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ANAEMIA IN PREGNANCY
A PRACTICE UPDATE FOR MIDWIVES IN AOTEAROA
ESTHER CALJÉ REGISTERED MIDWIFE, PHD CANDIDATE
Iron-deficiency and anaemia are common problems in pregnancy and postpartum, however, even in well-resourced countries, the management of maternal anaemia and iron status is recognised as inconsistent and suboptimal. This may be due to clinical guidance that was, until recently, very limited.
Many district health boards (DHB) in Aotearoa New Zealand have responded with the development of guidelines, such as Canterbury DHB’s Maternal Blood Optimisation Pathways (MBOP), to assist midwives in managing anaemia and irondeficiency in pregnancy. The development of these multi-disciplinary guidelines may be driven by the increased use of intravenous (IV) iron, and the international focus on improving patient blood management (PBM). PBM is relevant to midwives, as pillar one of PBM aims to optimise blood volume and red cell mass in pregnancy to avoid the requirement - and risks - of blood transfusion around the time of birth. Midwives also understand that the management of anaemia and iron-deficiency in pregnancy and postpartum is important for the health and well-being of women, and their pēpi. WHAT IS ANAEMIA? Anaemia is a lack of haemoglobin (Hb) and red blood cells, which leads to reduced transport and supply of oxygen to the tissues and vital organs. Although physiological anaemia of pregnancy reflects plasma expansion and haemodilution associated with normal pregnancy, the boundary between physiological anaemia and anaemia as a disorder, is unclear. Internationally, definitions of anaemia in pregnancy are inconsistent, which can be confusing for maternity care providers. Ideally, we would define anaemia in pregnancy based on a large population study of healthy iron-replete pregnant women in Aotearoa, which would give us a statistically established definition of anaemia in our population. However, in the absence of such a population study, it is reasonable to adopt anaemia thresholds based on recognised international guidelines with similar populations (see Box 1).
ADVERSE EFFECTS OF ANAEMIA Anaemia is the most common indirect cause of adverse maternal outcomes and is associated with fatigue, lethargy, depression, reduced thermoregulation, impaired breastfeeding, bonding and cognition, and reduced physical performance and work capacity. Clinically, maternal anaemia is associated with increased mortality and morbidity, cardiovascular stress, increased risk of infection, poor wound healing, prolonged hospital stays, increased hospital costs and increased risk of interventions such as blood transfusion and intravenous iron. Furthermore, maternal anaemia is linked to reduced fetal growth and prematurity (especially when the anaemia is from early pregnancy), low neonatal/infant iron stores and infant neurodevelopmental delay. Conversely, high haemoglobin levels in pregnancy (Hb >130g/L) are associated with hypertension, increased blood viscosity, decreased placental perfusion, reduced fetal growth and prematurity.
WHO DOES IT AFFECT? Worldwide, it is estimated that anaemia in pregnancy significantly affects about half of all women in low-income countries, and 2530% of women in well-resourced countries.
The prevalence of postpartum anaemia is 30% in the United Kingdom (UK). In Aotearoa, the prevalence of antenatal and postnatal* anaemia is unreported, but it is reasonable to consider that they are comparable to the UK. Anaemia is often multifactorial, with multiple determinants of health as contributing factors. Across social strata, many women are at risk of anaemia
(see Box 2).
IRON-DEFICIENCY AND OTHER CAUSES OF ANAEMIA The term iron-deficiency is often used interchangeably with anaemia, but they are not the same. Iron-deficiency is when there are insufficient iron stores to meet the body’s demands. Iron deficiency is the most common cause of anaemia in pregnancy (50-60%), mostly due to the extraordinary iron demands of the increased red cell mass, placental development and fetal growth.
Iron replete women require approximately 1000-1300mg of extra elemental iron over the course of an entire pregnancy, and an extra 1mg per day during lactation; however, most women have insufficient iron stores to begin with, and are therefore ill-equipped to meet the increased demands of pregnancy and birth without the aid of iron therapy.
Following birth, for example, even a normal volume of blood loss can be problematic for a woman whose iron stores are absent or low (see Box 1), as there will be insufficient iron available to make new red blood cells (erythropoiesis), resulting in an inability to replenish blood volume and a concomitant drop in haemoglobin. This is known as irondeficiency anaemia.
