This document summarizes a conference on micronutrients and pregnancy. It discusses multiple micronutrient deficiencies that are prevalent in pregnant women, especially in low and middle income countries. Certain micronutrients like iodine, calcium, vitamin D, zinc, copper, manganese and magnesium are important during pregnancy but often neglected. Deficiencies in these can lead to adverse outcomes for both mother and baby. The timing and functions of various micronutrients that impact the offspring are highlighted. Maintaining adequate micronutrient status through diet and supplementation is important for fetal growth and development.

1. 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

2. 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 disorders
J O Warner
Correspondence to:
Prof. J O Warner
Professor of Child Health, Allergy & Inflammation Sciences, Division of Infection, Inflammation & Repair, School of Medicine,
University of Southampton, UK; jow@soton.ac.uk

3. 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 the
developing mammalian organism to a specific challenge during a
critical time window that alters the trajectory of development
with 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

4. 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
fetal
Environment
IntrauterineEnv
U –Placental
Unity
+ GENOME
Alterations:
•fetal growth
•Interaction pre-and-
post natal environments
FETAL ORIGIN OF DISEASE

5. 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
Uteroplacentral
blood flow
Placentral
transfer
Fetal
genome
Nutrient demand exceeds supply
FETAL UNDERNUTRITION
Brain sparing Down regulation
of growth
Early
Maturation
Altered
body
composition
Impaired development:
bloodvessels,liver,
kidneys,pancreas.
↓ Insulin/IGF-1
Secretion and
sensitivity
Central
obesity
Insulin
resistance
Hyperlipidaemia
Hypertension
Type 2 diabetes and CHD
Muscle ↓

6. 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 adaptations
Fe,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 function
Fe, Zn,Vitami n A foalte
•Impaired
nephrogenesis/
Reduced
nephronendowment
•Reduced GFR
•Increased sodium
sensitivity
Cardiovascular function
Fe,Zn,Viatmin A folate
•Impaired
vascularization
•Malformations
•Cardiac hpertrophy
Pancreas / β –cell
function
Fe,Zn,folate,Vitamin
B-12
•Reduction in
number and area of
β - cell
Body composition
Mg,Zn,folate,Vitamin
B-12
•Reduced lean body
mass
•Altered fat deposition
or metabolism
•Sedentary behaviour
•Altered appetite
•regulation
Primary Function
Vitamin A,Vitamin D
•Reduced bronchial
branching & alveoli
•Reduced elastin
•Reduced VEGF
•Chronic respiratory
infections
•Reduced lung
capacity
Hypertension
Insulin resistance
and β – cell
dysfunction
Cardio metabolic
risk

7. Nutritional Programming of the Brain
Brain Development

8. Perinatal period is a “Brain
Time”:
A window of opportunity for
Nutritional optimization of
brain development and
future health and performance

9. Maternal Nutrition and Cognition in offspring
Permanent, large
cognitive and
motor
effects of early
nutrition – with
structural changes
in
the brain

10. MRI Brain mapping
Suggests cognitive effects of
early nutrition related to
multiple effects on brain
structure
Ref: Edmonds CJ et al. Pediatrics 2010;126:e1095–e1101

11. Key cognitive educational
performance & motor
skills influenced by early
nutrition
Ref: Edmonds CJ et al. Pediatrics 2010;126:e1095–e1101

12. For each 1kg
reduction in birth weight
(compared to other
twin) there was a 13
Point loss in verbal IQ
Ref: Edmonds CJ et al. Pediatrics 2010;126:e1095–e1101

13. Programming for Diabetes:
Undernutrition and Overnutrition
Type2 Diabetes

14. fetal
undernutrition
Undernourished
(small) mother
Postnatal under
nutrition
Insulin resistance
Small baby
(Thin-fat)
Altered fuels
Pregestational
and gestational
hyperglycemia
Obesity and
hyperglycemia
Macrosomia
fetal adiposity &
islet dysfunction
Postnatal over nutrition
(Urbanisation)
Dual - Teratogenesis
Undernutrition Overnutrition
Nutrient-mediated
teratogenesis
Fuel-mediated
teratogeneis
Ref: Yajnik CS, Deshmukh U, 2009

15. 12Y
6Y
Postnatal
Birth
Intrauterine
Preconception
Children & parents Size, body
Composition IR CVD risk markers Cognition 690/722 (95%)
Children & parents Size, body Composition IR CVD risk markers
698/723 (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
19931994-962000-032006-08
Pune Maternal Nutrition Study
Ref: Indian J Med Res 130, Caroline Fall ,November 2009, pp 593-599

