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Folate Fruits

This current page is a start page for your exploration of topics related to nutrition and development.

While there are many sites and information available concerning postnatal nutrition, prenatally research has mainly focussed on developmental effects of specific deficiencies (folate and iodine) and the teratogenic effects of retinoic acid.

See Australian Pregnancy Care Guidelines (2018)[1] and also the National Health and Medical Research Council (NHMRC) (2006) publication NHMRC - Nutrient Reference Values for Australia and New Zealand Including Recommended Dietary Intakes.[2] "The Nutrient Reference Values outline the levels of intake of essential nutrients considered to be adequate to meet the known nutritional needs of practically all healthy people for prevention of deficiency states. The document can be used by health professionals to assess the likelihood of inadequate intake in individuals or groups of people." Some text on this current page is modified from this report.

In Australia and New Zealand

Before mandatory folic acid fortification was introduced:

  • mean dietary folic acid intakes for women aged 16–44 years (the target population) in Australia was 108 micrograms (μg) of folic acid per day and in New Zealand was 62 μg of folic acid per day, well below the recommended 400 μg per day.
  • there were 149 pregnancies affected by NTDs in 2005 in Australia (rate of 13.3 per 10,000 births) in the three states that provide the most accurate baseline of NTD incidence (South Australia, Western Australia and Victoria), and 63 pregnancies affected by NTDs in 2003 in New Zealand (rate of 11.2 per 10,000 births).

Before mandatory iodine fortification was introduced:

  • large proportions of the Australian and New Zealand population had inadequate iodine intakes.
  • national surveys measuring median urinary iodine concentration (MUIC) in schoolchildren, an indicator of overall population status, confirmed mild iodine deficiency in both countries.
    • the concentration was 96 μg per litre in Australia, and 66 μg per litre in New Zealand, less than the 100–200 μg per litre considered optimal.

The Nobel Prize in Chemistry 1937 Walter Norman Haworth "for his investigations on carbohydrates and vitamin C" and Paul Karrer "for his investigations on carotenoids, flavins and vitamins A and B2".

Nutrition Links: nutrition | Vitamin A | Vitamin B | Vitamin C | Vitamin D | Vitamin E | Vitamin K | folate | iodine deficiency | neural abnormalities | Axial Skeleton Abnormalities

