Highlights
- A nationwide U.S. cohort study (2018-2023) reveals an anemia prevalence of 25.6% during pregnancy, with a dramatic increase from the first trimester (4.3%) to mid-pregnancy (24.5%).
- First-trimester iron deficiency without anemia (IDWA), defined as ferritin <30 ng/mL despite normal hemoglobin, is a potent predictor of progression to iron deficiency anemia (IDA), affecting one in four individuals.
- Anemia is a major risk factor for Severe Maternal Morbidity (SMM), particularly in patients with comorbid cardiac disease or those undergoing Cesarean hysterectomy.
- Intravenous ferric carboxymaltose has been identified as a cost-effective strategy for correcting prepartum anemia, potentially averting thousands of cases of postpartum hemorrhage.
Background
Anemia during pregnancy remains one of the most prevalent and modifiable risk factors for adverse maternal and neonatal outcomes. While the physiological expansion of plasma volume naturally lowers hemoglobin concentrations—a process known as hemodilution—pathological anemia, primarily driven by iron deficiency, poses significant threats. Historical data in the United States have often relied on selective sampling or administrative codes that lack the sensitivity of laboratory-based diagnosis. Recent longitudinal data from 2018 to 2023 suggest that the burden of anemia is significantly higher than previously estimated, transforming the clinical perception of this condition from a routine nutritional concern to a major public health and population health crisis.
Key Content
National Prevalence and Trimester-Specific Trends
In a landmark analysis of a U.S. nationwide cohort of commercially insured individuals (Igbinosa et al., 2026), the prevalence of anemia was found to be 25.6% (95% CI, 25.3-25.9%). The study utilized trimester-specific standards for hemoglobin and hematocrit, revealing a stark progression: only 4.3% of individuals were anemic at the initiation of prenatal care (4 to <14 weeks), but this rose to 24.5% by mid-pregnancy (22 to <30 weeks). These findings suggest that current screening and supplementation strategies may be failing to keep pace with the increasing iron demands of the second and third trimesters.
The Spectrum of Iron Deficiency: IDWA to IDA
Recent research has focused on the pre-anemic state known as Iron Deficiency Without Anemia (IDWA). A prospective study (Leonhard et al., 2026) demonstrated that 25% of individuals are iron-deficient (ferritin <30 ng/mL) in the first trimester despite having normal hemoglobin levels. Critically, 67% of those with IDWA progressed to overt IDA before delivery, representing a nearly two-fold increased risk compared to iron-replete individuals (aRR 1.91). This evidence supports the emerging clinical consensus that ferritin screening at the first prenatal visit may be necessary to identify those at risk for progressive depletion.
High-Risk Populations and Comorbidities
Anemia does not exist in isolation; its impact is magnified by other clinical conditions:
- Cardiac Disease: In patients with underlying cardiac conditions, anemia is associated with a significantly higher risk of SMM and mortality (aRR 1.90 for mWHO Class I-II disease).
- Bariatric Surgery: Post-bariatric surgery pregnancies require specialized care. While bariatric surgery reduces risks of macrosomia and preeclampsia, it complicates nutritional status. Roux-en-Y gastric bypass (RYGB) is associated with higher miscarriage risks compared to sleeve gastrectomy (SG), though both require intensive monitoring for anemia.
- Eating Disorders: Maternal eating disorders (ED) are associated with a nearly three-fold increase in anemia risk (aOR 2.8) and higher rates of preterm labor and uterine rupture.
Maternal and Neonatal Outcomes
Severe anemia is a known risk marker for short-term Major Adverse Cardiovascular Events (MACE), particularly pulmonary edema following postpartum hemorrhage (PPH). Furthermore, global data from India and Sri Lanka suggest a U-shaped relationship where both low and abnormally high hemoglobin levels correlate with adverse birth outcomes like low birth weight and small-for-gestational-age infants. At the neonatal level, advanced modeling such as NeonatalBERT is now being used to predict morbidities, including neonatal anemia, from unstructured clinical notes, underscoring the long-term developmental implications of maternal iron status.
Technological and Therapeutic Advances
From a therapeutic perspective, the cost-effectiveness of iron replacement has been rigorously evaluated. A Markov decision-analytic model found that treating prepartum anemia with intravenous ferric carboxymaltose is a dominant strategy, offering superior efficacy and cost-savings compared to oral iron or no treatment. It is estimated that optimized iron therapy could avert nearly 27,000 cases of PPH and hundreds of peripartum hysterectomies per 3.8 million pregnancies in the U.S.
Expert Commentary
The shift toward recognizing IDWA as a clinical priority represents a significant evolution in obstetric hematology. Experts argue that relying solely on hemoglobin levels ignores the early stages of iron depletion, which are more easily corrected. There is an ongoing controversy regarding the “universal ferritin screening” vs. “risk-based screening” approach. However, given that one in four commercially insured individuals in the U.S. enters mid-pregnancy with anemia, the threshold for screening and intravenous iron intervention is lowering. Clinicians should also account for social vulnerability; spatial analyses indicate that high anemia prevalence often clusters in areas with higher Social Vulnerability Indices (SVI), suggesting that biological risk is exacerbated by structural inequities.
Conclusion
Anemia during pregnancy is a pervasive and escalating health issue in the United States, affecting over one-quarter of the pregnant population. The transition from iron deficiency without anemia in early pregnancy to overt iron deficiency anemia by the third trimester provides a critical window for intervention. Future clinical practice should prioritize early ferritin screening, aggressive iron replacement—particularly in high-risk cardiac and bariatric cohorts—and the utilization of cost-effective intravenous therapies to mitigate the substantial risks of severe maternal morbidity and adverse neonatal outcomes.
References
- Igbinosa II, et al. Anemia During Pregnancy in a U.S. Nationwide Cohort, 2018-2023. Obstet Gynecol. 2026. PMID: 41886759.
- Leonhard SA, et al. The association between first trimester iron deficiency without anemia and the development of iron-deficiency anemia prior to childbirth. Am J Obstet Gynecol. 2026. PMID: 41864313.
- MACEPH Study Group. Short-Term Major Adverse Cardiovascular Events Following Postpartum Haemorrhage. BJOG. 2026. PMID: 41572582.
- Cost-Effectiveness of Oral versus Intravenous Iron for Anemia in Pregnancy. Am J Perinatol. 2026. PMID: 38290553.
- Maternal and neonatal outcomes among pregnant women with eating disorders. J Perinat Med. 2026. PMID: 41782583.
