Micronutrients and pregnancy effect of supplementation and its

Prof Narendra Malhotra

President ISPAT

Prof Jaideep Malhotra

President elect ISPAT

An ISPAT initiativ

Micronutrients and Pregnancy

Effect of Suplementation and its

Outcomes &

Vitamen D 3 in women’s health

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

Fetal origins of adult diseases

Ref:Effect of In Utero and Early-Life Conditions on Adult Health and Disease; Peter D. Gluckman et.al; N Engl J Med 2008;359:61-73.

The early life origins of asthma and related allergic disordersJ O WarnerCorrespondence to:Prof. J O WarnerProfessor of Child Health, Allergy & Inflammation Sciences, Division of Infection, Inflammation & Repair, School of Medicine,University of Southampton, UK; [email protected]

http://adc.bmj.com/search?author1=J+O+Warner&sortspec=date&submit=Submit

mailto:jowsoton.ac.uk

Early Programming and Fetal origins of adult diseases

Developmental plasticity: Ability of an organism to develop in various ways, depending on the particular environment or setting

Developmental programming is defined as the response by thedeveloping mammalian organism to a specific challenge during acritical time window that alters the trajectory of developmentwith resulting persistent effects on phenotype

Ref: Prenatal origins of adult disease; Current Opinion in Obstetrics and Gynecology 2008, 20:132–138

Peter D. Gluckman, et.al, N Engl J Med 2008;359:61-73

Fetal Origins of Adult Disease

Responses to adverse environments:1. Accelerated maturation

( G- corticoid level)1. Keeps nutrients

( growth & nutrition)3. Pregnancy termination

(abortion, prematurity)

MATERIAL ENVIRONMENT

+MATERIAL & PLACENTAL

PHYSIOLOGY

fetalEnvironment

IntrauterineEnvU –Placental

Unity

+ GENOME

Alterations:•fetal growth

•Interaction pre-and-post natal environments

FETAL ORIGIN OF DISEASE

Effects of undernutrition

Ref: Maternal nutrition: Effects on health in the next generation Caroline Fall; Indian J Med Res 130, November 2009, pp 593-599

Cortisol

Maternal diet

Uteroplacentralblood flow

Placentraltransfer

Fetal genome

Nutrient demand exceeds supplyFETAL UNDERNUTRITION

Brain sparing Down regulation of growth

Early Maturation

Altered body composition

Impaired development: bloodvessels,liver,kidneys,pancreas.

↓ Insulin/IGF-1Secretion and sensitivity

Centralobesity

Insulinresistance

HyperlipidaemiaHypertension

Type 2 diabetes and CHD

Muscle ↓

Conceptual frameworks for how maternal diet and micronutrients status may affect the development of chronic disease in the offspring

Ref: Stewart CP, J Nutr 2010 140(10): 437-445 PMID 20071652

Hormonal adaptationsFe,Zn,Ca

•Increased stress hormones•Decreased somatotrophic

hormones(GF,Insulin)

Epigenetic gene regulation

Folate ,Vitamin B-12

Restricted foetal growth and development

Maternal micronutrient deficiency

Renal functionFe, Zn,Vitami n A foalte•Impaired nephrogenesis/ Reduced nephronendowment•Reduced GFR•Increased sodium sensitivity

Cardiovascular functionFe,Zn,Viatmin A folate•Impairedvascularization•Malformations•Cardiac hpertrophy

Pancreas / β –cell function

Fe,Zn,folate,VitaminB-12

•Reduction in number and area of β - cell

Body compositionMg,Zn,folate,Vitamin

B-12•Reduced lean body mass•Altered fat deposition or metabolism•Sedentary behaviour•Altered appetite•regulation

Primary FunctionVitamin A,Vitamin D•Reduced bronchial branching & alveoli•Reduced elastin•Reduced VEGF•Chronic respiratory infections•Reduced lung capacity

