Haematologist Dr Renee Eslick answers GPs’ questions

Iron deficiency with or without anaemia is common in women of child-bearing age, and especially during pregnancy. Potential maternal consequences include increased fatigue and breathlessness, alongside decreased tolerance of blood loss at birth.

Canberra haematologist Dr Renee Eslick says that adequate maternal iron stores are also crucial for foetal development. “There is evidence that iron is essential for early brain development by supporting neuronal and glial energy metabolism, neurotransmitter synthesis and myelination,” she says.

Although the bulk of evidence is in women with established iron deficiency anaemia, Dr Eslick feels there is still potential for isolated iron deficiency to impact brain development.

Thresholds for iron deficiency

A 2020 systematic review and meta-analysis published in the Lancet found no clear threshold for maternal ferritin that correlates with neonatal iron deficiency. “However, many studies show that neonatal iron deficiency is more common in babies of women with established iron deficiency anaemia, rather than just an isolated low ferritin,” Dr Eslick says.

Different laboratories report different ferritin cut-offs, but Dr Eslick considers a ferritin of less than 30 to be deficient, in line with the RCPA guidelines, as this correlates well with bone marrow iron stores.

“I aim for the ferritin to be above 30, ideally targeting 50 to provide a reserve, as inevitably she will develop recurrent iron deficiency with postpartum blood loss and future pregnancies,” she says.

First line treatment for isolated iron deficiency is oral supplementation. “The established standard of care for oral iron is ferrous iron supplements (ferrous sulfate or ferrous fumarate) which tend to be the best-absorbed, at a potential cost of higher GI side effects,” says Dr Eslick.

She would only offer a non-ferrous oral supplement if side effects persist despite lower dose or alternate day dosing. (For menstruating women with recurrent iron deficiency, Dr Eslick sometimes recommends taking oral supplements during their period as an easy-to-remember top up. This means less side effects due to less frequent dosing.) She hopes to see more research on iron bisglycinate, which wasn’t included in a recent meta-analysis of iron preparations in pregnancy.

Oral supplements containing Vitamin C are popular as the ascorbic acid increases uptake. (Non-pregnant women on the oral contraceptive pill may be concerned that Vitamin C will reduce their contraceptive efficacy. Dr Eslick notes that this is usually only with high doses over 1000 mg, so the amount in Ferrograd-C is unlikely to interact. “You can always use a ferrous iron supplement without added vitamin C if concerned,” she says.)

When is IV iron recommended?

Intravenous iron preparations are PBS-listed for the treatment of laboratory-confirmed iron deficiency when oral preparations are not tolerated, ineffective or otherwise inappropriate.

“If you are just treating an isolated low ferritin, I tend to persist with oral iron as long as the ferritin is trending upward,” says Dr Eslick. She follows UK guidelines which recommend rechecking levels after two to three weeks.

She might consider offering infusion if the patient is unable to tolerate oral replacement and remains highly symptomatic or is otherwise at heightened risk of blood loss (such as Von Willebrand’s disease), especially at late gestation. Another situation where she considers offering IV iron earlier is in patients with previous bariatric surgery who may have poorer nutrient absorption, especially if their procedure bypassed the duodenum.

With mild anaemia, if the haemoglobin rises over 2-3 weeks of oral replacement, Dr Eslick would consider persisting with it. The UK guidelines recommend proceeding to IV replacement if the haemoglobin fails to improve, there is severe anaemia (Hb <70g/L or the patient is more than 34 weeks gestation. “I think this is a very reasonable approach,” she says.

Current guidelines contraindicate iron infusion in the first trimester.

Even with quite severe iron deficiency, Dr Eslick says there is still plenty of time for the oral replacement to be effective. “I try all the tricks to maximise oral iron tolerability – alternate day dosing, lower dose ferrous iron, or trying a supplement which may be better-tolerated such as maltofer.”

But if none of that works, IV iron can be offered from the second trimester.

Dr Eslick says there is no evidence of IV iron causing harm to the foetus from the second trimester. Most pregnancy iron infusions are done in hospital where CTG monitoring can be offered. “It’s certainly offered in some GP practices,” she says, “but you would need to ensure adequate resuscitation facilities were available in the unlikely event of an adverse reaction.”

“The easiest brands to administer in the GP setting are Ferinject and Monofer as both are administered quickly and have a low rate of adverse reactions,” but Dr Eslick says it is more important that you use a product you are familiar with, and follow the published product information in respect to dilution and administration. Monofer has a lower incidence of post-infusion hypophosphataemia.

There is not usually a need to check phosphate levels pre or post infusion, unless a patient develops symptoms. Symptoms of mild deficiency can include irritability, muscle aches and weakness, and paraesthesias. More severe deficiency can lead to seizures, delirium, cardiac arrhythmias and respiratory failure.

Oral phosphate supplementation can be used to treat mild to moderate hypophosphataemia, but severely low levels (<0.3 mmol/L) should be referred to the emergency department for IV phosphate replacement, which is typically followed by several weeks of oral replacement. Dr Eslick says correcting Vitamin D deficiency will improve phosphate absorption.

Oral iron supplements should be withheld for one week after infusion as they will not be well absorbed. “If the patient can tolerate it, it is often recommended to administer oral iron for three to four months after infusion to fully replenish stores,” says Dr Eslick. For iron deficiency anaemia, she recommends repeating blood tests four to six weeks after an infusion as some patients may require a repeat dose. She would routinely check again at three to six months, especially if the patient did not continue oral supplementation.

Even in pregnant or regularly menstruating women, recurrent iron deficiency should prompt a careful evaluation for underlying causes, says Dr Eslick, particularly excluding gastrointestinal blood loss.

To learn more about managing iron deficiency in pregnancy, register here for Healthed’s 25 July webcast, where clinical associate professor Pradeep Jayasuriya will share his insights on the topic.