Anaemia in pregnancy

• Anaemia is the commonest haematological problem in pregnancy, and iron deficiency is the commonest cause of it.
• It is usually defined by a fall in haemoglobin below trimester-specific cut-offs, with most guidelines using below 110 g/L in the first and third trimesters and below 105 g/L in the second.
• A haemoglobin below 110 g/L with a ferritin below 30 micrograms/L points to iron deficiency anaemia; ferritin alone can mislead when infection or inflammation is present.
• Treatment starts with oral iron, taken daily or on alternate days; intravenous iron is reserved for late pregnancy, severe anaemia, or failure of oral iron.
• Folate and vitamin B12 deficiencies produce a megaloblastic picture, and women with sickle cell disease or thalassaemia need differentiated pathways, multidisciplinary care, and 5 mg folic acid.

By the end of this page you should be able to:

1. Define anaemia in pregnancy using current international and UK thresholds, and explain why trimester-specific cut-offs exist.
2. Distinguish iron deficiency, iron deficiency anaemia, and anaemia from other causes, and interpret ferritin and transferrin saturation correctly in pregnancy.
3. Plan first-line, second-line and escalation treatment with oral iron, intravenous iron and blood transfusion, including doses, routes and monitoring.
4. Recognise folate and cobalamin deficiency in pregnancy and state the supplementation and treatment required.
5. Summarise antenatal screening and pregnancy management for sickle cell disease and thalassaemia, including when to refer.
6. Adapt investigation and treatment to low-resource settings and to women with haemoglobinopathies.

Anaemia in pregnancy is not simply a low haemoglobin. The circulating blood volume rises more than the red cell mass by the third trimester, so a modest fall in haemoglobin is physiological. Pathological anaemia is present when the haemoglobin falls below the pregnancy reference cut-off, when symptoms or signs are present, or when iron stores are depleted.

Normal pregnancy dilutes the blood. Plasma volume rises more than red cell mass, so a fall in haemoglobin of 0.5 to 1.0 g/dL in the second trimester is expected. This physiological haemodilution is a reason to know the cut-offs, not a reason to ignore them. ^[6]

Current definitions differ slightly between bodies, which matters for screening and audit:

The World Health Organization haemoglobin cut-offs are population-based. ^[6]

UK practice, as captured by the BSH 2020 guideline, is close to this but not identical: it uses Hb under 110 g/L in the first trimester and Hb under 105 g/L in the second and third trimesters, and ferritin is interpreted throughout at less than 30 micrograms/L. ^{[1][5] [6]}

NICE primary care information uses the same broad cut-offs: haemoglobin 110 g/L at first contact and 105 g/L after 12 weeks, with ferritin below 30 micrograms/L indicating early iron depletion that is expected to continue without treatment. ^[12]

Severity is usually described by haemoglobin concentration rather than by cause:

• Mild: 100 to 109 g/L
• Moderate: 70 to 99 g/L
• Severe: less than 70 g/L

These severity bands matter because a moderate or severe anaemia in late pregnancy shortens the time in which oral iron can work. ^[6][7]

A useful diagnostic separation is:

• Iron deficiency: low ferritin (and low transferrin saturation) with or without anaemia.
• Iron deficiency anaemia: iron deficiency plus haemoglobin below the pregnancy cut-off.
• Non-iron deficiency anaemia: haemoglobin below cut-off with normal or high ferritin, or with evidence of haemolysis, haemoglobinopathy, or inflammation.