Some Recent Findings

  • Diet Alters Micronutrient Pathways in the Gut and Placenta that Regulate Fetal Growth and Development in Pregnant Mice[3] "Maternal malnutrition and micronutrient deficiencies can alter fetal development. However, the mechanisms underlying these relationships are poorly understood. We used a systems physiology approach to investigate diet-induced effects on maternal gut microbes and folate/inositol transport in the maternal/fetal gut and placenta. Female mice were fed a control diet (CON) diet, undernourished (UN, restricted by 30% of CON intake) or a high-fat diet (HF, 60% kcals fat) during pregnancy to model normal pregnancy, fetal growth restriction or maternal metabolic dysfunction, respectively. At gestational day 18.5, we assessed circulating folate levels by microbiological assay, relative abundance of gut lactobacilli by G3PhyloChip™, and folate/inositol transporters in placenta and maternal/fetal gut by qPCR/immunohistochemistry. UN and HF-fed mothers had lower plasma folate concentrations vs. CON. Relative abundances of three lactobacilli taxa were higher in HF vs. UN and CON. HF-fed mothers had higher gut proton coupled folate transporter (Pcft) and reduced folate carrier 1 (Rfc1), and lower sodium myo-inositol co-transporter 2 (Smit2), mRNA expression vs. UN and CON. HF placentae had increased folate receptor beta (Frβ) expression vs. UN. mRNA expression of Pcft, folate receptor alpha (Frα), and Smit2 was higher in gut of HF fetuses vs. UN and CON. Transporter protein expression was not different between groups. Maternal malnutrition alters abundance of select gut microbes and folate/inositol transporters, which may influence maternal micronutrient status and delivery to the fetus, impacting pregnancy/fetal outcomes."
  • Review - Iron Deficiency and Iron Deficiency Anemia: Implications and Impact in Pregnancy, Fetal Development, and Early Childhood Parameters[4] "A normal pregnancy consumes 500-800 mg of iron from the mother. Premenopausal women have a high incidence of marginal iron stores or iron deficiency (ID), with or without anemia, particularly in the less developed world. Although pregnancy is associated with a "physiologic" anemia largely related to maternal volume expansion; it is paradoxically associated with an increase in erythrocyte production and erythrocyte mass/kg. ID is a limiting factor for this erythrocyte mass expansion and can contribute to adverse pregnancy outcomes. This review summarizes erythrocyte and iron balance observed in pregnancy; its implications and impact on mother and child; and provides an overview of approaches to the recognition of ID in pregnancy and its management, including clinically relevant questions for further investigation."
  • India - National Iodine Deficiency Disorders Control Programme: Current status & future strategy[5] Iodine deficiency disorders (IDDs) constitute a significant public health problem globally. In India, the entire population is prone to IDDs due to deficiency of iodine in the soil of the sub-continent and thus both animal and plant source food grown on the iodine-deficient soil. IDDs encompass the spectrum of disability and disease and include goitre, cretinism, hypothyroidism, abortion, stillbirth, brain damage, learning disabilities, mental retardation, psychomotor defects, hearing and speech impairment. Iodine deficiency is known to be the single largest cause of preventable brain damage. IDDs with their causal association with brain development, cognition, and learning disabilities impair the human resource development and progress of the country. The children born in iodine-deficient regions on an average have 13.5 intelligence quotient (IQ) points lesser than children born in iodine-sufficient regions. IDD control programme in India is a public health success story, with 92 per cent of the population consuming iodized salt. The partnership between government agencies, academic institutions, salt industry, development agencies and civil society has been key to achieve this success story. The sustainable elimination of iodine deficiency in India is within reach, what is required is accelerated and coordinated effort by all key stakeholder at national and State level."
  • The effect of Ramadan fasting during pregnancy on perinatal outcomes: a systematic review and meta-analysis[6] "Although exempt, many pregnant Muslim women partake in the daily fast during daylight hours during the month of Ramadan. In other contexts an impoverished diet during pregnancy impacts on birth weight. The aim of this systematic review was to determine whether Ramadan fasting by pregnant women affects perinatal outcomes. Primary outcomes investigated were perinatal mortality, preterm birth and small for gestational age (SGA) infants. Secondary outcomes investigated were stillbirth, neonatal death, maternal death, hypertensive disorders of pregnancy, gestational diabetes, congenital abnormalities, serious neonatal morbidity, birth weight, preterm birth and placental weight. ...Ramadan fasting does not adversely affect birth weight although there is insufficient evidence regarding potential effects on other perinatal outcomes. Further studies are needed to accurately determine whether Ramadan fasting is associated with adverse maternal or neonatal outcome."
  • Vitamin D - Lower vitamin D levels during the second trimester are associated with developing gestational diabetes mellitus: an observational cross-sectional study[7] "In this study, we aimed to compare serum 25(OH)D levels in women with and without gestational diabetes mellitus (GDM), and to identify the serum 25(OH)D levels associated with GDM. We recruited 40 women with GDM and 40 healthy pregnant women, aged 20-40 years and in the second trimester, at Gulhane Education and Research Hospital. We excluded women with chronic diseases, preeclampsia, pre-GDM, multiple pregnancies, and those taking medications related to calcium or vitamin D metabolism. We took anthropometric measurements and blood samples during the second trimester. Of the 80 pregnant women, pre-pregnancy body mass index was significantly higher among the GDM group than the healthy group (26.4 ± 5.73 kg/m2 vs. 22.6 ± 3.56 kg/m2, p = .001). Serum 25(OH)D levels in women with GDM were significantly lower than those in healthy women (16.8 ± 9.90 ng/mL vs. 20.9 ± 8.16 ng/mL, p = .016). The prevalence of severe vitamin D deficiency was as high as 72.5% among women in the GDM group, with a 1.74-fold increased risk of deficient status. Levels of 25(OH)D lower than a cutoff value of 14.0 ng/mL were determined to be related to GDM. These study results suggest that maternal vitamin D deficiency in mid-pregnancy is significantly associated with development of GDM."
More recent papers  
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This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.

