Iron supplements in pregnancy

During pregnancy, the requirement for iron, like many nutrients, increases significantly.

However, iron is a micronutrient that requires a delicate balance. Too little iron can have adverse effects on the mother and fetus, and over-supplementing can have harmful effects, including increased lipid peroxidation and disruption of natural mechanisms that regulate iron homeostasis.

For this reason, it is recommended to be aware of how much iron you are consuming and monitor your iron levels during pregnancy. You have probably noticed that the majority of prenatal vitamins contain iron. However, I do not recommend prenatals with iron, as you will read below. Iron supplementation is highly individual. In this blog, we’ll explore iron needs during pregnancy and how to supplement correctly.

How much iron is needed in pregnancy? (It depends on the trimester and the person!)

Requirements for absorbed iron increase gradually through gestation, starting at an additional need of 0.8mg/day in the first trimester to 7.5 mg/day in the third trimester. The total iron needed for a normal pregnancy is estimated to be around 1,240 mg (1).

For reference, absorbed iron pre-pregnancy is 1-2 mg/day, and the RDA for iron in nonpregnant menstruating women is 18 mg/day (2). The RDA for iron during pregnancy is 27 mg/day, although the optimal amount likely varies by trimester and may also depend on the stored iron a woman has preceding pregnancy.

Extra absorbed iron is needed to increase the mother’s erythrocyte (red blood cell) mass, provide the developing fetus with iron, and provide iron stores to make up for potential blood loss during delivery (1).

Iron metabolism in pregnancy

To meet the increased iron needs during pregnancy, more iron is absorbed from food, and the body also releases iron stores to maintain iron homeostasis.

Much of the iron balance is controlled by a peptide hormone called hepcidin. Hepcidin is produced in the liver and controls the delivery of iron as it is absorbed in the intestine, recycled from macrophages, or released from iron stores. Hepcidin acts by binding to the iron transporter, ferroportin, and inhibits its transportation of iron. Through these mechanisms, hepcidin controls plasma iron levels and total body stores of iron. Hepcidin operates on a feedback loop; when there is excess iron, hepcidin increases and lowers iron availability, and when iron is too low, hepcidin decreases to increase iron availability.

During the 2nd and 3rd trimesters of pregnancy, hepcidin decreases to increase available iron to match the mother’s needs (3). Hepcidin is kept at a low level even in women with healthy iron stores but is the lowest in women with iron-restricted erythropoiesis (4). Iron-restricted erythropoiesis is a category of iron deficiency where hematological function is impaired, but anemia is not present (5). Hepcidin stays low until after delivery, when it increases again. Because the body naturally keeps a tight rein on iron homeostasis, supplementation with excess iron can disrupt the hepcidin-feedback loop.

During pregnancy, transferrin production increases gradually to pick up more iron, and this is likely to provide iron to the placenta. The placenta has its own iron requirements, but the bulk is transported to the fetus (4). The fetus has the highest iron needs during the 3rd trimester, and this corresponds to the lowest levels of hepcidin in maternal circulation (because, remember, low hepcidin = increased iron needs).

The amount of iron-saturating transferrin (% saturation) gradually decreases after the 1st trimester as less iron becomes available to bind to the increased transferrin.

Iron panel markers in pregnancy

As you can guess, iron panel markers drastically change throughout pregnancy to values that appear out-of-range.

But don’t be alarmed by these values; blood chemistry is supposed to change during pregnancy!

Let’s discuss a few of the most significant changes to lab markers.

During the first trimester, RBC, hematocrit, and hemoglobin will be lower than pre-pregnancy.

Mean serum iron slightly decreases during pregnancy, but during the 1st trimester, there is a significant rise in the low end of the reference range, most likely due to the effect of non-menstruation on women who’ve previously had heavy bleeding.

The most pronounced changes in iron markers occur during the 3rd trimester when iron needs are highest.

Ferritin

Serum ferritin drops progressively starting in the 1st trimester. It reaches its lowest point by the 3rd trimester to approximately 50% of non-pregnancy values, independent of serum iron level (4,6).

Studies have shown that if ferritin is too high in the 3rd trimester (>40 ng/mg), the risk of oxidative stress, fetal birth restriction, and gestational diabetes increases (7, 8, 9).

Percent transferrin saturation

The amount of iron-saturating transferrin (% saturation) gradually decreases after the 1st trimester as less iron becomes available to bind to the increased transferrin (6).

Total iron-binding capacity (TIBC)

TIBC increases beginning in the 1st trimester and by the 3rd trimester is about 27% greater than non-pregnancy values (6).

Click here to learn more about interpreting lab work during pregnancy in my masterclass, What You Never Learned About Bloodwork in Preconception, Pregnancy, and Postpartum.

Anemia is not always due to iron deficiency

Anemia and iron deficiency anemia are not synonymous; there are several factors that can contribute to anemia. The most common culprit behind non-iron deficiency anemia is deficiency of B12 and folate. Lesser known causes of anemia include chronic inflammatory disease and thalassemia (a genetic disease involving red blood cells).

The presence of anemia in 1,456 healthy pregnant women in Camden, NJ, increased 6-fold from 1st to 3rd trimester. BUT…only a fraction of the anemic women had iron deficiency anemia (IDA) (10).

The same study shows that non-iron deficiency anemia was most present when ferritin levels were the highest ( >131.8 pmol/L or 58 ng/mL). However this is not always the rule—in my practice, I have also observed high ferritin coupled with iron-deficiency anemia. This is a great example of the complexity of anemia and why thorough analysis of blood chemistry is so crucial.