Iron deficiency in pregnancy begins early and progresses through the third trimester, so women who enter pregnancy with low stores are often anaemic before 28 weeks. ^[8]

Anaemia is common and unevenly distributed. The World Health Organization estimates that more than 40 percent of pregnant women worldwide are anaemic, and over one third have mild anaemia. ^[2] A large case-control comparison in a European population found anaemia prevalence ranging from 17 to 31 percent in Europe and North America, 44 to 53 percent in South-East Asia, and 53 to 61 percent in Africa. ^[9]

Iron deficiency is at least as common as anaemia. Up to 52 percent of pregnant women globally are iron deficient even when not all are anaemic. ^[9] Up to 30 percent of pregnant women in the United Kingdom are affected by iron deficiency anaemia, and it remains a frequent cause of maternal morbidity. ^[4]

The prevalence falls with supplementation but does not disappear: anaemia at delivery is still reported in a notable minority of women in recent UK audits. ^[12]

Causes group into three broad families:

1. Nutritional deficiency, of which iron deficiency is by far the most common. Folate deficiency and cobalamin deficiency are far less common but are the next most likely.
2. Haemoglobinopathies and other inherited red cell disorders, including sickle cell disease and thalassaemia major, intermedia and minor, and other haemoglobin variants.
3. Increased loss or destruction, including malaria, hookworm, schistosomiasis in endemic areas, haemolysis, chronic kidney disease and chronic inflammatory states.

Iron demand rises steeply. About 1000 mg of extra iron is needed in a singleton pregnancy, roughly 6.3 mg per day, and a further 1 mg per day is needed while breastfeeding. ^[4] Few women have enough stored iron to cover this, which is why even well-nourished women can become iron deficient.

Risk factors for iron deficiency anaemia include:

• anaemia before pregnancy or in a previous pregnancy
• multiple pregnancy, short interpregnancy interval, and adolescent pregnancy
• a vegetarian or vegan diet
• low socioeconomic status
• a history of menorrhagia or peripartum haemorrhage
• preeclampsia, in which ferritin behaves as an acute-phase reactant
• a haematocrit below 30 percent at booking ^[6]

For non-iron causes, suspect folate or cobalamin deficiency when the mean cell volume is high or when there is a dietary restriction or malabsorption. Suspect a haemoglobinopathy when the mean cell volume is low with a normal ferritin, or when the history and ethnicity suggest it. ^[8][9]

Iron is absorbed in the duodenum. In pregnancy the body increases absorption, mediated by suppression of hepcidin. Hepcidin is a peptide that blocks intestinal iron export; when it falls, more iron enters the plasma. Oral iron acutely raises hepcidin for up to 48 hours, which is why alternate-day dosing can be absorbed better than divided doses. ^[6]

Iron is also lost to the placenta and fetus, and from any postpartum bleeding.

Folate is absorbed in the jejunum and cobalamin in the terminal ileum after binding to intrinsic factor. Both are required for DNA synthesis and for myelination of the fetal nervous system. Folate needs double in pregnancy because of fetal growth, and cobalamin requirements rise to 2.6 micrograms per day against 2.4 micrograms per day outside pregnancy. ^[8]

Inherited haemoglobinopathies alter the globin chain structure or synthesis. Sickle cell disease and thalassaemia produce chronic haemolysis or ineffective erythropoiesis, and pregnancy adds volume expansion, placental consumption and, in sickle cell disease, vaso-occlusion and placental infarction. ^[10][11]

Most women are found on routine testing before symptoms appear. When symptoms are present they are those of anaemia generally: effort intolerance, palpitations, dizziness, headache, pallor, atrophic glossitis and angular cheilitis. Pica and restless legs are common with iron deficiency. Severe anaemia can produce angina or heart failure, particularly in women with underlying cardiac disease. ^[6][7]

Trimester-specific points:

• Early pregnancy: iron stores at booking predict later anaemia, because maternal iron is consumed by fetal growth and plasma expansion. ^[4]
• Late pregnancy: anaemia discovered after 34 weeks leaves less time to correct it before delivery, and postpartum haemorrhage risk is higher. ^[7]

Megaloblastic anaemia from folate or cobalamin deficiency gives macrocytosis, a falling haemoglobin and sometimes leukopenia or thrombocytopenia. Cobalamin deficiency also produces neuropsychiatric features, including peripheral neuropathy and cognitive change; in severe cases, neurological disease can occur without anaemia. ^[8][9]

Women with sickle cell disease present antenatally with recurrent vaso-occlusive crises, acute chest syndrome, infection, and a higher rate of fetal growth restriction, preterm birth and perinatal loss. ^[10][11]

Anaemia is a laboratory finding, not a diagnosis. The cause is found by combining the indices, the history, and targeted tests.

