Iron Deficiency Extremely Common by Third Trimester of Pregnancy

A longitudinal investigation into iron status during pregnancy revealed no women anemic in the first trimester, while more than 80% experienced iron deficiency by the third trimester, suggesting the need for routine iron screening in all pregnant individuals.¹

These findings were reported in one of the largest studies ever conducted to evaluate changes in iron status during pregnancy. International guidelines vary on the need for iron deficiency screening in pregnancy without agreed-upon diagnostic criteria—recent guidance from the US Preventive Services Task Force (USPSTF) deemed the current evidence ‘insufficient’ to assess the benefits and harm of screening for iron deficiency in pregnant women.²

“No women in this study were anemic in the first trimester, yet iron deficiency was exceedingly common among our primiparous cohort, particularly in the third trimester,” wrote the investigative team, led by Elaine K. McCarthy, BSc, PhD, Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork. “This is concerning and draws attention to the benefit of screening for iron deficiency with hemoglobin and ferritin in defined low-risk populations.”

Iron requirements increase nearly 10-fold during pregnancy to accommodate fetal development and elevated iron needs in the mother, with the ability to meet these needs dependent on iron stores at the beginning of pregnancy and physiological adaptions during pregnancy.³ However, these adaptations do not always support a pregnant woman’s total iron needs, particularly those who begin with depleted stores.

Maternal iron deficiency can lead to anemia, which can increase the risk for adverse outcomes, for mother and infant, including postpartum depression and hemorrhage, preterm birth, low birth weight, and small for gestational age at birth. However, well-powered analyses of longitudinal changes in iron status during pregnancy are scarce, and limited to small, retrospective studies, often in high-risk settings, rather than low-risk populations.

In this study, McCarthy and colleagues measured the longitudinal change in iron biomarkers during pregnancy, and the prevalence of iron deficiency in pregnant individuals, and proposed early pregnancy iron status benchmarks to predict iron deficiency in the third trimester.¹ The team collected data on 641 pregnant women in Ireland who successfully delivered for the first time and participated in the IMPROvED consortium project.

Samples, including iron (ferritin, soluble transferrin receptors, [sTfR], total body iron [TBI]) and inflammatory markers (C-reactive protein, α-glycoprotein) were collected at 15 weeks, 20 weeks, and 33 weeks of pregnancy. Within 72 hours after delivery, data on the pregnancy, delivery, and the baby were taken from an interview between the mother and a research midwife.

Upon analysis, iron deficiency (ferritin <15 µg/L) increased during the pregnancy, from 4.5%, 13.7%, and 51.2% at 15, 20, and 33 weeks of gestation, respectively. At a ferritin threshold of <30 µg/L, the deficiency rates were 20.7%, 43.7%, and 83.8% across each time point, respectively. Using sTfR thresholds of >4.4 mg/L, the prevalence was similar to ferritin <15 µg/L, at 7.2%, 12.6%, and 60.9%, respectively.

On the other hand, using a TBI of <0 mg/kg, the deficiency rates were lower than ferritin or sTfR (P <.001). A cutpoint analysis (area under the curve, 0.750), ferritin <60 µg/L represented the threshold at 15 weeks that predicted the presence of iron deficiency at 33 weeks.

Importantly, iron supplement use taken during pregnancy or the early pregnancy period was linked to a protective effect against iron deficiency during pregnancy, including reducing the risk of ferritin <15 µg/L in the third trimester (odds ratio [OR], 0.57; 95% CI, 0.39–0.82; P = .002).

"Further good-quality, large-scale longitudinal studies of iron status, with concurrent inflammatory status, are needed to provide the evidence base to help establish much-needed consensus,” McCarthy and colleagues wrote.

An editorial accompanying the findings, led by Michael Auerbach and Helain Landy of Georgetown University School of Medicine, labeled the lack of screening or treatment for iron deficiency in pregnant women as “misogyny.”⁴ They called on the American College of Obstetricians and Gynecologists (ACOG) and the USPSTF to adjust their screening recommendations.

“[THE ACOG and USPSTF should] change their approach to diagnosis to screen all pregnant women for iron deficiency, irrespective of the presence or absence of anemia, and recommend supplementation when present for the most frequent nutrient deficiency disorder that we encounter," they wrote.⁵

References

1. _{McCarthy EK et al. Longitudinal evaluation of iron status during pregnancy: A prospective cohort study in a high-resource setting. The American Journal of Clinical Nutrition. September 26, 2024. Accessed September 27, 2024. https://www.sciencedirect.com/science/article/pii/S0002916524006695?via%3Dihub.}
2. _{Iapoce C. USPSTF: Iron deficiency screening, supplementation in pregnancy lacks evidence. HCP Live. August 20, 2024. Accessed September 27, 2024. https://www.hcplive.com/view/uspstf-iron-deficiency-screening-supplementation-pregnancy-lacks-evidence.}
3. _{Iron homeostasis during pregnancy. The American Journal of Clinical Nutrition. December 1, 2017. Accessed September 27, 2024. https://www.sciencedirect.com/science/article/pii/S0002916522027253.}
4. _{Finally, a quality prospective study to support a proactive paradigm in anemia of pregnancy. Auerbach, Michael et al. The American Journal of Clinical Nutrition, Volume 0, Issue 0}
5. _{Study finds more than 80% of women iron deficient by third trimester. EurekAlert! September 26, 2024. Accessed September 27, 2024. https://www.eurekalert.org/news-releases/1058802.}