HypertensionInsulin resistance

and β – celldysfunction

Cardio metabolic risk

Nutritional Programming of the Brain

Brain Development

Perinatal period is a “BrainTime”:A window of opportunity forNutritional optimization ofbrain development andfuture health and performance

Maternal Nutrition and Cognition in offspring

Permanent, largecognitive and

motoreffects of early nutrition – withstructural changes

in the brain

MRI Brain mappingSuggests cognitive effects of

early nutrition related to

multiple effects on brain

structure

Ref: Edmonds CJ et al. Pediatrics 2010;126:e1095–e1101

Key cognitive educational performance & motor

skills influenced by early nutrition


For each 1kg

reduction in birth weight

(compared to other

twin) there was a 13

Point loss in verbal IQ


Programming for Diabetes: Undernutrition and Overnutrition

Type2 Diabetes

fetal undernutrition

Undernourished (small) mother

Postnatal under nutrition

Insulin resistance

Small baby (Thin-fat)

Altered fuels

Pregestationaland gestational hyperglycemia

Obesity and hyperglycemia

Macrosomia

fetal adiposity & islet dysfunction

Postnatal over nutrition (Urbanisation)

Dual - Teratogenesis

Undernutrition Overnutrition

Nutrient-mediatedteratogenesis

Fuel-mediated teratogeneis

Ref: Yajnik CS, Deshmukh U, 2009

12Y

6Y

Postnatal

Birth

Intrauterine

Preconception

Children & parents Size, bodyComposition IR CVD risk markers Cognition 690/722 (95%)

Children & parents Size, body Composition IR CVD risk markers698/723 (96%)

Growth every 6 months 743

Size Phenotype 770

Maternal Size Nutrition Metabolism Paternal size Metabolic variables fetal growth (USG) 814

Maternal Size Hemoglobin 2675

19

93

19

94

-96

20

00

-03

20

06

-08

Pune Maternal Nutrition Study

Ref: Indian J Med Res 130, Caroline Fall ,November 2009, pp 593-599

The nutritional status of pregnant women in

India

Current scenario in India

• 18% of pregnant women consumed < 50% of calories

• 34% of pregnant women consumed <50% of protein

• 85% of pregnant women consumed <50% iron

• 57% of pregnant women consumed <50% b-caroten - relative to their RDA(recommended dietary allowance)Ref: Indian Pediatrics 1999; 36: 991-998

Pregnancy Diet – 4 Pillars of development

CONTENTS OF THIS PRESENTATION

Introduction

Prevalence of Multiple Micronutrient Deficiencies

Risk Factors for Micronutrient Deficiency in Pregnancy

Function and Timing of Micronutrients that Affect Outcomesin Offspring

Are We Neglecting Few Micronutrients

Iodine

Calcium, Vitamin D

Metalloenzymes: Zinc, Copper, Manganese and Magnesium

Dietary Reference Values of Micronutrients in Pregnancy

Conclusions

CONTENTS

Introduction





Iodine

Calcium, Vitamin D



Conclusions

Introduction

Micronutrient is the umbrella term used to represent essential vitamins and minerals required from the diet

to sustain virtually all normal cellular and molecular functions

Cell signaling, motility, proliferation, differentiation and apoptosis that regulate tissue growth, function

and homeostasis

Ann Nutr Metab 2015;66(suppl 2):22–33Nat Rev Endocrinol 2016; 12(5): 274–289

CONTENTS

Introduction





Iodine

Calcium, Vitamin D



Conclusions


• Globally, approximately two billionpeople, the majority women andyoung children, are affected, bymicronutrient deficiencies, with evenhigher rates during pregnancy

• Concurrent deficiencies of morethan one or two micronutrients arewell documented among youngpregnant women, (and youngchildren), especially in Low- andMiddle-Income Countries