Thalassaemia trait is a common trap: a low mean cell volume with a normal or high ferritin does not mean iron deficiency, and iron should not be given unless ferritin is low. ^[6][10]

Start with a full blood count and a ferritin level. When anaemia is present and the anaemia is microcytic or normocytic, treat iron deficiency unless there is a known haemoglobinopathy. ^[5][6] The UK guideline approach commended to primary care and maternity services is a trial of oral iron as the first-line diagnostic test in microcytic or normocytic anaemia, with a repeat full blood count in 2 to 3 weeks. ^[1][7]

Interpretation of iron studies in pregnancy:

• Ferritin under 30 micrograms/L indicates iron deficiency at any stage of pregnancy. ^[5][6]
• Ferritin can be falsely normal or high in infection, inflammation or preeclampsia, because it is an acute-phase reactant. ^[6]
• When the ferritin is 30 micrograms/L or higher but iron deficiency is still suspected, a transferrin saturation below 20 percent supports iron deficiency. ^[5][6]
• A full blood count with a normal or raised mean cell volume makes iron deficiency less likely, so ferritin can be checked selectively. ^[12]

Red cell indices on automated counters: most beta-thalassaemia carriers have a mean cell volume under 80 fL and a mean corpuscular haemoglobin under 27 pg, with a relatively high red cell count for the degree of anaemia. ^[10]

Folate and cobalamin:

• Measure serum folate and cobalamin together; folate can mask cobalamin deficiency and cobalamin deficiency raises total homocysteine. ^[8]
• A serum cobalamin concentration below 148 pmol/L (200 ng/L) is taken as cobalamin deficiency, but the result must be interpreted in clinical context. ^[8][9]
• Vitamin B12 deficiency grows more common as pregnancy advances: below 200 pg/mL in about 15 percent of women by 12 weeks, rising to around 42 percent by 33 weeks in cohort studies. ^[9]
• Plasma methylmalonic acid above 0.75 micromol/L almost always indicates cobalamin deficiency, apart from renal disease and small bowel bacterial overgrowth. ^[8]

Haemoglobinopathy screening should be offered to all pregnant women, ideally before 10 weeks. A full blood count, sickling test or solubility test, and haemoglobin electrophoresis or high-performance liquid chromatography are the usual approach. ^[10][11] Where a mother is a carrier, the partner must be screened, and ferritin should also be checked, because iron deficiency can alter the mean cell volume and HbA2 level and lead to a missed thalassaemia trait. ^[6][10]

Anaemia is also tracked with the woman's antenatal schedule. International guidance recommends a full blood count with ferritin at booking, at 24 to 28 weeks, and at any time symptoms suggest anaemia; after delivery, haemoglobin is checked at 48 hours in women with bleeding or symptoms. ^[5]

The system used in the UK and many other programmes classifies iron deficiency anaemia of pregnancy by haemoglobin and by cause:

• Iron deficiency (ferritin below 30 micrograms/L) without anaemia.
• Mild iron deficiency anaemia (haemoglobin 100 to 109 g/L).
• Moderate iron deficiency anaemia (haemoglobin 70 to 99 g/L).
• Severe iron deficiency anaemia (haemoglobin below 70 g/L). ^[5][6]

The combination of severity with gestational age decides how aggressively to treat. Haemoglobin below 8 g/dL (80 g/L) with a gestation of 14 to 32 weeks, and haemoglobin below 100 g/L beyond 32 weeks, are thresholds for considering intravenous iron in more than one guideline. ^{[1][7] [4][6]}

