Final Recommendation Statement
Iron Deficiency and Iron Deficiency Anemia During Pregnancy: Screening and Supplementation
August 20, 2024
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Table of Contents |
---|
The US Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without obvious related signs or symptoms to improve the health of people nationwide.
It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.
The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.
The USPSTF is committed to mitigating the health inequities that prevent many people from fully benefiting from preventive services. Systemic or structural racism results in policies and practices, including health care delivery, that can lead to inequities in health. The USPSTF recognizes that race, ethnicity, and gender are all social rather than biological constructs. However, they are also often important predictors of health risk. The USPSTF is committed to helping reverse the negative impacts of systemic and structural racism, gender-based discrimination, bias, and other sources of health inequities, and their effects on health, throughout its work.
The aim of routine screening or iron supplementation for treatment of iron deficiency and iron deficiency anemia during pregnancy is to improve maternal and infant health outcomes. Iron deficiency is the leading cause of anemia during pregnancy.1 According to National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2006, overall estimated prevalence of iron deficiency during pregnancy is near 18% and increases across the 3 trimesters of pregnancy (from 6.9% to 14.3% to 28.4%).2 An estimated 5% of pregnant persons have iron deficiency anemia.1,2 In the US, there are disparities in prevalence of iron deficiency anemia by race, ethnicity, and social factors (eg, socioeconomic status, nutritional status, and food insecurity).1,2
Due to lack of available data, the USPSTF concludes that the current evidence is insufficient, and the balance of benefits and harms of screening for iron deficiency and iron deficiency anemia in asymptomatic pregnant persons on maternal and infant health outcomes cannot be determined (I statement).
Due to lack of available data, the USPSTF concludes that the current evidence is insufficient, and the balance of benefits and harms of iron supplementation in asymptomatic pregnant persons on maternal and infant health outcomes cannot be determined (I statement).
See Table 1 for more information on the USPSTF recommendation rationale and assessment. For more details on the methods the USPSTF uses to determine the net benefit, see the USPSTF Procedure Manual.3
Patient Population Under Consideration
This recommendation applies to asymptomatic pregnant adolescents and adults. This recommendation does not apply to pregnant persons who are severely malnourished, have symptoms of iron deficiency or iron deficiency anemia, or have specific hematologic conditions (eg, sickle cell anemia) or nutritional deficiencies that may increase their need for iron.
Definitions
Iron is necessary for production of hemoglobin, an essential protein in blood required to transport oxygen throughout the body. Iron is also necessary for the production of additional proteins that are vital to various metabolic pathways.4 Iron deficiency refers to depletion of iron stores and may progress to iron deficiency anemia.1 Increased demands for iron during pregnancy enhances vulnerability to iron deficiency and iron deficiency anemia.1 While iron deficiency is a leading cause of anemia, other conditions may also cause anemia. Screening for iron deficiency and iron deficiency anemia often includes measurement of hematologic indices (eg, hemoglobin level or hematocrit as proxies of iron deficiency anemia), and an abnormal screening test result may be followed by treatment with iron therapy.1 To establish the presence of iron deficiency or iron deficiency anemia, levels of iron biomarkers (eg, ferritin) may be measured, although there is no consensus on the exact ferritin level that is indicative of iron deficiency.1 Supplementation refers to routine provision of low-dose supplemental iron or intake of iron-fortified foods without specifically measuring hematologic indices.1
Suggestions for Practice Regarding the I Statements
In deciding whether to screen or supplement for iron deficiency with or without anemia during pregnancy, clinicians caring for pregnant persons should consider the following.
Potential Preventable Burden
The overall prevalence of iron deficiency anemia is uncertain due to the absence of universally accepted cutoffs in surveillance systems, older data, and use of hematologic indices as proxies rather than iron biomarkers to assess iron deficiency.2,5 It is known, however, that the prevalence increases through pregnancy.1 Based on recent survey data, Black and Mexican American pregnant persons are disproportionately affected by iron deficiency anemia in pregnancy, with social determinants of health as possible contributors to these disparities.1,2 However, factors such as nutritional status, food insecurity, or access to health care were not reported in the survey data.1,2
The USPSTF found limited evidence on current methods, including questionnaires and risk prediction tools, to identify pregnant persons at increased risk for iron deficiency with or without anemia. Commonly cited risk factors include a diet low in iron-rich foods (eg, vegan diet with inadequate sources of iron), gastrointestinal conditions or medications that can decrease iron absorption (eg, antacids), or a short interval between pregnancies.1 Tobacco use and living at a high altitude may affect hematologic indices and interpretation of test results due to increases in hematocrit and hemoglobin values.1 The evidence review identified 3 studies reporting strategies to predict iron deficiency or iron deficiency anemia during pregnancy.1 Generally, in all 3 studies,6-8 evidence was insufficient to evaluate the accuracy of risk prediction tools.1
Potential Harms
Potential screening approaches to identify asymptomatic pregnant persons with iron deficiency or iron deficiency anemia are unlikely to cause serious harms, but evidence is limited. For example, reviewed evidence did not report risk of iron overload.1 Common adverse effects of iron supplementation or treatment include gastrointestinal tract symptoms such as nausea, constipation, abdominal pain, and vomiting.1
Current Practice
The USPSTF found limited evidence on current practices of screening and supplementation to prevent adverse maternal or infant health outcomes from iron deficiency or iron deficiency anemia. Clinical practice guidelines on screening and supplementation vary (see the Recommendations of Others section for additional information).1,9 However, screening and supplementation are common. For screening, a surveillance report among Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) participants reported that more than one-half of enrolled pregnant persons (53%) underwent hemoglobin testing during their first trimester in 2018.1,10 There may be other reasons that clinicians measure hematologic indices, such as to prepare for cesarean delivery or anticipated blood loss during delivery. There is evidence for racial and ethnic disparities in screening rates. In a US study11 (n = 268,594) of Medicaid recipients across 4 states, Asian/Pacific Islander, Black, and Hispanic participants were less likely to receive a complete blood cell count in 3 of 4 states surveyed compared with White participants (raw odds ratios [ORs], 0.51 to 0.92).1 For supplementation, according to NHANES data from 1996 to 2006, many pregnant persons (77%) reported using a supplement, often containing iron, within the previous 30 days.1,12 Use of iron supplements may differ by race, geography, and social factors.1 For example, in a study using NHANES survey data from 1999 to 2010, pregnant persons who were food insecure had lower mean iron intake from supplements compared with pregnant persons who were food secure.1,13 Pregnant persons may be screened (eg, with measurement of hematologic indices in the first trimester) and supplemented (eg, with prenatal vitamins) concurrently.