Nutrients 2015, 7


Pe

rce

nta

ge o

f P

regn

ant

Wo

me

n D

efic

ien

t Community based cross sectional

survey To assess the prevalence of

multiple micronutrient deficiencies amongst pregnant

women

1Indian J Pediatr 2004 ;71(11):1007-142Indian J Endocr Metab 2014; 18:486-90

73.5

2.7

43.6

73.4

26.3

37

0

10

20

30

40

50

60

70

80

CONTENTS

Introduction





Iodine

Calcium, Vitamin D



Conclusions


Poor Quality Diets High Fertility RatesRepeated

Pregnancies

Short inter-pregnancy Intervals

Increased Physiological

Needs

Nutrients 2015, 7, 1744-1768

Increased Additional Demand During Pregnancy

CONTENTS

Introduction





Iodine

Calcium, Vitamin D



Conclusions

Nat. Rev. Endocrinol. doi:10.1038/nrendo.2016.37

Function and Timing of Micronutrients that Affect Outcomes in Offspring

Short-term Long-term

Miscarriage

Stillbirth

Birth defects

Small size for gestational age

Preterm birth

Death

Altered growth, body composition

Compromised cardiometabolic,

pulmonary and immune function

Poor neurodevelopment and cognition

Adverse health outcomes of gestational micronutrient deficiency

CONTENTS

Introduction





Iodine

Calcium, Vitamin D



Conclusions

Micronutrients During Pregnancy & LactationAre we Neglecting Few Micronutrients.......

Today in practice most of theattention has been given only tofew micronutrients, for exampleiron, folate, Vit B, Calcium and Vit-D3

Some micronutrients deserveattention as studies have shown thelinks between deficiency states andpoor pregnancy outcome. EgIodine, zinc, copper, Mangnese,magnesium .

Am J Clin Nutr May 2005 ; vol. 81 no. 5 1206S-1212S

CONTENTS

Introduction





Iodine

Calcium, Vitamin D



Conclusions

A Pregnant with Iodine DeficiencyThe Consequences

In General Population

Hypothyroidism

Goitre

Pregnancy

Abortion

Still Birth

Pregnancy and Fetal Health

IQ and Neuropsychological

Brain damage

Mental retardation

Psychomotor defects Indian J Endocrinol Metab. 2015 Sep-Oct; 19(5): 602–607. Thyroid. 2009 May;19(5):511-9.Nutrient requirements and recommended dietary allowances for indians .ICMR 2009 ReportIndian J Endocr Metab 2014;18:486-90

Prevention: Iodized Salt

PreventionAdditional Iodine Supplementation

Even with use of iodized salt & eating seafood, awoman’s daily iodine intake would be in the orderof 100–150 mcg per day approximately half theamount recently recommended during pregnancyand lactation (i.e 220 -290 mcg)

International Journal of Gynecology and Obstetrics 131 S4 (2015) S213–S253

FIGO recommends that all pregnant and Lactating women should take adequate supplementation of Iodine

CONTENTS

Introduction





Iodine

Calcium, Vitamin D



Conclusions

Calcium and Vitamin D Status in India

• Indian RDA for non-pregnant women- 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 deficiency exists in Indian adults-based on 25 hydroxy Vitamin D2

• 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

Ref: JAPI, 2009; (57):40-48

Calcium & Vitamin DMust for Pregnancy and Fetal Bone Development

Calcium Carbonate Higher Elemental CalciumHigher BioavailabilityEconomical and Safe

Vitamin DOptimal serum 25(OH)D level in pregnancy should be at least 20

ng/mL (50 nmol/L)

CALCIUM METABOLISM IN PREGNANCY

increased1,25(OH)2D

ProlactinPlacental Lactogen

Increased intestinal calcium absorption

CALCIUM METABOLISM IN PREGNANCY (Contd..)