Oral iron is first line in early pregnancy and for mild to moderate anaemia. ^[5][6]

Prevention and treatment doses differ:

• The World Health Organization recommends a prophylactic daily supplement of 30 to 60 mg of elemental iron plus 400 micrograms of folic acid for all pregnant women, combined with healthy-eating advice. ^[2]
• Where anaemia prevalence is below 20 percent, intermittent iron and folic acid with 120 mg elemental iron and 2.8 mg folic acid weekly is an acceptable alternative for women who cannot take daily iron. ^[2]
• Treatment of mild to moderate iron deficiency anaemia uses 60 to 120 mg of elemental iron daily (some local protocols use 80 to 100 mg daily), ideally on an empty stomach with water or a vitamin C source, starting at booking and reassessed at 2 to 4 weeks. ^[6]
• Enteric-coated and sustained-release preparations should be avoided, because most of the iron bypasses the duodenum. ^[7]

Practical guidance, from the UK guideline, is that if oral iron causes nausea or epigastric discomfort, alternate-day dosing or preparations with lower iron content should be tried. Women should be advised that gastrointestinal side effects affect 30 to 50 percent of users and are the main reason for stopping. ^[1][6]

Duration matters as much as dose: continue for at least 3 months after the haemoglobin returns to the normal range, and for at least 6 weeks postpartum, to replenish stores rather than just to correct the anaemia. ^[6]

Intravenous iron is indicated when:

• the pregnancy is beyond 14 weeks and the woman is intolerant of, or does not respond to, oral iron after 2 to 4 weeks of appropriate therapy ^[1][6]
• haemoglobin is below 8.0 g/dL (80 g/L) at 14 to 32 weeks ^[1][6]
• haemoglobin is below 100 g/L beyond 32 weeks ^[1][6]
• anaemia requires optimisation before an anticipated haemorrhage, such as placenta previa or placenta accreta spectrum ^[6]
• postpartum, haemoglobin is below 9.0 g/dL or symptoms are significant ^[6]

Intravenous iron must not be given together with oral iron or in the presence of active infection, it should not be given in the first trimester, and a total cumulative dose of 2000 mg should not be exceeded without a clear indication. ^{[1][6][7] [4]}

High-dose formulations (ferric carboxymaltose and others) allow complete repletion in one or two infusions, which matters when there are only a few weeks before delivery. ^[6]

Red cell transfusion is reserved for women with haemoglobin below 70 g/L without active bleeding, or for clinical signs of haemodynamic compromise. Transfuse the minimum number of units needed, reassess, and add pharmacological iron. ^[6] Each unit of red cells contains about 240 mg of iron, which is not enough to rebuild iron stores, so intravenous iron is considered at the same time. ^{[7] [4]}

Postpartum anaemia is managed on its own terms. Women with mild postpartum anaemia (haemoglobin 90 to 100 g/L) who are stable can take 60 to 120 mg of elemental iron daily for 6 to 12 weeks, and women with moderate to severe anaemia below 90 g/L should be offered intravenous iron. ^[6] A repeat full blood count and ferritin at 4 to 6 weeks confirms recovery. ^[6]

Folate 400 micrograms daily is recommended for all women from the moment they start trying to conceive until 12 weeks of gestation, and for at least the first 12 weeks, to prevent neural tube defects. ^[3][8][11] The World Health Organization uses the same 400 microgram dose. ^[3][7]

Women at higher risk (personal or family history of a neural tube defect, diabetes, epilepsy on anticonvulsants, or a haematological condition such as sickle cell anaemia or thalassaemia) should take 5 mg folic acid daily, continuing when local haemoglobinopathy guidance advises it. ^[11][10]

Treatment of established deficiency depends on severity and cause:

