Reader Responses: Should a pregnant patient with hemochromatosis receive iron?

Here’s how readers responded to a You Make the Call question about the treatment of iron deficiency during pregnancy in a patient with hereditary hemochromatosis.

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If she has no evidence of iron overload, I think it’s very reasonable to give her iron in this setting.

Salman Malad, MD
Lafayette, LA

The HH at this juncture is of no significance. This woman has absolute iron deficiency and needs treatment with intravenous iron. . At 36 weeks of pregnancy with a ferritin level of 15 µg/L, oral iron is insufficient because no oral iron would get to the baby and intranatal iron deficiency is associated with statistically significant increments in cognitive and behavioral abnormalities, which persist after iron repletion, especially autism spectrum disorders (JAMA Psychiatry, 2019). This is the most important time for fetal iron in brain development.

Michael Auerbach, MD
Baltimore, MD

Yes, order IV iron, but be cautious as to how high a dose to give.

Louis M. Aledort, MD
New York, NY

Yes, I would give her iron and monitor her levels post-delivery.

Mary Ann Skiba, DO
Fort Worth, TX

I would be inclined to go ahead with iron repletion, but I would like to know the other iron parameters like total iron binding capacity (TIBC) and transferrin saturation, as well as the patient’s complete blood count.

Evandro Bezerra, MD
Rochester, MN

IV iron would allow her to have a ferritin level above 30 µg/L.  One infusion should do it.  Furthermore, while central nervous system development is most pronounced in the first trimester, it continues throughout the pregnancy, so the sooner the better.  Because she will, presumably, resume active menstruation following the pregnancy, one or two infusions are unlikely to do any harm.  I would use sodium ferric gluconate 125 mg once or twice.

Albert M. Brady, MD
Yakima, WA

I think I would give her iron treatment. She is going to lose some iron during delivery. If her iron storage level after delivery is too high, it should be possible to perform venesection. 

Damian Szatkowski, MD, PhD
Førde, Norway

It depends whether she is still on venesection; if so, I would stop it, give her dietary advice, check iron on a weekly for 4 weeks and add iron supplements if she is becoming anemic.

Umar Khatab, MD
London, U.K.

It depends on how symptomatic she is and whether there has been a decrease in fetal growth. I have given patients with HFE mutations iron when they have become symptomatically iron deficient. I have also given IV iron to symptomatic pregnant women. However, close to term, there are some concerns about provoking premature labor, so I tend to use iron earlier in pregnancy as opposed to later. She could definitely get some IV iron postpartum.

Frank Basile, MD
Cambridge, MA

I would not just go by just the ferritin level. It is important to also know the hemoglobin level in deciding how much iron to give. The latest research from Elizabeta Nemeth, PhD, and Tomas Ganz, MD, PhD, shows that, at least in mice, maternal ferritin levels do not necessarily reflect the fetal iron supply, as the placenta may siphon iron away from the fetus for its high energy needs. I would give some iron since iron demands during the last trimester are very high. However, the amount and route would depend on whether her ferritin level was normal and is now falling or whether it has been staying stable for the previous weeks. If her ferritin level had dropped precipitously, then I may give a small dose of IV iron. Otherwise, I would be inclined to give oral iron.

Deborah Rund, MD
Jerusalem, Israel

I strongly agree that iron needs to be given. The priority now is the health of the fetus. After delivery, we can always perform phlebotomy as needed. Now, IV iron may be necessary.

Steve Chandler, MD
Longview, WA

It depends on her genotype and presence of organ damage from HH. If she has no evidence of organ damage from HH, I would certainly give IV iron based on the concerns about fetal development and risk of autism, but be careful with the dose and be sure not to overdo it. Given the risk to the fetus, I would still give her iron (cautiously) even if she has the homozygous HFE C282Y mutation and has evidence of organ damage.

Yazhini Vallatharasu, MD
Appleton, WI

I would not give her IV iron because her iron deposits are full.

Antonella Pitini, MD
Palermo, Italy

Yes, I would give her iron. The patient’s iron level is borderline low, which can produce third-trimester complications.

Roberto Velazquez Torres, MD
Ponce, Puerto Rico

I presume the questioner is indicating that the patient is homozygous for the HFE C282Y mutation. If so, there is no contraindication to giving IV iron to the patient if she is pregnant and iron deficient and cannot tolerate oral iron or if oral iron is ineffective.

David M. Baer, MD
Oakland, CA

Apparently the patient is not suffering from iron deficiency anemia, so I would not order IV iron.

Andreas Neubauer, MD
Marburg, Germany

It depends of the total amount of iron in her body. If she has low ferritin and low transferrin saturation values, I would order IV iron.

Juan Besalduch, MD, PhD
Calvià, Spain

Yes, you must treat her iron deficiency.  After delivery, you could perform phlebotomy if needed.

Raymond W. Lee, MD
San Jose, CA

Of course, give her iron! There is absolutely no risk with her ferritin level and she needs the treatment.

Gunnar Birgegard MD, PhD
Uppsala, Sweden

It is estimated that a normal pregnancy requires about 1,000 mg of elemental iron. In the case described, we are presented with hypoferritinemia, but we are not sure the patient is anemic. If she is anemic (presumably from iron deficiency), to what extent, both in terms of symptoms, red blood cell mass and hemoglobin concentration? My approach, regardless of the diagnosis of HH, would have been to try to correct any anemia by means of oral replacement early in the pregnancy. In this case, delivery is to happen in the next 4 weeks, and I believe the treating physician is trying to prevent further iron loss and anemia at the time of birth (about 350-500 mg of iron). Parenteral iron replacement is commonly used late in pregnancy. Ferric carboxymaltose and iron dextran (~1,000 mg) are safe and efficient ways of correcting the hemoglobin and iron deficiency in the mother in situations like this. The benefit of parental replacement on neonatal health (vs. oral replacement) at this stage of pregnancy is unclear. Regarding the HH diagnosis (I presume this is a HFE C282Y homozygote), at this point in her life, this patient is not exhibiting signs of iron overload, thus prudent iron replacement is indicated in case of deficiency. Keep in mind that the penetrance of clinical hemochromatosis is lower in women than in men, and it happens later in life. In addition, women, more commonly than men, may have a non-expressing HH phenotype. She will need to be followed with iron indices for the foreseeable future.