Due to the increased iron needs during pregnancy, women may be at greater risk of anemia and iron deficiency anemia. It’s estimated that around 50% of women have inadequate iron stores, and women with fewer resources may be at the greatest risk of developing iron deficiency or anemia by the 3rd trimester (7).

Iron metabolism is best understood by looking at the full iron panel with ferritin, a CBC with differential, and accounting for your patient’s symptoms. I want to emphasize this point: just an iron panel or CBC or just tracking symptoms alone is not enough to accurately assess iron needs in pregnancy and postpartum.

Based on the available research and my clinical experience, the 2nd trimester is a good time to test iron and assess supplementation needs.

The importance of bio-individual supplementation with iron

During a healthy pregnancy, the body suppresses hepcidin during the second and third trimesters to optimize iron status. Daily supplementation of iron during pregnancy has the potential to disrupt the homeostatic mechanism of hepcidin suppression.

Iron is usually recommended as a blanket supplement during pregnancy because iron requirements increase and inadequate iron can lead to pregnancy complications.

However, you can offer a much savvier and more effective approach in your practice.

When supplementing with iron, it is essential to take diet into account. Diets containing high iron may provide optimal amounts, while iron-deficient diets may require supplementation. Additionally, other nutrients interact with iron, including vitamin C, copper, non-meat proteins, and phytate. High intake of vitamin C with iron-containing foods (heme and non-heme) dramatically increases iron absorption, while high dietary copper, high amounts of dairy, and phytic acid can impair iron absorption (11). When it comes to dairy, casein and calcium are the main contributors to blocking iron absorption in the intestine, and this can be remedied by vitamin C, which greatly boosts absorption (12). Non-heme iron (iron from non-meat sources) is the most susceptible to impaired absorption from the substances above (11). Alternatively, heme iron found in meat, especially red meat, is very well absorbed and can even enhance iron absorption in meals containing high amounts of foods that reduce iron bioavailability. For example, combining heme iron-rich pork with phytate-rich beans would help boost overall iron absorption (11).

In cases where iron supplementation is warranted, many clinicians prefer supplementing iron every other day to prevent disruption of homeostatic mechanisms (4).

I recommend a prenatal that is free from iron so we can supplement with iron separately if and as needed.

Click here to access my free guide on picking the perfect prenatal for your patient.

Supplementing with iron when not needed may harm the mother and developing child

Although iron is vital for health, it is not an innocuous micronutrient. As with many vital substances, too much can have deleterious consequences. Excessive iron intake can increase free radicals, creating an inflammatory environment that is harmful to cellular function.

Lachili et al. (2001) found that iron supplementation combined with vitamin C in the 3rd trimester significantly increased lipid peroxidation, which may increase pregnancy complications (13).

In this study, women in their 3rd trimester were given 100 mg of iron and 500 mg of vitamin C daily as a routine supplement without checking their iron levels. Vitamin C was given to enhance iron absorption. This was compared to a matched group of pregnant women who did not take an iron supplement.

At delivery, women in the iron group had a significantly higher TBAR level, which is a measurement of lipid peroxidation, and lower vitamin E. Not surprisingly, they also had higher iron levels, although other blood markers were normal. Elevated TBARs and low vitamin E have been observed in various pregnancy complications, including preeclampsia (13).

Other studies show mixed findings on the relationship between iron supplementation and hypertensive disorders of pregnancy. One study found that iron supplementation in early pregnancy (before 16 weeks gestation) in non-anemic women was linked to significantly increased de novo hypertension later in pregnancy (14). Another found no association between a prenatal with iron and risk of hypertension (15), and another found that supplementing with an iron-containing prenatal was linked to a lower risk of hypertension during pregnancy (16).

Iron supplementation, particularly in iron-replete women, has been linked to an increased risk of gestational diabetes, although the evidence is conflicting (17). A 2018 meta-analysis found elevated ferritin, hemoglobin, and dietary heme intake to increase the odds of gestational diabetes (18).

Iron supplementation and celiac disease in the child

A novel 2014 study found a link between iron supplementation during pregnancy and an increased incidence of celiac disease in offspring. In this prospective cohort study, children of women who supplemented with iron during pregnancy were more likely to develop celiac disease, independent of confounding factors, including maternal celiac disease (19).

The reason behind this connection isn’t entirely understood, but the study authors suggest a few potential mechanisms. Iron may be influencing the fetus’ developing immune system and its response to food antigens like the gliadin found in gluten. Macrophages that accumulate iron may switch to a pro-inflammatory phenotype that contributes to autoimmune conditions (19). Additionally, excess iron in the gut can increase inflammation in the gut mucosa and reduce the number of beneficial microbes like Lactobacillus. Iron may also change the way that gliadin is transported through enterocytes (19). Could the effect of iron on gut health be a factor in the connection between iron supplementation and celiac disease in the offspring? For now, it’s just a hypothesis. Although there is abundant evidence supporting the important relationship between the maternal gut microbiome and the lifelong immune system of her offspring, the influence of iron supplementation isn’t well studied.

Practical takeaways: Balance is crucial

Iron metabolism is complicated, and it can easily make your head spin. Here are my practical recommendations to ensure optimal iron balance during pregnancy.

Check any supplements, including a prenatal, for iron. Swap to a prenatal that does not contain iron.
Get a ballpark idea of dietary iron intake. For dietary tracking I love to use Cronometer, a free tracking app that allows you to see how many micronutrients, like iron, you are getting in daily.
Test, don’t guess! Test iron status in the 2nd trimester by looking at a full iron panel with ferritin and a CBC with differential.
Supplement iron if and as needed – preferably on alternate days rather than daily.

References