Iron-deficiency has a number of causes: low dietary intake (including limited access to iron-rich food and/or food insecurity), intake of dietary iron inhibitors (e.g. tea, coffee, phytates), high demands (e.g. pregnancy, adolescence), decreased intestinal absorption (e.g. coeliac disease, bariatric surgery), and mechanisms associated with inflammation (e.g. inflammatory bowel disease or obesity). Inflammation (from any cause) affects iron absorption and bioavailability in the body by sequestering or hiding away iron so that iron is not available for erythropoiesis. Ferritin levels rise in response, reflecting inflammation rather than bioavailable iron stores. Diagnosis of iron-deficiency in the presence of inflammation can therefore be challenging.
There are many causes of anaemia other than iron-deficiency: acute or chronic blood loss, megaloblastic anaemia (usually caused by vitamin B12 or folic acid deficiency), haemolytic states (HELLP syndrome, sickle cell disease, malaria), haemoglobinopathies, parasitic infections (e.g. hookworm) and anaemia of chronic disease.
SIGNS AND SYMPTOMS Clinical signs of anaemia include: tachycardia, hypotension, dyspnoea, palpitations, syncope and pallor (of the skin, nails, lips and/or inner membrane of lower eye lids). The most common symptom of anaemia is fatigue; however, symptoms may be non-specific unless the anaemia is severe.
Women with anaemia may feel lightheaded, heart-racing, shortness of breath, lethargic, low mood, irritable, difficulty concentrating, restless legs, pica (craving nonnutritive substances e.g. ice), and cold hands or feet. Symptoms of iron-deficiency without anaemia are generally vague, and can include fatigue, muscle weakness, or cognitive impairment. However, currently the only way to correctly attribute these symptoms to non-anaemic iron-deficiency (NAID) is if the symptoms resolve after iron therapy.
DIAGNOSIS OF IRON-DEFICIENCY, IRON-DEFICIENCY ANAEMIA (IDA) AND OTHER CAUSES OF ANAEMIA NAID is the first stage on the spectrum of progression to IDA (see Figure 1). Haemoglobin is the last red cell indice to drop, reflecting end-stage IDA. By the time haemoglobin levels are low, iron stores are already depleted, which is why haemoglobin testing alone is an insensitive measure of iron status. It is therefore important to diagnose iron-deficiency early, to prevent anaemia during pregnancy and at birth.
Serum ferritin remains the most accurate, accessible measure of iron stores, although it is an acute-phase protein or inflammatory marker that increases dramatically with
*New research addressing evidence gaps on postpartum anaemia in Aotearoa will be presented to midwives at the 2021 College conference.
BOX 1
ANAEMIA
• 1st trimester: Hb < 110g/L • 2nd & 3rd trimester: Hb < 105g/L • Early postpartum period (24–48 hours after birth): Hb < 100g/L • 1 week postpartum: Hb < 110g/L • 8 weeks postpartum: Hb < 120g/L
Iron deficiency: ferritin < 30 mcg/L Absent iron stores (insufficient iron is available for erythropoiesis): ferritin < 12-15 mcg/L
• Serum ferritin is an inflammatory marker which increases in the presence of inflammation
• C-reactive protein (CRP) >5 mg/L indicates inflammation
• Diagnosis in the absence of inflammation is straightforward • Inflammation may mask an underlying iron-deficiency • There is no value in testing ferritin for at least one week postpartum, due to inflammatory processes associated with all births
• There is no value in testing ferritin within six weeks of intravenous iron, as ferritin increases dramatically and does not accurately reflect iron stores during this time.
BOX 2
• Previous anaemia
• Low-iron diet
• Low socio-economic status
• Inter-pregnancy interval < 1 year • Multiple pregnancy; Parity ≥3
• Teenage pregnancy • Smoking / Obesity • Bariatric surgery • Recent history of bleeding • High risk of obstetric bleeding (e.g. placenta praevia • Gastrointestinal disorders e.g. crohns or coeliac disease
• Jehovah’s Witness
• Women from ethnic backgrounds at high risk of haemoglobinopathies:
Southern Europe, Middle East, Africa,
South East Asia, India or Pacific Islands. inflammation. This can lead to missed diagnoses of iron-deficiency with the appearance of false normal results as a response to inflammation. Some hospital laboratories routinely test C-reactive protein (CRP) concurrently with serum ferritin to detect the presence (CRP >5mg/L) or absence (CRP ≤5mg/L) of inflammation.