VITAMIN D METABOLISM

NON-SKELETAL FUNCTIONS OF VITAMIN D

ROLE OF VITAMIN D

25(OH)D LEVELS URBAN INDIAN ADULTS

1. Goswami R, Gupta N, Goswami D, Marwaha RK, Tandon N, Kochupillai N. Prevalence and significance of low 25-hydroxyvitamin D concentrations in healthy subjects in Delhi. Am J Clin Nutr. 2000;72(2):472-5. 2. Arya V, Bhambri R,Godbole MM, Mithal A. Vitamin D status and its relationship with bone mineral density in healthy Asian Indians.Osteoporos Int. 2004;15(1):56-61. 3. Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineralparameters in healthy young Indian adults with optimal vitamin D availability. Natl Med J India. 2003;16(6):298-302.4. Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D. Vitamin D status in Andhra Pradesh : a population basedstudy. Indian J Med Res. 2008;127(3):211-8. 5. Marwaha RK, Tandon N, Reddy DR, Aggarwal R, Singh R, Sawhney RC,et al. Vitamin D and bone mineral density status of healthy schoolchildren in northern India. Am J Clin Nutr.2005;82(2):477-82.

Categories of patients Vitamin D levels

Physicians and nurses1 3.19 ng/ml (winter) ; 7.18 ng/ml (summer)

Pregnant women1 8.76 ng/ml

Hospital staff2 66% had <15 ng/ml; 20.6% had <5 ng/ml; 78% had <20 ng/ml

Para-military forces3 18.4 ng/ml (winter); 25.3 ng/ml (summer)

Urban children4 Male: 15.57+/-1.21 ng/ml; Female: 18.5+/-1.66 ng/ml

Urban adult4 Male: 18.54+/-0.8 ng/ml; Female: 15.5+/-0.3 ng/ml

Urban children withsocioeconomic status (SES)5

35.7% children had <9 ng/ml (42.3% in lower SES and 27% in upper SES)

PREVALENCE OF VITAMIN D DEFICIENCY

25(OH)D LEVELS: RURAL DATA

1. Sachan A, Gupta R, Das V, Agarwal A, Awasthi PK, Bhatia V. High prevalence of vitamin D deficiency amongpregnant women and their newborns in northern India. Am J Clin Nutr. 2005;8:1060–4. 2. Harinarayan CV,Ramalakshmi T, Prasad UV, Sudhakar D. Vitamin D status in Andhra Pradesh : a population based study. Indian J MedRes. 2008;127(3):211-8.

Categories Vitamin D levels

Adolescent girls1 88.6% had <20 ng/ml

Pregnant women1 74% had <20 ng/ml

Weather-wise1 Levels in summer [22 ng/ml ] > in winter [12ng/ml]

During winter1 Levels in boys [~25 ng/ml] > female siblings [~12 ng/ml]

Rural children2 Male: 17 +/- 1.3 ng/ml; Female: 19+/- 1.59 ng/ml

Rural adult2 Male: 23.73 +/- 0.8 ng/ml; Female: 19+/- 0.89 ng/ml

25 (OH)D LEVELS: ELDERLY INDIANS IN DELHI

Marwaha RK, Tandon N, Garg MK, Kanwar R, Narang A, Sastry A, et al. Bone health in healthy Indianpopulation aged 50 years and above. Osteoporos Int. 2011;22(11):2829-36.

Severity All (1346) Male Female

25(OH)D Levels (ng/dl) 9.79±7.61 9.81±6.79 9.78±8.30

Severe (<5 ng/ml) 376 (27.9%) 166 (25.8%) 210 (29.9%)

Moderate (5-<10 ng/ml) 457 (34.0%) 220 (34.2%) 237 (33.7%)

Mild (10-<20 ng/ml) 395 (29.4%) 201 (31.3%) 194 (27.6%)

VDI (20-<30 ng/ml) 92 (6.8%) 47 (7.3%) 45 (6.4%)

VITAMIN D DEFICIENCY IN INDIAN HEALTH PROFESSIONALS

Beloyartseva M, Mithal A, Kaur P, Kalra S, Baruah MP, Mukhopadhyay S, et al. Widespread vitamin D deficiency among Indian health care professionals. Arch Osteoporos. 2012;7(1-2):187-92.

