Iron ~ It's Role in Pregnancy, Post-partum & Early Infancy

The prevalence of anaemia in pregnancy is approximately 38% and the most common cause is due to iron deficiency anaemia (IDA) (1). There are various causes of anaemia, the result of which is a low concentration of red blood cells (RBCs) and haemoglobin (Hb) in the blood (1). Anaemia in pregnancy (in most people) is due to the passing of iron between mother and baby in the presence of pre-existing low iron stores (1). Iron deficiency anaemia (IDA) increases the rates of pre-term birth, small for gestational age, and low birth weight babies (1). When a mother’s iron levels are low, this is seen reflected in the cord blood of newborns. Infants with low iron stores are more likely to suffer the impact of IDA, but the effects are rarely observed until approximately two-years of age. IDA affects the hippocampus, a region of the brain responsible for hearing and memory recognition (1). These learning and memory issues can have far reaching effects into adulthood. Therefore, assessing iron status prior to pregnancy is an important consideration for the health and wellbeing of both mother and baby.

This article aims to address some basic questions like what iron is and why it’s important? How iron is absorbed and what factors promote or reduce its’ absorption? How to optimise iron absorption in pregnancy and breastfeeding? How to assess true IDA? And finally, what we might consider if supplementation is required?

What is iron?

Iron is a mineral micronutrient, like calcium, magnesium, and iodine (2). Unlike calcium and magnesium, there are very low levels of free iron circulating in the body because it can have a toxic effect on the cells and tissues when there is too much (2). To keep this in check, iron gets stored in large amounts in a protein called ferritin (2).

An average adult female contains approximately 30-45mg of iron per kilogram of body weight and a newborn infant 70mg per kg of body weight (2). The higher relative levels of iron in a newborn infant are due to the higher amounts of red blood cell turnover and iron storage in ferritin. An average 60-kg female body will contain between 2 to 3 kg of iron, and a 3.5 kg newborn infant will contain about 250gms of iron.

Infants are vulnerable to iron deficiency because of rapid growth and development and due to the high turnover of red blood cells required to meet growth demands. The most vulnerable time for iron deficiency is during infancy, menses and in childbirth due to an increase in blood loss around birth. 

Approximately 1mg of iron is lost via skin, poop, and urine each day, but a menstrual cycle increases losses by up to 100 times and incurs losses between 18 to 100mg of iron per cycle (1ml blood = 0.5mg iron / 35ml to 200 ml range of blood loss during a menstrual cycle) (2).

During childbirth, normal blood loss estimates between 200 and 500ml which equates to between 100 to 250mg of iron. Often women will lose much more especially if intervention or a caesarean has occurred. Losses of over 1000ml happen frequently and translate to between one-fourth and one-fifth of the total body iron for an average sized female body (1,2). Therefore, ferritin (stored iron) plays a crucial role for mother and for baby. A mother with optimal iron stores is a baby with optimal iron stores.

1 millilitre of blood = 0.5 milligrams iron

Average sized female body contains b/n 2000 to 3000 grams of iron (2-3 kilograms)

Menstrual cycle blood loss range b/n 35 to 200 millilitres =18 to 100 milligrams of iron

Childbirth blood loss range b/n 200 to 500 millilitres =100 to 250 milligrams of iron

Why is iron important?

Iron is needed for many processes and functions in the body. About 7% of our total body iron is incorporated into enzymes. An enzyme is a protein that helps to ignite chemical reactions in the body, they are like activators or spark plugs. Between 5-30% of our total iron is stored in the protein ferritin (the amount varies according to diet and individual factors). 4% of iron is stored in myoglobin, which is a short-term storage house for oxygen, located in our muscles. But 60% of our total body iron is contained in haemoglobin (Hb). Hb makes up 90% of the protein in one RBC (2). All the cells of our body are dependent on Hb for oxygen and without it, our body cells would simply die (1,3).

