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Dr.Revathi S. Rajan

on 9 November 2013

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‘ If doctors of today do not become the nutritionists of tomorrow then the nutritionists of today will become the doctors of tomorrow ! ‘
-Rockfeller Institute of Medicine Research.

Optimising maternal and child nutrition can positively influence the health of the future generation.

‘Health begins in the womb and even before that!!! ‘

Fetal Origin of Maternal Disease [FOAD]
[Developmental origins of health and disease paradigm]

Developmental Plasticity
Ability of the organism to develop in various ways depending on the particular environment or setting.
Developmental Programming
It is defined as a response of a developing organism to a specific challenge during a critical time window that alters the trajectory of development with resultant persistent effects on phenotype.

Hypothesis for
D O H a D

Multiphasic Nutritional Insult
Genes + early Under nutrition + subsequent Over nutrition
Fetal origins or later lifestyles or both `

Evidence shows that chronic diseases like diabetes, hypertension and cardiovascular disease may have their origins before birth.

Fetal Malnutrition & Adult Metabolic Diseases
Thrifty Genes

These could confer advantages in adverse nutritional environments but could become detrimental if the populations were exposed to an environment where food was abundant.

Predictive Adaptive Responses
Recognize responses that do not confer an immediate benefit but prepare the fetus to a later environment that is anticipated based on its developmental experience.

Disparities between the predicted and actual environment can result in disease.


Excess or deficits in nutrients ,hormones or metabolites trigger changes in DNA or histone methylation which in turn suppresses or enhances gene expression.

Changes in small non-coding RNA activity act by modulating gene expression without altering gene sequence.

Postulated that v.early stress inutero can cause changes in the mitochondrial activity that persists into adulthood !

Intergenerational effects
Low maternal birthwt is linked to increased risk of hypertension during pregnancy which subsequently translates into offsprings of low birth weight.

Effect of Glucocorticoids
Inutero glucocorticoid exposure can result in decrease in the no.of glucocorticoid receptors in the hypothalamus resulting in long term upregulation of the HPA axis after birth resulting in high blood pressure and glucose intolerance during adulthood.

Periconceptional Events
Human evidence suggests that there is an altered risk of adult disease linked to maternal nutritional status around conception and implantation, independent of the size of the offspring at birth.

Controversies for the



Size of the effect :
Though the associations of LBW to adult HTN has been contraversial due to small size of existing studies , there does exist a positive correlation between LBW and only systolic HTN.

Twins :
Most studies have reported a relationship between elevated BP in adulthood with LBW in twins.Some studies have not shown any association.

However the intrauterine environment is different for monozygotic and dizygotic twins.Evidence has shown that b.wt specific mortality is lower in twins than in singletons.

-Extent of associations with LBW as influenced by the gestational length is uncertain.
-However Insulin resistance ,elevated plasma insulin levels and elevated plasma cortisol levels have been reported in young adults born preterm independent of their b.wt.

The possibility of reversing the effect of adverse inutero fetal programming resulting in obesity and insulin resistance could be reversed in animal models after
Extrapolation of the same in humans is questionable.

Programming leading to Pathology
Evidence shows that infants who fail to put on weight have become resistant to Growth Hormone resulting in its high circulating concentrations which may cause cardiac enlargement and atheroma in
blood vessels

Who?? Can programme the fetus?
Obviously, one who sees the fetus first.

Neonatal size is strongly related to maternal BMI.
Nutriton of a woman throughout her life with particular emphasis during pregnancy influences growth of her fetus.
Babies born small in relation to the size of placenta have increase risk of developing hypertension in adulthood.

Role of Nutrition:
The role of nutrition in FOAD was best illustrated by the Dutch famine experience (1944 – 1945)
Pregnant women exposed to famine during their last trimester gave birth to babies who had a higher incidence of Type 2 Diabetes Mellitus and insulin resistance.
Early gestation exposure was associated with higher LDL/HDL levels and higher BMI.

Risk Factors for CVD, Adult Obesity & Type 2 DM
Age-adjusted Relative Risk of Non- fatal
Coronary Heart Disease and Stroke

Risk Factors for CVD
Low birth weight has been consistently associated with Insulin Resistance Syndrome, Type 2 Diabetes and high blood pressure.

Association of derranged lipids and clotting factors with low birth weight does exist but is not very consistent.

Increase in arterial intimal thickness and reduced endothelial function is seen in low birth weight men.