Aurangabad

Bangalore

Bhopal

Chennai

Kolkata

Lucknow

Vapi

JaipurJodhpur

Chandigarh

Hyderabad

Cochin

Madurai

Ahmedabad

Mumbai

Vitamin D deficiency

Vitamin D insufficiency

Vitamin D sufficiency

VITAMIN D STATUS IN ADULTS (>18 YEARS)

Wahl DA, Cooper C, Ebeling PR, Eggersdorfer M, Hilger J, Hoffmann K, et al. A global representation ofvitamin D status in healthy populations. Arch Osteoporos. 2012;7(1-2):155-72.

REASONS FOR WIDESPREAD DEFICIENCY

Latitude, season, time of the day

Cloud cover and atmospheric pollution

Time spent outdoors

Customary dress and sunscreen use

Skin pigmentation and age

Prentice A. Vitamin D deficiency: a global perspective. Nutr Rev. 2008;66(10 Suppl 2):S153-64.

SKIN COLOUR IS IMPORTANT

Skin type

Sun history Example

I Always burns easily, never tans, extremely sensitive skin

Red-headed, freckled, Celtic, Irish-Scots

II Always burns easily, tans minimally, very sensitive skin

Fair-skinned, fair-haired, blue-eyed Caucasians

III Sometimes burns, tans gradually to light brown, sun-sensitive skin

Average-skinned Caucasians, light-skinned Asians

IV Burns minimally, always tans to moderate brown, minimally sun-sensitive

Mediterranean-type Caucasians

V Rarely burns, tans well, sun-insensitive skin

Middle Easterners, some Hispanics, some African-Americans

VI Never burns, deeply pigmented, sun-insensitive skin

African-Americans

Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004;80(6):1678S-88S.

Indians have skin type V

PCOS Inverse association between 25(OH)D levels and insulin resistance,

features of hyperandrogenism, and circulating androgens in women with PCOS.

Normalisation of menstrual cycles with vitamin D and calcium supplementation over 6 months.

Dietary supplementation with vitamin D or an analog improves

• insulin sensitivity

• Circulating testosterone

• Parameters of ovarian folliculogenesis and ovulation

Luk J, Torrealday S, Neal Perry G, Pal L. Relevance of vitamin D in reproduction. Hum Reprod. 2012;27(10):3015-27.

IMPORTANCE OF VITAMIN D IN WOMEN

GYNECOLOGICAL DISORDERS ASSOCIATED WITH VITAMIN D DEFICIENCY

Disorder Strength of association

Recommendation for testing

Recommendation for supplementation

Polycystic Ovary Syndrome

+++ Routine 25(OH)Dtesting not recommended

60k once a month

Premenstrual Syndrome

+ As for normal population

Uterine Fibroid + As for normal population

Endometriosis + As for normal population

IVF +- As for normal population

It is prudent to optimize Vitamin D status in

women with polycystic ovary syndrome (PCOS)

and in women planning pregnancy.

PREVALENCE OF VITAMIN D DEFICIENCY IN PREGNANT INDIAN WOMEN

1. Sachan A, Gupta R, Das V, Agarwal A, Awasthi PK, Bhatia V. High prevalence of vitamin D deficiency amongpregnant women and their newborns in northern India. Am J Clin Nutr. 2005;8:1060–4. 2. Sahu M, Bhatia V, AggarwalA, Rawat V, Saxena P, Pandey A, et al. Vitamin D deficiency in rural girls and pregnant women despite abundantsunshine in northern India. Clin Endocrinol (Oxf). 2009;70(5):680-4. 3. Marwaha RK, Tandon N, Chopra S, Agarwal N,Garg MK, Sharma B, et al. Vitamin D status in pregnant Indian women across trimesters and different seasons and itscorrelation with neonatal serum 25-hydroxyvitamin D levels. Br J Nutr. 2011;106(9):1383-9.