Haemoglobin (Hb) is made of 'heme' and 'globin'. The heme portion binds iron which then binds oxygen. Of the 100 trillion cells in the human body, 25% of them are RBCs, and each single RBC contains approximately 270 million Hb molecules each of which can bind up to 4 iron ions. It is impossible to fathom this level of complexity. The body has many checks and balances that help to keep iron at low levels in our circulation due to its potential toxic effect. It helps that iron is recycled by our body, so when old red blood cells (RBCs) get broken down in the spleen, the iron is either sent back to the bone marrow to be re-used in the production of new RBCs or sent to the liver and stored in the protein ferritin (2). In pregnancy, due to the natural dilution of blood (haemodilution), Hb levels drop, reaching their lowest levels between 24 to 32 weeks’ gestation (1).

How is Iron Absorbed in the Body?

Iron absorption is a complex biochemical process. Essentially, the more iron in the body, the less it will be absorbed from either food or supplements. When we digest iron from our food, it goes to the stomach and is broken down (made bio-available) with the help of stomach acid and the vitamin C present in food. It then travels to the first portion of the small intestine – the duodenum (attached to the stomach), where it is absorbed. Here, the absorbed iron ions are transported to other cells in the body like the liver and the bone marrow. Approximately 75% of the absorbed iron is sent to the bone marrow where it is used to make new RBCs and Hb. The rest is sent to the liver and stored in the protein ferritin (2,3).

How is Iron Regulated

Iron is tightly regulated by ‘hepcidin’ which is known as the ‘master iron regulator’. One of hepcidin’s roles is to inhibit iron absorption. Defects in hepcidin production are responsible for the condition Hemochromatosis which causes an over-production of plasma iron (not discussed further) (2). Hepcidin production can also be stimulated by inflammation. Bacteria and other pathogens can cause ‘anaemia of inflammation’ – this is where the iron gets trapped by immune cells and is unavailable for either storage or to build new RBCs. Anaemia of inflammation can cause a false increase in ferritin levels, however there may still be underlying IDA; this is beyond the scope of this paper but important to understand the role inflammation may have when assessing iron status.

Symptoms of Anaemia

Signs of iron deficiency include anaemia, fatigue, brittle nails, shortness of breath, sore tongue, spooning of the nails, increased susceptibility to infection, hair loss, mental confusion, increased menstrual bleeding, restless leg syndrome, and canker sores (3).

Biomarkers Used to Assess IDA

It is important to understand ‘physiological anaemia of pregnancy’, a natural occurrence that reflects the expanding plasma blood volume of up to 50% relative to a 25% increase in RBC mass (1). As pregnancy progresses, it is therefore normal to see a drop in the bio-chemical markers used to assess iron deficiency, this drop does not equate to anaemia, but rather speaks to the dilution of the blood due to the massive increases in blood volume.

Ferritin, the storage protein for iron usually reaches its’ lowest levels between 35 to 38 weeks and begins a gradual increase in the final weeks of pregnancy. Ferritin rather than iron, is the most sensitive (92%) and specific (98%) marker to diagnose IDA during pregnancy (1). In the absence of co-morbidities, IDA is known to be the only condition associated with very low ferritin levels (=/<15ng/ml - supplement OR =/<20ng/ml + supplement), and therefore is a reliable marker for its’ diagnosis (1).

Unlike Ferritin, plasma iron levels are a poor indicator of IDA due to the diurnal variation caused by ingested meals. Blood iron levels rise in the morning after an overnight fast and fall in the evening (1). Since most iron is either stored, or incorporated into enzymes, RBCs and muscle, serum iron is a poor indicator of overall iron status.

Transferrin (Tf) is the vehicle by which iron is transported to either the bone marrow for RBC production or to the liver for storage in ferritin. Tf levels increase with IDA as the body attempts to increase iron transport to the liver and bone marrow. However, another marker Transferrin-Saturase (Tf-S) – indicating the amount of Tf saturated with iron will decrease. Both biomarkers offer clues about the presence of IDA.

Total Iron Binding Capacity (TIBC) can also be lowered in IDA; however, the cause of the decrease can also be due to acute or chronic inflammation, malignancies, liver disease, malnutrition and more, therefore it is not a reliable marker for assessing IDA (1).