Leptin concentrations are increased in low birth weight adults with higher incidence of central obesity in them.

Risk Factors for Type 2 DM
Low birth weight infants have an increase propensity for type 2DM as they are adversely programmed in utero due to exposure to cortisol and other stress hormones.

This manifests as obesity with predisposition to the metabolic syndrome in adult life.

Fetal macrosomia in mothers of uncontolled GDM also leads to an increased predisposition to Type 2 DM.

This could be extrapollated to offsprings born before and after the onset of maternal GDM but surprisingly not seen in offsprings of diabetic fathers.

Metabolic Syndrome
Increasing in incidence as a consequence of the continuing obesity epidemic.

Main cause-Ectopic fat [Increase in visceral adiposity]

Attributable to a paracrine effect that decreases tissue insulin sensitivity in key issues like the liver leading to ‘Non Alcoholic Fatty Liver Disease-NAFLD’; that causes liver fibrosis.

This could be developmentally primed inutero due to inappropriate maternal nutrition.

from ectopic fat promote a pro-inflammatory state decreasing insulin sensitivity and adversely modify cardiovascular risk factors.

Relevant Studies
Risk for Neurodegenerative Disease
Bacterial endotoxins during pregnancy result in cytokine stimulation which impair the development of dopaminergic system resulting in Parkinsons’ Disease in adult life.

Maternal infection in second trimester can increase the risk of Schizophrenia in the progeny.

Impaired nutrition inutero causes significant cognitive and motor effects due to structural changes in the fetal brain.

Early detrimental developmental effects on brain structure and synaptogenesis may permanently affect brain function across the life span.

Key cognitive educational performance & motor skills influenced by early nutrition

This relationship differed according to the degree of discrepancy in birth weight

Propensity to Autoimmune Disease

Inutero fetal programming can alter the fetal immune system in response to
adverse stimuli[ immunosuppressive drugs] resulting in loss of tolerance to self antigens
and increased propensity to autoimmune disease.

Essential SUMMARY:
-Was the first to establish the influence of the maternal micronutrition on the size of the offspring.
-Vegetarianism could be attributed to ‘B12 and Folate ‘ status of Indians which could be responsible for the differential susceptibility of to Metabolic Syndrome.
-Prevention of Type 2 DM must begin inutero and continue through the life course.

[Analysed the rationale for the increasing prevalence of non communicable diseases in developing countries]
-Pooled analysis
-Reported a positive correlation between height at 2 yrs and BP.


Goals of Maternal Nutrition
To ensure appropriate inutero fetal programming.
To reduce long term pregnancy related complications .
To promote maternal heath and adaptation to lactational needs of energy and essential nutrients.
To ensure adequacy of all essential nutrients to the infant.

Dietary Modifications
Wholesome balanced diet.
Easily digestible food to ensure prevention of hyperemesis gravidarum (excessive vomiting during pregnancy)
Daily intake of 8-10 glasses of quality fluids
Intake of milk for adequate vitamin D and Calcium
Diet modification to ensure adequacy of all essential vitamins and minerals

Role of Micronutrients
- Long chain Omega-3 fatty acid
- Important component of cell membranes
- Visual development

DHA accumulates in the fetus rapidly during the last trimester of pregnancy and during the first year of life optimising brain development.
Essentially a dietary supplement.

Folate and Choline
Maternal deficiency of either Folate or Choline diminishes neurogenesis and hastens neuronal death in the fetal brain.
Folic acid deficiency is associated with neural tube defects,recurrent pregnancy loss,fetal growth restriction,abruptio placentae and low birth weight babies.

Besides supplements, you can obtain folic acid from natural sources such as green leafy vegetables, whole grains, wheat germ and citrus fruits.

Folate plays an important role in the synthesis of DNA and RNA and is a cofactor in other metabolic processes during fetal development

Choline is essential as cannot be sufficiently synthesized to meet metabolic needs
Essential for brain development and prevention of memory impairment in infants
Choline and folate are also important in later periods of pregnancy when the memory center of brain (hippocampus) is developing.

* RDA of Choline during pregnancy is 450mg.

Iodine is an essential part of the thyroid hormones thyroxine (T4) and Triiodothyronine (T3) which play an important role in
Growth regulation
Bone metabolism
Brain development
Human metabolism

*Maternal iodine deficiency is associated with cretinism, aberrations in brain development, deaf-mutism and altered psychomotor development in the infant.