Additional Tools and Resources
The Centers for Disease Control and Prevention includes resources on perinatal quality collaboratives (https://www.cdc.gov/maternal-infant-health/pqc/index.html), including state collaborative toolkits, such as the California Maternal Quality Care Collaborative toolkit on improving the health care response to obstetric hemorrhage (https://www.cmqcc.org/resources-tool-kits/toolkits/ob-hemorrhage-toolkit).
The National Institutes of Health’s Office of Dietary Supplements provides a fact sheet on iron for consumers in English (https://ods.od.nih.gov/factsheets/Iron-Consumer/) and Spanish (https://ods.od.nih.gov/factsheets/Iron-DatosEnEspanol/) and for clinicians (https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/).
The US Department of Health and Human Services’ Office on Women’s Health provides a fact sheet about iron deficiency anemia for patients (https://www.womenshealth.gov/a-z-topics/iron-deficiency-anemia).
Other Related USPSTF Recommendations
The USPSTF has issued separate recommendations on screening for iron deficiency anemia in children aged 6 to 24 months14 and folic acid supplementation to prevent neural tube defects in persons who plan to or could become pregnant.15
This recommendation is consistent with the 2015 recommendation statement on screening and supplementation for iron deficiency anemia in pregnancy. In 2015, the USPSTF concluded that the current evidence was insufficient to assess the balance of benefits and harms of screening for iron deficiency anemia in pregnant women to prevent adverse maternal health and birth outcomes (I statement).16 The USPSTF also concluded that the current evidence was insufficient to assess the balance of benefits and harms of routine iron supplementation for iron deficiency anemia in pregnant women to prevent adverse maternal health and birth outcomes (I statement).16
Scope of Review
The USPSTF commissioned a systematic review1,17 to update its 2015 recommendation on screening and supplementation for iron deficiency anemia during pregnancy. In this current recommendation, the USPSTF broadened its review to include iron deficiency without anemia; it reviewed evidence on the benefits and harms of screening and supplementation for iron deficiency with and without anemia on maternal and infant health outcomes in asymptomatic pregnant persons. To assist with efforts to generalize the evidence to an asymptomatic US pregnant population, the USPSTF considered studies conducted in settings similar to the US (ie, categorized as “high” or “very high” on the United Nations Human Development Index). In addition, to address critical gaps in the evidence identified in 2015,18 the USPSTF sought evidence on the association between change in maternal iron status and improvement in infant and maternal outcomes in pregnant persons with iron deficiency with or without anemia. Eligible study designs for the review included randomized clinical trials (RCTs), controlled observational studies, and large uncontrolled observational studies on harms.1,17
Benefits of Screening (Early Detection) and Treatment
The review found no evidence on the benefits of screening and treatment for screen-detected iron deficiency and iron deficiency anemia during pregnancy on maternal and infant health outcomes.1,17 A single observational study addressed the association between change in maternal iron status in pregnant persons with iron deficiency with or without anemia and clinical outcomes.1,17 In the study19 (n = 20,690) in pregnant persons responding to treatment (defined as persons with a normal hemoglobin value at delivery who reported taking iron supplementation), therapy was associated with reduction in the odds of preeclampsia (adjusted odds ratio [OR], 0.75 [95% CI, 0.61-0.91]) and preterm birth (adjusted OR, 0.59 [95% CI, 0.47-0.72]) compared with persons without anemia.1,17,19 Nonresponse to therapy or untreated anemia was also associated with increased risk of preterm birth and preeclampsia (adjusted OR, 1.44 [95% CI, 1.16-1.76] and 1.45 [95% CI, 1.26-1.67], respectively) compared with no anemia.1,17,19 Comparison on these outcomes between pregnant persons taking iron therapy (whether or not successfully treated) with persons not taking iron therapy was not reported, limiting assessment of the association between iron therapy and improvement in health outcomes.1,17 Additional limitations to generalizing the study’s findings included the definition of anemia (based on reported iron intake) and unclear or unreported iron dose, timing, and therapy duration.1,17
Benefits of Supplementation
Maternal Health Outcomes
