The impact of response to iron therapy on maternal and neonatal outcomes among pregnant women with anemia

Abstract

Background: Anemia during pregnancy is associated with increased risks of preterm birth, preeclampsia, cesarean delivery, and maternal morbidity. The most prevalent modifiable cause of pregnancy-associated anemia is iron deficiency. However, it is still unclear whether iron therapy can reduce the risks of adverse outcomes in women with anemia.

Objective: This study aimed to determine whether response to iron therapy among women with anemia is associated with a change in odds of adverse maternal and neonatal outcomes.

Study design: This was a population-based cohort study (2011-2019) using an institutional database composed of obstetrical patients from 2 delivery hospitals. Patients with adequate prenatal care were classified as being anemic or nonanemic (reference). Patients with anemia were further stratified by success or failure of treatment with oral iron therapy using the American College of Obstetricians and Gynecologists criteria for anemia at the time of admission for delivery: successfully treated (Hgb≥11 g/dL) or unsuccessfully treated ("refractory;" Hgb<11 g/dL). All categories of women with anemia categories were compared with the reference group of women without anemia using chi-square and logistic regression analyses. The primary outcomes were preterm birth and preeclampsia.

Results: Among the 20,690 women observed, 7416 (35.8%) were anemic. Among women with anemia, 1319 (17.8%) were refractory to iron therapy, 2695 (36.3%) had a successful response to therapy, and 3402 (45.9%) were untreated. Successfully treated patients with anemia had a significant reduction in the odds of preterm birth (5.1% vs 8.3%; adjusted odds ratio, 0.59; 95% confidence interval, 0.47-0.72) and preeclampsia (5.9% vs 8.3%; adjusted odds ratio, 0.75; 95% confidence interval, 0.61-0.91). Refractory and untreated patients had significantly increased odds of preterm birth (adjusted odds ratio, 1.44 [95% confidence interval, 1.16-1.76] and 1.45 [95% confidence interval, 1.26-1.67], respectively) and preeclampsia (adjusted odds ratio, 1.54 [95% confidence interval, 1.24-1.89] and 1.44 [95% confidence interval, 1.25-1.67], respectively). All groups of women with anemia had increased odds of postpartum hemorrhage and decreased odds of delivering a small for gestational age neonate. There was no difference in composite neonatal morbidity.

Conclusion: Successful treatment of anemia with oral iron therapy was associated with a reduction in the odds of preterm birth and preeclampsia. Women with refractory anemia had similar outcomes to those who were untreated, emphasizing the importance of monitoring response to iron therapy during pregnancy.

Keywords: iron deficiency anemia; maternal morbidity; neonatal morbidity; preeclampsia prevention; preterm birth prevention.

FIGURE 1. Study population

^aInadequate prenatal care as defined by the Kotelchuck Adequacy of Prenatal Care Index; ^bMissing data included hemoglobin and gestational age at delivery. PO, orally.

FIGURE 2. aORs and cORs of adverse maternal and neonatal outcomes of the study group compared with the reference population

There was a significant reduction in the odds of preterm birth (aOR, 0.59; 95% CI, 0.47–0.72) and preeclampsia (aOR, 0.75; 95% CI, 0.61–0.91) among successfully treated patients. aOR, adjusted odds ratio; CI, confidence interval; cOR, crude odds ratio.

FIGURE 3. Incidence of PTB stratified by cause in anemia

There was a significant reduction in the odds of PTB for successfully treated patients. This can be attributed to a significant reduction in the odds of PTL, PPROM, and PreE. ^aOther causes included placenta previa, placental abruption, oligohydramnios, growth restriction, fetal demise, and unknown. NRFHT, nonreassuring fetal heart tones; PPROM, preterm premature rupture of membranes; PreE, preeclampsia; PTB, preterm birth; PTL, preterm labor.