Metabolic bone disease of prematurity – an overview

With improved survival of extreme preterm and very low birth weight infants, there has been an increased incidence of metabolic bone disease (MBD). The last couple of decades have seen better awareness of the condition which in turn has led to improvement in the management and prevention of MBD. MBD occurs because there is difficulty in matching intrauterine mineral accretion rate after birth. The lack of a single specific and sensitive diagnostic test frustrates early diagnosis in many babies. Investigations like dual energy X-ray absorptiometry (DEXA) and quantitative ultrasound scanning are helpful in establishing a diagnosis but currently used mostly in research studies. A pragmatic approach for paediatricians is to pre-empt the formal diagnosis and supplement those at risk with adequate minerals and vitamin D, whilst monitoring the blood markers of MBD. Despite the noticeable short-term complications and stunting effect on childhood height, the prognosis of MBD is generally good. The aim of this article is to provide the reader with an improved understanding of the aetiopathogenesis, and offer some practical guidance on when and how to investigate and manage the metabolic bone disease of prematurity.     

早产儿代谢性骨病诊治的研究进展

早产儿代谢性骨病(MBD)是由于多种因素引起钙磷代谢紊乱导致骨矿物质含量减少,从而引起临床、生化及骨影像学相关改变,多发生于极低和超低出生体重儿。临床症状通常发生在生后6~12周,主要表现为呼吸困难、长时间依赖呼吸机治疗、佝偻病样表现,严重者甚至骨折。目前MBD主要依赖生化标记物、放射学及超声学等进行诊断。由于早产儿MBD的临床表现发生较晚,故对于高危人群进行早期筛查及预防有重要意义。     

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??Objective??To explore whether late-onset sepsis??LOS?? is associated with an increased risk of encephalopathy of prematurity in preterm infants with gestational age??32 weeks. Methods??Four hundred preterm infants with gestational age??32 weeks who were admitted to our hospital from January 1st??2013 to December 31st??2014 underwent magnetic resonance imaging at term-equivalent age. All the perinatal data were collected prospectively. The infants were divided into different groups based on different type of sepsis. Results??Of 400 preterm infants??79??19.8%?? had LOS??of whom 45??11.3%?? were positive in blood culture. Coagulase-negative staphylococci was the commonest pathogen of postnatal infection??33.3%??. According to the result of magnetic resonance imaging??133??28.2%?? preterm infants had encephalopathy of prematurity. Compared with non-sepsis group??infants in LOS group had significantly higher risk to have encephalopathy of prematurity??36.7% vs. 26.2%??OR??1.759??95% CI??1.033??2.997??P??0.038??. Conclusion??Preterm infants with LOS have greater risks of developing encephalopathy of prematurity??which indicates that LOS might be a risk factor of encephalopathy of prematurity.     

高危晚期早产儿脑病临床特点及磁共振影像学评估

目的了解高危晚期早产儿(LPI)脑病的危险因素、临床特点及磁共振(MRI)影像学变化。方法对2009年1月至2014年12月住院且存在脑损伤高危因素的LPI,进行头颅MRI检查,分析LPI脑病危险因素、临床特点及头颅MRI特征。结果完成MRI检查的LPI共1 007例,影像学符合早产儿脑病患儿313例(31.1%)。LPI脑病中白质损伤占76.7%。LPI脑病的发生与胎龄无相关性,但随着出生体重增加,脑病检出率逐渐增高(P0.05)。Logistic回归分析结果显示:复苏史是早产儿脑病发生的独立危险因素(P0.01)。结论早产儿脑病在高危LPI中亦较常见,特别是脑白质损伤。复苏病史是LPI脑病的独立危险因素,需引起重视。     

Retinopathy of prematurity: An update on screening and management

Retinopathy of prematurity is a proliferative disorder of the developing retinal blood vessels in preterm infants. The present practice point reviews new information regarding screening and management for retinopathy of prematurity, including the role of risk factors in screening, optimal scheduling for screening examinations, pain management, digital retinal photography and antivascular endothelial growth factor therapy.     

