HO CHI MINH NATIONAL UNIVERSITY

UNIVERSITY OF TECHNOLOGY

OFFICE FOR INTERNATIONAL STUDY PROGRAMS (OISP)

FACULTY OF CHEMICAL ENGINEERING

DEPARTMENT OF FOOD TECHNOLOGY

Nutrition topic: Scurvy, Vitamin B12 deficiency anemia

and Neural Tube Defects

Instructor: Accs. Prof. Võ Đình Lệ Tâm

Students: Đỗ Thành Nhân 1852626

Trần Hiến 1752195
Nguyễn Thị Minh Thu 1752523

Class: CC01

School year: 2020 – 2021

 Table of contents
I. Scurvy.........................................................................................................................................................5
1.1 Definition.............................................................................................................................................5
1.2 Diagnosis of scurvy.............................................................................................................................6
1.3 Severe complications...........................................................................................................................6
1.4 Energy required...................................................................................................................................7
1.5 Nutitional requirement.........................................................................................................................7
1.6 Design a meal for scurvy 70 years old patient..................................................................................13
References........................................................................................................................................................14
II. Vitamin B12 deficiency........................................................................................................................15
2.1 Theory................................................................................................................................................15
2.2 The chemical structure of Vitamin B12............................................................................................15
2.3 Types of Vitamin B12.......................................................................................................................16
2.4 Absorption.........................................................................................................................................16
2.5 Metabolism........................................................................................................................................17
2.6 Cause and Deficency.........................................................................................................................17
2.7 Treatment of Deficiency....................................................................................................................18
2.8 Energy requirement...........................................................................................................................18
2.9 Design a meal for Vitamins 70 years old patient..............................................................................18
References........................................................................................................................................................21
III. Neural tube defects.....................................................................................................................................21
3.1 Definition...........................................................................................................................................22
3.2 Causes................................................................................................................................................22
3.3 How to prevent NTDs?......................................................................................................................27
3.4 Diagnose............................................................................................................................................28
3.5 Some treatment methods for NTDs...................................................................................................29
3.6 Nutrition for pregnant mother...........................................................................................................30
References........................................................................................................................................................35
 List of figures
Figure 1: Interdental papillae sympton............................................................................................................................6
Figure 2: Bone lesions sympton......................................................................................................................................6
Figure 3: Osteoporosis sympton......................................................................................................................................6
Figure 4: Percentage of vitamin C retention during processing and cooking.................................................................13
Figure 5: Vitamin B12 functions in our body................................................................................................................16
Figure 6: Chemical structure of Vitamin B12................................................................................................................17
Figure 7: Type of substance of vitamin B12..................................................................................................................17
Figure 8: Metabolic pathway of vitamin B12 in human body.......................................................................................18
Figure 9: Defiency of vitamin B12................................................................................................................................18
Figure 10: Causes of vitamin B12 dificiency................................................................................................................19
Figure 11: Developmental origin of malformations broadly classified as neural tube defects in humans.....................24
Figure 12: Overview of folate one-carbon metabolism.................................................................................................26
Figure 13: Open bifida surgency...................................................................................................................................30
Figure 14: Hydrocephalus treatment method.................................................................................................................30
 List of tables
Table 1: Clinical manifestations of scurvy in adults........................................................................................................8
Table 2: Clinical manifestations of scurvy in infants and children..................................................................................8
Table 3: Energy intakes of eldery....................................................................................................................................9
Table 4 : Daily reference intakes for adults.....................................................................................................................9
Table 5: Protein intakes of older people aged 65 years and over...................................................................................10
Table 6: Classification of major dietary carbohydrates.................................................................................................10
Table 7: Dietary fibre intakes of old people..................................................................................................................11
Table 8: Carbohydrate intakes of old people.................................................................................................................11
Table 9: Fat intakes of old people.................................................................................................................................11
Table 10: Recommended micronutrient intakes............................................................................................................12
Table 11: Recommended calcium intakes for old people..............................................................................................12
Table 12: Adequate intakes for vitamin D for old people..............................................................................................13
Table 13: Recommended dietary intakes for iodine for old people...............................................................................13
Table 14: Recommended Zinc intakes for old people...................................................................................................13
Table 15: Recommended Vitamin C intakes.................................................................................................................14
Table 16: My recommend menu for Vitamin B12 dificiency patients...........................................................................21
Table 17: Recommended daily dietary allowances for pregnant and lactating women................................................33
Table 18: Typical composition of micronutrients in a prenatal vitamin........................................................................34
Table 19: Recommendations for pregnancy weight gain..............................................................................................35
Table 20: Balanced diet for a pregnant..........................................................................................................................36
Table 21: My recommended menu for pregnant mother in the first trimester...............................................................37
 Vitamin C
I. Scurvy
I.1 Definition
A disease caused by prolonged severe dietary deficiency of ascorbic acid in which the breakdown of
intercellular cement substances (chất gắn gian bào) leads to capillary haemorrhages (xuất huyết mao mạch)
and defective growth of fibroblasts (nguyên bào sợi) , osteoblasts (nguyên bào xương) , and odontoblasts (tế
bào trứng) results in impaired synthesis of collagen, osteoid (chất tạo xương), and dentine (chất béo); it is
characterized by haemorrhagic gingivitis (viêm nướu xuất huyết) affecting especially the interdental
papillae (nhú kẽ răng )(in the absence of teeth, the gums are normal),

Figure 1: Interdental papillae sympton

subperiosteal haemorrhages (xuất huyết dưới sụn) , bone lesions (tổn thương xương) (including the corner
fraction sign, a ground-glass appearance, and trabecular atrophy) seen on radiography,

Figure 2: Bone lesions sympton

perifollicular haemorrhages (xuất huyết quang nang), and frequently petechial haemorrhages (xuất huyết
thường xuyên) (especially on the feet).
Sudden death may occur as a result of cerebral or myocardial haemorrhage (xuất huyết não và cơ tim).
Megaloblastic anaemia, usually due to concomitant iron and/or folate deficiency, is usual.
In the adult form there are intraarticular and intramuscular haemorrhages, and osteoporosis may occur.
 Figure 3: Osteoporosis sympton
The disorder may occur in infants born to mothers who are consuming large doses of ascorbic acid, and in
adults following the abrupt discontinuation of large supplemental doses (despite relatively normal dietary
intake of ascorbic acid).
I.2 Diagnosis of scurvy
Table 1: Clinical manifestations of scurvy in adults