  • This search now requires a manual link as the original PubMed extension has been disabled.
  • The displayed list of references do not reflect any editorial selection of material based on content or relevance.
  • References also appear on this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

More? References | Discussion Page | Journal Searches | 2019 References | 2020 References

Search term: Fetal Nutrition

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Vitamin D - Antenatal Status Is Not Associated with Standard Neurodevelopmental Assessments at Age 5 Years in a Well-Characterized Prospective Maternal-Infant Cohort [8] "Although animal studies show evidence for a role of vitamin D during brain development, data from human studies show conflicting signals. We aimed to explore associations between maternal and neonatal vitamin D status with childhood neurodevelopmental outcomes. Comprehensive clinical, demographic, and lifestyle data were collected prospectively in 734 maternal-infant dyads from the Cork BASELINE Birth Cohort Study. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were quantified at 15 weeks of gestation and in umbilical cord sera at birth via a CDC-accredited liquid chromatography-tandem mass spectrometry method. Children were assessed at age 5 y through the use of the Kaufman Brief Intelligence Test (2nd Edition, KBIT-2) and the Child Behaviour Checklist (CBCL). Linear regression was used to explore associations between 25(OH)D and neurodevelopmental outcomes. ...In this well-characterized prospective maternal-infant cohort, we found no evidence that antenatal 25(OH)D concentrations are associated with neurodevelopmental outcomes at 5 y."
  • Effects of micronutrients on placental function: evidence from clinical studies to animal models[9] "Micronutrient deficiencies are common in pregnant women due to low dietary intake and increased requirements for fetal development. ...Interestingly, there is emerging evidence that deficiencies in all micronutrients examined induce a pro-inflammatory state in the placenta, drawing parallels with the inflammation detected in FGR, pre-eclampsia, stillbirth and preterm birth. Beneficial effects of supplementation are apparent in vitro and in animal models, and for combined micronutrients in clinical studies. However, greater understanding of the roles of these micronutrients, and insight into their involvement in placental dysfunction, combined with more robust clinical studies, is needed to fully understand ascertain the potential benefits of supplementation in pregnancy."
  • Association of maternal nutrition with transient neonatal hyperinsulinism[10] "The objective was to determine whether maternal nutritional factors are associated with transient neonatal hyperinsulinism (HI). DESIGN AND SETTING: Case control study in 4 French tertiary Obstetrics and Neonatology Departments between 2008 and 2015....A diet rich in fresh cooked vegetable and reduced in fat, together with the avoidance of a high gestational weight gain may be protective against transient neonatal hyperinsulinism."
  • Vitamin D - Maternal BMI Associations with Maternal and Cord Blood Vitamin D Levels in a North American Subset of Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Participants[11] "Obesity in pregnancy may be associated with reduced placental transfer of 25-hydroxyvitamin D (25-OHD). The objective of this study was to examine associations between maternal BMI and maternal and cord blood levels of 25-OHD in full term neonates born to a single racial cohort residing at similar latitude. Secondary objectives were to examine associations between maternal glucose tolerance with maternal levels of 25-OHD and the relationship between cord blood 25-OHD levels and neonatal size. With adjustment for maternal age, field center, birth season and maternal serum 25-OHD, the association of cord blood 25-OHD with maternal BMI was attenuated. Neither birth weight nor neonatal adiposity was significantly associated with cord blood 25-OHD levels. CONCLUSION: These results suggest that maternal levels of 25-OHD are associated with maternal BMI. The results also suggest that interpretation of neonatal 25-OHD levels may need to incorporate specific maternal factors in addition to season of birth and latitude."
  • Protein - Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy[12] "During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. ... These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling." Maternal Diabetes | Rabbit Development
  • Vitamin C - Depletion in Prenatal Guinea Pigs as a Model of Lissencephaly Type II[13] "Humans and guinea pigs are unable to produce vitamin C, with deficiency resulting in a well-known disorder of collagen synthesis. Pial basement membrane structure preservation is essential in the proper migration of neurons. In our study, intrauterine deprivation of vitamin C in guinea pig fetuses led to a collagen synthesis disorder, weakness, and finally a breach of pial basement membrane. ...The most severe form of dysplastic changes was characterized by marked irregularity of the cerebellar cortex similar to that in lissencephaly type II. Thus, prenatal vitamin C deficiency represents a novel animal model to study the effects of collagen synthesis on development of breaches in the pial basement membrane, disordered migration of neurons, dysplasia of cerebellar cortex, and the pathogenesis of lissencephaly." Cerebellum Development
  • Vitamin A and Vitamin E status in very low birth weight infants[14] "High prevalence of vitamin A and vitamin E deficiency was found in VLBW infants starting from birth to term postmenstrual age."