Iodine needs to be supplemented in mid and late pregnancy as it significantly influences infant cognitive development.
WHO recommends a RDA of 200-250 microgrammes/day during pregnancy.
Breast feeding mothers require even higher supplementation.

Calcium and Vitamin D status in India
Most Indian women are Vitamin D deficient.

There is substantial evidence of calcium deficiency in parous indian women with recurrent pregnancy loss and after lactation.

Vitamin C is an antioxidant which improves general health, reduces stress and growth of fetus.

Calcium is important for women who are pregnant.

Vitamin D supplements significantly reduces recurrent ascending infections,preterm deliveries,small for gestational age babies,worsening of insulin reimportantlysistance and most increases calcium absorption.

400 iu/ day suits caucasian standards.
Higher doses of about 1000-2000 iu/day starting from 14 weeks till delivery is preferable in Indian women.
However the optimal dose needs to be validated by large studies!!!!!

Limited intake of Calcium and other minerals adversely affects fetal skeletal development simultaneously affecting maternal bone-mineral content during pregnancy.
RDA during pregnancy -1000 mg/dl.

Iron requirement increases during pregnancy due to increased iron utilisation by the developing fetus and placenta alongside blood volume expansion.

Increased B complex vitamins
B complex vitamins for increased maternal metabolism & accretion of different maternal & fetal tissues

Increased Vitamin A requirement for:
Sustain the growth of fetus
Limited reserve in fetal liver
Maintaining maternal tissue growth

Additional Vitamin C (especially during the 3rd trimester) for:
Protecting the Mother & fetus against oxidative stress
Growing needs of the fetus

VitaminB12 helps in
preventing miscarriages.

Iron helps prevent miscarriages.

Green leafy vegetables are a good natural source of iron.

Iron requirement increases during pregnancy
due to increased iron utilisation by the developing fetus and placenta alongside blood volume expansion.

Zinc is needed for
Central role in cell division
Growth of fetus
Protein synthesis
Natural sources of zinc include wheat germ, seeds and soy.

RDA in pregnancy is 10-20mgs

Boot the immune system.
Have lipid reducing property
Clear the gut of harmful microorganisms
Aid mineral absorption and balance.
They are nondigestive food ingredients that beneficially affect the host by
selectively stunting the growth of beneficial bacterial species resident in the colon improving host health[Fructose oligosaccharides].

Diet Modification
Should start preconceptionally.
Should be healthy and of good quality.
Enriched with micronutrients to meet
the demands of the growing fetus, also averting pregnancy complications and enhancing lactation.

Healthy Diet
Should consist of a right balance of,
-Milk and Dairy products.
-Cereals and grains.
-Fats and oils.
Should suit personal food preferences and lifestyle habits.

Breast Milk
Comprehensive nutritional plan for the newborn.
Contains DHA and other aminoacids for the braindevelopment of the newborn as well as good amounts of ‘Taurine and Choline’ for neuronal growth and mental health.
Provides immunological factors to protect against infections and also is a source of easily digestable fat,carbohydrates and proteins.

The mother would require additional calories and vitamins [a diet rich in fruits,vegetables,whole grains,lean meats and dairy products] for successful maintainance of lactation.

Evidence suggests that weight,diet and physical activity patterns are in part established or even programmed early in life.
Several interventions to counter malnutrition in all its forms have been discussed which include:
-improving wt and micronutrient status of mother,
-promoting breast feeding

-adjusting protein and fat content of early diets both in terms of quality and quantity.
-increasing physical activity of mother and children wherever appropriate.

Implications of FOAD/DOAHaD-A Public Health Perspective
The FOAD –DOHaD paradigm has contributed immensely for the better understanding of health and nutrion transitions of countries with a lifecourse,multidisciplinary and transgenerational perspective.
Optimising’Maternal Nutrition’ , must be a global priority!!!

1] The development origins of adult disease[Barker Hypothesis].
2] Fetal origin of coronary disease- P.Barker.
3] The metabolic syndrome- common origins of a multifactorial disorder-K.D.Bruce,C.D.Bryne.
4] Obesity and the DOHaD-Mathew W.Kemp et al.po
5]A critical evaluation of the FOAD Hythesis and its implications for developing countries-C.S Yagnik.
6] Micronutients in Maternal nutrition- Dr.Kamini A.Rao.

Thank You!!
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