779例新生儿眼底筛查结果及新生儿眼底疾病高危因素分析

目的 应用广角数码视网膜成像系统(RetCam3)进行新生儿眼底筛查,了解早产儿及足月小于胎龄儿视网膜疾病的患病率及影响因素.方法 回顾性分析2013年1~12月在我院新生儿病房行RetCam3眼底筛查的早产儿及足月小于胎龄儿的临床病例资料.结果 779例早产儿及足月小于胎龄儿接受筛查,检出有眼底病变患儿100例(12.8%),其中视网膜出血69例(8.9%)、早产儿视网膜病(ROP)10例(1.3%)、眼底渗出9例(1.2%)、视网膜有髓神经纤维4例(0.5%)、视网膜色素沉着3例(0.4%)、先天性白内障和结晶样变性各2例(0.3%)、视网膜母细胞瘤1例(0.1%).Logistic回归分析表明低出生体重、胎龄小和有吸氧史是ROP发病的高危因素(分别OR=0.209、0.248、0.049,均P<0.01);阴道分娩和有机械通气史是导致视网膜出血的高危因素(分别OR=3.196、1.731,均P<0.05).结论 新生儿眼底病变多样且危害严重,早产儿及足月小于胎龄儿应该是眼底筛查的重点人群,临床应加强对高危因素的干预,从而降低ROP和视网膜出血的发生率.     

Calcium and phosphorus nutrition in preterm infants

Metabolic bone disease is a common event in preterm infants. Between 24 wk gestation and term, the fetus accrues approximately 80% of body Ca, P and Mg. Consequently, preterm infants miss in part or completely the period of greatest mineral accretion. Ca and P requirements in preterm infants are based on demands for matching intrauterine bone mineral accretion rates and on maintenance of normal serum Ca and P concentrations. Daily physical therapy may be a useful adjunct, as it is associated with a significant increase in bone mineral density and content. Osteopenia/rickets of prematurity seems to be a self-resolving disease. However, this does not imply that a period of demineralization is acceptable. While the potential long-term consequences on peak bone mass are unclear at the moment, the short-term benefits include the avoidance of fractures, less marked dolicocephaly and improved linear growth.     

Calcium and phosphorus nutrition in preterm infants

Metabolic bone disease is a common event in preterm infants. Between 24 wk gestation and term, the fetus accrues approximately 80% of body Ca, P and Mg. Consequently, preterm infants miss in part or completely the period of greatest mineral accretion. Ca and P requirements in preterm infants are based on demands for matching intrauterine bone mineral accretion rates and on maintenance of normal serum Ca and P concentrations. Daily physical therapy may be a useful adjunct, as it is associated with a significant increase in bone mineral density and content. Osteopenia/rickets of prematurity seems to be a self-resolving disease. However, this does not imply that a period of demineralization is acceptable. While the potential long-term consequences on peak bone mass are unclear at the moment, the short-term benefits include the avoidance of fractures, less marked dolicocephaly and improved linear growth.     

Fracture and fortified breast milk in an extremely preterm infant

Metabolic bone disease (MBD) in the newborn predominantly affects preterm infants. The risk of MBD is inversely proportional to gestational age and birthweight, and directly related to postnatal complications. Poor bone mineralization has been shown in 55% of infants born at less than 1000 g. Optimal nutrition for very preterm infants is thought to be mother's own milk but supplementation is required to meet dietary requirements. However, there is insufficient evidence to determine that supplementation of human milk with commercial fortifiers has an effect on bone mineral content. We report a case of severe MBD with fractures in an extremely preterm infant who was fed with fortified mother's milk.     

Improved Bone Mineral Status in Very Low Birthweight Infants Fed Human Milk Mixed with Preterm Formula

The bone mineral status of very low birthweight (VLBW) infants fed exclusively their own mother's milk (group I) was compared with that of VLBW infants fed mother's milk in the initial 4 weeks followed by a 1:1 mixture of mother's milk and preterm formula containing high phosphorus (P) and calcium (Ca) (group II). In both groups, most infants showed a biochemical picture characteristic of phosphorus deficiency syndrome by the fourth week. Thereafter, serum alkaline phosphatase activity (ALP) decreased and serum P increased in all group II infants. Conversely, serum ALP rose and hypophosphatemia persisted in most group I infants. Group II had a significantly higher serum P at weeks 8 and 12 and a significantly lower ALP at week 12 than group I. Furthermore, group II had a lower incidence of severe radiographic abnormalities than group I at week 12. We confumed previous observations that VLBW infants fed exclusively human milk require P and Ca supplementation to prevent metabolic bone disease of prematurity.     

Quantitative ultrasound (QUS): a useful tool for monitoring bone health in preterm infants?