16. The nutritional status of
pregnant women in
India

17. 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

18. Pregnancy Diet – 4 Pillars of
development

19. CONTENTS OF THIS PRESENTATION
 Introduction
 Prevalence of Multiple Micronutrient Deficiencies
 Risk Factors for Micronutrient Deficiency in Pregnancy
 Function and Timing of Micronutrients that Affect Outcomes
in Offspring
 Are We Neglecting Few Micronutrients
 Iodine
 Calcium, Vitamin D
 Metalloenzymes: Zinc, Copper, Manganese and Magnesium
 Dietary Reference Values of Micronutrients in Pregnancy
 Conclusions

20. CONTENTS
 Introduction
 Prevalence of Multiple Micronutrient Deficiencies
 Risk Factors for Micronutrient Deficiency in Pregnancy
 Function and Timing of Micronutrients that Affect Outcomes
in Offspring
 Are We Neglecting Few Micronutrients
 Iodine
 Calcium, Vitamin D
 Metalloenzymes: Zinc, Copper, Manganese and Magnesium
 Dietary Reference Values of Micronutrients in Pregnancy
 Conclusions

21. 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):22–33
Nat Rev Endocrinol 2016; 12(5): 274–289

22. CONTENTS
 Introduction
 Prevalence of Multiple Micronutrient Deficiencies
 Risk Factors for Micronutrient Deficiency in Pregnancy
 Function and Timing of Micronutrients that Affect Outcomes
in Offspring
 Are We Neglecting Few Micronutrients
 Iodine
 Calcium, Vitamin D
 Metalloenzymes: Zinc, Copper, Manganese and Magnesium
 Dietary Reference Values of Micronutrients in Pregnancy
 Conclusions

23. Prevalence of Multiple Micronutrient
Deficiencies
• Globally, approximately two billion
people, the majority women and
young children, are affected, by
micronutrient deficiencies, with even
higher rates during pregnancy
• Concurrent deficiencies of more
than one or two micronutrients are
well documented among young
pregnant women, (and young
children), especially in Low- and
Middle-Income Countries
Nutrients 2015, 7

24. Prevalence of Multiple Micronutrient
Deficiencies
PercentageofPregnant
WomenDeficient
 Community based cross sectional
survey
 To assess the prevalence of
multiple micronutrient
deficiencies amongst pregnant
women
1Indian J Pediatr 2004 ;71(11):1007-14
2Indian 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

25. CONTENTS
 Introduction
 Prevalence of Multiple Micronutrient Deficiencies
 Risk Factors for Micronutrient Deficiency in Pregnancy
 Function and Timing of Micronutrients that Affect Outcomes
in Offspring
 Are We Neglecting Few Micronutrients
 Iodine
 Calcium, Vitamin D
 Metalloenzymes: Zinc, Copper, Manganese and Magnesium
 Dietary Reference Values of Micronutrients in Pregnancy
 Conclusions

26. Risk Factors for Micronutrient Deficiency in
Pregnancy
Poor Quality Diets High Fertility Rates
Repeated
Pregnancies
Short inter-
pregnancy
Intervals
Increased
Physiological
Needs
Nutrients 2015, 7, 1744-1768
Increased Additional
Demand During Pregnancy

27. CONTENTS
 Introduction
 Prevalence of Multiple Micronutrient Deficiencies
 Risk Factors for Micronutrient Deficiency in Pregnancy
 Function and Timing of Micronutrients that Affect Outcomes
in Offspring
 Are We Neglecting Few Micronutrients
 Iodine
 Calcium, Vitamin D
 Metalloenzymes: Zinc, Copper, Manganese and Magnesium
 Dietary Reference Values of Micronutrients in Pregnancy
 Conclusions

28. 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

29. CONTENTS
 Introduction
 Prevalence of Multiple Micronutrient Deficiencies
 Risk Factors for Micronutrient Deficiency in Pregnancy
 Function and Timing of Micronutrients that Affect Outcomes
in Offspring
 Are We Neglecting Few Micronutrients
 Iodine
 Calcium, Vitamin D
 Metalloenzymes: Zinc, Copper, Manganese and Magnesium
 Dietary Reference Values of Micronutrients in Pregnancy
 Conclusions

30. Micronutrients During Pregnancy & Lactation
Are we Neglecting Few Micronutrients.......
Today in practice most of the
attention has been given only to
few micronutrients, for example
iron, folate, Vit B, Calcium and Vit-
D3
Some micronutrients deserve
attention as studies have shown the
links between deficiency states and
poor pregnancy outcome. Eg
Iodine, zinc, copper, Mangnese,
magnesium .
Am J Clin Nutr May 2005 ; vol. 81 no. 5 1206S-1212S

31. CONTENTS
 Introduction
 Prevalence of Multiple Micronutrient Deficiencies
 Risk Factors for Micronutrient Deficiency in Pregnancy
 Function and Timing of Micronutrients that Affect Outcomes
in Offspring
 Are We Neglecting Few Micronutrients
 Iodine
 Calcium, Vitamin D
 Metalloenzymes: Zinc, Copper, Manganese and Magnesium
 Dietary Reference Values of Micronutrients in Pregnancy
 Conclusions