There is a natural decline in Hb levels, yet due to considerable variations, Hb alone cannot be used to assess IDA (1). There is a physiological increase in pregnancy of the Mean Corpuscular Volume (MCV)  (measure of RBC size) due to the significant increase in RBC production. An MCV of below 80fl is a highly sensitive marker for IDA, however, it is not specific enough for diagnosis (3).

Hepcidin is being evaluated as a possible biomarker for IDA, as its’ levels reliably decline as pregnancy progresses, but it is not one that is currently used in diagnosis. Soluble Transferrin Receptor (sTfR) (found on cell surfaces) increases with IDA and unlike TIBC, it is not affected by the presence of inflammation and has a sensitivity of 86% and a specificity of 75%, yet it is not routinely used to assess IDA (1). To summarise, when assessing for IDA in pregnancy the most reliable biomarkers are Hb, ferritin, Tf-s and Tf. We would expect a drop in Hb, ferritin, and Tf-s, and a rise in Tf (1).

Biomarker	Value	Trimester
Ferritin	<30ug/L very low: <15ng/ml (no supplement) OR <20ng/ml (with supplement sensitivity 92% / specificity 98%	Lowest levels b/n 35-38 wks.
Iron	Diurnal variation caused by ingested food Morning levels rise /evening levels fall	*Poor indicator of overall iron status
Haemoglobin (Hb)	<11g/dL	1st & 3rd
Transferrin saturase (Tf-s)	<15%
	<10.5g/dL	3rd
Mean Corpuscular Volume (MCV)	<80fl/oz	*Not a reliable marker
Soluble Transferrin Receptor (sTfR)	sensitivity 86% / specificity 75% not affected by inflammation	*Not routinely used
Hepcidin	regulates iron bioavailability /decreases as pregnancy progresses	lowest in 3rd *Being evaluated as a biomarker

(3)

What Factors Promote the Absorption of Iron?

The intelligence of our human body is masterful, but it can only do so much, we need to supply the right raw materials to help it do its job well. The most obvious factor that supports iron absorption, is iron containing food, both animal (heme) and non-animal (non-heme) sources. The integrity of the food we eat is of vital importance to the health and wellbeing of our body, and to give our children the best start in life. Iron is more easily absorbed from food than it is from supplements, so ensuring enough iron via your diet is a good place to start. Strong blood is a term used in traditional medicine, and it refers to ‘sufficiency’ – we need to cultivate strong, sufficient blood during pregnancy, and this will flow on forwards to a healthy postpartum and an infant rooted in sufficiency rather than deficiency.

To ensure optimal absorption and storage of iron in pregnancy, it is helpful to understand physical and dietary factors that promote or reduce its’ bioavailability. A good healthy digestive system promotes the absorption of iron. Digestion and absorption of nutrients begins with the smell of our food, the salivation that occurs in response to those smells, real hunger, the way we chew our food and the environment in which we consume it, all play an important role in how our food is assimilated. When we observe good habits around what and how we eat, and the physical conditions required; like a strong digestive fire, (presence of enzymes & stomach acid) the nutrients present in the food are more likely to be absorbed and utilised by our bodies (2,5).

Vitamin C (ascorbic acid) is contained in many foods – not just citrus and increases the bioavailability of iron. If the body is deficient in iron, squeezing citrus juice on to food, or eating foods high in vitamin C, will help to make the iron more bioavailable. Iron deficiency ironically increases iron absorption from food and supplements. However, hepcidin, our body’s ‘master iron regulator’ decreases iron absorption in response to adequate levels (2,5).

What Factors Inhibit the Absorption of Iron?

Our digestive system is eroded by stress, poor eating habits such as too much coffee, sugar, soft drinks, eating on the run, use of antacids, refined and highly processed foods. Over time, poor nourishment weakens the integrity of the body’s digestive capacity and contributes to inflammation.

Secondary causes of anaemia can be due to any inflammatory condition and chronic diseases of the body. Inflammation, pathogens, and certain bacteria can stimulate hepcidin (master iron regulator) production and thereby decrease iron absorption (2). This means that even when enough iron is consumed through diet and dietary supplements, if chronic states of inflammation are not addressed, it can be difficult to get the iron that the body needs.

