From trimester-based hemoglobin thresholds to ferritin interpretation, from oral elemental iron dosing (including every other day regimen) to intravenous iron indications in the second-third trimester; A current evidence-based clinical review in the diagnosis and management of anemia of pregnancy.
⚕️ Target audience: This clinical review is intended for physicians and healthcare professionals; It is a summary of current literature and guidelines for educational purposes. Clinical decisions should be made based on patient-specific evaluation and applicable institutional protocols.
Anemia is defined as a decrease in erythrocyte mass or hemoglobin (Hb) concentration and is the most common hematological abnormality in pregnancy (ACOG Practice Bulletin No. 233, 2021). Diagnostic thresholds in pregnancy differ from those in the non-pregnant adult; because the physiological increase in plasma volume dilutes the Hb concentration. The World Health Organization (WHO) updated the hemoglobin thresholds in 2024, especially revising the second trimester value, but preserved the basic threshold structure in pregnancy (WHO 2024 revised thresholds; summary compilation PMID 38910369). The current definition is based predominantly on data in non-pregnant women and varies by trimester (table 1).
ACOG and the US Centers for Disease Control and Prevention (CDC) define anemia in pregnancy as Hb <11 g/dL (hematocrit <33%) in the first and third trimesters and Hb <10.5 g/dL (hematocrit <32%) in the second trimester (ACOG PB 233, 2021; CDC). The threshold in the postpartum period is Hb <10 g/dL (UK/WHO compliant) (UpToDate, "Anemia in pregnancy", 2026). Thresholds that were historically differentiated by race have now been abandoned; The same standard is applied to all pregnant women to reduce disparities (ACOG PB 233, 2021; CDC).
| Period | Hemoglobin threshold | Approximate hematocrit |
|---|---|---|
| 1st trimester | <11 g/dL | <33% |
| 2nd trimester | <10.5 g/dL | <32% |
| 3rd trimester | <11 g/dL | <33% |
| Postpartum | <10 g/dL | <30% |
Epidemiologically, anemia is a global health problem. According to WHO 2019 data, the prevalence of anemia during pregnancy varies significantly by region: Southeast Asia 48%, Africa 46%, Eastern Mediterranean 37%, Europe 24% and the Americas 19% (WHO; UpToDate 2026). In a report based on NHANES data in the USA in 2026, the prevalence of anemia in pregnant women was found to be 9.6% (95% CI 6.5-12.6), iron deficiency anemia was found to be 6.9%, and iron deficiency accounted for approximately 72% of all anemias (UpToDate 2026). Approximately 30% of women of reproductive age are anemic, and the overwhelming majority of anemias worldwide are due to iron deficiency—iron deficiency anemia is the most common type of anemia globally (ACOG PB 233, 2021; UpToDate 2026).
Anemia is not just a laboratory finding; More severe maternal anemia in the study covering more than 18 million pregnancies; It has been associated with an increased risk of placental abruption, preterm birth, postpartum hemorrhage, maternal shock, and intensive care admission (UpToDate 2026). Each gradual decrease in hemoglobin correlates with an increase in the adjusted relative risk for serious neonatal morbidity and mortality (UpToDate 2026).
The two main causes of anemia in pregnancy are physiological (dilutional) anemia and iron deficiency; these two explain the vast majority of low Hb values (UpToDate 2026). In physiological anemia, plasma volume increases by 10–15% at 6–12 weeks of gestation, expands rapidly until 30–34 weeks, and plateaus at term; Total plasma volume at term is 40-50% higher than before pregnancy. Erythrocyte mass also increases, but to a lesser extent (~15-25%). The result is typically mild anemia (Hb 10-11 g/dL); There is no single Hb value to distinguish physiological anemia from other causes, and physiological anemia is a diagnosis of exclusion (UpToDate 2026).