Table 2: Clinical manifestations of scurvy in infants and children

I.3 Severe complications

Symptoms and complications associated with long-term, untreated scurvy include:
  severe jaundice, which is yellowing of the skin and eyes
 generalized pain, tenderness, and swelling
 hemolysis, a type of anemia where red blood cells break down
 fever
 tooth loss
 internal hemorrhaging
 neuropathy, or numbness and pain usually in the lower limbs and hands
 convulsions
 organ failure
 delirium
 coma
 death
I.4 Energy required
Harris Benedict (kcal)=BEE (Based energy expenditure)
 66.5 + 13.75 x weight in kgs + 5 x height in cm - 6.78 x age (for male)
 65.5 + 9.56 x weight + 1.85 x height – 4.68 x age (for female)
Activity factor = 1-1.2
Stress factor = 1.5 – 1.7
Required energy: RE (kcal/day) = BEE x AF x SF
Table 3: Energy intakes of eldery

I.5 Nutitional requirement

Daily reference intakes for adults are:
Energy: 8,400kJ/2,000kcal
Total fat: less than 70g
Saturates: less than 20g
Carbohydrate: at least 260g
Total sugars: 90g
Protein: 50g
Salt: less than 6g
Table 4 : Daily reference intakes for adults

Macronutrient goals GOAL

 Protein 1.13 g/kg/day
Lipid 20-25% of daily energy intake
Carbohydrate 55-65% of daily energy intake
Water 2.1–2.6L/day

Macronutrients
Protein
Table 5: Protein intakes of older people aged 65 years and over

Sources of protein in the diet

The principal sources of protein in the diet of older women are: bread, milk, beef and veal, fish/seafood and
poultry. The principal sources of protein in the diet of older men are: bread, milk, beef and veal,
fish/seafood, pork and poultry.
Good sources of protein not listed above include eggs, milk products, legumes, cereals and cereal-based
foods, nuts, and meat alternatives (eg, soy protein in tofu).
Carbohydrate
Sugars
Older people may consume more sugar as a way of making food palatable in response to
age-associated declines in taste and smell. This change in diet may increase the risk of
dental problems as there is a strong link between poor dental health and frequent sucrose
intake. Although there is no direct evidence to support the hypothesis that a high sucrose
intake causes obesity, the Food and Agriculture Organization (FAO) and World Health
Organization (WHO) Expert Consultation has reiterated that excess energy in any form
could contribute to the accumulation of body fat (FAO 1998).
Table 6: Classification of major dietary carbohydrates

Dietary fibre
Table 7: Dietary fibre intakes of old people

Classification of carbohydrates is based primarily on molecular size and is outlined in

Table 8: Carbohydrate intakes of old people

Sources of carbohydrate in the diet

The principal sources of carbohydrate in the diet of women and men aged 65–75+ years are: bread, fruit,
potatoes/kūmara/taro. The principal dietary sources of fibre for older people are: bread, vegetables,
potatoes/kūmara/taro and fruit. Bread is the principal energy source for the older population, and is also a
significant source of carbohydrate and fibre for older people. Good sources of carbohydrates and dietary
fibre not listed above include cereal grains other than breakfast cereals (eg, barley, wheat and rye products,
and rice), other vegetables, legumes and seeds. The principal sources of sugar in the diet of older people are:
fruit, sugar/sweets and non-alcoholic beverages (eg, carbonated soft drinks, cordial and powdered drinks).
Fat
Table 9: Fat intakes of old people

Sources of fat in the diet

The principal sources of total fat in the diet of women aged 65–74 years are: butter and margarine, cakes and
muffins. The principal sources of total fat in the diet of women aged 75+ years are: butter and margarine,
milk, beef and veal, bread, cakes and muffins. The principal sources of total fat in the diet of men aged 65–
74 years are: butter and margarine, milk, beef and veal. The principal sources of total fat in the diet of men
aged 75+ years are: butter and margarine, beef and veal, milk and bread. Older people consume a greater
proportion of their total fat intake from butter and margarine compared with those aged 15–64 years. Older
people are more likely than younger adults to add discretionary butter and margarine to their food (ie, after
preparation but prior to consumption) (Simpson et al 2002). In the total adult population, the discretionary
addition of fat to food contributed 23 percent of the total fat intake of adult New Zealanders (Simpson et al
2002). Most (83%) of the discretionary butter and margarine was added to bread, followed by potatoes and
kūmara, cakes and muffins. Butter – but not margarine – was more likely to be added to vegetables
(Simpson et al 2002).
Micronutrients
Table 10: Recommended micronutrient intakes

Micronutrient goals GOAL

Vitamin C 250 mg/day

Folate ( vitamin B9) 400µg/day
Calcium 1000 mg/day
Iron 11 mg/day
Zinc 14 mg/day
Sodium Upper intake limit 2300 mg/day

Calcium
Table 11: Recommended calcium intakes for old people
Sources of calcium in the diet
The principal sources of calcium in the diet of women aged 65–75+ years are: milk, bread, dairy products,
cheese and vegetables. The principal sources of calcium in the diet of men aged 65–74 years are: milk,
bread, cheese, vegetables and dairy products. The principal sources of calcium in the diet of men aged 75+
years are: milk, bread, vegetables and cheese. Foods fortified with calcium (eg, reduced-fat milk, milk
products and calcium-fortified milk substitutes eg, soy milks) are good sources of calcium. Other good
sources of calcium not listed above include canned fish with bones, legumes, nuts, leafy vegetables, dried
fruit and tofu (Goulding 2007). For natural food sources of calcium, calcium content is of equal or greater
importance than bioavailability. The efficiency of calcium absorption varies across foods because calcium
may be poorly absorbed from foods rich in oxalic acid (eg, spinach, rhubarb, beans) or phytic acid (seeds,
nuts, grains, certain raw beans and soy isolates). Absorption from soy beverages can be – but is not always –
as high as that from milk. Compared with milk, calcium absorption from dried beans is about 50 percent and
from spinach, 10 percent (NHMRC 2006).