Vegetarian and vegan diets will naturally have lower levels of available iron in the diet and may need supplementation, particularly if preparing to conceive a baby. Low stomach acid impedes iron absorption and is common to those on a vegetarian diet, along with advancing age, regular antacid use, and general inflammation of the digestive tract.

If a person is vegetarian, we know that iron, along with vitamin B12 will need greater consideration. In addition, folate levels will need to be checked in people with a vegetarian diet, as vitamin B12 is needed for its’ absorption. Vitamin B12 and folate deficiency can result in reductions in RBC production, and therefore be a cause of anaemia. Vitamin B12 deficiency anaemia is called pernicious anaemia, and folate deficiency anaemia is called megaloblastic anaemia; these are not covered in this article (3,5).

Just as nutrient deficiencies such as low levels of vitamin B12 (sourced from animal protein) and folate (greens, grains, pulses) can impact iron absorption, there are certain compounds in some foods called phytates (phytic acid) and oxalates (oxalic acid) that can also inhibit irons’ absorption (2). These compounds are mostly found in grains and pulses (phytates) as well as leafy greens such as spinach, silver beet, turnip greens, black tea (oxalates) and others (2,5). Soaking and sprouting grains neutralizes the phytic acid, as does cooking. Adding lemon to greens and to black tea helps to neutralize oxalic acid. This is helpful to understand, especially if you are consuming large amounts of these foods, which is often the case in vegetarian or vegan style diets.

Factors Promoting Iron Absorption	Factors Inhibiting Iron Absorption
Healthy digestion	Gut inflammation
Strong stomach acid (Hydrochloric Acid)	Low stomach acid (Hydrochloric acid)
Diet rich in iron rich / nutrient dense foods	Highly processed foods
Healthy eating practices, slow food	Eating on the run, fast food
Presence of citrus, vitamin C	Lack of vitamin C or citrus
Digestive enzymes / chewing food well	Stress
Eating when hungry	Antacids
Regular exercise	Vegan / vegetarian diets
Adequate sleep	High phytic and oxalic acid containing foods
	Infections and liver disease
	Parasitic worms like hookworm, roundworm & tapeworm

(3,5)

Optimising Iron Absorption for a Healthy Mother & Baby

Planning a pregnancy should be more than simply falling pregnant, but an opportunity to ensure the best conditions possible for both the mother and the growing baby. Early pregnancy requires a rapid use of iron stores to increase RBC volume (gradual increase up to 50%) and to meet the demands of growing a placenta and a baby (1,2). Working with a naturopath, integrative physician, nutritionist or traditional Chinese or Ayurvedic practitioner, is highly recommended, ideally 6-months before intentions to conceive. This way, a clear baseline of health and wellbeing can be assessed and therapeutically fine-tuned. Husbands or partners should be included in this preparation too, as the quality of the sperm reflects health status for future generations. Getting off to a good start prior to conception, increases the likelihood that healthy nourishment habits will continue throughout the first year postpartum, a time of recovery for the mother and of exponential growth and development for the infant.

Iron & Breastfeeding

Breastfeeding is a time of greater demand as the body continues to provide nutrients to the infant via breastmilk. During the life cycle of breastfeeding there is an increased requirement for iron, vitamin D, protein, calcium, and vitamin B12 (vegetarian or vegan). During the first 6-months of life, the infant receives all their nutrients via breastmilk. Breastmilk is low in iron but iron from breastmilk is well absorbed. Another reason for a woman to ensure a diet rich in iron, is to increase the newborn baby’s iron stores (ferritin). Ferritin stores along with the iron supplied in breastmilk, sustains the newborn baby for the first 6-months of life, without a need for supplementation. If a baby has been born prematurely, iron supplements may be needed (6).

Heme verus Non-heme Iron

The most absorbable form of dietary iron is from red and dark meats. This kind of iron is referred to as ‘heme’ iron, and it is more readily absorbed compared to non-animal iron sources. However, iron is generally poorly absorbed, therefore small amounts of iron-rich foods from both heme and non-heme sources every day will help overall absorption. The best sources of heme iron are liver and organ meats, game meats, dark poultry meat, oysters, sardines, salmon, clams, and sprinkling some lemon juice will make the iron even more bioavailable.