Folic Acid

In 2001, the Australian estimated birth prevalence of neural tube defects was 0.5 per 1,000 births (National Perinatal Statistics Unit). Low maternal dietary Vitamin B9 as folic acid (folate, folacin) has been shown to be associated with the development of neural tube defects.

USA spina bifida rates.jpg

In the U.S.A. the Food and Drug Administration in 1996 authorized that all enriched cereal grain products be fortified with folic acid, with optional fortification beginning in March 1996 and mandatory fortification in January 1998.

Links: Vitamin B | folate



Thyroxine (T4) molecular structure showing iodine positions (red rings)

"Iodine is an essential nutrient that humans need in very small quantities. The thyroid uses iodine to produce hormones vital to ensure normal development of the brain and nervous system before birth, in babies and young children. For this reason, it is very important that pregnant and breastfeeding women get enough iodine.

The National Health and Medical Research Council recommends that all women who are pregnant, breastfeeding or considering pregnancy, take an iodine supplement of 150 micrograms (μg) each day. Women with pre-existing thyroid conditions should seek advice from their medical practitioner prior to taking a supplement."

Text from [15]

 ICD-11 5B5K.3 Iodine deficiency - Iodine deficiency disorders (IDD), caused mainly by a low dietary supply of iodine, refer to all of the consequences of iodine deficiency in a population that can be prevented by ensuring that the population has an adequate intake of iodine. Iodine deficiency is the most frequent cause of preventable brain damage in childhood.

5A00.04 Congenital hypothyroidism due to iodine deficiency - Hypothyroidism is a condition which arises at birth where the thyroid gland produces too little or no thyroid hormone and it can be induced by iodine-deficiency.

Links: iodine deficiency | Iodine supplementation for Pregnant and Breastfeeding Women NHMRC - Nutrition & Diet Publications


Australian 2018 Pregnancy Care Guidelines[1]

"Supplements of vitamins A, C and E are not of benefit during pregnancy and may cause harm"

There are several different vitamins with a standardised classification by a letter and number.

Vitamin A

Retinoic acid is a metabolite of Vitamin A (retinol) and may affect prenatal development. Postnatal dietary supplementation of children is recommended when diet may be inadequate. Vitamin A is required for many systems including: visual system, cell function for growth, epithelial integrity, red blood cell production, immunity, and reproduction.

The following text is from a review of published data.[16]

What is already known on this topic

  • Vitamin A is an essential nutrient; it must be obtained through diet
  • In low and middle income countries, many people (especially children) do not eat enough vitamin A
  • Vitamin A deficiency is related to vision problems and increased susceptibility to infectious disease and death
  • WHO recommends vitamin A supplements for children, pregnant women, and breastfeeding mothers

What this study adds

  • There have been 43 trials of vitamin A for children aged 6 months to 5 years old, including about 215,633 children
  • In low and middle income countries, vitamin A supplementation is associated with a 24% reduction in mortality
  • Vitamin A supplementation might reduce mortality by preventing measles and diarrhoea; it also prevents blindness
  • The evidence for vitamin A is compelling and clear; further trials comparing vitamin A with placebo would be unethical
  • spermatozoa - "Retinoic acid appears to act in a pulsatile manner, periodically driving spermatogonial differentiation and meiotic onset at discrete points along testis tubules, and as a result, is likely to be responsible for generating and maintaining the cycle of the seminiferous epithelium."[17]
 ICD-11 5B55 Vitamin A deficiency - Vitamin A deficiency (VAD) is a major public health problem affecting an estimated 190 million preschool-age children and 19 million pregnant women, principally in Africa and South-East Asia. This corresponds to 33.3% of the preschool-age population and 15.3% of pregnant women in populations at risk. Vitamin A deficiency is one of the most important causes of preventable childhood blindness; however, the prevalence of ocular manifestations is now recognized to far underestimate the magnitude of the problem of functionally significant deficiency. Many more preschool-age children, and perhaps older children and women who are pregnant or lactating, have their health compromised when they are sub-clinically deficient. In young children, subclinical deficiency, like clinical deficiency, incre

Links: Developmental Signals - Retinoic acid | Spermatozoa Development | Cell Division - Meiosis

Vitamin B

The Vitamin B group consists of eight separate water-soluble vitamins that play important roles in cell metabolism. See also Folic Acid

Vitamin B3

Vitamin B3 (niacin, nicotinic acid, nicotinamide) A recent Spanish study of dietary intake of vitamins during pregnancy and risk of having a small for gestational age (SGA) newborn, showed a protective effect vitamin B3 and B6.[18] Using 3 mouse models of preeclampsia, vitamin B3 alleviated or prevented miscarriage, prolonged pregnancy period, and improved the growth of the fetuses.[19]

Vitamin B3 and L-tryptophan together are the main dietary precursors for synthesis of nicotinamide adenine dinucleotide (NAD), a key cofactor in many cellular metabolic processes.

