Division of Endocrinology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Division of Endocrinology and Diabetes Children's Hospital of Philadelphia, Associate Professor of Clinical Pediatrics, Perelman School of Medicine at the University of Pennsylvania, 3500 Civic Center Blvd, Buerger Center, 12th floor, Philadelphia, PA, USA.
Semin Fetal Neonatal Med. 2020 Feb;25(1):101086. doi: 10.1016/j.siny.2020.101086. Epub 2020 Jan 16.
Metabolic bone disease (MBD) of prematurity remains a significant comorbid condition in preterm, low birth weight infants. As the majority of in utero calcium (Ca) and phosphorus (Phos) accretion occurs during the third trimester, many of these children have inadequate mineral stores and are at risk for deficiencies of Ca and Phos. While fortification of formula has allowed for increased mineral delivery to premature infants, intestinal immaturity prevents optimal absorption. This is compounded by immobilization, delayed establishment of enteral feeds, long term parenteral nutrition and medications that may alter mineral levels. Over time, biochemical changes occur and accompany MBD, with poor bone mineralization during this period increasing the risk for complications such as osteopenia, rickets and fractures. Screening is largely based on risk factors, but despite the 2013 AAP Consensus Statement, there remains significant variation in screening practices across institutions. A combination of laboratory and radiologic testing is often used to diagnose and manage MBD of prematurity, but there exists a lack of consensus on which screening tests and thresholds to use. This is in part related to a lack of normative data and clinical trials for preterm infants, and a result, a lack of evidence-based guidelines on the diagnosis and timing of potential treatment. Biochemical markers, such as serum Phos, alkaline phosphatase (ALP) and parathyroid hormone (PTH), have shown some benefit in the diagnosis of MBD in some studies, but have not always been reproducible. Radiographs may identify different degrees of skeletal changes, but these changes may not be detected until later in MBD development. Other modalities, such as DXA and ultrasound, have also been used, but these may be limited by lack of standards in preterm infants or lack of availability in some centers. Further research, more specifically clinical trials, are needed to determine which combination of tests can detect MBD at its earliest, in order to promote early treatment and prevent short- and long-term complications of MBD.
早产儿代谢性骨病（MBD）仍然是早产儿和低出生体重儿的一种严重合并症。由于大多数胎儿的钙（Ca）和磷（Phos）在妊娠晚期积累，这些儿童中许多人的矿物质储备不足，存在 Ca 和 Phos 缺乏的风险。虽然配方奶的强化允许向早产儿提供更多的矿物质，但肠道不成熟会阻止最佳吸收。再加上固定不动、肠内喂养延迟建立、长期肠外营养和可能改变矿物质水平的药物，情况就更加复杂了。随着时间的推移，会发生生化变化并伴有 MBD，在此期间，骨矿物质化不良会增加骨质疏松症、佝偻病和骨折等并发症的风险。筛查主要基于风险因素，但尽管 2013 年 AAP 共识声明，各机构之间的筛查实践仍然存在很大差异。实验室和放射学检查的组合通常用于诊断和管理早产儿 MBD，但在使用哪种筛查测试和阈值方面存在共识。这在一定程度上与缺乏针对早产儿的规范数据和临床试验有关，因此，缺乏关于诊断和潜在治疗时机的循证指南。生化标志物，如血清 Phos、碱性磷酸酶（ALP）和甲状旁腺激素（PTH），在一些研究中显示出对 MBD 诊断有一定益处，但并不总是具有可重复性。放射线照片可能会识别出不同程度的骨骼变化，但这些变化可能要到 MBD 发展的后期才会被发现。其他方式，如 DXA 和超声，也已被使用，但这些可能会因早产儿缺乏标准或某些中心缺乏可用性而受到限制。需要进一步研究，特别是临床试验，以确定哪些测试组合可以最早发现 MBD，以便促进早期治疗并预防 MBD 的短期和长期并发症。