Iron deficiency is the most common pathological cause of anemia in pregnancy. Iron requirements increase dramatically during pregnancy: a pregnant woman weighing approximately 55 kg requires approximately 1 gram of additional elemental iron during pregnancy (300-350 mg for fetus and placenta, 500 mg for maternal erythrocyte mass expansion, ~250 mg for blood loss at birth) (UpToDate 2026). While daily iron demand is 1-2 mg/day in the first trimester, it increases to 4-5 mg/day in the second trimester and ~6 mg/day in the third trimester. Losses from previous pregnancies and menstruation, short interpregnancy intervals, inadequate diet and malabsorption (celiac disease, bariatric surgery, inflammatory bowel disease, pregnancy nausea and vomiting) predispose to iron deficiency (UpToDate 2026).
Causes other than iron deficiency are much less common in pregnancy, but should not be overlooked (table 2): hemoglobinopathies (thalassemia, sickle cell disease), erythrocyte membrane disorders (hereditary spherocytosis), folate deficiency (the most common cause of megaloblastic anemia in pregnancy), vitamin B12 deficiency (gastrectomy, Crohn's, Roux-en-Y bypass history), autoimmune hemolytic anemia, hypothyroidism and chronic kidney disease (UpToDate 2026). For folate intake, 400-800 mcg/day is recommended for all pregnant women, starting at least one month before conception; 1 mg/day is appropriate for documented folate deficiency, and 4 mg/day is appropriate for a previous pregnancy with neural tube defect (UpToDate 2026).
Screening for anemia in pregnancy is universally accepted. All pregnant women should be screened for anemia with a complete blood count (CBC) at the first prenatal visit and have CBC repeated at 24–28 weeks of pregnancy (ACOG PB 233, 2021; UpToDate 2026). Every pregnant woman with anemia should be evaluated for the cause; The most likely cause is iron deficiency.
The critical point is that CBC alone is insufficient to screen for or exclude iron deficiency, because anemia and microcytosis are late signs of iron deficiency. In an analysis of more than 17,000 pregnant women, Hb <11 g/dL or low MCV (<80 fL) in the first trimester had only 30% sensitivity in detecting iron deficiency (defined by ferritin <30 ng/mL); Approximately half of pregnant women with iron deficiency who underwent ferritin testing had neither anemia nor microcytosis (UpToDate 2026). The prevalence of iron deficiency in pregnancy can increase from 21% (week 15) to 84% (week 33), depending on the ferritin threshold used and the week of gestation (UpToDate 2026).
Therefore, iron deficiency screening is increasingly recommended in all pregnant women, even if not anemic: the 2023 FIGO statement, the 2024 European Hematology Association (EHA) guideline and the Australian HOW Collaborative consensus recommend iron deficiency screening (UpToDate 2026). In contrast, ACOG PB 233 (2021) addresses anemia screening only; It does not mention screening for iron deficiency. The US Preventive Services Task Force (USPSTF) 2024 report concluded that the evidence for screening for iron deficiency anemia in asymptomatic pregnant women is insufficient, but emphasized that this is not a recommendation against screening (UpToDate 2026). This is a current point of debate (see below).
Mean erythrocyte volume (MCV) and other CBC findings guide the differential diagnosis in an anemic pregnant woman (table 2). Microcytosis (MCV <80 fL) is suggestive of iron deficiency or thalassemia; However, the absence of microcytosis does not exclude iron deficiency, nor does it prove its presence (UpToDate 2026). Macrocytosis (MCV >100 fL) suggests B12 or folate deficiency or reticulocytosis due to hemolysis. Accompanying thrombocytopenia/neutropenia may indicate a bone marrow problem or thrombotic microangiopathy. Because iron deficiency may mask B12/folate-induced macrocytosis, the absence of macrocytosis is not sufficient to exclude these deficiencies if there is clinical suspicion (UpToDate 2026).
| MCV finding | Highlights | Priority test(s) |
|---|---|---|
| Microcytic (<80 fL) | Iron deficiency, thalassemia | Ferritin (±TSAT); Hb electrophoresis in doubt |
| Normocytic (80-100 fL) | Early iron deficiency, physiological anemia, CKD | Ferritin, reticulocyte; physiological = diagnosis of exclusion |
| Macrocytic (>100 fL) | B12/folate deficiency, hemolysis (reticulocytosis) | B12, folate, reticulocyte count |
Serum ferritin alone is sufficient to diagnose iron deficiency in most pregnant women without comorbidities (UpToDate 2026):
Oral iron may falsely normalize TSAT by increasing serum iron (effect peaks ~4 hours after oral dose); Therefore, iron parameters should be taken after 5-9 hours of fasting (UpToDate 2026). Screening for hemoglobinopathy is important to identify pregnant women whose children may be at risk for a hereditary hemoglobinopathy.