Vitamin D
Table 12: Adequate intakes for vitamin D for old people

Sources of vitamin D in the diet

Vitamin D is found in small quantities in a few foods such as fatty fish (North Sea salmon, herring and
mackerel), liver, eggs and fortified foods such as margarine; some low-fat dairy products (milk and yoghurt)
also contain very small amounts of vitamin D. Adequate intake of vitamin D is hard to achieve through diet
alone (Ministry of Health 2012). Dietary intake data from the National Nutrition Survey were analysed for
vitamin D in 1992. The main sources of dietary vitamin D intake at that time were margarine, fish, eggs and
milk (LINZ 1992).
Iodine
Table 13: Recommended dietary intakes for iodine for old people

Sources of iodine in the diet

Marine animals and plants concentrate iodine from seawater, so seafoods (including seameal, seaweed and
kelp) are rich sources. Iodine is secreted into milk, so milk and milk products are a useful source. Other
sources of iodine include eggs, some meat and cereals, and bread (when fortified with iodised salt). Iodised
salt is readily available in New Zealand (Thomson 2004). If required, iodine supplementation should be
managed by a medical practitioner. Kelp tablets are not recommended as their iodine content is highly
variable and an excessive iodine intake can be harmful to health.
Zinc
Table 14: Recommended Zinc intakes for old people

Vitamin C
Table 15: Recommended Vitamin C intakes

Factors affecting vitamin C reserves

Age
Decreased intakes by the elderly is the main factor influencing age-related changes in vitamin
C reserves.
Institutionalization
There are increased losses of vitamin C during large-scale institutional food preparation (see
chapter ‘Stability in Foods’).
 Figure 4: Percentage of vitamin C retention during processing and cooking
Vitamin C reserves are also affected by the following factors that influence vitamin C metabolism:
Sex
There is considerable evidence that mean plasma and leucocyte vitamin C concentrations are
lower in males than in females and that this difference persists into old age. The reason for
these sex differences is not known.
Smoking
There is general agreement that smoking lowers the level of vitamin C in both plasma and
leucocytes even if the precise reason is not known. Some believe that it is due to smokers’
reduced ability to absorb the vitamin.
Chronic conditions
Most sick people have low vitamin C reserves, for example in the case of gastrointestinal
disease, liver disease, alcoholism, asthma and diabetes. A number of studies indicate that
plasma vitamin C concentrations also decrease gradually throughout pregnancy. Lactation
can lead to significant losses of maternal vitamin C—as much as 32 mg/day.
I.6 Design a meal for scurvy 70 years old patient
Total Calories: 2,250 calories, with 55% of those calories coming from carbohydrates, 20% from fat, and
25% from protein. It also has about 34 grams of fiber.
The calories from protein = 450calories/day
1 gram of protein provide 4 calories => need to eat 112.5 gram protein per day.
Refer Nutrient handbook to calculate the gram of food to have enough protein for 1 days
EX: in 100 gram beef has 26 gram protein => need to eat 432 gram beef per day
The calories from protein = 1237.5 calories/day
1gram carbohydrate provides 4 calories => need to eat 309 gram carbohydrate for 1 day
Refer Nutrient handbook to calculate the gram of food to have enough carbs for 1 days
EX: in 100 gram of rice provides 28 gram carbohydrate => need to eat 1103 gram rice per day
The calories from fat = 450 calories/day
1gram fat provides 9 calories => need to eat 50 gram fat for 1 day
Refer Nutrient handbook to calculate the gram of food to have enough fat for 1 days
EX: in 100 gram of oil provides 100 g fat => need to eat 50 gram oil per day
Base on this fomular, we can design a meal for scurvy patient with accurate energy requires and nutrient
requires
Breakfast
 One grapefruit
 Two poached eggs
 Two slices whole-grain toast
 One cup low-fat milk
 One cup of herbal tea
(Macronutrients: Approximately 555 calories with 27 grams protein, 63 grams carbohydrates, and 23 grams
fat)

Lunch
 Chicken breast, baked or roasted
 Large garden salad with tomato and onion with one cup croutons, topped with one tablespoon oil and
vinegar
 Glass of water
(Macronutrients: 425 calories, 44 grams protein, 37 grams carbohydrates, 9 grams fat)
Snack
One banana
One cup plain yogurt with two tablespoons honey
Glass of water
(Macronutrients: 360 calories, 14 grams protein, 78 grams carbohydrates, 1 gram fat)
Dinner
 One cup steamed broccoli
 One cup of brown rice
 Small garden salad
 Sparkling water with lemon or lime slice
(Macronutrients: 646 calories, 42 grams protein, 77 grams carbohydrates, 8 grams fat)

References
 II. Vitamin B12 deficiency
II.1 Theory
 B12 is a water-soluble complex organic compound
 It has a complex structure and contains a metallic ion along with cobalt
 Human beings get this vitamin from diet consisting of cows flesh
 Being water-soluble, B12 can flush out from organisms. Further, fat cells or fatty acid unable to stored
it
 Source of vitamin B12
 Being micronutrient, B12 is essential for production and maintenance of health and myelination of
nerve cells.
It also aids in neurotransmitter, DNA, and RNA production. 
 Figure 5: Vitamin B12 functions in our body

II.2 The chemical structure of Vitamin B12

The chemical structure of cobalamin shows 1 cobalt atom with 4 pyrrole rings in corrin ring as a central part.
Cobalamin has different names due to attached radical.

Figure 6: Chemical structure of Vitamin B12

II.3 Types of Vitamin B12
Other forms include methyl cobalamin, deoxyadenosylcobalamin, hydroxocobalamin, and cyanocobalamin.
Methylcovalamin is the most active circulating form in humans and present in nutrition supplements.
 Figure 7: Type of substance of vitamin B12
II.4 Absorption
-Digestive system absorbs the cobalamin in three steps:
-Food protein bounded with B12 is released by the action of gastric acid and pepsin and then taken by
transcobalamin I (TCI) and then transported to the duodenum.
-An alkalizing action performed by pancreatic juices with its enzymes breakdown TCI and liberates
cobalamin which joins an intrinsic factor (IF).
- Finally, IF-cobalamin complex shows tendency of binding towards cubilin and then taken up the
enterocyte by a calcium-dependent passive transport mechanism system.
II.5 Metabolism

Figure 8: Metabolic pathway of vitamin B12 in human body

II.6 Cause and Deficency

 Figure 9: Defiency of vitamin B12
Causes:
 Pernicious anemia is the most common cause of B12 deficiency
 Malabsorption of HCl, pepsin and haptocorrin, R-protein
 Disorder in stomach lining, insufficient sliva and gastric juice
 Intrinsic factor such as pancreatic juice and calcium
 Vegan diet