Preterm infants are at risk of osteopenia and metabolic bone disease (MBD) of prematurity. There is a need for simple, reliable methods to detect and monitor this condition. Aims: The aims were first to describe longitudinal changes in speed of sound (SOS) measured using quantitative ultrasound (QUS; Sunlight Omnisense, Israel) in preterm neonates: and second to determine whether SOS predicts the development of MBD. Methods: SOS was measured in the tibia in 99 preterm infants (mean (SD)) gestation 29.7 (3.6) weeks; birthweight 1340 (550) g, with longitudinal measurements in 75. SOS z‐scores were generated for gestation and sex. Clinical data were recorded. Results: Baseline SOS (but not SOS z‐score) was positively associated with gestational age. SOS and SOS z‐score fell with age. In multivariate models, peak ALP, minimum phosphate concentrations and markers of illness severity were not predictors of the fall in SOS z‐score, and baseline SOS measurements did not predict the development of high peak ALP or low phosphate. Interpretation: Speed of sound measurements fell with age in all infants, but we found no evidence that this measurement could predict biochemical indicators of MBD. We cannot exclude the possibility that this technique could be useful in monitoring the response to interventions designed to improve bone health in this population.     

Retinopathy of prematurity: overview of new global problem

Retinopathy of prematurity (ROP) is a disease characterized by abnormal retinal vasculature in preterm infants. It is an important cause of visual disability in premature infants and although the incidence varies among different countries it is increasing as advances in neonatal care result in improved survival. Oxygen, growth factors like vascular endothelial growth factor, and poor postnatal growth play a significant role in the pathogenesis of ROP. Targeting lower oxygen saturation is associated with a reduction in ROP, but with increased mortality. Screening for ROP varies between centres and countries but generally it includes preterm infants (less than 32 weeks’ gestation) and/or those with a birth weight of less than 1500g. ROP has been recently reclassified as type-1-needing treatment and type-2 ROP needing observation, based on the benefits and treatment efficacy. Laser therapy and anti-VEGF are the two main treatments. Recent reports suggest that anti-VEGF therapy may have better visual outcomes (myopia) and a better safety profile. ROP is a global disease of prematurity and understanding the pathogenesis, course of ROP, preventive strategies, treatment options and outcomes are essential for all healthcare professionals caring for preterm babies. This short article describes the evidence for screening, prevention and treatment options and looks ahead to possible advances in the near future.     

Retinopathy of prematurity: Recommendations for screening

Retinopathy of prematurity (ROP) is a disorder of the developing retinal blood vessels of the preterm infant. New recommendations for screening and treatment of ROP have been published in the past few years. Current evidence suggests that screening infants with gestational ages of 30 6/7 weeks or less (regardless of birth weight) and birth weights of 1250 g or less is a strategy with a very small likelihood that an unscreened baby would have treatable ROP. Individual centres may choose to extend birth weight screening criteria to 1500 g. Initial screening should be performed at 31 weeks' postmenstrual age in infants with gestational ages of 26 6/7 weeks or less at birth, and at four weeks' chronological age in infants with gestational ages of 27 weeks or more at birth by an ophthalmologist skilled in the detection of ROP. Follow-up examinations are conducted according to the ophthalmologist's recommendation. Infants with high-risk prethreshold ROP and threshold ROP are referred for retinal ablative therapy. Developing processes for ROP screening, documenting results and communicating results to parents as well as health professionals involved in the infant's care are important responsibilities for all nurseries providing care for preterm infants.     

Relationship of tibial speed of sound and lower limb length to nutrient intake in preterm infants

BACKGROUND: Metabolic bone disease of prematurity is characterised by impaired postnatal mineralisation of the rapidly growing infant skeleton. OBJECTIVE: To longitudinally evaluate postnatal changes in tibial speed of sound (tSOS; which reflects cortical thickness and bone mineral density) and lower limb length (LLL; a measure of tibial growth) in very low birthweight preterm infants receiving contemporary neonatal care. METHODS: tSOS and LLL were measured using a quantitative ultrasound device and an electronic neonatal knemometer, respectively, in the same limb, weekly, for a median period of four weeks (3-16 weeks) in 84 preterm infants (median gestation 26.8 weeks (range 23-35.2 weeks) and median birth weight 869.5 g (range 418-1481 g)). RESULTS: Initial tSOS and LLL were correlated with gestation (r = 0.42, p<0.001; r = 0.76, p<0.001, respectively) and birth weight (r = 0.23, p = 0.038; r = 0.93, p<0.001, respectively). Postnatally, tSOS decreased (r = -0.15, p = 0.011) whereas LLL increased (r = 0.96, p<0.001) with age. The rate of postnatal change in LLL, but not in tSOS, was positively influenced by intake of calcium (p = 0.03), phosphorus (p = 0.01) and vitamin D (p = 0.03). CONCLUSIONS: The postnatal decline in tSOS, which is probably due to cortical thinning secondary to endocortical bone loss, and increase in LLL provide new insight into the development of long bones in preterm infants.     