• Folate deficiency: folic acid 5 mg daily until deficiency is corrected. ^[8][11]
• Cobalamin deficiency: parenteral cobalamin (for example hydroxocobalamin injections) is used; oral B12 is only appropriate for dietary deficiency in a compliant patient. ^[8]
• Where neurological disease is present, treat promptly and do not give folate alone, because folate can correct the blood picture while neurology progresses. ^[8]

Although daily folate is universal, vitamin B12 supplementation receives less attention. For women at risk of cobalamin deficiency (vegan or vegetarian diet long term, gastric surgery, inflammatory bowel disease, metformin, proton pump inhibitor use, or tropical sprue), check cobalamin and treat before conception if possible. ^[8][9]

Antenatal screening at 8 to 10 weeks and rechecking the partner means a sickle cell disease or thalassaemia pregnancy is usually identified early. ^[10][11] Management principles:

• Women with sickle cell disease require multidisciplinary care from pre-conception through the postpartum period, with maternal-fetal medicine, haematology and anaesthetics involved. ^[11]
• Folic acid 5 mg daily is continued throughout pregnancy in sickle cell disease and thalassaemia. ^[10][11]
• Iron should not be given unless ferritin is low; many of these women are not iron deficient, and inappropriate iron loading adds to the iron burden of transfusion. ^[6][10]
• Penicillin prophylaxis, vaccination and transfusion planning are continued, and women with vaso-occlusive pain usually need pregnancy-adjusted analgesia. ^[11]
• Blood transfusion is not an automatic part of sickle cell pregnancy care; it is individualised for high-risk women, with extended Rh and Kell matching and cytomegalovirus-negative units. ^[11]
• Women with transfusion-dependent thalassaemia need their usual transfusion schedule, close monitoring of cardiac iron and assessment of chelation, which is often adjusted in pregnancy. ^[10]
• Delivery is usually planned with the haematology team; caesarean section is reserved for obstetric indications rather than for the haemoglobinopathy itself. ^[10][11]

• Recheck haemoglobin 2 weeks after starting oral iron; an appropriate response is a rise of at least 1.0 g/dL. ^[6]
• If there is no response, reconsider the diagnosis: concurrent infection, bleeding, malabsorption, non-adherence, or coexisting folate, cobalamin, or haemoglobinopathy. ^[1][6]
• Restart assessment after delivery and continue iron through the early postpartum weeks to correct anaemia before the next pregnancy. ^[6]

Untreated iron deficiency anaemia is associated with:

• maternal fatigue, depressed mood and reduced lactation ^[6]
• preterm birth (odds ratio 1.63; 95 percent confidence interval 1.33 to 2.01), low birth weight and small-for-gestational-age infants when anaemia occurs in the first or second trimester ^[6]
• severe maternal outcome: maternal anaemia of less than 70 g/L during pregnancy or the postpartum period doubles the risk of death ^{[7] [6]}
• postpartum haemorrhage, which affected 62 percent of women with haemoglobin below 85 g/L in one large UK cohort ^[7]
• impaired fetal neurodevelopment and infant psychomotor outcomes, because iron is needed for myelination ^[6]

For folate deficiency, neural tube defects remain the best known complication, despite modern fortification. For cobalamin deficiency, neurodevelopmental injury and, rarely, intrauterine death can occur. ^[8][9]

For women with sickle cell disease, vaso-occlusive crises, acute chest syndrome, preeclampsia, venous thromboembolism, and higher fetal loss dominate. ^[11]

The prognosis is excellent when the cause is identified and treated in time. Ferritin should return to above 30 micrograms/L, not just the haemoglobin, before discharge from maternity care. ^[6] Postpartum anaemia often resolves with 6 to 12 weeks of oral iron, but women with moderate or severe anaemia, or after major haemorrhage, should be rechecked at 4 to 6 weeks. ^[6]

International and UK practice converges on these points:

