Iron supplementation has been shown to be effective in raising hemoglobin concentrations among pregnant and postpartum women, and it has been suggested as a public health solution to improving maternal and child health outcomes in various age groups [14,15].
In this study we demonstrated that iron replacement therapy with Sucrosomial® iron, an innovative oral formulation, was well tolerated (no woman discontinued treatment due to gastrointestinal adverse events) and effective at treating mild and moderate PPIDA. Mean Hb increment was 3.6 ± 1.5 g/dL and 81% of patients attained a Hb ≥ 12 g/dL at the end of treatment period. These data are comparable to those obtained 6–24 weeks after the administration of IV iron to women with moderate PPIDA (mean Hb increment, 3.8 g/dL; anemia correction, 88%; n = 658) [16–19].
It has been argued that administration of IV iron to women with moderate PPIDA results in a faster increase of Hb concentrations compared to oral iron (ferrous sulfate). However, in moderate IDA, the Hb increment (2.4 ± 0.9 g/dL) registered after 10 days of iron replacement therapy with Sucrosomial® iron (60 mg/day, Hb in) was also similar to those observed 2 weeks after the administration of intravenous iron (2.2 g/dL – 3.2 g/dL) [17,20–23], and this reflected in the rapid improvement of clinical symptoms (Fig. 3). These effects of Sucrosomial® iron in quality of life have been also observed in heart failure patients with reduced ejection fraction and iron deficiency [24].
As mentioned above, Sucrosomial® iron absorption is mostly hepcidin-independent, as it is taken up to the lymphatic circulation through transcellular and M cell-mediated endocytosis routes [9]. This confers Sucrosomial® iron the ability to increase Hb, even in the presence of inflammation, as has been shown in cardiac surgery [25,26] and in patients with chronic kidney disease [27], cancer [28] or inflammatory bowel disease [29,30]. Remarkably, efficacy of Sucrosomial® iron is observed at much lower dose and with fewer gastrointestinal adverse events, compared to oral iron sulfate.
In addition, the difference in Hb increment between the study groups at T10 also suggests a correlation in terms of speed with the dose used (60 mg/day vs. 30 mg/day). As endogenous erythropoietin production is higher at low Hb concentrations, higher initial oral Sucrosomial® iron dose might result in faster recovery from PPIDA. Subsequently, the dose could be reduced to ensure iron supply to the bone marrow. In this regard, Giordano et al. (2021) [14] have recently demonstrated the efficacy and tolerability of high-dose, oral Sucrosomial® iron (120 mg elemental iron/day) for 4 weeks, compared to intravenous ferric gluconate, in severe IDA patients intolerant/refractory to iron sulfate.
Regarding iron biomarkers, an accurate assessment of the actual effect of Sucrosomial® iron on the improvement of ferritin and TSAT levels was hampered by the influence of inflammation on the levels of these biomarkers at T0 [31]. Therefore, instead of evaluating the differences between T0 and T60, we assessed the percentage of patients presenting with ferritin and TSAT levels above their thresholds for defining ID at T60, when no inflammation is present.
A serum ferritin level < 30 ng/mL is the most sensitive (92%) and specific (98%) cut-off level for the identification of true ID (with or with-out anaemia) and a TSAT < 20% is insufficient to meet the iron requirements for erythropoiesis [32]. In our study, 45% achieved a TSAT level within normal range (≥ 20%), and 36% a ferritin level within normal range (≥ 30 ng/mL) at T60. We used these thresholds in accordance with current guidelines for the diagnosis of ID [1,5,33], though more conservative thresholds are generally used in women (12–18 ng/mL for ferritin, and 15% for TSAT).
Moreover, as mean ferritin levels remained largely unmodified at T60, it can be assumed that absorbed was mainly used for erythropoiesis and other physiological functions (e.g. energy production), rather than for building up iron stores. Therefore, Sucrosomial® iron replacement should be extended, at least, up to the third month of the postpartum period to replenish iron stores, as recommended in guidelines [5].
This research has a range of limitations. Compared to previous studies, our study had a limited follow-up time and a comparatively limited sample size, which may result in diminished predictive capacity, minimal value for demographic variables, and lower implication in conclusions. We understand the value of undertaking broader and longer trials on various cohorts of postpartum anemia women to validate our results. However, the demonstrated effectiveness of Sucrosomial® iron and the absence of associated gastrointestinal side effect in a difficult-to-treat population may have significance to clinical practice [30,33,34]. In particular, commitment to therapy remains a core determinant of positive health results for postpartum women in need of iron supplementation. We assume that Sucrosomial® iron has the ability to enhance adherence to iron supplementation in postpartum women.