Vitamin B9

Vitamin B9 (folacin, Folic acid) and folate the naturally occurring form, are an important dietary requirement for normal neural development. Low levels have been show associated with neural tube defects including spina bifida.

Vitamin B12

Vitamin B12 has been shown to enhances TBX1 gene expression that can improve DiGeorge syndrome (velocardiofacial syndrome) outcomes in the mouse model of the disease.[20]

Abnormalities - Pernicious anaemia is an autoimmune condition that results in an inability to absorb vitamin B12.

  • 5B5A Vitamin B1 deficiency - Thiamine (vitamin B1, aneurin) deficiency can result in the disease called beriberi, which has been classically considered to exist in dry (paralytic) and wet (oedematous) forms. Beriberi occurs in human-milk-fed infants whose nursing mothers are deficient. It also occurs in adults with high carbohydrate intakes (mainly from milled rice) and with intakes of anti-thiamine factors, such as the bacterial thiaminases that are in certain ingested raw fish. Beriberi is still endemic in Asia. Risk factors include pregnancy, alcohol consumption, fevers, chronic disability, exercise, diabetes and dysentery.
  • 5B5B Vitamin B2 deficiency - Children in developing countries will commonly demonstrate clinical signs of riboflavin deficiency during periods of the year when gastrointestinal infections are prevalent. Decreased assimilation of riboflavin also results from abnormal digestion, such as that which occurs with lactose intolerance.
  • 5B5C Vitamin B3 deficiency - Niacin deficiency classically results in pellagra, which is a chronic wasting disease associated with a characteristic erythematous dermatitis that is bilateral and symmetrical, a dementia after mental changes including insomnia and apathy preceding an overt encephalopathy, and diarrhoea resulting from inflammation of the intestinal mucous surfa]ces. Pellagra occurs endemically in poorer areas of Africa, China and India.
  • 5B5D Vitamin B6 deficiency - A deficiency of vitamin B6 alone is uncommon because it usually occurs in association with a deficit in other B-complex vitamins.
  • 5B5E Folate deficiency - During pregnancy, there is an increased risk of fetal neural tube defects (NTDs), with risk increasing 10-fold as folate status goes from adequate to poor.
  • 5B5F Vitamin B12 deficiency - Vegetarianism and poverty-imposed near-vegetarianism are the most common causes of nutritional cobalamin insufficiency worldwide in all age groups. In such populations, low maternal cobalamin status is associated with adverse pregnancy outcomes (preterm birth, intrauterine growth retardation, early recurrent miscarriage), neural tube defects, reduced neurocognitive performance in children, accelerated bone turnover, and low bone mineral density with fractures. Insufficient cobalamin intake is also seen in breast-fed infants of mothers with pernicious anaemia.

Links: Folic Acid and Neural Tube Defects | DiGeorge syndrome | Neural System - Abnormalities | Neural System Development

Vitamin C

Ascorbic acid (vitamin C) is necessary for the formation of collagen, reducing free radicals, and aiding in iron absorption. Scurvy is a disease of dietary ascorbic acid deficiency that is very uncommon today, except in economically disadvantaged populations with poor nutrition. Occurance in children is very rare and can lead to musculoskeletal abnormalities, and has also been seen in neurologic illness.[21]

 ICD-11 5B56 Vitamin C deficiency - This condition groups several clinical consequences secondary to vitamin C deficiency with scurvy being the most severe presentation. The populations at risk of vitamin C deficiency are those for whom the fruit and vegetable supply is minimal. Epidemics of scurvy are associated with famine and war, when food supply is small and irregular. Children fed predominantly heat-treated (ultra-high-temperature or pasteurized) milk or unfortified formulas and not receiving fruits and fruit juices are at significant risk for symptomatic disease.