25 (OH) D levels Prevalence

Less than 22.5 ng/ml 84% pregnant women1

Less than 20 ng/ml74% rural pregnant women2

96.5% pregnant women3

99.7% lactating women3

MATERNAL SERUM VITAMIN D3 AND NEONATAL OUTCOMES

Insufficient serum levels of 25-OHD were associated with

• Gestational Diabetes (pooled odds ratio 1.49, 95% confidence interval 1.18 to 1.89),

• Pre-eclampsia (1.79, 1.25 to 2.58), and

• Small For Gestational Age Infants (1.85, 1.52 to 2.26).

Pregnant women with low serum 25-OHD levels had an increased risk of

• bacterial vaginosis and

• low birth weight infants

• but not delivery by caesarean section.

Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O'Beirne M, Rabi DM. Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observationalstudies. BMJ. 2013;346:f1169.

EFFECTS OF VITAMIN D DEFICIENCY IN PREGNANCY

NEONATAL OUTCOMES

Maternal and cord blood levels of 25(OH)D closely correlate

Maternal vitamin D deficiency may affect femoral bone development as early as 19 week (Mahon et al 2010)

Lower bone mineral density (Javaid et al 02006)

Neonatal birth weight (Ert et al 2012)

VITAMIN D DEFICIENCY IN PREGNANCY IS ASSOCIATED WITH..

Maternal Disorders Strength of association

Preecclampsia +++

Gestational Diabetes +

Bacterial Vaginosis ++

Neonatal Disorders Strength of association

Small for Gestational Age (SGA) +++

WHAT CUT-OFF TO BE USED IN PREGNANCY?

For birth variables: 15 ng/ml (37.5nmol/l)

Rise in PTH: 22.5 ng/ml (56.25nmol/l)

For pregnancy outcomes: 30 ng/ml (75nmol/l)

25(OH)D less than 20ng/ml or 50 nmol/l: Deficient

25(OH)D between 20-30ng/ml or 50-75 nmol/l : insufficient

Rabi et al, BMJ 2013; Sachan et al, AJCN, 2005

VITAMIN D3 CONCENTRATION IN MOTHERS AND INFANTS

Mean serum 25(OH)D of 8.2 ng/mL at enrollment.

Cholecalciferol 400 units vs 2000 units vs 4000 units per day

The percent who achieved 25(OH)D greater than 32 ng/mL and greaterthan 20 ng/mL concentrations in mothers and infants was highest in 4000IU/d group.

No adverse event related to vitamin D supplementation.

Hollis BW, Wagner CL. Clinical review: The role of the parent compound vitamin D with respect to metabolism andfunction: Why clinical dose intervals can affect clinical outcomes. J Clin Endocrinol Metab. 2013;98(12):4619-28.

HOW TO SUPPLEMENT VITAMIN D DURING PREGNANCY

VITAMIN D REPLACEMENT IN RURAL NORTH INDIAN PREGNANT WOMEN

Pregnant women received

• no cholecalciferol (Group A) or

• 60000U (Group B) in the fifth month of gestation or

• 120000U each in the fifth and seventh gestational months (Group C).

Cholecalciferol in doses of 120 000 U each in fifth and seventh gestational months was effective in raising 25OHD at delivery.

Sahu M, Das V, Aggarwal A, Rawat V, Saxena P, Bhatia V. Vitamin D replacement in pregnant women in rural northIndia: a pilot study. Eur J Clin Nutr. 2009;63(9):1157-9.

VITAMIN D SUPPLEMENTATION IN PREGNANT INDIAN WOMEN

All pregnant women after 12 weeks

2000 units per day

4000 to 5000 units per day in those with high risk (with calciummonitoring)

• High risk for hypertension or preecclampsia

• High risk for GDM

• High risk for preterm delivery

• Clinical features of osteomalacia

• Previous baby with SGA/ rickets/ hypocalcemia

Vitamin D requirements during lactation: high-dose maternal supplementation as therapy to prevent hypovitaminosis D for both the mother and the

nursing infantBruce W Hollis and Carol L Wagner

A maternal intake of 4000 IU/d could achieve substantial progress towardimproving both maternal and neonatal nutritional vitamin D status.