早产儿视网膜病的影响因素

目的 探讨早产儿视网膜病(ROP)的影响因素.方法 选择本院患ROP早产儿为观察组,32周以下的早产儿为对照组,对2组患儿胎龄、出生体质量、出生方式、性别、多胎、使用呼吸机时间、休克、呼吸暂停、新生儿寒冷损伤综合征、肺透明膜病(Ⅲ级以上)、严重感染、肺出血及并发症合计数等临床资料进行单因素分析,并对有意义的因素进行多因素Logistic分析.结果 本资料共有早产儿358例,胎龄均小于32周.ROP 34例,其中Ⅰ期13例,Ⅱ期18例,Ⅲ期3例.二组患儿窒息、呼吸暂停、新生儿寒冷损伤综合征、肺透明膜病、严重感染、肺出血等并发症的发生率比较差异均有统计学意义(Pa<0.05),并发症合计数(OR=2.152,P=0.048)、使用呼吸机时间(OR=1.514,P=0.009)是危险因素.结论 早产儿ROP的发生率和发生并发症的多少及使用呼吸机的时间长短有关.在临床工作中要更多关注并发症的情况.     

Bacterial infection in preterm infants during xanthine therapy for idiopathic apnoea of prematurity

Three preterm infants who acquired systemic bacterial infection during xanthine derivative therapy for idiopathic apnoea of prematurity are described. Apnoea, despite therapeutic serum levels of theophylline, was the presenting symptom of infection in two of the infants. Apnoea did not develop in the third infant, despite co-existent hyponatraemia and intraventricular haemorrhage, though sepsis was diagnosed from other signs. All three infants, including one with Pseudomonas aeruginosa meningitis, responded rapidly to antimicrobial therapy and survived. An increase in the frequency and/or severity of apnoea in a preterm infant being treated with xanthines should alert the physician to symptomatic apnoea such as that associated with bacterial infection. Conversely, the development of symptomatic apnoea may be suppressed by concurrent xanthine derivative therapy for idiopathic apnoea of prematurity.     

AP-ROP in an infant with minimal oxygen exposure

Abstract   Retinopathy of prematurity (ROP) is a multifactorial disease affecting the developing retinal vasculature and remains an important cause of blindness in very preterm infants. Rush disease, or aggressive posterior ROP (AP-ROP), progresses rapidly to stage 5 disease without exhibiting the classical course that includes stages 1–3. We describe an infant with minimal exposure to oxygen who developed AP-ROP that led to bilateral retinal detachments and a poor visual outcome, despite following current recommended screening guidelines.     

Retinopathy of prematurity: New developments bring concern and hope

Blindness from retinopathy of prematurity (ROP) in Australian and New Zealand is an uncommon event although 3% of <31 weeks gestation infants receive treatment for the disease. New world‐wide estimates of the incidence of blindness from ROP are much higher than previously at 20 000 children annually. The impact of severe ROP can be reduced through good evidence‐based care of very preterm infants and careful organisation of eye examinations and follow‐up services. Recent oxygen saturation targeting trial results might mean the adoption of higher targets than formerly in very preterm infants and will require vigilance to ensure all eligible infants are examined appropriately. A true screening examination for acute ROP might involve non‐opthalmologists obtaining photographic retinal images and remote reading of these. Although treatment with laser gives good outcomes, there is interest in intravitreal anti‐vascular endothelial factor agents, but issues concerning the systemic safety and retinal results of such treatment are unresolved.     

极低/超低出生体重早产儿代谢性骨病危险因素的全国多中心调查

目的 分析极低/超低出生体重(very/extremely low birth weight,VLBW/ELBW)早产儿代谢性骨病(metabolic bone disease of prematurity,MBDP)的发生率及危险因素.方法 回顾性调查2013年9月1日至2016年8月31日全国多中心61786例新生...     

Osteopenia of prematurity - the role of exercise in prevention and treatment

Premature infants have an increased risk of osteopenia due to limited bone mass accretion in utero and a greater need for bone nutrients. Currently, the diagnosis of osteopenia is based on clinical and radiological signs and measurements of biochemical markers. Recent studies suggest that measurements of circulating bone turnover markers, and bone strength assessment using quantitative ultrasound measurements of bone speed of sound (SOS) may help in the evaluation of bone metabolism in preterm infants. So far, most of the preventive efforts of osteopenia of prematurity focused on nutritional changes. Recent studies indicate that the passive range of motion exercise of the extremities results in a significantly greater increase of body weight, increased bone mineralization, increased bone formation markers and leptin levels, and attenuation of the natural post-natal decline in bone SOS. These results suggest that exercise may play an important role in the prevention and treatment of osteopenia of prematurity.