Figure 10: Causes of vitamin B12 dificiency

II.7 Treatment of Deficiency
Supplementation with B12 is conducted to treat deficiency either orally (if vegan diet) or parenterally (if
atrophy gastritis).
Monitoring is necessary with treatment, and cognition should return to normal
II.8 Energy requirement
Formular: energy Requirement = BMR x physical activity factor x stress factor
BMR for women and men over 70 years old:
Men:13.5W + 487
Ex: W= 60kg =>> BMR=1290
Women:10.5W + 596
Ex: W= 51.8kg =>> BMR =1070
Physical activity of who is over 70 is almost 1.45 (light activity)
Energy requirements calculation:
Energy requirement of men = 1290x1.45x1.5=1870.5 Kcal/dau
Energy requirement of women = 1070x1.45x1.5 =1500.23 Kcal/day
II.9 Design a meal for Vitamins 70 years old patient
Total Calories: 1598 calories, with 49% of those calories coming from carbohydrates, 20% from fat, and
23% from protein. It also has about 28 grams of fiber.
The calories from protein = 480calories/day
1 gram of protein provide 4 calories => need to eat 109 gram protein per day.
Refer Nutrient handbook to calculate the gram of food to have enough protein for 1 days
EX: in 100 gram beef has 26 gram protein => need to eat 402 gram beef per day
The calories from protein = 1124.5 calories/day
1 gram carbohydrate provides 4 calories => need to eat 289 gram carbohydrate for 1 day
Refer Nutrient handbook to calculate the gram of food to have enough carbs for 1 days
EX: in 100 gram of rice provides 28 gram carbohydrate => need to eat 1083 gram rice per day
The calories from fat = 439 calories/day
1gram fat provides 9 calories => need to eat 40 gram fat for 1 day
Refer Nutrient handbook to calculate the gram of food to have enough fat for 1 days
EX: in 100 gram of oil provides 100 g fat => need to eat 40 gram oil per day
Base on this fomular, we can design a meal for Vitamin B12 patient with accurate energy requires and
nutrient requires
Table 16: My recommend menu for Vitamin B12 dificiency patients
References
III. Neural tube defects

3.1 Definition

Neural tube defects are birth defects of the brain and spinal cord. Birth defects are health conditions that are
present at birth. They change the shape or function of one or more parts of the body. Birth defects can cause
problems in overall health, how the body develops or how the body works.

A baby’s neural tube normally starts out as a tiny, flat ribbon that turns into a tube by the end of the first
month of pregnancies pregnancy. If the tube doesn’t close completely, an NTD can happen. NTDs can cause
serious problems for babies, including death.

NTDs happen in about 3,000 each year in the United States. Hispanic women are more likely than non-
Hispanic women to have a baby with an NTD.

The two most common NTDs are spina bifida and anencephaly. Spina bifida affects about 1,500 babies a
year in the United States. If your baby has spina bifida, the tiny bones of the spine don’t close completely,
and part of the spinal cord pokes through the spine. Children with spina bifida may have paralyzed legs and
problems controlling their bladder and bowel . Milder forms of spina bifida may cause fewer problems for
children.

Anencephaly is one of the most severe NTDs. It affects about 1,000 babies each year in the United States.
Anencephaly is caused when the upper part of the neural tube that forms the brain doesn’t close completely.
Babies with this condition are missing major parts of the brain, skull and scalp. They do not survive long
after birth, usually for just a few hours. Girls are 3 times more likely than boys to have anencephaly.

Taking folic acid before and during early pregnancy can help prevent NTDs in your baby. Folic acid is a B
vitamin that every cell in your body needs for normal growth and development.
Although the unifying feature of open NTDs is incomplete neural tube closure, evidence points to many
different possible causes, both genetic and environmental. In humans, it appears that most NTDs are
multifactorial, resulting from an additive contribution of several risk factors, which are each individually
insufficient to disrupt neural tube closure (Harris & Juriloff 2007). The challenge of identifying the primary
cause of NTDs in individual patients is highlighted by the numerous candidate genes and environmental
factors indicated by epidemiologic studies and experimental models. Moreover, the potential for gene-gene
and gene-environment interactions introduces further potential complexity.
3.2 Causes
Determining the specific causes of NTDs is best achieved in the context of an understanding of the
mechanisms underlying neural tube closure. Given the inaccessibility of the neurulation-stage human
embryo, our knowledge of the key principles of neural tube closure comes mainly from analysis of
experimental models, particularly other mammals, amphibians, and birds, in which primary neural tube
closure is achieved through folding and fusion of the neuroepithelium.
Primary Neurulation: Subtypes of NTDs Relate to Stages of Closure
In the prospective brain and most of the spinal cord, neural tube formation essentially involves the bending
of the neuroepithelium at the midline to generate neural folds that elevate, meet, and fuse in the dorsal
midline. Rather than simultaneously rolling up along the extent of the rostrocaudal axis, neural tube closure
is discontinuous with distinct sites of initiation located at characteristic axial levels. Moreover, the
morphological and molecular requirements for closure vary along the body axis, such that an individual
NTD usually affects only a portion of the neural tube. NTDs can thus be attributed to failure of particular
initiation events or disruption of the progression of closure between these sites (Figure 1).