32. A Pregnant with Iodine Deficiency
The 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 Report
Indian J Endocr Metab 2014;18:486-90
Prevention: Iodized Salt
Prevention
Additional
Iodine Supplementation

33. Even with use of iodized salt & eating seafood, a
woman’s daily iodine intake would be in the order
of 100–150 mcg per day approximately half the
amount recently recommended during pregnancy
and 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

34. CONTENTS
 Introduction
 Prevalence of Multiple Micronutrient Deficiencies
 Risk Factors for Micronutrient Deficiency in Pregnancy
 Function and Timing of Micronutrients that Affect Outcomes
in Offspring
 Are We Neglecting Few Micronutrients
 Iodine
 Calcium, Vitamin D
 Metalloenzymes: Zinc, Copper, Manganese and Magnesium
 Dietary Reference Values of Micronutrients in Pregnancy
 Conclusions

35. 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

36. Calcium & Vitamin D
Must for Pregnancy and Fetal Bone Development
Calcium Carbonate
Higher Elemental Calcium
Higher Bioavailability
Economical and Safe
Vitamin D
Optimal serum 25(OH)D level in
pregnancy should be at least 20
ng/mL (50 nmol/L)

37. CALCIUM METABOLISM IN PREGNANCY

38. increased
1,25(OH)2D
Prolactin
Placental Lactogen
Increased intestinal calcium
absorption
CALCIUM METABOLISM IN PREGNANCY (Contd..)

39. VITAMIN D METABOLISM

40. NON-SKELETAL FUNCTIONS OF VITAMIN D
ROLE OF VITAMIN D

41. 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 mineral
parameters 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 based
study. 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 with
socioeconomic 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

42. 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 among
pregnant 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 Med
Res. 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

43. 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 Indian
population 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%)

44. 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.
Aurangaba
d
Bangalore
Bhopal
Chennai
Kolkata
Lucknow
Vapi
JaipurJodhpur
Chandigarh
Hyderabad
Cochin
Madurai
Ahmedaba
d
Mumbai
Vitamin D deficiency
Vitamin D insufficiency
Vitamin D sufficiency

45. VITAMIN D STATUS IN ADULTS (>18 YEARS)
Wahl DA, Cooper C, Ebeling PR, Eggersdorfer M, Hilger J, Hoffmann K, et al. A global representation of
vitamin D status in healthy populations. Arch Osteoporos. 2012;7(1-2):155-72.

46. 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.

47. 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

48. 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

49. GYNECOLOGICAL DISORDERS ASSOCIATED WITH
VITAMIN D DEFICIENCY
Disorder Strength of
association
Recommendation
for testing
Recommendation for
supplementation
Polycystic Ovary
Syndrome
+++ Routine 25(OH)D
testing 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

50. It is prudent to optimize Vitamin D status in
women with polycystic ovary syndrome (PCOS)
and in women planning pregnancy.

51. 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 among
pregnant women and their newborns in northern India. Am J Clin Nutr. 2005;8:1060–4. 2. Sahu M, Bhatia V, Aggarwal
A, Rawat V, Saxena P, Pandey A, et al. Vitamin D deficiency in rural girls and pregnant women despite abundant
sunshine 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 its
correlation 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/ml
74% rural pregnant women2
96.5% pregnant women3
99.7% lactating women3

52. 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 observational
studies. BMJ. 2013;346:f1169.
EFFECTS OF VITAMIN D DEFICIENCY
IN PREGNANCY

53. 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)

54. 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) +++

55. 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

56. 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 greater
than 20 ng/mL concentrations in mothers and infants was highest in 4000
IU/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 and
function: Why clinical dose intervals can affect clinical outcomes. J Clin Endocrinol Metab. 2013;98(12):4619-28.
HOW TO SUPPLEMENT VITAMIN D
DURING PREGNANCY

57. 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 north
India: a pilot study. Eur J Clin Nutr. 2009;63(9):1157-9.

58. 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 calcium
monitoring)
• 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

59. Vitamin D requirements during lactation: high-dose
maternal supplementation as therapy to prevent
hypovitaminosis D for both the mother and the
nursing infant
Bruce W Hollis and Carol L Wagner
 A maternal intake of 4000 IU/d could achieve substantial progress toward
improving both maternal and neonatal nutritional vitamin D status.
Hollis BW, Wagner CL. Vitamin D requirements during lactation: high-dose maternal supplementation as therapy to
prevent hypovitaminosis D for both the mother and the nursing infant. Am J Clin Nutr. 2004;80(6):1752S-8S.