• Screen every woman for anaemia with a full blood count at booking and at 28 weeks, and whenever symptoms suggest it. ^[5][12]
• Add ferritin at booking for women with risk factors for iron deficiency; in women with normocytic or microcytic anaemia at any stage, check ferritin. ^[6]
• Advise all pregnant women to eat iron-rich foods with a source of vitamin C, and to separate iron tablets from tea, coffee, milk and antacids. ^[7]
• Women in populations with anaemia prevalence below 20 percent may be offered intermittent rather than daily iron. ^[2]
• Folate 400 micrograms daily should be offered preconception and to the 12th week, or 5 mg for high-risk women, with a haematological condition such as sickle cell anaemia or thalassaemia requiring 5 mg throughout pregnancy. ^[3][10][11]
• Women should be offered healthy-start or low-cost supplements and told how to obtain them. ^[11]

Where resources allow, adding a postpartum full blood count and ferritin at 4 to 6 weeks prevents women leaving maternity care still iron deficient. ^[6]

• Vegetarian or vegan women are at higher risk of folate and cobalamin deficiency; screening and supplementation should start early, and 5 mg folic acid continues for the first trimester. ^[8]
• Women with multiple pregnancy, a very short interpregnancy interval, or a previous postpartum haemorrhage need early ferritin testing and often therapeutic iron doses. ^[6]
• Women with sickle cell disease or thalassaemia are dealt with above; they need specialist care, not just iron. ^[11]
• Immunocompromised women and those on erythropoiesis-stimulating agents are outside the scope of this page and should be managed with haematology.
• Women with diabetes need 5 mg folic acid and have a higher rate of iron deficiency and anaemia. ^[11]

• A full blood count and ferritin are often unavailable; a haemoglobin colour scale, or a reliable haemoglobinometer, is better than nothing, and clinical features should guide referral. ^[10]
• Where iron studies are unavailable, a trial of oral iron for 2 to 4 weeks with reassessment is a reasonable and safe diagnostic test. ^[1][6]
• Treat empirically with elemental iron 60 to 120 mg daily when diet is poor, interpregnancy intervals are short, or infection and hookworm are endemic. ^[6]
• In malaria-endemic areas, routine iron and folic acid should follow the national malaria programme's antenatal protocol, and daily iron should be continued while monitoring infection. ^[2]
• Refer early when haemoglobin is below 70 g/L, breathlessness or heart failure is present, or expected delivery is soon, because transfusion and obstetric capacity may be far away. ^[6]

• Anaemia in pregnancy is defined by trimester-specific haemoglobin cut-offs: 110 g/L in the first and third trimesters, 105 g/L in the second. ^[6]
• Iron deficiency is the commonest cause; ferritin below 30 micrograms/L is the best single marker, but it can be falsely normal in inflammation.
• Pregnancy increases iron demand to roughly 1000 mg, which is why prophylactic 30 to 60 mg elemental iron is recommended for all pregnant women.
• First-line treatment of iron deficiency anaemia is oral iron 60 to 120 mg elemental iron daily, with reassessment at 2 weeks and continuation for 3 months after correction. ^[6]
• Intravenous iron is used after 14 weeks for intolerance, non-response, severe anaemia (below 8 g/dL), or late presentation beyond 34 weeks (haemoglobin below 100 g/L); it must not be given in the first trimester and cumulative dose must stay below 2000 mg. ^[4][6]
• Red cell transfusion is reserved for haemoglobin below 70 g/L or haemodynamic compromise.
• Folate 400 micrograms daily (5 mg for high risk) prevents neural tube defects; cobalamin needs rise to 2.6 micrograms daily in pregnancy and deficiency can injure mother and fetus.
• Sickle cell disease and thalassaemia require multidisciplinary care, continued 5 mg folic acid, and avoidance of unnecessary iron.
• Postpartum haemoglobin below 70 g/L doubles the risk of maternal death, so correction before delivery is the central aim.

Iron deficiency anaemia; megaloblastic anaemia; sickle cell disease; thalassaemias; antenatal care; normal ranges in pregnancy; postpartum haemorrhage; transfusion medicine.