All pregnant women are recommended 27-30 mg of oral elemental iron (“low-dose” supplementation) daily throughout pregnancy to meet the increased iron demand; this corresponds to the amount of iron in most iron-containing prenatal vitamins and is consistent with CDC and ACOG recommendations (ACOG PB 233, 2021; CDC; UpToDate 2026). For those who cannot tolerate the iron in a prenatal vitamin, taking an iron-free prenatal vitamin and taking oral iron every other day (typical dose 60 mg every other day; or Monday-Wednesday-Friday) is an option (UpToDate 2026).
High-quality evidence on the benefit of prophylaxis is difficult to obtain. A 2024 Cochrane review of 57 studies (Finkelstein et al., CD004736.pub6) reported that daily iron supplementation reduced maternal anemia and iron deficiency at term, but there was little difference in other maternal and infant outcomes or the evidence was uncertain (Cochrane 2024, PMID 39145520). The USPSTF 2015 review similarly stated that routine prophylaxis may improve maternal hematological indices, but the evidence for clinical outcomes is insufficient (UpToDate 2026).
The standard treatment for uncomplicated iron deficiency (regardless of Hb level) is to give a higher dose of iron than is contained in the prenatal vitamin. Oral iron is preferred in most pregnant women diagnosed in the first trimester and who tolerate oral iron; It is cheap, easily accessible, and effective when tolerated. The recommended oral dose of elemental iron is in the range of 40-200 mg/day (UpToDate 2026; Ferrous sulfate is the most commonly used formulation).
Two important trends have emerged in recent years: (1) the use of doses at the lower end of this range and (2) alternate-day dosing. It is understood that higher and more frequent doses may increase side effects without increasing iron intake. UpToDate authors often recommend applying 60 mg of elemental iron every other day (or Monday-Wednesday-Friday) (UpToDate 2026). The physiological basis for this approach is hepcidin: after an iron dose, hepcidin increases and suppresses iron absorption for the next 24 hours; With alternate day dosing, hepcidin returns to baseline within 48 hours. In two open-label randomized studies by Stoffel et al., single dosing every other day significantly increased cumulative fractional iron absorption compared to sequential daily dosing (21.8% vs. 16.3%; p=0.0013) (Stoffel et al., Lancet Haematol 2017, PMID 29032957).
The main disadvantage of oral iron is gastrointestinal side effects (metallic taste, gastric irritation, nausea, diarrhea, constipation); Constipation is exacerbated by progesterone slowing down intestinal transit and the pressure of the growing uterus on the rectum. Up to 70% of those prescribed oral iron report significant gastrointestinal discomfort (UpToDate 2026). Absorption can be improved by avoiding coffee, tea and milk during iron intake. Enteric-coated or slow-release formulations are not recommended (Ferro-Sequels, Slow-Fe) because the coating may reduce absorption in the distal duodenum and proximal jejunum (UpToDate 2026). With antenatal treatment, Hb level begins to rise in approximately two weeks (new erythrocyte production time).
IV iron is used in cases of oral iron intolerance, severe anemia (especially later in pregnancy), and failure of oral iron to raise Hb and/or ferritin (UpToDate 2026). IV iron is not used in the first trimester because safety data for first-trimester use are lacking; it may be started after 13–14 weeks (UpToDate 2026). By contrast, IV iron is considered safe and effective during the second and third trimesters; compared with oral iron, the rate of side effects is much lower and serious adverse events are negligible.
