Antenatal iron supplementation, FGF23, and bone metabolism in Kenyan women and their offspring: secondary analysis of a randomized controlled trial
Antenatal iron supplementation, FGF23, and bone metabolism in Kenyan women and their offspring: secondary analysis of a randomized controlled trial
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DOI：
10.1093/ajcn/ngaa417
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发表时间：
2021-05-01
影响因子：
7.1
通讯作者：
Verhoef, Hans
中科院分区：
文献类型：
--
作者：
Braithwaite, Vickie S.;Mwangi, Martin N.;Verhoef, Hans
背景：成纤维细胞生长因子-23 （FGF23）主要通过增加磷酸尿来调节体内磷酸盐稳态。它还可以作为一种维生素d调节激素。母体铁缺乏与FGF23的表达和/或调控紊乱有关，因此可能与后代低磷血症驱动的佝偻病的发病机制有关。目的：我们旨在确定产前口服补铁对FGF23浓度和母婴骨矿物质调节标志物的影响。方法：我们对一项试验进行了二次分析，在这项试验中，470名肯尼亚农村的单胎妊娠妇女，血红蛋白浓度>= 90 g/L，随机分配到从妊娠13-23周到产后1个月，每天在监督下补充60毫克元素铁，如富马酸亚铁或安慰剂。正如先前报道的那样，补充铁可以改善母亲和新生儿的铁状态。就目前的研究而言。我们重新分析了母亲和新生儿出生时收集的所有可用血浆样本，主要结果是FGF23的浓度，通过两种检测方法测量：一种检测完整的激素和c端切割产物（total-FGF23），另一种检测完整的激素（incomplete -FGF23）。结果：对433例妇女进行分析，其中铁组216例，铁组217例。414例新生儿（铁组207例，安慰剂组207例）。产前补铁可使母亲和新生儿的几何平均总fgf23浓度分别降低62.6% （95% CI: 53.0%, 70.3%）和15.2% （95% CI: -0.3%）。28.4%, p = 0.06)。分别。此外，它使新生儿完整- fgf23几何平均浓度提高了21.6% (95% CI: 1.2%, 46.1%)，使母体hepcidin几何平均浓度提高了136.4% (95% CI: 86.1%, 200.3%)，使母体25-羟基维生素D平均浓度降低了6.1 nmol/L （95% CI: -11.0, -1.2 nmol/L）。结论：这项随机试验的分析证实，铁补充剂可以逆转缺铁母亲及其新生儿因缺铁而导致的FGF23生成升高。需要进一步的研究来评估补铁在多大程度上可以预防fgf23介导的低磷性佝偻病或骨软化症。
Background: Fibroblast growth factor-23 (FGF23) regulates body phosphate homeostasis primarily by increasing phosphaturia. It also acts as a vitamin D-regulating hormone. Maternal iron deficiency is associated with perturbed expression and/or regulation of FGF23 and hence might be implicated in the pathogenesis of hypophosphatemia-driven rickets in their offspring.Objectives: We aimed to determine the effect of antenatal oral iron supplementation on FGF23 concentration and maternal and infant markers of bone-mineral regulation.Methods: We performed a secondary analysis of a trial in which 470 rural Kenyan women with singleton pregnancies and hemoglobin concentrations >= 90 g/L were randomly allocated to daily, supervised supplementation with 60 mg elemental iron as ferrous fumarate or placebo from 13-23 weeks of gestation until 1 mo postpartum. As previously reported, iron supplementation improved iron status in mothers and neonates. For the present study. we reanalyzed all available plasma samples collected in mothers and neonates at birth, with primary outcomes being concentrations of FGF23, measured by 2 assays: 1 that detects intact hormone and C-terminal cleavage products (total-FGF23) and another that detects the intact hormone only (intact-FGF23).Results: Analysis was performed on 433 women (n = 216, iron group; n = 217. placebo group) and 414 neonates (n = 207, iron group; n = 207, placebo group). Antenatal iron supplementation reduced geometric mean total-FGF23 concentrations in mothers and neonates by 62.6% (95% CI: 53.0%, 70.3%) and 15.2% (95% CI: -0.3%. 28.4%, P = 0.06). respectively. In addition, it increased geometric mean neonatal intact-FGF23 concentrations by 21.6% (95% CI: 1.2%, 46.1%), increased geometric mean maternal hepcidin concentrations by 136.4% (95% CI: 86.1%, 200.3%), and decreased mean maternal 25-hydroxyvitamin D concentrations by 6.1 nmol/L (95% CI: -11.0, -1.2 nmol/L).Conclusions: Analysis of this randomized trial confirms that iron supplementation can reverse elevated FGF23 production caused by iron deficiency in iron-deficient mothers and their neonates. Further investigations are warranted to assess to what extent iron supplementation can prevent FGF23-mediated hypophosphatemic rickets or osteomalacia.