Vitamin D

Vitamin D3
Vitamin D3

Vitamin D3 is produced in the skin from 7-dehydrocholesterol in a photoreaction induced by ultraviolet B (UVB) radiation from the sun. This is then released into circulation where it is hydroxylated in the liver and kidney to a more active form. Circulating 25-hydroxyvitamin D3 (25[OH]D), the most commonly used index of vitamin D status, is converted to the active hormone 1,25 dihydroxyvitamin D3 (1,25[OH]2D), which, operating through the vitamin D receptor (VDR). The vitamin D receptor belongs to the nuclear receptor superfamily and singling regulates calcium homeostasis. (See 2008 review[22])

Tissue Substrate Product
Integument 7-dehydrocholesterol Vitamin D3
Liver Vitamin D3 25-hydroxyvitamin D3 (calcidiol)
Kidney 25-hydroxyvitamin D3 1,25-dihydroxyvitamin D3 (calcitriol, 1α,25-dihydroxyvitamin D)

Vitamin D3 synthesis.png

In the skin Vitamin D3 regulates both epidermal proliferation and differentiation. As a circulating hormone, it regulates calcium levels in the blood, required for bone and muscle development.

USA Institute of Medicine expert committee "calcium requirements varied with age, from 700 mg a day for children aged 1-3 years up to 1200 mg a day for women aged 51 to 70 and 1300 mg a day for teenagers and pregnant and lactating women."

  • Australia - Newborn-serum 25OHD concentrations depend on the maternal circulating plasma 25OHD level at least during the third trimester. Neonatal 25OHD levels obtained by EIA correlated well with liquid chromatography/tandem mass spectrometry (LC-MSMS). Although the EIA values for neonates were greater than LC-MSMS values, this difference was not statistically significant.[23]
  • UK - Avoidance of vitamin D deficiency in pregnancy in the United Kingdom: the case for a unified approach in National policy.[24]
  • USA 2004 - Vitamin D requirements during pregnancy.[25]

The vitamin D receptor (VDR) is found on most non-skeletal human cells that may indicate a role in more than the bone and calcium metabolism.[26]

  • respiratory tract is a consequence of its activity in the immune system.
  • vitamin D deficiency occurs with gastrointestinal diseases such as inflammatory bowel disease, coeliac disease, liver, pancreas or cardiac diseases.
  • links to diabetes. VDR and 1α-hydroxylase have been detected in the cutaneous capillary vessels, endothelium, vascular smooth muscles, myocytes and cardiac fibroblasts.
Kidney Endocrine
Hormone Function Comment
Renin increase angiotensin-aldosterone system paracrine, renin is released by juxtaglomerular cells
Prostaglandins decrease sodium (Na+) reabsorption paracrine, (PGE2) vasodilator regulate renal vascular reactivity
Erythropoietin increase Erythrocyte production endocrine, promotes red blood cell formation in bone marrow
1,25 (OH)2 vitamin D Calcium homeostasis endocrine, biologically active form of vitamin D
Prekallikreins increase Kinin production paracrine, act locally to induce vasodilation and contraction of smooth muscle

Calcium - For women with low dietary intake and high risk of pre-eclampsia, increased intake of calcium-rich foods or supplements may be beneifcial. (Australian Guideline 2018[1])

 ICD-11 5B57 Vitamin D deficiency - Vitamin D is a fat-soluble vitamin contained naturally in very few foods, added to milk, available as a supplement, and produced endogenously with exposure to sunlight. Vitamin D deficiency can be caused by inadequate intake due to dietary factors (e.g., special diets (veganism), lactose intolerance or allergies) and/or limited exposure to sunlight due to geographic location, sun avoidance, or shiftwork. Severe deficiency results in disordered bone modelling called rickets in childhood (open growth plates), and osteomalacia in adults (fused growth plates).

Links: Vitamin D3 | Vitamin D3 synthesis | Integumentary | Nutrition | Endocrine Kidney | Parathyroid

Dietary Reference Intakes for Calcium and Vitamin D | Paediatric Endocrine Group; Paediatric Bone Australasia. Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand: a consensus statement (2006) [27]

Vitamin E

Vitamin E has a role in immunity and cell function (controls free radicals mediated disturbances and maintains membrane integrity). Animal studies suggest a protective role for asthma risk.[28]

Tocotrienols are natural compounds acting as dietary members of the vitamin E family.[28] They are found in a number of vegetable oils, wheat germ, barley, and certain types of nuts and grains.