The review identified 16 studies comparing the effects of routine iron supplementation with no supplementation during pregnancy.1,17 Timing of starting supplementation varied across studies, from the first prenatal visit to 20 weeks’ gestation, and continued to delivery.1,17 Across the 16 studies, evidence on the effects of iron supplementation during pregnancy on maternal or infant health outcomes was limited, inconsistent, or without clear benefit.1,17 One trial (n = 430) reported no differences in maternal quality of life (across 8 health concepts) with iron supplementation compared with placebo.1,17,20 Five trials21-25 (n = 13,610) found no statistically significant differences on rates of hypertensive disorders of pregnancy with iron supplementation compared with placebo or no iron (4.7% vs 3.1% [pooled, weighted rates]; relative risk [RR], 1.24 [95% CI, 0.75-2.06]; I2 = 48.0%).1,17 Based on a pooled analysis, 8 trials20,21,24-29 (n = 4919) found no statistically significant differences in rates of cesarean delivery (42.8% vs 41.5%; RR, 1.01 [95% CI, 0.90-1.14]; I2 = 42.7%).1,17 Generally, studies of cesarean delivery did not report procedure indications, which could reflect practice variability, limiting interpretation of this evidence.1,17 In 4 trials reporting maternal gestational diabetes and maternal hemorrhage, results were imprecise and uncertain.1,17 Two trials24,26 (n = 2214) found no differences in rates of maternal gestational diabetes in pregnant persons receiving iron supplementation vs placebo, and 2 trials21,29 (n = 341) found no statistically significant differences in rates of maternal hemorrhage.1,17
Infant Health Outcomes
Across 6 supplementation trials (n = 17,863)20,21,23,25,27,30 reporting infant health outcomes, evidence was limited or demonstrated no benefit.1,17 Five trials reported no association between supplementation and infant mortality.1,17 In post hoc analysis, 1 trial (n = 3929) reported a statistically significant difference in rates of neonatal deaths in the supplementation group compared with the control group (1.1% vs 2.0%; RR, 0.53 [95% CI, 0.29-0.97]).1,17 Five trials22,24,26,30,31 (n = 16,827) of maternal iron supplementation reported no statistically significant differences in risk of preterm birth (5.5% vs 6.0%; RR, 0.92 [95% CI, 0.81-1.04]; I2 = 0.0%).1,17 Pooled analysis of 6 trials20-22,27,30,31 (n = 15,591) of maternal iron supplementation reported no statistically significant differences in infants with low birth weight (2.7% vs 2.9%; RR, 0.95 [95% CI, 0.79-1.14]; I2 = 0.0%).1,17 Across 4 trials24-26,30 (n = 5386) reporting infants small for gestational age, evidence was inconsistent and imprecise, with most studies reporting no differences (15.3% vs 15.2%; RR, 0.94 [95% CI, 0.67-1.31]; I2 = 75.5%).1,17 A pooled analysis reported few differences between supplementation compared with placebo.1,17 Low birth weight was defined as less than 2500 g and small for gestational age or intrauterine growth restriction was defined as birth weight less than 10th percentile for gestational age.1,17
Maternal Hematologic Outcomes
Although the USPSTF found inconsistent evidence on maternal iron supplementation during pregnancy to improve maternal and infant health outcomes, there was, across 16 trials,20-42 evidence of an association between supplementation and improved maternal hematologic indices (eg, hemoglobin and ferritin values) and decreased risk of maternal iron deficiency anemia, iron deficiency, and anemia compared with placebo or no therapy.1,17 Studies included persons at average risk of anemia with baseline hemoglobin levels ranging from 11.9 to 14.3 g/dL. Studies excluded pregnant persons with low hematologic indices at baseline (<8 to 11 g/dL). Seven trials20,22,27,28,32,38,41 (n = 4045) reported on maternal iron deficiency anemia with supplementation; iron supplementation was associated with decreased risk of maternal iron deficiency anemia during the third trimester (3 trials; n = 330; 9.1% vs 13.8%; RR, 0.63 [95% CI, 0.41-0.97]; I2 = 0%; absolute risk difference [ARD], −4% [95% CI, −8% to 0%]) and at term (4 trials; n = 2230; 8.6% vs 19.8%; RR, 0.40 [95% CI, 0.26-0.61]; I2 = 20.5%; ARD, −10% [95% CI, −16% to −3%]).1,17 Studies defined iron deficiency anemia as hemoglobin values less than 11.0 g/dL and serum ferritin levels less than 12 or 20 μg/L.1,17 Nine trials20,22,28,31-33,36,39,41 (n = 16,556) reported on maternal iron deficiency with supplementation; iron supplementation was associated with decreased risk of maternal iron deficiency during the third trimester (4 trials; n = 1220; 40.3% vs 57.1%; RR, 0.70 [95% CI, 0.53-0.92]; I2 = 77.4%; ARD, −17% [95% CI, −24% to −10%]) and at term (6 trials; n = 2361; 46% vs 70%; RR, 0.47 [95% CI, 0.33-0.67]; I2 = 81.9%; ARD, −34% [95% CI, −46% to −22%]).1,17 Studies defined iron deficiency as serum ferritin values less than 12 or 20 μg/L.1,17 Nine trials20,28,30-33,36,39,41 (n = 20,330) reported on maternal anemia; iron supplementation was associated with