Alternatively, midwives can request CRP alongside ferritin testing if inflammation is suspected, or ferritin levels are normal or elevated and haemoglobin
is low (see Table 1). One method that the World Health Organisation recommends to account for inflammation-related increases in ferritin, is to raise the cut-off for irondeficiency to 30mcg/L in pregnancy (from 15-20mcg/L previously). This approach has been adopted in international and some DHB guidelines. It is beyond the scope here to detail the pathophysiology and management of anaemia and iron status in the presence of inflammation. Box 1 outlines diagnostic criteria and key practice points for iron-deficiency and anaemia in pregnancy and postpartum.
It is important to interpret all the red cell indices in the complete blood count, when diagnosing anaemia and the possible causes (see Table 1). Normocytic, normochromic red blood cells (RBCs) have a normal mean cell volume (MCV) and mean corpuscular haemoglobin (MCH). Microcytic (low MCV), hypochromic (low MCH) RBCs are small and pale. Macrocytic (high MCV) RBCs are large, and are associated with megaloblastic anaemia.
Because the aetiology of anaemia is complex and multifactorial, women may have multiple causes of anaemia. Haemoglobinopathies, for example, are the most common genetic disorder worldwide. This is significant for midwives in Aotearoa because our birthing population is increasingly multi-ethnic, comprising more migrant women than ever before. Many birthing women come from countries where haemoglobinopathies are endemic (Southern Europe, Middle East, Africa, South East Asia, Indian Subcontinent or Pacific Islands), and are at greater risk of anaemia.
There are many haemoglobinopathy disorders including, α- and β-thalassaemia and sickle cell disease. The clinical characteristics range from being asymptomatic, to requiring regular blood transfusion, and reduced life expectancy. Women with a known haemoglobinopathy require obstetric referral; however, midwives should be aware of the possibility of an undiagnosed
FIGURE 1: THE SPECTRUM AND PROGRESSION OF IRON-DEFICIENCY ANAEMIA
Iron replete
Normal Hb; Normal iron stores; Normocytic and normochromic red blood cells (RBCs)
Non-anaemic iron deficiency
Normal Hb; Low iron store
Iron-deficiency anaemia (IDA)
Low Hb; Low iron stores; RBCs may be microcytic (small, long-arrow-down MCV); and hypochromic (pale, long-arrow-up MCH)
Source: Canterbury District Health Board MBOP Guideline and Practice Improvement Strategy. Reproduced with permission.
Long standing IDA
Low Hb; Low iron stores; RBCs may be microcytic (small, long-arrow-down MCV); and hypochromic (pale, long-arrow-up MCH)
TABLE 1: INTERPRETING LABORATORY TEST RESULTS TO ASSESS FOR IRON-DEFICIENCY AND ANAEMIA
DIAGNOSIS
HAEMOGLOBIN g/L SERUM FERRITIN mcg/L C-REACTIVE PROTEIN (CRP) mg/L MEAN CELL VOLUME (MCV) AND MEAN CELL HAEMOGLOBIN (MCH)
[with classification]
Iron replete Normal
Non-anaemic Normal iron-deficiency (NAID)
Iron-deficiency Low anaemia (IDA) > 30
< 30
< 30 Normal (normocytic normochromic
Normal (or low)
Low (or normal in early IDA)
NAID with inflammation Normal
Anaemia of Low chronic disease Normal CRP > 5 Normal or elevated* (may be mildly low)
Normal CRP > 5 Normal or elevated* (may be mildly low)
Thalassaemia Low (or normal) Normal minor or elevated* Low (or normal)
Megaloblastic or Low (or normal) pernicious anaemia platelet levels may
(folate or vitamin B12 deficiencies be low are common causes) Elevated MCV Normal MCH [macrocytic, normochromic]
* in the presence of inflammation, ferritin is elevated and is not an accurate measure of iron stores Source: Canterbury District Health Board MBOP Guideline and Practice Improvement Strategy. Reproduced with permission.
Key practice points for midwives to consider
• Introduce advice/information from pre-conception, or in early pregnancy, on increasing dietary iron, enhancing absorption, and minimising inhibiters of iron absorption (e.g. tea and coffee) • Haemoglobin (Hb) alone is an insensitive measure of iron status
• For all 1st trimester women: test complete blood count (CBC) and ferritin to establish baseline iron status, and maximise early opportunities to prevent or treat iron-deficiency and/or anaemia • 2nd trimester: repeat CBC and ferritin for all women
• 3rd trimester: repeat CBC and ferritin, especially for women at higher risk of anaemia, or women with 2nd trimester iron deficiency or anaemia • Untreated iron-deficiency without anaemia progresses to iron-deficiency anaemia (IDA) • Consider alternate day dosing of oral iron (≥60mg elemental iron) or lower doses of daily oral iron (not less than 40mg) if higher daily doses not well tolerated
• At any stage, obstetric referral if
Hb<90g/L • CBC 7-10 days postpartum if history of PPH and/or iron-deficiency or anaemia prior to birth • Consider CBC and ferritin at 4-6 weeks postpartum for at-risk women and/or significant PPH • Women who have received intravenous iron should have CBC and ferritin tested 6-12 weeks post iron infusion haemoglobinopathy in women who are from an ethnic group with a high prevalence of haemoglobinopathy. Haemoglobinopathy screening is expensive and time consuming, so as a first step, CBC and ferritin results need to be assessed. If these are normal and there are no unusual red cell indices, continue with routine pregnancy care.