60. 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

61. 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.

62.  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

63. CONTENTS
 Introduction
 Prevalence of Multiple Micronutrient Deficiencies
 Risk Factors for Micronutrient Deficiency in Pregnancy
 Function and Timing of Micronutrients that Affect Outcomes
in Offspring
 Are We Neglecting Few Micronutrients
 Iodine
 Calcium, Vitamin D
 Metalloenzymes: Zinc, Copper, Manganese and Magnesium
 Dietary Reference Values of Micronutrients in Pregnancy
 Conclusions

64. METALLOENZYMES
 There are more than 300 enzymes whose functions can be
impacted if diet is deficient on zinc, copper, manganese and
magnesium
 They are important trace metals which are responsible for normal
metalloenzyme activity
 All 4 play important role in maintaining maternal gestational
health and ensuring birth of healthy offspring
 Some of the enzymes where zinc, copper, manganese magnesium
are linked are alcohol dehydrogenase, glucokinase, chymotrypsin,
aldolases, triosephosphate isomerase, and pyruvate carboxylase...
J. Nutr. 2000; 130: 1437S—1446S
Comprehensive Reviews in Food Science and FoodSafety Vol.13,2014

65. Zinc : A Necessary Micronutrient for
Infantile Growth and development
Literature suggests a
beneficial effect of maternal
zinc supplement on
 Infancy growth and
developmental parameters
 Neonatal immune system
 Preventing infectious
disease
Relationship between mother
plasma zinc (Zn) and newborn
length in the supplemented group
Eur J Clin Nutr. 2004 Jan;58(1):52-9.

66.  Important role in pregnancy for the formation
of a wide variety of enzymatic and other
processes within the developing foetus
 Lower plasma concentrations of copper, were
found in cases of spontaneous abortion,
threatened abortion, missed abortion and
blighted ovum.
Copper Linked to Pregnancy and Placenta
 Some authors suggest that serum copper levels can be used as a
very sensitive indicator of certain pathological conditions and
further possible course of pregnancy and placental functions
 Serum copper decrease leads to a reduction of elastin and
collagen resulting in premature rupture of membranes
Srp Arh Celok Lek. 2012 J;140(1-2):42-46
Placenta 2000; 21:773-81
Proc Nutr Soc 2004; 63(4):553-62.

67.  Serum manganese conc. during pregnancy is significantly
lower than non-pregnant women
 Manganese plays a role in bone formation, protein and
energy metabolism, metabolic regulation, and functions as
a 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

68.  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 documented
an association with
 Fewer maternal hospitalizations
 Reduction in pre-term delivery
 Less intrauterine growth retardation
 Less frequent referral of the new born to the neonatal
intensive care unit.

69. CONTENTS
 Introduction
 Prevalence of Multiple Micronutrient Deficiencies
 Risk Factors for Micronutrient Deficiency in Pregnancy
 Function and Timing of Micronutrients that Affect Outcomes
in Offspring
 Are We Neglecting Few Micronutrients
 Iodine
 Calcium, Vitamin D
 Metalloenzymes: Zinc, Copper, Manganese and Magnesium
 Dietary Reference Values of Micronutrients in Pregnancy
 Conclusions

70. Dietary Reference Values of Micronutrients in
Pregnancy
Srp Arh Celok Lek. 2014;142(1-2):125-130

71. CONTENTS
 Introduction
 Prevalence of Multiple Micronutrient Deficiencies
 Risk Factors for Micronutrient Deficiency in Pregnancy
 Function and Timing of Micronutrients that Affect Outcomes
in Offspring
 Are We Neglecting Few Micronutrients
 Iodine
 Calcium, Vitamin D
 Metalloenzymes: Zinc, Copper, Manganese and Magnesium
 Dietary Reference Values of Micronutrients in Pregnancy
 Conclusions

72. 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

73. Planning healthy meals
• Include all food groups in diet
– Vegetables & fruits
– Milk and dairy foods
– Cereals & Grains
– Meat, beans, and eggs
– Fats and oils

74. 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.

75.  Micronutrient deficiencies during pregnancy are a global
public health concern
 Although evidence has rapidly accrued about roles of
antenatal micronutrients on the health of the offspring, gaps
in our knowledge still remain
 Micronutrient deficiencies have been linked to pregnancy
loss, preterm delivery, small birth size, birth defects, and long-
term metabolic disturbances
 Global Guidelines & Voice from Scientific Bodies recommend
supplementation with micronutrients during pregnancy &
lactation
CONCLUSIONS

77. NINE MONTHS ARE WINDOW OF OPPURTUNITY
Prevention, in order to be truly preventive, must
be antenatal
J. W. Ballantyne, 1902
Daily
Weeklys
Pt friendly and efective drugs and combinations
should be chosen
Nano particles,micillisation etc