decreased risk of maternal anemia during the third trimester (7 trials; n = 2148; 18.1% vs 26.0%; RR, 0.71 [95% CI, 0.51-0.97]; I2 = 64.2%; ARD, −7.97% [95% CI, −15.28% to −0.66%]) and at term (4 trials; n = 2261; 10.9% vs 22.5%; RR, 0.43 [95% CI, 0.26-0.72]; I2 = 43.7%; ARD, −11.73% [95% CI, −14.87% to −8.60%]).1,17 Studies defined anemia as hemoglobin values less than 10.0 or 11.0 g/dL in the third trimester and at term and less than 12.0 or 12.1 g/dL postpartum.1,17 Fifteen trials21,22,24-30,32,39,41 (n = 20,069) reported maternal hemoglobin values and 13 trials20-22,24,26-29,31,32,39,41 (n = 19,075) reported maternal ferritin values compared with placebo; most studies found higher hemoglobin and serum ferritin values at term compared with placebo, with inconsistent findings at other time points.1,17
Infant Hematologic Outcomes
Evidence of intermediate outcomes in infants was limited to 2 trials20,31 (n = 12,943) reporting no differences in infant hematologic indices at 6 months or 1 year.1,17
Maternal and Infant Hematologic Outcomes
Evidence on the association between maternal supplementation and change in maternal iron status on improvement in infant and maternal outcomes was limited to the same single study (n = 20,690)19 of pregnant persons discussed in the screening section.
Harms of Screening and Supplementation
No trials reported on harms of screening. Twelve trials20,24,26-28,30-33,39,41,43 (n = 22,716) reported evidence on the harms of routine supplementation during pregnancy.1,17 Most trials reported transient gastrointestinal effects such as nausea, constipation, and diarrhea, with 5 trials reporting no difference in transient gastrointestinal effects in comparison groups.1,20,27,28,30,43 A single trial (n = 12,513) reported that iron supplementation starting in the second trimester was associated with increased risk of gastrointestinal symptoms vs placebo (3.6% vs 2.3%; RR, 1.59 [95% CI, 1.28-1.97]).1,17,31 Using medication adherence as a proxy for harms, 9 studies reported no statistically significant differences in adherence to supplementation between comparison groups.1,17 In a separate trial (n = 111), nonadherence to iron therapy was lower in adults taking supplementation compared with those taking placebo (2.2% vs 16.1%; P = .036) and not statistically significant in adolescents (4.5% vs 12.6%; P = .320).1,17,27 Infant harms were not reported in any studies.1,17
Response to Public Comments
A draft version of this recommendation statement was posted for public comment on the USPSTF website from February 27 to March 25, 2024. Some comments agreed with the draft recommendation. In response to comments, the USPSTF added language on iron-rich foods for supplementation, limitations of interpreting prevalence of iron deficiency and iron deficiency anemia, and additional information on screening and supplementation in the Recommendation of Others section. Some comments requested tools to identify potential risk factors for iron deficiency, such as food insecurity and social instability, to assist clinicians in determining which pregnant persons could benefit from screening. Despite careful review, the USPSTF found limited evidence on approaches (such as questionnaires or risk prediction tools) to identify pregnant persons at increased risk for iron deficiency with or without anemia.
Some comments expressed that the current I statements could be misinterpreted as recommendations against screening and supplementation. Others noted that the evidence was limited to RCTs and did not include clinically relevant health outcomes. In response, the USPSTF would like to reiterate that it is not making a recommendation for or against screening or supplementation during pregnancy for iron deficiency without or without anemia. Rather, the I statement is a call for more research on the benefits and harms of screening and supplementation. Further, the USPSTF carefully considers benefits and harms and makes recommendations when supported by sufficient evidence. The USPSTF cast a broad net, as outlined in the final research plan, including evidence from RCTs, controlled cohort studies, and other controlled observational studies. Some key questions also considered large uncontrolled observational studies and association studies. Clinically relevant potential outcomes included, but were not limited to, maternal health-related quality of life, postpartum hemorrhage, blood transfusions, and postpartum depression. The USPSTF continues to call for high-quality research, particularly on the critical gap of the association between changes in maternal iron status and improvement in infant and maternal outcomes in pregnant persons.
See Table 2 for research needs and gaps related to screening and supplementation for iron deficiency and iron deficiency anemia during pregnancy.