For women with a family history of a haemoglobinopathy, seek obstetric or laboratory advice on whether screening should be recommended. For any women who have unexplained microcytic/ hypochromic RBCs, or unexplained anaemia, seek obstetric or laboratory advice on whether a haemoglobinopathy could be present and which screening tests are warranted, given the clinical picture. Include gestation and ethnicity on any referral forms. When haemoglobinopathy screening is indicated, it is optimal to do this in the first trimester, if possible, to allow sufficient time for genetic testing/counselling and appropriate management of pregnancy if required.
HOW TO TREAT IRON-DEFICIENCY AND ANAEMIA Due to the risks of iron-overload, routine iron supplementation is not recommended without a confirmed diagnosis of iron-deficiency or anaemia. Current recommendations for the treatment of IDA are 100-200mg daily of elemental iron (actual iron content). If started early in pregnancy, the treatment for NAID is 40-80mg day. For detailed guidance on which iron supplements are recommended and subsidised, as well as dosages, see Canterbury DHB’s Recommended oral iron preparations for Maternal Blood Optimisation Pathways (MBOP), a highly practical visual resource for midwives and women alike. Iron supplementation is not recommended if Hb ≥ 130 g/L.
Elemental iron is the total amount of iron available for absorption in the body, which is different to the total amount of iron ingested in the diet, or the ‘total dose’ of iron in oral iron supplements (read the label carefully).
Recent research in women with NAID has shown that the absorption of multiple, high daily doses of oral iron is impaired due to inflammation in the gut as a result of the high doses of iron. This paradoxically interferes with iron absorption in subsequent doses. Although this research has not been replicated in pregnant women with IDA, international and local guidelines are recommending that consideration of a single dose on alternate days may improve absorption, compliance and reduce side effects. Women should also be informed on how to reduce sideeffects and maximise absorption of oral iron supplements: taken on an otherwise empty stomach (one hour before or two hours after a meal) with vitamin C-rich fruit, such as kiwifruit or an orange (also reduces constipation), and without inhibitors such as tea or coffee. Taking an iron tablet before bed can be an easy time to remember.
FOLLOW-UP Women on iron supplementation should have repeat CBC and ferritin testing, and follow-up. When treating IDA, it is recommended to continue with oral iron for three months to replenish iron stores, once haemoglobin levels have normalised. Non-responsiveness to oral iron is persistent anaemia after 4-8 weeks of regular oral iron where haemoglobin levels rise less than 10-20g/L, and ferritin remains low. If iron-deficiency or anaemia persists, is unexplained, or difficult to treat despite iron supplementation, further investigations for the underlying cause should be considered. There may be underlying pathologies beyond iron-deficiency and increased requirements of pregnancy. As well as repeating CBC and ferritin, obstetric or laboratory input is recommended, in order to identify whether further screening is advised, i.e. CRP, B12, folate, renal function and haemoglobinopathy. Other causes that may need to be excluded are malabsorption from inflammatory bowel disease, coeliac disease, gastrointestinal tract blood loss, or other systemic disease. An obstetric referral is appropriate promptly if Hb <90 g/L.
CONCLUSION Although we don’t know the optimal haemoglobin levels for pregnant women in Aotearoa, there is evidence that low and high haemoglobin levels are problematic. Anaemia is associated with a wide range of adverse clinical and quality of life outcomes. Maternal iron-deficiency and anaemia are largely preventable and treatable using simple measures in partnership with women, based on timely testing and interpretation of red cell indices and ferritin levels from early pregnancy. Healthy iron levels in pregnancy and postpartum improve maternal wellbeing and perinatal outcomes, reducing morbidity and the likelihood of requiring intravenous iron or blood transfusions around the time of birth. square
References available on request.
