Nutraceuticals in pregnancy 1

NARENDRA MALHOTRAM.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 HOSPITALS84, M.G. Road, Agra-282 010

Phone : (O) 0562-2260275/2260276/2260277, (R) 0562-2260279, (M) 98370-33335; Fax : 0562-2265194E-mail : [email protected] / [email protected]

Website : www.malhotrahospitals.comApollo 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 malhotrajaideep [email protected]@gmail.com

www.malhotrahospitals.com

mailto:[email protected]

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


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


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

Indian Pediatrics 1999; 36: 991-998

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

Presentation TitleDate

Company Confidential© 200X Abbott

Nutrient Intake of Lactating Mothers from Hisar - Ind Jr Social Research 1998;39(2):91-99

Women …. Pregnancy…. Baby Ultimate Desire

BUT IF

AT RISKIUGR PIH

Preeclampsia

Preterm labor

Oligohydramnios

Then it’s a matter of concern

POLYHYDRAMNIOS

PLACENTAL COMPLICATIONS

As it leads to

Fetal Morbidity &

Mortality

Maternal Morbidity &

Mortality

http://www.google.co.in/imgres?imgurl=http://www.unicef.org/malaysia/NYHQ2006-2706_Noorani.jpg&imgrefurl=http://www.unicef.org/malaysia/media_10384.html&usg=__S2Xj7VuA6VaIAPvMSfbN9cNj85s=&h=190&w=150&sz=18&hl=en&start=88&zoom=0&tbnid=JQQS1Jg4q1IFuM:&tbnh=103&tbnw=81&prev=/images%3Fq%3Dmaternal%2Bmortality%2Bpregnancy%2Bcomplications%26start%3D80%26hl%3Den%26safe%3Dactive%26sa%3DN%26gbv%3D2%26tbs%3Disch:1&itbs=1

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

Umbilicalvessels Chorionic

vessels

Chorionicplate Amnion

Spiralartery

Placentalseptum

Basalplate

Uteroplacentalveins

Normal Placental Development

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

The Challenge of Obstetrics

• Preterm labor

• Preterm Rupture of membranes

• Pre-eclampsia

• SGA/IUGR

• Fetal Death

Obstetrical DiseaseObstetrical DiseaseThe great obstetrical syndromeThe great obstetrical syndrome

Obstetrical DiseaseObstetrical DiseaseThe great obstetrical syndromeThe great obstetrical syndrome

PRE ECLAMPSIA



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?

32

Normal Levels of:TxA2

ProstacyclinNitric OxideFree Radicals

Altered Levels of: TxA2

Prostacyclin Nitric Oxide Free Radicals

THE RESULT:

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.

Normal function of endothelial cells

Line all blood vessels providing vessel wall integrityPrevent intravascular coagulationRegulate smooth muscle contractilityMediate immune and inflammatory responses

VASCULAR ENDOTHELIAL DYSFUNCTION

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 NOIncreased production of TxA2Increased Free radicals

Increase blood pressureDecrease Utero-Placental Blood Flow

Cuningham FG, MacDonald PC, Leveno K, Gant NF, Gilstrap LC II Williams Obstetrics 1993

The Supply Line to the Human Fetus

Oxidative stress is the imbalance of:

Pro-oxidants: Homocysteine LDL Hypertriglyceride

mia Increased iron

Antioxidants:

• HDL • transferrin, a blood protein 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

Stage 2: Multisystemic, maternal syndrome

ReducedPlacental perfusion

Release of Toxins-

Maternal Endothelial

damage

Reduced uterine blood flow

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 as a

“Great Obstetrical Syndrome”

SGA-FGR as a

“Great Obstetrical Syndrome”

• Multiple etiologies

• Long pre-clinical phase

• Fetal diseases

• Clinical manifestations are adaptive

• Symptomatic treatment is ineffective

• Genetic/environmental factors

““Great Obstetrical Syndromes”Great Obstetrical Syndromes”““Great Obstetrical Syndromes”Great Obstetrical Syndromes”

Type I

Type II

Type III

<28 weeks

30 weeks

36 weeks

Symmetric

Asymmetric

Postmature

IUGR According to the Timing of the Insult

Villar J and Belizan J. Obstet Gynecol Surv. 1982:37:499

Type I

Type II

Type III

<28 weeks

30 weeks

36 weeks

Symmetric

Asymmetric

Postmature


Asymmetric Growth Restriction38 weeks

BW:2,200 grams (<10th)

Length: 47 cm (>25th)

Type I

Type II

Type III

<28 weeks

30 weeks

36 weeks

Symmetric

Asymmetric

Postmature


Post-Maturity Syndrome

42 weeks

BW:2,600 grams (<10th)

Length: 49 cm ( 50th)