Figure 11: Developmental origin of malformations broadly classified as neural tube defects in humans
Disorders of primary neurulation include craniorachischisis in which the neural tube fails to initiate closure,
leaving most of the brain and the entire spine open. If closure initiates successfully, then the cranial and/or
spinal neural folds may fail to close generating exence-phaly/anencephaly and open spina bifida,
respectively. Disorders of secondary neurulation comprise failure of the neural tube to separate completely
from adjacent tissues, resulting in tethering and diminished mobility. The spinal cord is covered by skin and
often associated with fatty tissue accumulation through as-yet-unknown mechanisms. Postneurulation
defects can arise when the bony structure of the skeleton fails to develop fully. Herniation of the meninges,
with or without brain tissue, through a skull defect generates encephalocele, while an analogous defect in the
spinal region produces meningocele 2.
Bending of the neural plate begins at approximately 18 days after fertilization, with an event equivalent to
closure 1 at approximately 21 days and completion of closure at the posterior neuropore by 26--28 days
postfertilization. It appears that closure of the forebrain and midbrain in human embryos may be achieved by
progression between the site of closure 1 and the rostral end of the neural plate without an intervening
initiation site analogous to closure.
Secondary Neurulation
In mice and humans, the neural tube caudal to the midsacral region is continuous with the caudal end of the
primary neural tube but forms by a distinct process, termed secondary neurulation . This process involves
condensation of a population of tail bud--derived cells to form an epithelial rod that undergoes canalization
to form the lumen of the tube in the lower sacral and coccygeal regions. Malformations resulting from
disturbance of secondary neurulation are closed and often involve tethering of the spinal cord, with
associated ectopic lipomatous material.
Causes of NTDs
NTDs are among the most common birth defects worldwide with a prevalence that varies from 0.5 to more
than 10 per 1,000 pregnancies. This variance likely reflects differing contributions from risk factors such as
nutritional status, prevalence of obesity and diabetes, usage of folic acid supplementation and/or
fortification, the presence of environmental toxicants, and differing genetic predisposition among ethnic
groups. In most populations, there is also a striking gender bias: Anencephaly is more prevalent among
females than males. Many NTD mouse strains also show a female preponderance among cranial NTDs,
apparently reflecting a fundamental higher sensitivity of cranial neural tube closure to disturbance in female
embryos. Overall, although studies have identified numerous risk factors, these may account for less than
half of NTDs, suggesting that additional genetic and nongenetic factors remain to be identified.
Various teratogenic agents induce NTDs in rodent models. In humans, teratogens that have been associated
with NTDs include the anticonvulsant drug valproic acid and the fungal product fumonisin. Other
nongenetic risk factors include maternal fever and excessive use of hot tubs, consistent with the induction of
NTDs by hypothermia in rodent models.
Maternal obesity and diabetes are well-recognized risk factors for NTDs. Determining the cause of diabetes-
related NTDs is hampered by the complexity of the diabetic milieu, although hyperglycemia alone is
sufficient to cause NTDs in cultured rodent embryos. NTDs may result from increased oxidative stress,
altered expression of genes such as Pax3, and neuroepithelial cell apoptosis. Recent findings suggest that
activation of apoptosis signal-regulating kinase 1 in hyperglycemic conditions leads to activation of the
apoptosis mediator caspase 8 by stimulating the FoxO3a transcription factor.
Nutritional factors and folate
The historical link between lower socioeconomic status and higher risk of birth defects led investigators to
examine the possible involvement of nutritional factors in NTDs. Lower blood levels of the B-vitamin folate
were observed in mothers of NTD fetuses, prompting an intervention trial of a folic acid containing
multivitamin supplement to prevent NTD recurrence. A multicenter randomized controlled trial confirmed
that maternal folic acid supplementation significantly reduces the recurrence risk. Additional clinical trials
provided evidence for reduction of occurrence risk.
Questions remain concerning the mechanism by which folic acid prevents NTDs. Although maternal folate
status is a risk factor, in most cases, maternal folate levels are within the normal range and rarely clinically
deficient. Nonetheless, data have shown an inverse relationship between blood folate concentration and risk
of an affected pregnancy. Suboptimal folate levels may contribute to NTD development in individuals who
are genetically susceptible. Such a gene-environment interaction has been demonstrated in mice, where
folate deficiency does not cause NTDs unless deficiency is present in combination with a mutation of a
predisposing gene, such as Pax3.
Folate one-carbon metabolism (figure 12) comprises a complex network of interlinked reactions that
mediate transfer of one-carbon groups for several biosynthetic process. Among these, attention has focused
particularly on the requirement for nucleotide biosynthesis and methylation reactions in neural tube closure.
Abnormal thymidylate and purine biosynthesis have been identified in mouse NTD models and in a
proportion of NTD cases, whereas deficient methylation may also be implicated in NTDs.
Folates provide a backbone for the transfer of one-carbon units. Key outputs include nucleotide biosynthesis
and methylation. Among methylation cycle intermediates, homocysteine may also be converted to
cystathionine in the transulfuration pathway and S-adenosylmethionine is involved in polyamine
biosynthesis. FOCM is compartmentalised: one-carbon units from the mitochondria enter cytoplasmic
FOCM as formate while reactions of thymidylate biosynthesis also operate in the nucleus. In loss-of-
function mouse models, NTDs arise in mutants for Mthfd1l and genes encoding the glycine cleavage
system. Shmt1 and Mthfr null mice are viable to birth but may develop NTDs under folate-deficient
conditions.
.

