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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)
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
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
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.
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
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
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
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.
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
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
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
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.
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
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
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
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.
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.
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
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
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.
177. THANK YOU FOR THIS OPPURTUNITY
AND FOR THE PATIENT HEARING
WELCOME TO AGRA for SAFOG FEB 2013
Notas del editor
4th Report - The World Nutrition Situation: Nutrition throughout the Life Cycle (IFPRI - UNSSCN, 2000, 136 p.)
Slide 4: Maternal Malnutrition: A Life-Cycle Issue (one) Women are vulnerable to malnutrition throughout the life cycle for both biological and social reasons. Infancy and early childhood (0–24 months) . Most young girls living in poor environments are suboptimally breastfed in infancy and early childhood, receive infrequent and poor complementary foods (both in quantity and/or quality), and suffer frequent infections. Such nutritional neglect during the first two years of life has immediate and long-term negative consequences on women’s survival, growth, development, and productivity. Childhood (two to nine years) . At two years of age, many of the girls who survive under such nutritional stress are stunted with little chance of recovery. Moreover, in some parts of the world, girls are discriminated against in access to food, health care, and education throughout childhood .
Slide 5: Maternal Malnutrition: A Life-Cycle Issue (two) Adolescence (10–19 years). During adolescence, girls experience rapid physical growth and sexual maturation which significantly increases their needs for macronutrients and micronutrients (especially iron). Adolescent girls’ growth spurt occurs before menarche (first menstruation). Adolescent girls continue to grow in height long after menarche. Linear growth, particularly of the long bones, is not complete until the age of 18, and peak bone mass is not achieved until the age of 25. A malnourished adolescent girl whose menarche has been delayed may achieve full height as late as 23 years and will, therefore, be capable of conceiving before her body size is fully developed. Moreover, the development of the birth canal is slower than that of height and does not reach mature size until about two to three years after the growth in height has ceased. Pregnancy puts adolescent women at increased risk of malnutrition (diverting nutrients from the mother to the fetus), pregnancy complications, and poor pregnancy outcomes (including death). Early pregnancy contributes to the cycle of maternal malnutrition in two ways: Indirectly, through the premature cessation of the mother’s growth. Directly, through the increased risk of delivering a low birth weight baby. Pregnancy and lactation. In most developing countries, women spend a large proportion of their reproductive years pregnant, lactating or pregnant and lactating. McGuire and Popkin (1990) estimate that on average, African and Asian women between the ages of 15 and 45 are pregnant or lactating 30–48 percent of their time. The nutritional demands during pregnancy and lactation are multiple to support fetal growth and breastmilk production. These added nutritional requirements specific to pregnancy and lactation manifest themselves both at the macronutrient and the micronutrient level. More calories are needed to achieve adequate pregnancy weight gain and build stores for lactation. More iron is needed because of the growth of the fetus and placenta and the expansion of plasma volume. More vitamin A may be needed to ensure adequate vitamin A concentration in breastmilk. Closely spaced reproductive cycles, negative energy balance, and micronutrient deficiencies can lead to a condition known as “maternal depletion syndrome”. Nutritional stress is greatest when an adolescent woman is pregnant and lactating.
Slide 6: Maternal Malnutrition: a Life-Cycle Issue (three) Throughout life. Most women living in developing countries experience various biological and social stresses that increase the risk of malnutrition throughout life. These include: Food insecurity Inadequate diets Recurrent infections Frequent parasites Poor health care Heavy work burdens Gender inequities
Fetal growth has become fashionable because of the hypothesis of the fetal origins for adult disease which has been advocated by David Barker and his team. These two books summarize much of evidence which I will discuss at the end of the talk.
Let begin by addressing the definition of growth
Let begin by addressing the definition of growth
This baby has a growth disorder. It was born at term but starved in utero. It lacks sub-cutaneous tissue as can be seen by the prominent iliac wing and a thin leg (Pat insert arrows). So there is no question that intra-uterine starvation occurred.
More than a decade ago, we have proposed that preterm labor is a syndrome characterized by the presence of uterine contractions, cervical ripening and membrane/decidual activation caused by (click) infection/inflammation, which is the most common cause studied in the context of preterm labor and delivery. Our group and others have clearly demonstrated the importance of infection, the prevalence and the clinical significance of infection in preterm birth. The other potential causes are … (click) X 5
In contrast, intrauterine growth retardation is the failure to achieve an individual optimal growth potential Such a failure may occur even in the infants is above the 10 th percentile
Fetal growth has become fashionable because of the hypothesis of the fetal origins for adult disease which has been advocated by David Barker and his team. These two books summarize much of evidence which I will discuss at the end of the talk.
Some salts, bread and seafood have been supplemented with iodine. Iodine may be found in other locally available foods. The US recommended daily allowance is 150 g/day for adults, 175 g/day for pregnant women and 200 g/day for lactating women.
Therefore, both nutrients play important roles in immune function and the modulation of host resistance to infectious agents, reducing the risk, severity, and duration of infectious diseases
Classifications of anemia were taken from the World Health Organization (WHO). December 2000. Essential Care Practice Guide: Pregnancy, Childbirth and Newborn Care . Draft. Severe anemia is associated with a significantly increased risk of complications in pregnancy, specifically low birth weight newborns, premature birth, perinatal mortality, and increased maternal mortality and morbidity. This increase is due to low oxygen-carrying capacity for both fetus and mother.
Foods abundant in iron include: red meat (especially liver), poultry, fish, whole grains, dark green leafy vegetables, shellfish and dried fruit. Absorption is improved if taken with foods containing vitamin C. Adult females should get 30 mg/day, especially if they are pregnant.
Slide 40: Improving Maternal Weight Increases in weight can be achieved within a woman’s reproductive life by: Increasing caloric intake and/or by Reducing energy expenditure and/or by Reducing caloric depletion (delaying the first pregnancy and increasing birth intervals)