For screening, recommendations generally focus on screening for anemia, rather than iron deficiency, and use variable cutoffs to define anemia. The American College of Obstetricians and Gynecologists (ACOG), American Academy of Family Physicians, and Centers for Disease Control and Prevention recommend that all pregnant persons be screened for anemia at their first prenatal visit, preferably during the first trimester of pregnancy.44-46 ACOG recommends repeat screening at 24 to 28 weeks of gestation.44
The Centers for Disease Control and Prevention recommends universal supplementation for all pregnant persons with an oral low-dose iron supplement (30 mg/d).46 ACOG recommends universal supplementation with low-dose iron during pregnancy except in the setting of certain conditions such as hemochromatosis.44 It recommends evaluation for pregnant women who meet criteria for anemia to determine the cause, followed by treatment with low-dose supplemental iron for those with iron deficiency anemia along with prenatal vitamins.44 The US Department of Agriculture and US Department of Health and Human Services’ “Dietary Guidelines for Americans, 2020-2025” recommends that pregnant women or women planning to become pregnant take a supplement with iron when recommended by a clinician.47 In addition, women following a vegetarian or vegan dietary pattern should discuss with a clinician whether supplementation of iron, vitamin B12, other nutrients, or some combination thereof is needed.47
The authors of this recommendation statement include Task Force members serving at the time of publication and former members who made significant contributions to the recommendation. Any member with a level 3 conflict of interest (COI) recusal is not included as an author (see below for relevant COI disclosures for this topic).
The US Preventive Services Task Force authors of this recommendation statement include the following individuals: Wanda K. Nicholson, MD, MPH, MBA (George Washington University, Washington, DC); Michael Silverstein, MD, MPH (Brown University, Providence, Rhode Island); John B. Wong, MD (Tufts University School of Medicine, Boston, Massachusetts); David Chelmow, MD (Virginia Commonwealth University, Richmond); Tumaini Rucker Coker, MD, MBA (University of Washington, Seattle); Esa M. Davis, MD, MPH (University of Maryland School of Medicine, Baltimore); Carlos Roberto Jaén, MD, PhD, MS (University of Texas Health Science Center, San Antonio); Marie Krousel-Wood, MD, MSPH (Tulane University, New Orleans, Louisiana); Sei Lee, MD, MAS (University of California, San Francisco); Li Li, MD, PhD, MPH (University of Virginia, Charlottesville); Goutham Rao, MD (Case Western Reserve University, Cleveland, Ohio); John M. Ruiz, PhD (University of Arizona, Tucson); James Stevermer, MD, MSPH (University of Missouri, Columbia); Joel Tsevat, MD, MPH (University of Texas Health Science Center, San Antonio); Sandra Millon Underwood, PhD, RN (University of Wisconsin, Milwaukee); Sarah Wiehe, MD, MPH (Indiana University, Bloomington).
JAMA Citation: US Preventive Services Task Force; Nicholson WK, Silverstein M, Wong JB, et al. Screening and supplementation for iron deficiency and iron deficiency anemia during pregnancy: US Preventive Services Task Force recommendation statement. JAMA. 2024;332(11):906-913. doi: 10.1001/jama.2024.15196.
Conflict of Interest Disclosures: Authors followed the policy regarding conflicts of interest described at https://uspreventiveservicestaskforce.org/uspstf/about-uspstf/conflict-interest-disclosures. All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings. Dr Lee reported receiving grants from the National Institute on Aging (K24AG066998, R01AG079982) outside the submitted work. No other disclosures were reported.
No Task Force members had a level 3 COI recusal from this topic.
Funding/Support: The USPSTF is an independent, voluntary body. The US Congress mandates that the Agency for Healthcare Research and Quality (AHRQ) support the operations of the USPSTF.
Role of the Funder/Sponsor: AHRQ staff assisted in the following: development and review of the research plan, commission of the systematic evidence review from an Evidence-based Practice Center, coordination of expert review and public comment of the draft evidence report and draft recommendation statement, and the writing and preparation of the final recommendation statement and its submission for publication. AHRQ staff had no role in the approval of the final recommendation statement or the decision to submit for publication.
Disclaimer: Recommendations made by the USPSTF are independent of the US government. They should not be construed as an official position of AHRQ or the US Department of Health and Human Services.
Copyright Notice: USPSTF recommendations are based on a rigorous review of existing peer-reviewed evidence and are intended to help primary care clinicians and patients decide together whether a preventive service is right for a patient's needs. To encourage widespread discussion, consideration, adoption, and implementation of USPSTF recommendations, AHRQ permits members of the public to reproduce, redistribute, publicly display, and incorporate USPSTF work into other materials provided that it is reproduced without any changes to the work of portions thereof, except as permitted as fair use under the US Copyright Act.
AHRQ and the US Department of Health and Human Services cannot endorse, or appear to endorse, derivative or excerpted materials, and they cannot be held liable for the content or use of adapted products that are incorporated on other Web sites. Any adaptations of these electronic documents and resources must include a disclaimer to this effect. Advertising or implied endorsement for any commercial products or services is strictly prohibited.
This work may not be reproduced, reprinted, or redistributed for a fee, nor may the work be sold for profit or incorporated into a profit-making venture without the express written permission of AHRQ. This work is subject to the restrictions of Section 1140 of the Social Security Act, 42 U.S.C. §320b-10. When parts of a recommendation statement are used or quoted, the USPSTF Web page should be cited as the source.
