein production  wound healing  erectile function  fertility
  • 125. L- arginine to nitric oxide Potent Vasodilator
  • 126. L- arginine in pregnancy L arginine Vascular Uterine Dilatation relaxation Inhibit Improved antihypertensive Preterm Fetoplacental in gestational Uterine Circulation IUGR hypertension contractions
  • 127. Intra-Uterine Growth Retardation Indian 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
  • 128. Poverty Ignorance Inadequate diet Poor utilization and Poor environmental And Manual labor Hygiene Lack of health facility Malnutrition Infection IUGR
  • 129. 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
  • 130. acceleration of fetal growth in pregnancy 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.
  • 131. Oligohydramnios  Means less amniotic fluid Amniotic 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
  • 132. 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)
  • 133. 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.
  • 134. L arginine on neonatal outcome in pregnancy complicated 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
  • 136. 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
  • 137. 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 effective Human Reprod Update 1998;4:25-42. J Perinat Med 1996;24:283-285.
  • 138. DIGESTVE NUTRIENTS Presentation Title Company Confidential Date © 200X Abbott
  • 139. Digestive Health FOS (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
  • 140. Digestive Health FOS  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.
  • 141. 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.
  • 142. 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
  • 143. nutraceuticals  There is a lot of confusion regarding the terminologies like “nutraceuticals”  “functional foods”  “dietary supplements”  “designer foods”  “medical foods”  “pharmafoods”  “phytochemicals” etc.
  • 144. 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
  • 145.  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
  • 146. 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.
  • 147. Actions of nutraceuticals in PIH  Antioxidant pathway  Inflamatory pathway  Immunomodulation
  • 148. 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
  • 149. Nutritional Supplementation and 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
  • 150. 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.
  • 151. Some examples of nutrients and nutraceuticals •Vit c •Vit e •Zn •Beta carotenes •Carotenoids •Glutathione Flavonides Selenium Copper Mangnese Vit a Lycopene L arginine
  • 152. Supplemental therapy proved of benefits  L arginine  Folic acid  Zinc  Iron  Calcium  Omega 3 fatty acids
  • 153. Herbs , flowers , ayurvedic medicinal plants
  • 154. Fruits , legumes , vegetables Tomatoes, oranges, apricots, garlic, brocolli, Fruit- juices, legumes, sprouts
  • 155. 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.
  • 156.
  • 157. The evidences A Peer-Reviewed Journal on Nutraceuticals and Nutrition ISSN-1521-4524 The Role of Vascular Biology, Nutrition and Nutraceuticals in the Prevention and Treatment of Hypertension Mark C. Houston,MD, SCH, FACP, FAHA The Journal of the American Nutraceutical Association Supplement No. 1 April 2002
  • 158.  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."
  • 159. 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
  • 160. Overall care during pregnancy and lactation
  • 161. 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 http://www.acog.org/publications/patient_education/bp056.cfm
  • 162. 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 labour Dutta D.C. Text book of obs, 2004
  • 163. 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 http://www.acog.org/publications/patient_education/ bp001.cfm Dutta D.C. Text book of obs, 2004
  • 164. Planning healthy meals  Include all food groups in diet • Vegetables & fruits • Milk and dairy foods • Cereals & Grains • Meat, beans, and eggs • Fats and oils
  • 165. 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
  • 166. 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
  • 167. 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
  • 168. 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
  • 169. 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
  • 170. Method to enhance active components 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
  • 171. 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
  • 172. 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
  • 173. “The doctor of the future will give no medicine, but will interest his patient in the care of the human frame, in diet and in the cause and prevention of disease” – Thomas Edison.
  • 174. And Finally… the goal is HEALTHY & SAFE
  • 175. thank you from a healty methyl folate baby
  • 177. THANK YOU FOR THIS OPPURTUNITY AND FOR THE PATIENT HEARING WELCOME TO AGRA for SAFOG FEB 2013

Notas del editor

  1. 4th Report - The World Nutrition Situation: Nutrition throughout the Life Cycle (IFPRI - UNSSCN, 2000, 136 p.)
  2. 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 .
  3. 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.
  4. 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
  5. 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.
  6. Let begin by addressing the definition of growth
  7. Let begin by addressing the definition of growth
  8. 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.
  9. 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
  10. 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
  11. 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.
  12. 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.
  13. 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
  14. 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.
  15. 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.
  16. 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)