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Objective
To decrease the risk of adverse maternal and neonatal outcomes, , iron therapy is recommended for pregnant people with iron deficiency anemia (IDA). To support our ongoing multicenter randomized trial on the optimal iron therapy for antenatal IDA (NCT05462704), we initiated universal ferritin screening, although this practice is not currently recommended. Nevertheless, perhaps because normal pregnancy physiology may cause first trimester iron deficiency without anemia (IDWA), defined as ferritin <30 ng/mL with hemoglobin ≥11 g/d, to progress to IDA, a clinical consensus based on expert opinion recommended treating iron deficiency in pregnancy regardless of anemia. Here, we examine the association between first trimester IDWA and the development of IDA later in pregnancy.
AJOG at a Glance
Why was this study conducted?
First trimester iron deficiency without anemia (IDWA) (ferritin <30 ng/mL with hemoglobin ≥11 g/dL) may progress to iron deficiency anemia (IDA), which is associated with adverse perinatal outcomes for mother and infant. We aimed to examine the association between first trimester IDWA and subsequent development of antenatal IDA.
Key findings
Among 511 people, 129 (25%) had first trimester IDWA. Of these, 87 (67%) were diagnosed with IDA and/or were treated for IDA with iron therapy prior to delivery, compared with 35% (n=118 among those who were iron-replete, nonanemic).
What does this add to what is known?
First trimester IDWA is common and associated with high likelihood of being diagnosed with and/or being treated for IDA during pregnancy. These findings suggest that identifying and treating IDWA in the first trimester may provide an opportunity to prevent IDA and associated morbidity.
Methods
Our pregnant patients receive a complete blood count and ferritin as part of their intake obstetric laboratory panel and are prescribed prenatal vitamins with iron. In this prospective cohort study, individuals with singleton first-trimester gestations who obtained an intake obstetric laboratory panel from February 2023 to July 2025 were included. Those with anemia were excluded. The primary outcome was IDA prior to childbirth, defined as being prescribed intravenous or oral iron therapy at any gestational age or progression to IDA before delivery. Secondary outcomes are described in Table 2 . Relative risks were calculated adjusting for race and ethnicity. This study was institutional review board–approved.
Table 1
Patient demographic and obstetric characteristics, stratified by first trimester ferritin and hemoglobin results
| Characteristics | No anemia, no iron deficiency (n=336) | Iron deficiency without anemia (n=129) | P value |
|---|---|---|---|
| Age <35 y | 261 (78) | 105 (81) | .5 |
| Race | <.001 | ||
| White | 157 (47) | 38 (29) | |
| Black | 49 (15) | 21 (16) | |
| Hispanic | 16 (4.5) | 19 (15) | |
| Asian | 16 (4.8) | 8 (6.2) | |
| Native American | 6 (1.8) | 1 (0.8) | |
| Multiracial | 35 (11) | 18 (14) | |
| Prepregnancy body mass index | 30 (26, 34) | 29 (25, 33) | .3 |
| Federal health insurance | 177 (53) | 75 (58) | .6 |
| Multiparity | 333 (99) | 129 (100) | .6 |
Data presented as n (%) or median (interquartile range).
Results
Among 511 people, 46 (9%) had first trimester IDA and were excluded, while 129 (25%) had first trimester IDWA, and 336 (66%) were iron replete and nonanemic. Those with IDWA were more likely to be Hispanic or Native American than those who were iron replete and nonanemic despite similar age, parity, and body mass index ( Table 1 ). After adjusting for race/ethnicity, those with first trimester IDWA were at nearly a 2-fold higher risk of developing IDA prior to childbirth (IDWA n=87 [67%] vs iron-replete, nonanemic n=118 [35%]; adjusted relative risk, 1.91; 95% confidence interval, 1.57–2.31). There was no difference in secondary outcomes ( Table 2 ).
Table 2
Perinatal outcomes, stratified by first trimester ferritin and hemoglobin results
| Outcome | No anemia, no iron deficiency (n=336) | Iron deficiency without anemia (n=129) | P value | Relative risk (RR) (95% confidence interval [CI]) | Adjusted RR (95% CI) |
|---|---|---|---|---|---|
| Maternal outcomes | |||||
| Iron deficiency anemia during pregnancy | 118 (35) | 87 (67) | <.001 | 1.92 (1.59, 2.31) | 1.91 (1.57, 2.31) |
| Anemia during delivery hospitalization | 52 (16) | 31 (24) | 0.045 | 1.50 (1.01, 2.23) | 1.62 (1.09, 2.42) |
| Blood transfusion during delivery hospitalization | 24 (7.3) | 10 (7.9) | .8 | — | — |
| Mode of delivery | .7 | — | — | ||
| Spontaneous vaginal delivery | 198 (60) | 77 (60) | — | — | |
| Operative vaginal delivery | 11 (3) | 6 (5) | — | — | |
| Cesarean delivery | 122 (36) | 45 (35) | — | — | |
| Screen positive for postpartum depression at 6 weeks postpartum |
n=224
15 (7) |
n=93
9 (10) |
.4 | — | — |
| Neonatal outcomes | |||||
| Preterm delivery | 33 (10) | 18 (14) | .2 | — | — |
| Infant birthweight (grams) | 3315 (2290, 3675) | 3300 (3035, 3590) | .8 | — | — |
| Neonatal intensive care unit admission | 35 (11) | 14 (11) | 1.0 | — | — |
| Perinatal morbidity | 1 (0.3) | 3 (2) | .067 | — | — |
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