1. Cantor A, Holmes R, Bougatsos C, Atchison C, DeLoughery T, Chou R. Screening and Supplementation for Iron Deficiency and Iron Deficiency Anemia in Pregnancy: A Systematic Review for the US Preventive Services Task Force. Evidence Synthesis No. 239. Agency for Healthcare Research and Quality; 2024. AHRQ publication 24-05313-EF-1.
2. Mei Z, Cogswell ME, Looker AC, et al. Assessment of iron status in US pregnant women from the National Health and Nutrition Examination Survey (NHANES), 1999–2006. Am J Clin Nutr. 2011;93(6):1312-1320. Medline:21430118 doi:10.3945/ajcn.110.007195
3. US Preventive Services Task Force. US Preventive Services Task Force Procedure Manual. Updated May 2021. Accessed June 24, 2024. https://uspreventiveservicestaskforce.org/uspstf/about-uspstf/methods-and-processes/procedure-manual
4. Griffin IJ, Abrams SA. Iron and breastfeeding. Pediatr Clin North Am. 2001;48(2):401-413. Medline:11339160 doi:10.1016/S0031-3955(08)70033-6
5. Scholl TO. Iron status during pregnancy: setting the stage for mother and infant. Am J Clin Nutr. 2005;81(5):1218S-1222S. Medline:15883455 doi:10.1093/ajcn/81.5.1218
6. Kirschner W, Dudenhausen JW, Henrich W. Are there anamnestic risk factors for iron deficiency in pregnancy? Results from a feasibility study. J Perinat Med. 2016;44(3):309-314. Medline:25803071 doi:10.1515/jpm-2014-0308
7. Yefet E, Yossef A, Nachum Z. Prediction of anemia at delivery. Sci Rep. 2021;11(1):6309. Medline:33737646 doi:10.1038/s41598-021-85622-7
8. Casanova BF, Sammel MD, Macones GA. Development of a clinical prediction rule for iron deficiency anemia in pregnancy. Am J Obstet Gynecol. 2005;193(2):460-466. Medline:16098871
9. Jefferds ME, Mei Z, Addo Y, et al. Iron deficiency in the United States: limitations in guidelines, data, and monitoring of disparities. Am J Public Health. 2022;112(S8):S826-S835. Medline:36288529
10. Kanu FA, Hamner HC, Scanlon KS, Sharma AJ. Anemia among pregnant women participating in the Special Supplemental Nutrition Program for Women, Infants, and Children—United States, 2008–2018. MMWR Morb Mortal Wkly Rep. 2022;71:813-819. Medline:35737575 doi:10.15585/mmwr.mm7125a1
11. Gavin NI, Adams EK, Hartmann KE, Benedict MB, Chireau M. Racial and ethnic disparities in the use of pregnancy-related health care among Medicaid pregnant women. Matern Child Health J. 2004;8(3):113-126. Medline:15499869 doi:10.1023/B:MACI.0000037645.63379.62
12. Branum AM, Bailey R, Singer BJ. Dietary supplement use and folate status during pregnancy in the United States. J Nutr. 2013;143(4):486-492. Medline:23365107 doi:10.3945/jn.112.169987
13. Park CY, Eicher-Miller HA. Iron deficiency is associated with food insecurity in pregnant females in the United States: National Health and Nutrition Examination Survey 1999-2010. J Acad Nutr Diet. 2014;114(12):1967-1973. Medline:24953790 doi:10.1016/j.jand.2014.04.025
14. Siu AL; US Preventive Services Task Force. Screening for iron deficiency anemia in young children: US Preventive Services Task Force recommendation statement. Pediatrics. 2015;136(4):746-752. Medline:26347426 doi:10.1542/peds.2015-2567
15. US Preventive Services Task Force. Folic acid supplementation to prevent neural tube defects: US Preventive Services Task Force reaffirmation recommendation statement. JAMA. 2023;330(5):454-459. Medline:37526713 doi:10.1001/jama.2023.12876
16. Siu AL; US Preventive Services Task Force. Screening for iron deficiency anemia and iron supplementation in pregnant women to improve maternal health and birth outcomes: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;163(7):529-536. Medline:26344176
17. Cantor AG, Holmes R, Bougatsos C, Atchison C, DeLoughery T, Chou R. Screening and supplementation for iron deficiency and iron deficiency anemia during pregnancy: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. Published August 20, 2024. doi:10.1001/jama.2024.13546
18. Kemper AR, Fan T, Grossman DC, Phipps MG. Gaps in evidence regarding iron deficiency anemia in pregnant women and young children: summary of US Preventive Services Task Force recommendations. Am J Clin Nutr. 2017;106(Suppl 6):1555S-1558S. Medline:29070541 doi:10.3945/ajcn.117.155788
19. Detlefs SE, Jochum MD, Salmanian B, McKinney JR, Aagaard KM. The impact of response to iron therapy on maternal and neonatal outcomes among pregnant women with anemia. Am J Obstet Gynecol MFM. 2022;4(2):100569. Medline:35033748
20. Makrides M, Crowther CA, Gibson RA, Gibson RS, Skeaff CM. Efficacy and tolerability of low-dose iron supplements during pregnancy: a randomized controlled trial. Am J Clin Nutr. 2003;78(1):145-153. Medline:12816784 doi:10.1093/ajcn/78.1.145
21. Barton DP, Joy MT, Lappin TR, et al. Maternal erythropoietin in singleton pregnancies: a randomized trial on the effect of oral hematinic supplementation. Am J Obstet Gynecol. 1994;170(3):896-901. Medline:8141223 doi:10.1016/S0002-9378(94)70305-1
22. Falahi E, Akbari S, Ebrahimzade F, Gargari BP. Impact of prophylactic iron supplementation in healthy pregnant women on maternal iron status and birth outcome. Food Nutr Bull. 2011;32(3):213-217. Medline:22073795 doi:10.1177/156482651103200305
23. Li Z, Mei Z, Zhang L, et al. Effects of prenatal micronutrient supplementation on spontaneous preterm birth: a double-blind randomized controlled trial in China. Am J Epidemiol. 2017;186(3):318-325. Medline:28472219 doi:10.1093/aje/kwx094
24. Ouladsahebmadarek E, Sayyah-Melli M, Taghavi S, Abbasalizadeh S, Seyedhejazie M. The effect of supplemental iron elimination on pregnancy outcome. Pakistan J Med Sci. 2011;27(3):641-645.
