铁剂治疗血液学反应与中度缺铁性贫血单胎妊娠死产风险的关系

原文

BACKGROUND: Maternal iron deficiency anemia is a persistent global health challenge associated with an increased risk of adverse perinatal outcomes. A recent multicenter clinical trial found reduced rates of low-birthweight infants in mothers treated initially (early second trimester of pregnancy) with intravenous ferric carboxymaltose infusion compared with those treated with oral iron supplement. The secondary findings included improved hematologic indices 4 weeks after treatment and reduced rate of stillbirth with single-dose intravenous iron infusion. OBJECTIVE: This study aimed to determine whether initial response to iron therapy is associated with the risk of stillbirth and other adverse perinatal outcomes in pregnant patients with singleton pregnancies and moderate iron deficiency anemia. STUDY DESIGN: This was a secondary analysis of a multicenter randomized controlled trial in India that compared single-dose intravenous iron infusion with oral iron supplement for the initial management of moderate iron deficiency anemia (hemoglobin level of 7.0-9.9g/dL) at 14 to 17 weeks of gestation. The primary outcome for this secondary analysis was stillbirth. The secondary outcomes were early preterm birth at <34 weeks of gestation and small-for-gestational-age infants (<10th percentile). The predictors of interest were maternal hemoglobin, ferritin, and transferrin saturation levels, measured at 20 to 24 weeks of gestation. In addition, longitudinal hematologic and iron indices throughout pregnancy and their association with outcomes were assessed. The relative risk of each outcome based on posttreatment hemoglobin, ferritin, and transferrin saturation levels was assessed using Poisson regression, adjusting for maternal age, body mass index, parity, treatment modality, baseline hemoglobin level, and study site. A 2-sided alpha level of .05 was used for all analyses. Given that most nutrients exhibit U-shaped or threshold risk curves, we also fit models, allowing for a quadratic function for the relationship between hematologic parameters at all times and the risk of each event. RESULTS: A total of 4252 participants were included in this analysis, of whom 1421, 1424, and 1407 received intravenous ferric derisomaltose infusion, intravenous ferric carboxymaltose infusion, and oral iron supplement, respectively. In evaluating the linear relationship, each unit increase in hemoglobin response at 20 to 24 weeks of gestation was significantly associated with a reduced risk of stillbirth (relative risk, 0.74 [95% confidence interval, 0.56-0.98]). In evaluating the quadratic relationship, a significantly progressive increase in the risk of stillbirth (P<.0001) and early preterm birth at <34 weeks of gestation (P=.01) was determined with decreasing Hb <10.5. Although a significant quadratic relationship was identified between small-for-gestational-age infant and hemoglobin level (P=.008), the relative risk of small for gestational age and lower hemoglobin level was not statistically significant. CONCLUSION: Inadequate improvement in hemoglobin level at 20 to 24 weeks of gestation after iron therapy in pregnancies complicated by moderate iron deficiency anemia was associated with an increased risk of stillbirth and early preterm birth. Our findings highlight the potential importance of early screening and treatment of maternal anemia. Given the association between persistent anemia at 20 to 24 weeks of gestation and adverse outcomes, prospective trials should focus on whether early pregnancy, or even preconception, improvement in hemoglobin level is an effective intervention to prevent adverse perinatal outcomes, such as stillbirth and early preterm birth.