Julio Hajdenberg, MD
Orlando, FL

I don’t think there is harm in giving 1 to 2 doses of iron sucrose injection to bump up her hemoglobin level. She will eventually menstruate and should not become overloaded.

Arunabh Sekhri, MD
Warren, NJ

Yes, I would use IV iron in a pregnant patient especially as the ferritin is very low.

Mian K. Khalid, MD
Baltimore, MD

Yes, I would give IV iron to the patient.. She may have many more pregnancies and is still premenopausal.

Satvir Singh, MD
Snellville, GA

Given the history, current pregnancy, and low ferritin levels, I would recommend iron supplementation to avoid negative effects on the fetus.  A short course of iron therapy in this situation should not have any adverse effect on the hemochromatosis.

Koyamangalath Krishnan, MD
Johnson City, TN

It depends how far along in her pregnancy the patient is and the risk of iron infusion on the fetus.

Robert Fenning, MD
Greenville, SC

HH mutations generally have a very low penetrance. Even homozygous individuals rarely have clinical iron overload. Therefore, it would be not surprising for an otherwise-healthy young woman like this patient with either heterozygosity or even homozygosity for the disease to become iron deficient, particularly during pregnancy. I would not hesitate to replete iron for such a patient in whom it would otherwise (in individuals without HH mutations) be clinically indicated, especially when it’s only temporarily needed, such as during pregnancy.

Andrew I. Schafer, MD
New York, NY

In this situation, I would give iron to replete her ferritin level to around 150 µg/L. At approximately 6 weeks postpartum, I would recheck her iron levels and then proceed as appropriate. For example, if her level is higher than 150 µg/L and she is not anemic, then she can recommence phlebotomy unless this would negatively affect her ability to breastfeed. Not giving the patient iron could cause more harm (in the form of unnecessary blood transfusions) than giving it to her (potentially some inflammatory effects, but no long-term downside regarding her hemochromatosis if well-managed postdelivery).

Joanna Katarzyna Czerwinski, MD
Bedford Park, Australia

I have occasionally treated patients with HH with iron tablets. In those cases, the women in question were anemic, one due to hypermenorrhea, and the other due to rectal bleeding. Another male patient was a regular blood donor who became symptomatic due to iron deficiency. If iron treatment is limited to a modest dose, e.g. 50- to 60-mg elemental iron per day, given for a month or so, or periodically to correct for the menstrual loss, I cannot see that any harm could ensue. In the case in question, a single shot of IV iron ~500 mg will do no harm, considering the fetal needs in the last 4 weeks of pregnancy, and the expected blood loss at delivery. 

Aleksandar Mijovic, PhD, FRCPath
London, U.K.

One should also look at the patient’s hemoglobin, transferrin saturation, and C-reactive protein (CRP) levels to determine whether she is iron deficient or anemic. If her CRP and hemoglobin levels are normal, her ferritin level is below than 30 ng/mL, and her transferrin saturation is less than 16%, the patient is iron deficient without anemia.  If her CRP level is high, hemoglobin level is normal, ferritin level is less than 100 µg/L, and transferrin saturation is less than 20%, the patient is iron deficient without anemia.

In these two circumstances, I would talk with the patient before prescribing IV iron, preferably ferric carboxymaltose or ferumoxytol injection. If her hemoglobin level is low and she is anemic, I would discuss the role of blood transfusion vs. IV iron.  I would prescribe IV iron, preferably ferric carboxymaltose, to raise the ferritin level above 50 µg/L, but keep it around or below 150 µg/L. . . There are no definite guidelines regarding this particular issue, so. one has to individualize and consider the adverse effects of iron deficiency on the fetus and mother.

Saifudeen Abdulrahman, MD
Salalah, Oman

I would give the patient some iron, as most of it will be consumed by the growing fetus and it will help prevent her from getting very anemic to a point that she may require a packed red blood cell transfusion. She can always get phlebotomies later, if needed.

Ian Rabinowitz, MD
Albuquerque, NM

It is very hard to “iron overload” a menstruating and now pregnant woman, even with HH.  I would see no issue in giving judicious IV iron in a pregnant woman with HH with such a low ferritin. However, it’s unclear what benefit IV iron would have for the fetus at 36 weeks. You probably won’t even increase the hemoglobin by much prior to delivery. If she’s very anemic and you’re worried that she will remain so after delivery (due to increased iron needs with breastfeeding, etc.), you could consider dosing her now.  But you should not give her iron at 36 weeks just to benefit the fetus.

Rebecca Karp Leaf, MD
Boston, MA

A premenopausal female is very unlikely to develop iron overload. Moreover, only 70% of those with homozygous HFE C282Y status eventually develop iron overload, so I would infuse iron if she can’t tolerate oral iron.

Amjad Hayat MRCP, FRCPath, PhD
Galway, Ireland

Since the patient’s ferritin level is lower than 50 µg/L and she is 36 weeks pregnant, I would give her IV iron and would reassess postpartum to determine the need for phlebotomy. I am not certain of the need of iron for such a fully formed, third-trimester embryo, or whether the IV iron should have been implemented earlier.

Stamatis Karakatsanis, MD
Athens, Greece