Small for Gestational Age/FGR

Nutritional Nutritional

Placental Placental

EnvironmentalEnvironmental

EndocrineEndocrine

Infection/Infection/InflammationInflammation

GeneticGenetic

Maternal Maternal

UnknownUnknown

Failure to achieve its

optimal growth potential

Failure to achieve its

optimal growth potential

Intrauterine Growth Restriction

IUGR MorbidityIUGR Morbidity

• Perinatal hypoxia

• Meconium aspiration

• Fetal distress

• Hypothermia

• Hypoglycemia

• Polycythemia

• Impaired postnatal growth

• Neurodevelopmental handicap

Normal uterine artery Doppler Abnormal uterine artery Doppler

Abnormal Uterine Artery Doppler Velocimetry

Figueroa-Diesel H , Hernandez-Andrade E, Acosta-Rojas R, Cabero L, Gratacos E. Ultrasound Obstet Gynecol 2007;30:297-302

Study of the Arterial Cerebral Circulation

Middle cerebral artery (MCA)

Posterior cerebral artery (PCA)

Anterior cerebral artery (ACA)

Pericallosal artery

Diastolic

Systolic Systolic

Diastolic

*

*

* *

**

**

**

**

**

* *

*

**

*

*

*

Disease Treatment

Preterm labor Tocolysis

Preterm PROMExpectant

management

Pre-eclampsiaAntihypertensive

agents

IUGR Delivery

MANAGEMENT OF GREAT OBSTETRICAL SYNDROMES

Adult LifeFetal Life

?

Etiology of THE GREAT OBSTETRICAL SYNDROME

• Fetal• Placental• Maternal

There is considerable overlap in these categories

GENETICENVIORNMENTAL

Traditional View of Disease

Genetic Component

Environment Factors

© 2006 VR

Personalized Medicine ParadigmPersonalized Medicine ParadigmPersonalized Medicine ParadigmPersonalized Medicine Paradigm

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

disease or to improve treatment” disease or to improve treatment”

Collins F and Guttmacheer AE. JAMA 2001;286:2332.

Fetal Origins of Adult DiseaseFetal 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

Confidential © 2011 Abbott Nutrition

Nine Months of pregnancy …….Nine Challenges

NTDs Spontaneous miscarriage

Recurrent abortionIUGR

Pre-eclampsiaPlacental abruption

Intrauterine fetal deathPre-term labour

Other Congenital defects

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.


Pregnant women with hyperhomocysteinemia have a 7.7-fold risk for preeclampsia –

LÃ³pez-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.


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

IUGR

Pre-eclampsia

VTE

ENDOTHELIAL FUNCTION

IUGR

PIH - Pre-eclampsia

VTE

ENDOTHELIAL FUNCTION

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.





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


Brain Nutrients

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 3rd 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

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.

Important cofactor in the Remethylation of Homocysteine

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.

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


Brain Nutrients

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

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.

A cofactor, Methionine Synthetase (MS) in methylation

VITAMIN B6

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

A cofactor, Pyridoxal Phosphate in methylation

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


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


Brain Nutrients

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.

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


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

Nutr Rev. 2006 April ; 64(4): 197–203

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

Brain Nutrients

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)

Growth Nutrients

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.

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


Arch. Dis. Child. 2007;92;737-740

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

Growth Nutrients

IMMUNE NUTRIENTS



ANTIOXIDANTSSelenium..a trace element which has antioxidant &

anticancer properties

Vitamin E …A powerful antioxidant…protects against damaging effect of free radicalsCombats oxidative stress….which is an important factor in IUGR, NTD, PLACENTAL ABRUPTION

Vitamin C……Antioxidant & has a role in immune system.

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

Immune Nutrients

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

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

Am J Clin Nutr l99l;53: 10505- 55

Immune Nutrients

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

Improved Fetoplacental

Circulation IUGR

L arginine

antihypertensive in gestational hypertension

Uterine relaxation

Vascular Dilatation

InhibitPreterm Uterine

contractions

Poverty

Ignorance

Inadequate diet and

Manual labor

Poor utilization And

Lack of health facility

Poor environmental Hygiene

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

Lampariello C. Minerva Ginecol. 1997 Dec;49(12):577-81

L-arginine is the precursor for nitric oxide (NO)

NO improves uteroplacental blood circulationIncrease oxygen delivery to fetus Reverse IUGR

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

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

Amniotic fluid volume predictive of IUGR

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.

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



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.

J. Nutr. 125: 1401-1412, 1995

Digestive Health

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

Some examples of nutrients and nutraceuticals

•Vit c•Vit e•Zn•Beta carotenes•Carotenoids•GlutathioneFlavonides 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

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 conditionshttp://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

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 willinterest his patient in the care of the human frame, in diet andin the cause and prevention of disease” –

Thomas Edison.

And Finally… the goal is HEALTHY & SAFE

thank you from a healty methyl folate baby

THANK YOUTHANK YOU

THANK YOU FOR THIS OPPURTUNITY AND FOR THE PATIENT HEARING

WELCOME TO AGRA for SAFOG FEB 2013

Health & Medicine

Nutraceuticals in pregnancy 1