25. Ziaei S, Norrozi M, Faghihzadeh S, Jafarbegloo E. A randomised placebo-controlled trial to determine the effect of iron supplementation on pregnancy outcome in pregnant women with haemoglobin 13.2 g/dl. BJOG. 2007;114(6):684-688. Medline:17516958
26. Chan KK, Chan BC, Lam KF, Tam S, Lao TT. Iron supplement in pregnancy and development of gestational diabetes—a randomised placebo-controlled trial. BJOG. 2009;116(6):789-798. Medline:19432567
27. Meier PR, Nickerson HJ, Olson KA, Berg RL, Meyer JA. Prevention of iron deficiency anemia in adolescent and adult pregnancies. Clin Med Res. 2003;1(1):29-36. Medline:15931282 doi:10.3121/cmr.1.1.29
28. Zhao G, Xu G, Zhou M, et al. Prenatal iron supplementation reduces maternal anemia, iron deficiency, and iron deficiency anemia in a randomized clinical trial in rural China, but iron deficiency remains widespread in mothers and neonates. J Nutr. 2015;145(8):1916-1923. Medline:26063068
29. Ziaei S, Mehrnia M, Faghihzadeh S. Iron status markers in nonanemic pregnant women with and without iron supplementation. Int J Gynaecol Obstet. 2008;100(2):130-132. Medline:17977537 doi:10.1016/j.ijgo.2007.07.027
30. Zeng L, Dibley MJ, Cheng Y, et al. Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial. BMJ. 2008;337:a2001. Medline:18996930 doi:10.1136/bmj.a2001
31. Liu JM, Mei Z, Ye R, Serdula MK, Ren A, Cogswell ME. Micronutrient supplementation and pregnancy outcomes: double-blind randomized controlled trial in China. JAMA Intern Med. 2013;173(4):276-282. Medline:23303315 doi:10.1001/jamainternmed.2013.1632
32. Cogswell ME, Parvanta I, Ickes L, Yip R, Brittenham GM. Iron supplementation during pregnancy, anemia, and birth weight: a randomized controlled trial. Am J Clin Nutr. 2003;78(4):773-781. Medline:14522736 doi:10.1093/ajcn/78.4.773
33. Eskeland B, Malterud K, Ulvik RJ, Hunskaar S. Iron supplementation in pregnancy: is less enough? A randomized, placebo controlled trial of low dose iron supplementation with and without heme iron. Acta Obstet Gynecol Scand. 1997;76(9):822-828. Medline:9351406 doi:10.3109/00016349709024359
34. Chen S, Li N, Mei Z, et al. Micronutrient supplementation during pregnancy and the risk of pregnancy-induced hypertension: a randomized clinical trial. Clin Nutr. 2019;38(1):146-151. Medline:29428785 doi:10.1016/j.clnu.2018.01.029
35. Liu Y, Li N, Mei Z, et al. Effects of prenatal micronutrients supplementation timing on pregnancy-induced hypertension: secondary analysis of a double-blind randomized controlled trial. Matern Child Nutr. 2021;17(3):e13157. Medline:33594802 doi:10.1111/mcn.13157
36. Milman N, Agger AO, Nielsen OJ. Iron supplementation during pregnancy. Effect on iron status markers, serum erythropoietin and human placental lactogen. A placebo controlled study in 207 Danish women. Dan Med Bull. 1991;38(6):471-476. Medline:1802636
37. Milman N, Byg KE, Agger AO. Hemoglobin and erythrocyte indices during normal pregnancy and postpartum in 206 women with and without iron supplementation. Acta Obstet Gynecol Scand. 2000;79(2):89-98. Medline:10696955 doi:10.1034/j.1600-0412.2000.079002089.x
38. Milman N, Agger AO, Nielsen OJ. Iron status markers and serum erythropoietin in 120 mothers and newborn infants. Effect of iron supplementation in normal pregnancy. Acta Obstet Gynecol Scand. 1994;73(3):200-204. Medline:8122498 doi:10.3109/00016349409023439
39. Romslo I, Haram K, Sagen N, Augensen K. Iron requirement in normal pregnancy as assessed by serum ferritin, serum transferrin saturation and erythrocyte protoporphyrin determinations. Br J Obstet Gynaecol. 1983;90(2):101-107. Medline:6824608 doi:10.1111/j.1471-0528.1983.tb08891.x
40. Serdula MK, Zhou Y, Li H, Liu JM, Mei Z. Prenatal iron containing supplements provided to Chinese women with no or mild anemia had no effect on hemoglobin concentration in post-partum women or their infants at 6 and 12 months of age. Eur J Clin Nutr. 2019;73(11):1473-1479. Medline:30446762 doi:10.1038/s41430-018-0365-x
41. Siega-Riz AM, Hartzema AG, Turnbull C, Thorp J, McDonald T, Cogswell ME. The effects of prophylactic iron given in prenatal supplements on iron status and birth outcomes: a randomized controlled trial. Am J Obstet Gynecol. 2006;194(2):512-519. Medline:16458655 doi:10.1016/j.ajog.2005.08.011