Figure 12: Overview of folate one-carbon metabolism

Genetics of NTDs
Most NTDs occur sporadically, with a relative scarcity ofmultigenerational families. Nevertheless, strong
evidence demonstrates a genetic component in the etiology of NTDs, and the pattern of inheritance favors a
multifactorial polygenic or oligogenic model, as opposed to an effect of single genes with partial penetrance.
Most studies of NTD genetics have focused on one or more candidate genes. In general, candidates have
been human orthologs of genes whose mutation causes NTDs in mice, of which there are more than 200
examples; or genes related to environmental risk factors, particularly folate metabolism.
Case-control association studies have implicated several genes, whereas mutation screening by sequencing
has identified putative pathogenic mutations. However, the definitive assignment of a gene variant as
causative is complicated by the apparent multigenic nature of NTDs and by the large number of possible
candidate genes, modifier genes, epigenetic factors, and environmental influences. Moreover, where putative
mutations have been identified in specific genes, each has been involved in only a small proportion of NTD
patients, suggesting that there is considerable heterogeneity underlying the genetic basis of NTDs. Thus,
although the morphological and cellular bases of neural tube closure have become increasingly well
understood, the genetic basis of NTDs in individual cases remains largely unclear.
Gene-gene interactions and effect of modifier genes
Mouse studies suggest three broad mechanisms by which genetic interactions may result in NTDs. First, in
some instances functional redundancy makes it necessary for two orthologous genes to be mutated, Cdx1-
Cdx2 double knockouts, in order to reveal a requirement in neural tube closure. Second, additive effects of
heterozygous mutations may result in NTDs that resemble those of individual. Third, variation in the
penetrance and expressivity of NTD phenotypes between inbred mouse strains is widely reported to reflect
variants in modifier genes. For example, the rate of exencephaly resulting from Cecr1 mutation is strongly
affected by strain background. Whereas the identity of modifier genes for NTDs has rarely been determined,
a variant in Lmnb1 is present in some mouse strains and significantly increases the frequency of NTDs
in curly tail embryos.
Genes implicated through experimental models
In mice, mutation of genes encoding components of the PCP pathway causes NTDs. Sequencing of PCP
genes in humans has identified putative mutation in some patients with craniorachischisis, spina bifida,
anencephaly, or closed forms of spina bifida. As in mice, heterozygous human PCP mutations may interact
with other genetic NTD risk factors in a digenic or polygenic fashion to cause a range of NTD types. This
interaction could involve summation of multiple variants in PCP genes. For example, a putative mutation
in DVL2 was identified in a spina bifida patient in combination with a second, previously identified
missense variant in VANGL2.
Among other genes implicated in NTDs from mouse models, association studies have not provided evidence
for a major contribution to risk, and few positive results have emerged from sequencing-based mutation
screens. As data begin to emerge from large-scale exome sequencing studies of NTD patients, it will become
possible to evaluate the contribution of multiple genes in the same patient cohorts and the mutational load
associated with individual risk.
Analysis of genes related to environmental risk factors
The identification of environmental factors such as maternal diabetes and folate status as risk factors for
NTDs provides impetus for researchers to analyze related genes in affected families. Risk could be
associated with maternal genotype if genetic variation alters maternal metabolism and secondarily affects
the developing embryo. However, the inheritance of maternal alleles by the embryo complicates
interpretation of such effects. Alternatively, a genetically determined abnormality in the embryo itself could
influence risk of NTDs, potentially through interaction with a predisposing environmental factor. For
example, it may be informative to analyze genetic data on folate-related genes in the context of maternal
folate.
Association with risk of spina bifida has been reported for several genes implicated in diabetes, obesity,
glucose metabolism, and oxidative stress. These potential ‘risk’ genes include GLUT1, SOD1, and SOD2.
Maternal variants in the obesity-related genes FTO, LEP, and TCF7L2 are also associated with NTDs,
consistent with maternal obesity as a risk factor.
Genes related to folate one-carbon metabolism have been perhaps the most intensively studied group of
candidates for NTDs. The C677T polymorphism of MTHFR, which encodes an alanine-to-valine
substitution, has been associated with NTDs. The TT genotype is found at higher frequency among NTD
cases than in controls in some populations but not others. Several studies indicate positive associations with
other folate-related genes, including MTRR, although these have generally not been observed in all study
populations.
In mice, mutations in folate-metabolizing enzymes are sometimes lethal before the stage of neural tube
closure whereas others do not disrupt closure. Null embryos for the folate receptor, Folr1, die preneurulation
but develop NTDs when supplemented with sufficient folic acid to prevent early lethality. NTDs are also
observed in Shmt1 knockouts, under folate-deficient conditions. In contrast, NTDs occur spontaneously in
mice carrying loss-of-function alleles of Amt or Mthfd1L, both of which encode enzymes of mitochondrial
folate metabolism. The homologous genes in humans have also been linked to NTDs. Missense mutations
have been identified in NTD patients in AMT as well as in GLDC, which encodes its partner enzyme in the
glycine cleavage system. Genetic associations with NTDs have been reported
for MTHFD1L and SLC23A32, encoding a mitochondrial folate transporter. Altogether, these findings
suggest that NTD risk is influenced by the function of mitochondrial folate metabolism, a major source of
one-carbon units to the cytoplasm.
Gene-Regulatory Mechanisms and NTDs
Identification of causative genes may be complicated, in addition to the potential multigenic nature of
NTDs, by the potential involvement of aberrant gene expression, perhaps resulting from mutations in
regulatory elements. For example, mutations resulting in insufficient expression of Grhl3 or excess
expression of Grhl2 cause NTDs in mice in the absence of coding mutation. Further complexity may be
added by the potential for regulation by epigenetic modifications such as DNA methylation, histone
modification, or chromatin remodeling, each of which has been associated with NTDs in mice and in some
cases in humans. For example, methylation of LINE-1 genomic elements was lower than normal in DNA of
anencephalic but not spina bifida fetuses.
A simple model predicts a positive correlation between folate status and methylation. However, data from
human pregnancy suggest that the relationship is not straightforward. A recent study found an inverse
correlation of LINE-1 methylation with maternal and cord blood folate, whereas different imprinted genes
showed positive or negative associations. Somewhat counterintuitively, use of folic acid supplements was
associated with reduced LINE-1 methylation.
A requirement for DNA methylation in mouse neural tube closure is suggested by the occurrence of NTDs
in knockouts of Dnmt3b, encoding a DNA methyltransferase, and in embryos cultured with 5-azacytidine.
Similarly, inhibition of the methylation cycle reduces DNA methylation and causes NTDs in cultured mouse
embryos. However, Mthfr null embryos do not develop NTDs despite a significant reduction in global DNA
methylation, nor is there an exacerbating effect of Mthfr loss-of-function on Pax3 or curly tail mutants,
although both show increased rates of NTDs under folate-deficient conditions. Thus, questions remain about
the relationships among folate status, DNA methylation, and risk of NTDs.
Other epigenetic mechanisms include various modifications of histone proteins, which potentially
misregulate genes that influence neurulation. NTDs occur in mice carrying mutations in the histone
demethylases Jarid2 and Fbxl10. Similarly, histone acetylases and deacetylases, which regulate the
equilibrium of histone acetylation, are implicated in NTDs. An acetylase-specific knockin mutation
of Gcn5 causes cranial NTDs, as does loss-of-function of another histone acetylase, p300. Increased
acetylation is also associated with NTDs. For example, cranial NTDs occur in mice carrying mutations in
histone deacetylases Sirt1 or Hdac4. The teratogenic effects of valproic acid and trichostin A may also be
mediated through their inhibition of histone deacetylases.
3.3 How to prevent NTDs?
Once the neural tube has failed to close, ensuing damage to the exposed neural tissue is irreversible, despite
possible palliative benefit of in utero surgery. Therefore, primary prevention is the optimal approach for
reducing the burden of NTDs.
Folic Acid Supplementation and Fortification
The reduction in risk of NTDs following maternal folic acid supplementation led to public health
recommendations that women who may become pregnant should consume 0.4 mg of folic acid daily or 4 mg
daily following a previous affected pregnancy. To ensure that additional folate was received, food
fortification programs were introduced in many countries. This approach has raised blood folate levels and
has been associated with lower NTD frequency. The magnitude of effect varies, with greatest reduction
found where preexisting rates were highest. Some countries have delayed a decision on fortification owing
to safety concerns, but a recent meta-analysis found no evidence for increased cancer rates following folic
acid supplementation.

You can get folic acid from foods that are fortified with folic acid. Fortified means a food has folic acid
added to it. Check the product label to see how much folic acid you get in each serving. Look for the word
“fortified” or “enriched” on labels on foods like: Bread, Breakfast cereal, Cornmeal, Flour, Pasta, Products
made from a kind of flour called corn masa, like tortillas, tortilla chips, taco shells, tamales and pupusas,
White rice
Some fruits and vegetables are good sources of folic acid. When folic acid is naturally in a food, it’s called
folate. Foods that are good sources of folate are:,Beans, like lentils, pinto beans and black beans; Leafy
green vegetables, like spinach and Romaine lettuce; Asparagus; Broccoli; Peanuts; Citrus fruits, like oranges
and grapefruit; Orange juice
It’s hard to get all the folic acid you need from food. Even if you eat foods that have folic acid in them, take
your vitamin supplement each day, too.