 ICD-11 5B58 Vitamin E deficiency - Vitamin E deficiency is a condition that causes haemolysis and/or neurologic manifestations. Red blood cell fragility occurs and can produce a haemolytic anemia. Neuronal degeneration produces peripheral neuropathies, ophthalmoplegia, and destruction of posterior columns of spinal cord. Neurologic disease is frequently irreversible if deficiency is not corrected early enough. Vitamin E deficiency may also contribute to the hemolytic anemia and retrolental fibroplasia seen in premature infants.

Vitamin K

A generic term for derivatives of 2-methyl-1,4-naphthoquinone that have coagulation activity. Daily requirement for vitamin K is about 1 µg/kg. In newborns vitamin K nutrition is at risk.

  • Required for synthesis of prothrombin and proconvertin (stable factor, factor VII).
  • May also be involved in synthesis of Stuart-Prower factor (factor X) and PTC (plasma thromboplastic factor, factor IX) since clotting defects due to deficiencies of these factors as well as to deficiencies of prothrombin and proconvertin occur in states of vitamin K deficiency.
  • CDC finds cluster of newborns in Tennessee with bleeding disorder Report highlights importance of vitamin K shot at birth.

 ICD-11 5B59 Vitamin K deficiency - Vitamin K is necessary for the synthesis of clotting factors II, VII, IX, and X, and deficiency of vitamin K can result in clinically significant bleeding. Vitamin K deficiency typically affects infants, who experience a transient deficiency related to inadequate intake, or patients of any age who have decreased vitamin K absorption. Mild vitamin K deficiency can affect long-term bone and vascular health.

Links: American Academy of Pediatrics Report Of Committee On Nutrition - Vitamin K Compounds And The Water-Soluble Analogues (1961)


Heme b
Heme b

Maternal iron (Fe) deficiency can be a common disorder during pregnancy and also in the postnatal period for neonatal neural development. Haemoglobin is the iron-containing oxygen-transport metalloprotein located in maternal and fetal red blood cells and myoglobin is the equivalent protein located in muscle. Iron is also required in some cellular enzymatic processes as a cofactor.

During pregnancy the maternal blood volume increases and the packed cell volume and haemoglobin (Hb) concentration can fall, a condition is known as "anaemia of pregnancy" (haemoglobin value below 11 g/dL). Therefore an increase of about 50% above the recommended daily dietary intake of Fe is suggested during pregnancy. [29] Preventive treatment can include prophylaxis iron supplements and food fortification with iron.[30]

Fetal demands for iron are maximal during the third trimester. Prenatal maternal use of iron can also improve birth weight, in a linear dose-response fashion, perhaps reducing the risk of low birth weight.[31]

Similar micronutrient requirements have been identified for other trace metals such as copper (Cu), see the review.[32]

Australian 2018 Pregnancy Care Guidelines[1]

  • Increasing intake of iron-rich foods reduces the risk of iron deficiency
  • Unnecessary iron supplementation offers no benefit and has side effects at higher doses
  • For women with low dietary intake, intermittent supplementation is as effective as daily supplementation in preventing iron-deficiency anaemia, with fewer side effects
  • For women with identified iron-deficiency anaemia, low-dose supplementation is as effective as high dose, with fewer side effects

 ICD-11 5B5K.0 Iron deficiency - Iron deficiency is defined as a condition in which there are no mobilizable iron stores and in which signs of a compromised supply of iron to tissues, including the erythron, are noted. The more severe stages of iron deficiency are associated with anaemia. Nutritional iron deficiency implies that the diet cannot supply enough iron to cover the body’s physiological requirements for this mineral. Populations most at risk for iron deficiency are infants, children, adolescents, and women of childbearing age, especially pregnant women.