All IV iron products demonstrate similar safety and efficacy; the choice is based on cost and administration burden (Table 3). Modern formulations such as ferric carboxymaltose offer the advantage of complete replacement in a single infusion. In a randomized trial conducted in Malawi (REVAMP), a single dose of ferric carboxymaltose (20 mg/kg, up to 1000 mg) in the second trimester significantly reduced rates of iron deficiency compared with standard oral iron, but the reduction in anemia prevalence did not reach statistical significance at all time points (UpToDate 2026; Mzembe/Pasricha et al., PMID 39577976; ferric carboxymaltose RCT in late pregnancy, Nat Med 2025, PMID 39762420). In a meta-analysis, IV iron resulted in higher post-treatment Hb (weighted mean difference on admission for delivery 0.66 g/dL; 95% CI 0.31–1.02) and fewer side effects than oral iron, while neonatal birth weight (mean difference 69 g) and neonatal ferritin levels were higher in the IV iron group (UpToDate 2026).
Formulations containing benzyl alcohol (e.g. ferric gluconate preparation Ferrlecit) are avoided due to potential risk to the fetus; Additionally, iron sucrose is not preferred over single-dose formulations due to its administration schedule requiring four to five separate infusions (UpToDate 2026). IV iron is preferred because oral iron is ineffective in patients with a history of inflammatory bowel disease and bariatric surgery (Roux-en-Y, biliopancreatic diversion) (UpToDate 2026).
| Feature | Oral iron | Intravenous iron |
|---|---|---|
| Dose | Prophylaxis 27-30 mg/day; Treatment 40-200 mg/day elemental (frequently 60 mg every other day) | Ferric carboxymaltose 20 mg/kg, maximum 1000 mg in a single dose |
| Trimester | In each trimester; Preferred route in the 1st trimester | NOT for use in the 1st trimester (no safety data); after 13–14 weeks |
| Main indication | Most pregnant women who tolerate it; first-line | Oral intolerance, severe/late anemia, oral unresponsiveness, malabsorption (IBD, bariatric surgery) |
| Side effect | Gastrointestinal (up to 70%); reduces adherence | Fewer side effects; Serious adverse events are negligible |
| Response speed | Hb begins to rise in ~2 weeks | Faster; Complete replacement with a single infusion |
Erythrocyte transfusion is not necessary for mild symptoms of anemia. Transfusion is reserved for those with significant symptoms due to severe anemia or for those for whom transfusion is indicated for other reasons (UpToDate 2026). Transfusion and/or specialist (hematology) referral may be appropriate in pregnant women with severe anemia where a two-week response delay will cause significant morbidity (UpToDate 2026).
First trimester: Oral iron is the preferred route; IV iron is not used because there is no safety data. It is ideal to correct iron deficiency before the third trimester; because iron-dependent neurogenesis and fetal brain development are most intense in the third trimester and early neonatal life (UpToDate 2026).
Second-third trimester: IV iron (after 13-14 weeks) is considered safe; It is preferred especially in cases of oral intolerance or malabsorption, when there is not enough time for oral iron repletion after the 30th week. Some experts turn to IV iron in the second half of pregnancy out of concern that oral iron may not provide enough iron to the developing fetus (UpToDate 2026).
Comorbidities: Oral iron absorption is impaired in pregnant women with inflammatory bowel disease, bariatric surgery (Roux-en-Y, biliopancreatic diversion), celiac disease, and gestational hyperemesis; IV iron is recommended in these populations (UpToDate 2026). TSAT is critical in interpretation as ferritin can increase with inflammation up to 100 ng/mL in chronic kidney disease.
B12 and folate: About half of those who undergo bariatric surgery (especially Roux-en-Y) develop B12 deficiency; B12 monitoring and supplementation is required in these pregnant women (UpToDate 2026).
Correction of iron deficiency before birth is important for tolerance to peripartum blood loss and reducing the risk of postpartum anemia; It is associated with the risk of anemia, postpartum bleeding and transfusion (UpToDate 2026). The threshold for postpartum anemia is Hb <10 g/dL. Response to treatment is assessed by Hb elevation approximately two weeks after antenatal iron initiation; if response is inadequate, compliance, absorption, and alternative diagnoses (ongoing blood loss, B12/folate deficiency, hemoglobinopathy) should be reconsidered (UpToDate 2026).
As a surveillance strategy, one protocol screened for iron deficiency in the second and third trimesters; Oral iron was administered for Hb 9.5-11 g/dL, IV iron was administered for Hb <9.5 g/dL; This protocol provided higher Hb at birth but did not show a statistically significant reduction in blood product use (UpToDate 2026).