42. Wang L, Mei Z, Li H, Zhang Y, Liu J, Serdula MK. Modifying effects of maternal Hb concentration on infant birth weight in women receiving prenatal iron-containing supplements: a randomised controlled trial. Br J Nutr. 2016;115(4):644-649. Medline:26824731 doi:10.1017/S0007114515004870
43. Jafarbegloo E, Ahmari Tehran H, Dadkhah Tehrani T. Gastrointestinal complications of ferrous sulfate in pregnant women: a randomized double-blind placebo-controlled trial. Iran Red Crescent Med J. 2015;17(8):e15001. Medline:26430520 doi:10.5812/ircmj.15001
44. American College of Obstetricians and Gynecologists. Anemia in pregnancy: ACOG practice bulletin, number 233. Obstet Gynecol. 2021;138(2):e55-e64. Medline:34293770
45. Short MW, Domagalski JE. Iron deficiency anemia: evaluation and management. Am Fam Physician. 2013;87(2):98-104. Medline:23317073
46. Centers for Disease Control and Prevention. Recommendations to prevent and control iron deficiency in the United States. MMWR Recomm Rep. 1998;47(RR-3):1-29. Medline:9563847
47. US Department of Agriculture, US Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. Accessed June 24, 2024. https://www.dietaryguidelines.gov/resources/2020-2025-dietary-guidelines-online-materials
Rationale | Screening | Supplementation |
---|---|---|
Detection | The USPSTF found inadequate evidence to assess the effectiveness of risk prediction tools to identify pregnant persons who are at increased risk for iron deficiency or iron deficiency anemia. | |
Benefits of early detection and intervention and treatment |
|
|
Harms of early detection and intervention and treatment |
|
The USPSTF found adequate evidence to bound the harms of routine iron supplementation during pregnancy as no greater than small based on studies that reported harms as minimal. |
USPSTF assessment | Due to lack of available data, the USPSTF concludes that the current evidence is insufficient, and the balance of benefits and harms of screening for iron deficiency and iron deficiency anemia in asymptomatic pregnant persons on maternal and infant health outcomes cannot be determined. | Due to lack of available data, the USPSTF concludes that the current evidence is insufficient, and the balance of benefits and harms of iron supplementation in asymptomatic pregnant persons on maternal and infant health outcomes cannot be determined. |
Abbreviation: USPSTF, US Preventive Services Task Force.
To fulfill its mission to improve health by making evidence-based recommendations for preventive services, the USPSTF routinely highlights the most critical evidence gaps for making actionable preventive services recommendations. For each evidence gap below, research should focus on settings similar to those in the US to assist in generalizability to a US primary care population. This table summarizes the key bodies of evidence needed for the USPSTF to make a recommendation for screening and supplementation for iron deficiency and iron deficiency anemia during pregnancy. For additional information on research needed to address these evidence gaps, see the Research Gaps Taxonomy table on the USPSTF website (https://www.uspreventiveservicestaskforce.org/home/getfilebytoken/aRJ-3-AWuVvmC_kmoGCVHp). |
Screening and Supplementation for Iron Deficiency and Iron Deficiency Anemia During Pregnancy |
Research is needed in pregnant persons with iron deficiency and iron deficiency anemia to assess whether changes in maternal iron status (eg, because of supplementation or treatment for screen-detected populations) improves maternal and infant health outcomes in settings relevant to US primary care clinical practice. |
Research is needed to assess the benefits and harms of screening (eg, with hemoglobin, hematocrit, or ferritin values) for iron deficiency and iron deficiency anemia during pregnancy on maternal (eg, quality of life or need for transfusion) and infant (eg, low birth weight or preterm birth) health outcomes. |
Research is needed to assess the benefits and harms of treatment (eg, oral or intravenous iron) in asymptomatic, screen-detected populations with iron deficiency and iron deficiency anemia during pregnancy on maternal and infant health outcomes in settings relevant to US primary care clinical practice. |
Research is needed to assess the benefits and harms of routine iron supplementation in asymptomatic pregnant persons without known iron deficiency or iron deficiency anemia on maternal and infant health outcomes. |
Abbreviation: USPSTF, US Preventive Services Task Force.