Folate-Resistant NTDs
Folic acid supplementation in clinical trials has not approached 100% NTD prevention, and an estimated
one-third of NTDs may be folic acid resist Folic acid supplementation in clinical trials has not approached
100% NTD prevention, and an estimated one-third of NTDs may be folic acid resistant. A study in the
United States, where folate fortification of food is mandatory, found no apparent protective effect of folic
acid supplements, suggesting that increased dosage would not necessarily provide additional preventive
effects.
Given the multifactorial causation of NTDs it seems reasonable to suppose that optimal prevention will
require a combination of multiple interventions. Possible approaches may relate to folate one-carbon
metabolism. For example, as with folate, evidence shows a graded relationship between lower levels of
circulating vitamin B12 and increased risk of an NTD-affected pregnancy. Perhaps use of B12 supplements
would further reduce NTD frequency, although this approach remains to be tested.
Another possibility is that folic acid cannot ameliorate some defects that result from abnormal folate
metabolism, owing to defects in the intervening enzymes required to transfer one-carbon units to key
downstream metabolites. In this case, supplementation with alternative folates, such as 5-methyl THF, or
key downstream molecules may be advantageous. For example, supplementation with formate prevented
NTDs in Mthfd1L null mice, whereas combinations of thymidine and purine precursors prevented NTDs in
curly tail mice, in which folic acid is not protective.
In addition to low levels of folate and vitamin B12, lower maternal levels of other vitamins, including
vitamin C, have been reported in NTDs. Conversely, intake of several vitamins and maternal diet are
associated with lower risk of NTDs, which suggests that nutrients other than folic acid may be beneficial.
Experimental analysis of individual vitamins found that myo-inositol deficiency caused NTDs in cultured
rodent embryos. Inositol supplementation significantly reduced NTD frequency in curly tail mice and in
rodent models of diabetes and inositol is in clinical testing for prevention of NTD recurrence.
3.4 Diagnose

You can get prenatal tests called screening tests to find out if your baby is at increased risk of having an
NTD. Screening tests for NTDs include: Maternal blood screening. It’s called a quad screen because it
measures four substances in your blood. The test is done at 15 to 22 weeks of pregnancy. As well as
ultrasound test. This test uses sound waves and a computer screen to show a picture of your baby inside the
womb. You usually get an ultrasound at 16 to 20 weeks of pregnancy.
If a screening test shows an increased risk of NTDs, your provider may recommend a diagnostic test to find
out for sure if your baby has an NTD. Diagnostic tests for NTDs include:
 Amniocentesis. In this test, your provider takes some amniotic fluid from around your baby in
the uterus to check for birth defects, like NTDs, in your baby. You can get this test at 15 to 20
weeks of pregnancy.
 Detailed ultrasound of your baby’s skull and spine
If you find out during pregnancy that your baby has an NTD, talk to your health care provider to learn more
about your baby’s condition and options for birth and treatment. For example:
 You can plan to have your baby in a hospital that specializes in caring for babies with NTDs.
This way your baby can have any necessary surgery or treatment soon after birth.
 You can decide whether to have a vaginal or cesarean birth . During vaginal birth, the uterus
contracts to help push the baby out through the vagina. A c-section is surgery in which your baby
is born through a cut that your doctor makes in your belly and uterus. In some cases, a c-section
may be safer for you and your baby than vaginal birth.
 If your baby has spina bifida, you can find out about surgery for your baby in the wom.
 3.5 Some treatment methods for NTDs
Treatment for spina bifida depends on the severity of the condition and the presence of complications. For
some people, treatment needs may change over time, depending on the condition’s severity or compli-
cations:
 An infant with myelomeningocele, in which the spinal cord is exposed, can have surgery to close the
hole in the back before birth or within the first few days after birth.

Figure 13: Open bifida surgency

 If an infant with spina bifida has hydrocephalus, a surgeon can implant a shunt—a small hollow tube
to drain fluid—to relieve pressure on the brain. Treating hydrocephalus can prevent problems such as
blindness.

Figure 14: Hydrocephalus treatment method

 People with encephaloceles—sac-like bulges where the brain and surrounding membranes protrude
through the skull—are sometimes treated with surgery. During the surgery, the bulge of tissue is
placed back into the skull. Surgery also may help to correct abnormalities in the skull and face.
 Tethered spinal cord. Surgery can separate the spinal cord from surrounding tissue.1
  Paralysis and limitations in mobility. People with spina bifida use different means to get around,
including braces, crutches, walkers, and wheelchairs.
 Urinary tract infections and lack of bladder and bowel control. People with myelomeningocele often
have nerve damage that keeps the bladder from completely emptying. This can cause urinary tract
infections and damage to the kidneys. Health care providers may address this problem by using a
tube to fully empty the bladder. Medications, injections, and surgery also can help prevent urine from
leaking accidentally and keep the kidneys and bladder working for the long term.
There is no treatment for anencephaly or iniencephaly.2 Infants with these conditions usually die shortly
after birth. Before birth, surgery to repair spina bifida in the womb before birth is more effective than
surgery after birth.