Hollis BW, Wagner CL. Vitamin D requirements during lactation: high-dose maternal supplementation as therapy toprevent hypovitaminosis D for both the mother and the nursing infant. Am J Clin Nutr. 2004;80(6):1752S-8S.

VITAMIN D SUPPLEMENTATION IN LACTATING WOMEN

Cholecalciferol supplementation to all women

2000 units per day

4000 units

• in exclusively breast-fed infant

• if parents chose not to supplement the infant with vitamin D

CHALLENGES IN CURRENT CONVENTIONAL FORMULATION OF VITAMIN D3

Absorption of Vitamin D3 from conventional formulation is highly dependent on high-fat meal

Bioavailability of Vitamin D3 is dependent on bile secretions, micelle formation, and diffusion through unstirred-water layer

Compliance/ Convenience becomes a challenge as most Vitamin D3 preparations are to be administered along with milk or clarified butter

Raimundo FV, Faulhaber GA, Menegatti PK, Marques Lda S, Furlanetto TW. Effect of High- versus Low-Fat Meal on Serum 25-Hydroxyvitamin D Levels after a Single Oral Dose of Vitamin D: A Single-Blind, Parallel, Randomized Trial. Int J Endocrinol. 2011;2011:809069.

Absorption via 3 pathways (Paracellular, Transcellular and Persorption) is not fat-dependent and is unaffected by fed fast variation1

Bioavailability of nanoparticles is 3 times higher than conventional drugs as it penetrates the mucous layer easily2

Convenience of taking nanoparticle formulation is high as it does not require milk or clarified butter for absorption

VITAMIN D3 NANO PARTICLES – OVERCOMES THE CHALLENGE

1. McClements DJ. Edible lipid nanoparticles: Digestion, absorption, and potential toxicity. Progress in Lipid Research. 2013;52:409-23

2. Huang Q, Yu H, Ru Q. Bioavailability and delivery of nutraceuticals using nanotechnology. J Food Sci. 2010;75(1):50-7

CONTENTS

Introduction





Iodine

Calcium, Vitamin D



Conclusions

METALLOENZYMES

There are more than 300 enzymes whose functions can beimpacted if diet is deficient on zinc, copper, manganese andmagnesium

They are important trace metals which are responsible for normalmetalloenzyme activity

All 4 play important role in maintaining maternal gestationalhealth and ensuring birth of healthy offspring

Some of the enzymes where zinc, copper, manganese magnesiumare linked are alcohol dehydrogenase, glucokinase, chymotrypsin,aldolases, triosephosphate isomerase, and pyruvate carboxylase...

J. Nutr. 2000; 130: 1437S—1446SComprehensive Reviews in Food Science and FoodSafety Vol.13,2014

Zinc : A Necessary Micronutrient for Infantile Growth and development

Literature suggests abeneficial effect of maternalzinc supplement on

Infancy growth and developmental parameters

Neonatal immune system

Preventing infectious disease

Relationship between motherplasma zinc (Zn) and newbornlength in the supplemented group

Eur J Clin Nutr. 2004 Jan;58(1):52-9.

Important role in pregnancy for the formationof a wide variety of enzymatic and otherprocesses within the developing foetus

Lower plasma concentrations of copper, werefound in cases of spontaneous abortion,threatened abortion, missed abortion andblighted ovum.