Early post-natal iron was originally acquired and stored from the mother in the final trimester of pregnancy and is supplemented by breast milk.[33]

Links: WHO Micronutrient deficiencies | WHO Anaemia database


For women with low dietary intake and high risk of pre-eclampsia, increased intake of calcium-rich foods or supplements may be beneifcial. (Australian Guideline 2018[1])

 ICD-11 5B5K.1 Calcium deficiency - Hypocalcaemia is defined as a total serum calcium concentration of less than 8.4 mg/dl (2.1 mmol/liter) or an ionized calcium concentration of less than 4.48 mg/dl (1.12 mmol/liter). There are numerous causes of hypocalcaemia, being chronic kidney disease the most common cause. Other causes are: vitamin D deficiency, disorders associated with acquired or genetic hypoparathyroridism, including intravenous bisphosphonate therapy, post-thyroidectomy and post-parathyroidectomy, and acute pancreatitis. Hypocalcaemia may be associated with a spectrum of clinical manifestations, ranging from few symptoms if the hypocalcaemia is mild, to life-threatening seizures, refractory heart failure, or laryngospasm if it is severe. In addition to severity, the rate of development of hypocalcaemia and chronicity determine the clinical manifestations. Hypocalcaemia can develop in children who receive intravenous nutrition without adequate calcium.


There are normally 20 amino acids found in proteins, some of which can be made by the body while nine are essential (unable to synthesise from simpler molecules) in the diet. Modified amino acids are the basis of several hormones, such as noradrenaline (norepinepherine), adrenalin (epinepherine) and thyroid hormone. (More? Endocrine System Development)

Essential amino acids

  • histidine
  • isoleucine
  • leucine
  • lysine
  • methionine
  • phenylalanine
  • threonine
  • tryptophan
  • valine

Cysteine and tyrosine can partly replace methionine and phenylalanine.


  • Fats are the highest form of energy for the body.
  • Aid in the absorption of the fat-soluble vitamins (A, D, E and K) and other fat-soluble biologically-active components.
  • Three major types of naturally-occurring fatty acids:
    • saturated - mainly in animal-based foods. For example, found in milk, cream, butter and cheese, land animal meats.
    • cis-monounsaturated - mainly in plant-based foods. For example, oleic acid found in olive, canola and peanut oils.
    • cis-polyunsaturated - mainly in plant-based foods. For example, linoleic acid found in seed oils, eg sunflower, safflower and corn.
  • trans fatty acids are produced by partial hydrogenation of polyunsaturated oils in food processing and also occur in ruminant animal foods.


  • Dietary carbohydrate provides energy to specific tissues, for example the brain requires glucose.
    • Note, infant's brain is large relative to body size and uses 60% of the infant’s total energy intake.

Docosahexaenoic Acid

Docosahexaenoic Acid (DHA, C22: 6n-3) is required for neural development[34] and is the most abundant polyunsaturated fatty acid in neuronal phospholipids. DHA sourced mainly from food as well as by hepatic and astroglia synthesis from essential a-linolenic acid (C18: 3n-3).

A recent study of maternal DHA supplementation[35] sconcluded: "Although we provide evidence that maternal DHA status is related to child cognitive performance, the association of maternal and child DHA intake and status limits the interpretation of whether DHA before or after birth is important."


  • Dietary fibre is essential for proper gut function
  • Related also to risk reduction for some chronic diseases (heart disease, certain cancers and diabetes).


  • Water is essential because it is required in quantities above the body’s production.
  • Water loss from lungs and skin are responsible for 50% of total water turnover.


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  • Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington (DC): National Academies Press (US); 2001. Available from:

Search Pubmed


  • Adequate Intake - (AI) The average daily nutrient intake level based on observed or experimentally-determined approximations or estimates of nutrient intake by a group (or groups) of apparently healthy people that are assumed to be adequate. Used when an RDI cannot be determined.
  • Estimated Average Requirement - (EAR) A daily nutrient level estimated to meet the requirements of half the healthy individuals in a particular life stage and gender group.
  • Median Urinary Iodine Concentration - (MUIC) Urinary iodine concentration is the prime indicator of nutritional iodine status and is used to evaluate population-based iodine supplementation. The median value is determined from a population sample.
  • Recommended Dietary Intake - (RDI) The average daily dietary intake level that is sufficient to meet the nutrient requirements of nearly all (97–98 per cent) healthy individuals in a particular life stage and gender group.
  • Transient hypoglycemia - Refers to a slow or immature fasting adaptation process. often related to conditions or events occurring during birth and can occur during the first hours of life.
  • Upper Level of Intake - (UL) The highest average daily nutrient intake level likely to pose no adverse health effects to almost all individuals in the general population. As intake increases above the UL, the potential risk of adverse effects increases.
  • Urinary Iodine Concentration - (UIC)

Some terms from NHMRC publication, adapted from Food and Nutrition Board: Institute of Medicine (USA and Canada).

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