Non heme iron comes from plant-based sources and is said to be two to four times less well absorbed compared to heme iron (3). The presence of anti-nutrients (discussed earlier) requires some attention to how these foods are prepared.  Neutralizing anti-nutrients can be achieved by soaking, sprouting, and fermenting foods. Spinach, for example, is high in oxalates which can be neutralised by adding citrus juice. The best sources of plant-based iron include legumes such as kidney, black, pinto, lentil, soybeans, cooked green leafy vegetables with added citrus or apple cider vinegar for iron absorption, Pumpkin seeds (activated, soaked, or sprouted), and spirulina algae (1500mg daily). Legumes are best soaked for a minimum of 24-hours prior to cooking.

Recommendations to Enhance Oral Iron Absorption in Pregnancy, Post-partum & Breastfeeding

Consume a combination of heme & non-heme rich foods daily with added ascorbic acid (vitamin C)

Seek support at least a few months prior to conception to establish nourishing eating patterns

Fortify sauces and soups with meats and fish

Avoid combining iron rich foods or supplements with dairy or calcium supplementation / black tea or coffee

Avoid the overuse of antacids or avoid all together

Using cast iron pans for cooking has shown to significantly increase iron content in foods

Soak, ferment, or sprout legumes, seeds, and nuts

Consider supplementing with spirulina, chlorella and other algae sources of iron if vegetarian

**Some seafood may contain high levels of heavy metals. Check out the Environmental Working Agency for more info: www.ewg.org.

Supplementation

There is no consensus world-wide about recommendations for supplementation in pregnancy. The World Health Organisation (W.H.O.) recommends 60mg/day for all pregnant women, the Centre for Disease Control (C.D.C.)  recommends 30mg/day and in Australia like the UK there are no such recommendations (1). The recommended daily intake of iron is 18mg per day, this almost doubles in pregnancy to 27mg per day (3). For those on a vegan or vegetarian diet the recommended daily intake increases 1.8 times that of the pregnancy dose due to the poorer absorption of non-heme iron. Iron bis-glycinate has shown to be better absorbed with less side effects (7). More common preparations are ferrous sulphate and ferrous fumerate, both of which are cheaper but twice as likely to cause uncomfortable side-effects and are less well absorbed (7). Side effects include nausea, constipation, vomiting, diarrhoea (1). Desiccated liver supplementation is a good option for those wanting a highly bio-available food-based iron supplement (7). Spirulina capsules, 1500mg daily is shown to be safe and effective throughout pregnancy and breastfeeding. This is an ideal option for those on vegan and vegetarian diets (4).

Conclusion

In summary, a mother with optimal iron stores is a baby with optimal iron stores and taking the time to prepare the body for pregnancy, is highly beneficial and has the potential to mitigate the adverse outcomes associated with IDA.

References & Resources

Achebe, M. M., & Gafter-Gvilli, A. (2017). How I treat anemia in Pregnancy: Iron, Cobalamin, and Folate. Blood, 23 February 2017 (vol. 129: No. 6). (1)

Brody, T. (1999). Nutritional Biochemistry, 2nd Ed. Pp. 752-58. Academic Press, California (2)

Marz, R.B. (2002). Medical Nutrition from Marz, 2nd Ed. pp. 115-119. Portland, Oregon (3)

Spirulina in Pregnancy: https://www.scirp.org/Journal/PaperInformation.aspx?PaperID=73643 (4)

Bland, J., Costarella, L., & Levin, B., et.al. (1999). Clinical Nutrition a Functional Approach. Pp.170-73,197. Institute for Functional Medicine, Gig Harbor, Washington. (5)

Lawrence, R. A. & Lawrence, R. M. (2016). Breastfeeding: a guide for the medical professional, 8th Ed. Pp. 285-229. Elsevier, PA. (6)

Nichols, L. (2018). Supplements. Real Food for Pregnancy, 1st Ed. Chapter 6. pp. 106-108,49-50. USA (7)

Anaemia in Pregnancy: https://www1.racgp.org.au/ajgp/2019/march/anaemia-in-pregnancy

RANZCOG: Vitamin and Mineral Supplementation in Pregnancy /pdf.