This section summarizes primary randomized evidence expanding the indications for intravenous (IV) iron therapy beyond the date of publication of the current guideline (2024–2026). The general framework has not changed; However, concrete data is accumulating regarding the earlier introduction of IV iron in selected moderate and even non-anemic iron deficiency.
In the RAPIDIRON study (Derman et al., AJOG 2025; PMID 39909327), conducted at 4 centers in India, 4,368 pregnant women with moderate iron deficiency anemia (Hb 7.0–9.9 g/dL) in the 2nd trimester (14–17 weeks) were compared for oral ferrous sulfate (60 mg×2) versus single-dose IV ferric carboxymaltose (FCM) or ferric derisomaltose (FDM). Single-dose IV FCM significantly reduced low birth weight (25.2% versus oral 29.3%; RR 0.87; 97.55% CI 0.75–0.99; p=0.017); No difference was seen in FDM. Achieving a non-anemic state without the need for additional IV iron/transfusion was significantly increased in both IV arms (FCM RR 1.24; FDM RR 1.25; p<0.0001). The authors recommend that guidelines consider single-dose IV iron as the primary treatment for moderate iron deficiency anemia. This finding does not invalidate the REVAMP/Pasricha (Malawi) data in the current guidance; It is complementary evidence with a larger sample size and positive results in low birth weight.
In a two-arm RCT conducted in Lahore (Wasim et al., Lancet Haematol 2026;13(1):e22–e29; PMID 41482443), 600 pregnant women diagnosed with non-anemic iron deficiency (Hb 11–13 g/dL + ferritin <30 µg/L) at the first antenatal visit received 1000 mg IV iron in addition to routine oral prophylaxis. Prenatal maternal Hb was significantly higher than with oral prophylaxis alone (11.6 vs 10.8 g/dL; mean difference 0.74 g/dL; 95% CI 0.64–0.85; p<0.0001); cord blood ferritin was also higher in the IV arm. However, neonatal clinical outcomes were not different between groups and no serious adverse events were observed. The accompanying editorial (Lancet Haematol 2026) discussed a re-evaluation of ferritin screening in early pregnancy—which adds new RCT evidence directly to the guideline discussion of “screening in the nonanemic pregnant woman.”
In secondary analysis of RAPIDIRON (Somannavar et al., J Matern Fetal Neonatal Med 2026; PMID 42045095), IV iron at 26–30 weeks corrected all erythrocyte indices more rapidly than oral iron (MCV +2.87–3.02 fL; reticulocyte Hb equivalent Ret-He +1.31–1.32); The differences closed on the 42nd postpartum day. Ret-He and immature reticulocyte fraction are early-sensitive indicators of treatment response, in addition to the "Hb rises in 2 weeks" information. Two meta-analyses published in 2025 were in the same direction: in one (6 studies, n=3,842) IV iron increased maternal Hb (MD +1.21 g/dL; 95% CI 0.83–1.59; p<0.001) and was superior in correcting anemia (OR 2.47; 95% CI 1.69–3.61); the other concluded that the maternal hematological gain was clear, while the solid neonatal clinical benefit was not yet proven.
Guideline status (confirmation): ACOG Practice Bulletin No. 233 (2021), reaffirmed in 2024; There is no new replacement bulletin in 2025–2026—ACOG references to existing guidance remain current and valid. USPSTF 2024 “evidence insufficient (I statement)” decision based on systematic review of 17 RCTs and 24,023 participants (PMID 39163033): supplementation reduces maternal iron deficiency and anemia at term, but showed no significant effects on GDM, hypertensive disorders, cesarean section, preterm birth, low birth weight, and SGA.
Practical summary: The “oral intolerance alone, severe/late anemia or malabsorption” framework for IV iron expands after RAPIDIRON — can be considered as first line in selected moderate anemia, maternal haematological gain has been demonstrated in non-anaemic iron deficiency; The benefit of neonatal hard outcome is not yet clear.
Last updated: . Guide numbers and publication years have been verified against current catalogues.