Copper Linked to Pregnancy and Placenta

Some authors suggest that serum copper levels can be used as avery sensitive indicator of certain pathological conditions andfurther possible course of pregnancy and placental functions

Serum copper decrease leads to a reduction of elastin andcollagen resulting in premature rupture of membranes

Srp Arh Celok Lek. 2012 J;140(1-2):42-46Placenta 2000; 21:773-81Proc Nutr Soc 2004; 63(4):553-62.

https://www.google.co.in/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjhnpeco-XJAhXjN6YKHciFCrIQjRwIBw&url=http://www.nutraingredients.com/Regulation-Policy/Pregnant-women-need-more-copper-but-not-iron-EFSA&bvm=bv.110151844,d.dGY&psig=AFQjCNH1-ZQgpdimPVX2Kj4E5KNVOY6tgQ&ust=1450523479989345

https://www.google.co.in/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjhnpeco-XJAhXjN6YKHciFCrIQjRwIBw&url=http://www.nutraingredients.com/Regulation-Policy/Pregnant-women-need-more-copper-but-not-iron-EFSA&bvm=bv.110151844,d.dGY&psig=AFQjCNH1-ZQgpdimPVX2Kj4E5KNVOY6tgQ&ust=1450523479989345

Serum manganese conc. during pregnancy is significantlylower than non-pregnant women

Manganese plays a role in bone formation, protein andenergy metabolism, metabolic regulation, and functions asa cofactor in a number of enzymatic reactions

Parameters Non-pregnant Pregnant Women P-Value

Serum Mn (nmol/l) 0.102±0.02 0.090±0.01*** 0.001

*** Significant differences at P≤0.001

Biosci., Biotech. Res. Asia 2013; 10(2), 837-841

Manganese: Also Called Mothering Nutrient

Magnesium levels low in pregnancy versus non-pregnant state.

Deficiency associated Pre-eclampsia Pre-term delivery Low birth weight Increases neonatal mortality and morbidity Leg cramps, fluid retention and restless legs during pregnancy

*Biosci., Biotech. Res. Asia; 2013: 10(2), 837-841 The Indian Journal of Pediatrics 2004; 71 (11) 1003-1005

Magnesium in Pregnancy

Parameters Non-pregnant Pregnant Women

P-Value

Serum Mg (nmol/l) 1.02±0.20 0.093±0.07* 0.05

Earlier supplementation trials during pregnancy have documentedan association with

Fewer maternal hospitalizations

Reduction in pre-term delivery

Less intrauterine growth retardation

Less frequent referral of the new born to the neonatalintensive care unit.

CONTENTS

Introduction





Iodine

Calcium, Vitamin D



Conclusions


Srp Arh Celok Lek. 2014;142(1-2):125-130

CONTENTS

Introduction





Iodine

Calcium, Vitamin D



Conclusions

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

Ref: http://www.acog.org/publications/patient_education/bp001.cfmDutta 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

Gestation is a critical opportunity for future health

• Gestation is a most critical period for future maternal and infant health, wellbeing, performance and diseases.

• Maternal undernutrition/obesity increases risk for pregnancy complications, and future health.

• Transitional diets (i.e westernization) add risk of imbalance and deficiencies, especially vs. increased calorie-dense foods and the obesity epidemic.

• Multiparous women represent especially relevant target population for nutritional support.

Micronutrient deficiencies during pregnancy are a globalpublic health concern

Although evidence has rapidly accrued about roles ofantenatal micronutrients on the health of the offspring, gapsin our knowledge still remain

Micronutrient deficiencies have been linked to pregnancyloss, preterm delivery, small birth size, birth defects, and long-term metabolic disturbances

Global Guidelines & Voice from Scientific Bodies recommendsupplementation with micronutrients during pregnancy &lactation

CONCLUSIONS

NINE MONTHS ARE WINDOW OF OPPURTUNITY

Prevention, in order to be truly preventive, must be antenatal

J. W. Ballantyne, 1902

DailyWeeklys

Pt friendly and efective drugs and combinations should be chosen

Nano particles,micillisation etc

Health & Medicine

Micronutrients and pregnancy effect of supplementation and its