3.6 Nutrition for pregnant mother.

Energy Requirement
Harris Benedict =BEE
 66.5 + 13.75 x weight in kgs + 5 x height in cm - 6.78 x age
 65.5 + 9.56 x weight + 1.85 x height – 4.68 x age
Activity factor = 1-1.2 (base on your age and job, for traditional housewife, we consider AF according to
moderate physical activity)
Stress factor = 1.5 – 1.7 (for pregant mother)
Required energy: RE = BEE x AF x SF
Energy Expenditure during Pregnancy
Caloric intake should increase by approximately 300 kcal/day during pregnancy. This value is derived from
an estimate of 80,000 kcal needed to support a full-term pregnancy and accounts not only for increased
maternal and fetal metabolism but for fetal and placental growth. Dividing the gross energy cost by the mean
pregnancy duration yields the 300 kcal/day estimate for the entire pregnancy. However, energy requirements
are generally the same as non-pregnant women in the first trimester and then increase in the second
trimester, estimated at 340 kcal and 452 kcal per day in the second and third trimesters, respectively.
Furthermore, energy requirements vary significantly depending on a woman’s age, BMI, and activity level.
Caloric intake should therefore be individualized based on these factors
Macronutrients
Recommended protein intake during pregnancy is 60g/day, which represents an increase from 46g/d in non-
pregnant states. In other words, this increase reflects a change to 1.1g of protein/kg/day during pregnancy
from 0.8g of protein/kg/day for non-pregnant states.2 Carbohydrates should comprise 45-64% of daily
calories and this includes approximately 6-9 servings of whole grain daily. Total fat intake should comprise
20-35% of daily calories, similar to non-pregnant women.
Micronutrients
The recommendations for daily micronutrient intake for a pregnant woman are determined by the
“Recommended Dietary Allowances” or RDA data. In general, these RDA refer to the levels of intake of
essential nutrients that are judged by the Food and Nutrition Board of the Institute of Medicine to be
adequate to meet the known nutrient needs of practically all healthy persons. The RDA have been modified
for pregnant women. Table 17 shows the dietary allowances for most vitamins and minerals during
pregnancy and they are reviewed in further detail below.
Daily prenatal multivitamin is generally recommended before conception and during pregnancy. Table
17 describes the typical composition of a prenatal vitamin. The critical difference compared to other
multivitamins is the folic acid dose, which is necessary to support rapid cell growth, cell replication, cell
division, and nucleotide synthesis for fetal and placental development.
Table 17: Recommended daily dietary allowances for pregnant and lactating women.

Nutrient Non-Pregnant Pregnant* Lactation*

Vitamin A 700 770 1300

Vitamin D 5 15 15

Vitamin E 15 15 19

Vitamin K 90 90 90

Folate 400 600 500

Niacin 14 18 17

Riboflavin 1.1 1.4 1.6

Thiamin 1.1 1.4 1.4

Vitamin B6  1.3 1.9 2

Vitamin B12  2.4 2.6 2.8

Vitamin C 75 85 120

Calcium 1,000 1,000 1,000

Iron 18 27 9
 Phosphorus 700 700 700

Selenium 55 60 70

Zinc 8 11 12

While there is data to support additional folic acid and iron supplementation during pregnancy, there is no
high quality evidence demonstrating that all women require the increased levels of nutrients in a prenatal
vitamin.
Table 18: Typical composition of micronutrients in a prenatal vitamin

Component Amount % Daily Value for Pregnant

and Lactating Women

Vitamin A 4,000 IU as beta carotene 50%

Vitamin D3 400 IU as Cholecalciferol 100%

Vitamin E 11 IU as dl-Alpha Tocopheryl acetate 37%

Folic acid 800 μg 100%

Niacin 18 mg as niacinamide 90%

Riboflavin 1.7mg as thiamin mononitrate 85%

Thiamin 1.5 mg 88%

Vitamin B6 2.6 mg as pyridoxine hydrochloride 104%

 Vitamin B12 4 μg as cyanocobalamin 50%

Vitamin C 100 mg as ascorbic acid 167%

Calcium 150 mg as calcium carbonate 12%

Iron 27 mg as ferrous fumarate 150%

Zinc 25 mg as zinc oxide 167%

Folic acid is the synthetic form of the naturally occurring B vitamin, folate. Folic acid is the form used in
most vitamin supplements and food fortification. As mandated by the Food and Drug Administration,
commonly fortified foods include bread, cereal, and pasta. Folate-rich food sources are citrus fruits, dark-
green leafy vegetables, nuts, and liver. Folate requirements increase during pregnancy as a result of rapidly
dividing cells related to fetal growth. Notably, folic acid supplements taken prior to conception can reduce
the risk for neural tube defects in the fetus. Since the FDA mandate, blood folate levels have increased and
neural tube defects have declined. In order to reduce the risk for neural tube defects in their offspring,
women are recommended to take folic acid from fortified food or supplements daily in addition to
consuming a diet rich in food sources of folate. Women with a history of a neural tube defect in a prior
pregnancy should take a higher dose of folic acid daily for subsequent pregnancies. Deficiencies in folate
have been associated with megaloblastic anemia in pregnancy, though not with other pregnancy outcomes
such as preterm birth or stillbirths.
Weight Gain

Weight gain is important during your pregnancy and something you and your doctor will monitor for nine
months until you give birth.  However, gaining too much or too little weight can contribute to problems
during your pregnancy for both you and your baby.
Just because you are eating for two doesn’t mean you should eat twice the amount of food. If you are a
healthy weight before your pregnancy, you only need to eat an average of about 300 extra calories a day.
Recent recommendations by the Institute of Medicine for pregnancy weight gain begin your pre-pregnancy
body mass index.

Table 19: Recommendations for pregnancy weight gain.

BMI category Weight gain goal: Weight gain goal:

single twins
BMI < 18.5: 28-40 lbs Not enough data
underweight
BMI: 18.5-24.9: healthy 25-35 lbs 37-54 lbs
weight
BMI: 25-29.9: 15-25 lbs 31-50 lbs
overweight
BMI: >30: obese 11-20 lbs 25-42 lbs
Design meals in a week for pregnants
Aim for nutrition intake:

 About 1,800 calories per day during the first trimester

 About 2,200 calories per day during the second trimester

 About 2,400 calories per day during the third trimester

My meals are designed for the first trimester, food highlighted with green color are rich in folate.

The calories from protein = 450calories/day

1 gram of protein provide 4 calories => need to eat 112.5 gram protein per day.
Refer Nutrient handbook to calculate the gram of food to have enough protein for 1 days
EX: in 100 gram beef has 26 gram protein => need to eat 432 gram beef per day
The calories from protein = 1237.5 calories/day
1 gram carbohydrate provides 4 calories => need to eat 309 gram carbohydrate for 1 day
Refer Nutrient handbook to calculate the gram of food to have enough carbs for 1 days
EX: in 100 gram of rice provides 28 gram carbohydrate => need to eat 1103 gram rice per day
The calories from fat = 450 calories/day
1 gram fat provides 9 calories => need to eat 50 gram fat for 1 day
Refer Nutrient handbook to calculate the gram of food to have enough fat for 1 days
EX: in 100 gram of oil provides 100 g fat => need to eat 50 gram oil per day
Base on this fomular, we can design a meal for pregnant woman with accurate energy requires and nutrient
requires
Table 20: Balanced diet for a pregnant
Table 21: My recommended menu for pregnant mother in the first trimester.

Green ones are rich in folate.

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