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Do you know about Metabolic Bone Disease of Prematurity?

By Dr. Namrata Todurkar


Metabolic Bone Disease (MBD) of prematurity is a serious complication in extremely preterm babies. It is one of those issues that emerges after the initial storm of instability settles in a preterm baby. Although it may seem to emerge out of the blue, the NICU team would have taken steps to prevent this situation from the day 1 of a preemie’s life. Each baby’s NICU journey is different and this condition can surface despite all measures. Early clinical diagnosis of MBD is difficult, and clinical manifestations often lag far behind blood biochemical changes or bone changes seen on x-ray.  

 

In this blog we shall understand : 

  • what metabolic disease of prematurity is 

  • its symptoms 

  • diagnosis 

  • treatment 

  • complications 

  • prevention 

  • Role of families in managing MBD 

 

What is MBD? 

MBD of prematurity is a state of reduced mineralisation (Calcium and Phosphate deposition) of the skeleton in preterm infants leading to decreased bone density, in other words ‘weak bones’. At the extreme end, it can be associated with fragility fractures and cause breathing compromise. MBD of prematurity is sometimes referred to in the literature as ‘Rickets of prematurity’ and ‘Osteopenia of prematurity’. 

 

How common is MBD? 

About one fourth of very low-birthweight infants (<1500 gram) and 55% of extremely low-birthweight infants (<1000 gram) develop MBD, with increasing prevalence in those with additional risk factors (discussed next). 

 

What are the risk factors? 

The cause of MBD is multifactorial. Several risk factors have been associated, although the main pathogenetic mechanism is represented by the reduced placental transfer of calcium and phosphate related to preterm birth. 

The identified risk factors are: 

  • Placental insufficiency (conditions like high blood pressure in mum, pre eclampsia, placental anomalies) 

  • Prolonged delivery of IV nutrition or total parenteral nutrition (TPN) for more than 4 weeks 

  • Bronchopulmonary dysplasia (BPD) 

  • Chorioamnionitis (infection of placental membranes) 

  • Necrotizing enterocolitis (NEC) 

  • Neuromuscolar disorders like myotonic dystrophy, spinal muscular atrophy etc 

  • Intraventricular hemorrhage and its complications 

  • Liver and Kidney disease 

  • Genetic polymorphisms (example: vitamin D receptor gene) 

  • Medications (diuretics, steroids) 

 

What are the symptoms? 

There may not be any symptoms of MBD until it is diagnosed accidentally on x-ray. Severe cases (1-10%) may present with fractures of long bones. The radiographic changes occur between weeks 8 and 12 postnatally, and a reduction in bone density of 20–40% is required before this is apparent. 


Picture source: Chinoy A, Mughal MZ, Padidela RMetabolic bone disease of prematurity: causes, recognition, prevention, treatment and long-term consequencesArchives of Disease in Childhood - Fetal and Neonatal Edition 2019;104:F560-F566. 


How is the diagnosis made? 

A comprehensive diagnosis of MBD is largely made based on : 

  1. Declines in serum calcium and phosphorus levels. 

  1. Elevation of an enzyme named alkaline phosphatase (ALP) and a hormone named parathyroid hormone (PTH). 

  1. Thinning bones or fractures revealed by x-ray. 

 

How is MBD managed? 

The initial management goal is to prevent MBD by providing adequate Calcium and Phosphorous to mimic placental transfer of these minerals. After the first few days of life, upward adjustment of phosphorus should ensue to optimize bone mineralization. When TPN is required, close biochemical monitoring and adjustments are critical. 

 

Once infants are transitioned to oral feedings, fortified breast milk or preterm formulas should be used along with Vitamin D (recommended upto 800-1000 IU/day). Despite reaching higher mineral intake, some infants still develop MBD and may require targeted supplementation with Calcium and Phosphorous.  

 

Complications: 

MBD has a negative impact on the growth and development of preterm infants. Short-term, this disease can cause ventilator dependence and increase the risk of fractures. It can result in increased risk of nearsightedness, kidney failure, and abnormal bone development, which impairs breathing function, affects adult height or lead to osteoporosis in the long term.  

 

Prevention: 

The basic approach to MBD prevention involves improving calcium and phosphorous intake from the first day of life, limiting the use of medications that increase bone resorption or calcium loss (like diuretics and steroids), promoting oral/ enteral feeding, and early identification of at-risk babies.  Routine biochemical screening is recommended in very low birth weight infants in order to individualize subsequent management.  

 

Can families do anything to prevent or treat MBDP? 

Fracture prevention is the cornerstone of management for infants at risk. Bedside signage alerting members of the medical team to safe handling of at-risk infants should be displayed. Therapeutic positioning can promote opportunities for the infant to move and build bone and muscle strength. Physical therapy programs with 5–15 min/day of activity can promote body weight, length, muscle mass, bone strength, bone mineral content, and mineralization in the tiniest infants. Massage may also be used as an adjunct to physical therapy and may positively affect bone formation markers. These therapies can be taught to parents to practice with infants at the bedside and at home and can improve bonding. 

 

Summary: 

Metabolic bone disease of prematurity involves more than ‘weak bones’, and its prevention is among the highest priorities in modern neonatal care. Diagnosis requires the assessment of several biochemical markers, and X ray findings. The optimization of total parenteral nutrition and the early achievement of a full oral/enteral feeding are important goals for the prevention and management of MBD of prematurity. Preterm infants at high risk of developing MBD should have Calcium and Phosphorous intake tailored to their specific needs along with Vitamin D. Despite all measures, MBD can still manifest in extremely preterm neonates. 

 

Resources: 

 

  1. Faienza MF, D'Amato E, Natale MP, Grano M, Chiarito M, Brunetti G, D'Amato G. Metabolic Bone Disease of Prematurity: Diagnosis and Management. Front Pediatr. 2019 Apr 12;7:143. doi: 10.3389/fped.2019.00143. PMID: 31032241; PMCID: PMC6474071. 

  1. Chinoy A, Mughal MZ, Padidela RMetabolic bone disease of prematurity: causes, recognition, prevention, treatment and long-term consequencesArchives of Disease in Childhood - Fetal and Neonatal Edition 2019;104:F560-F566. 


Dr. Namrata Todurkar, MBBS, MD (Pediatrics), DNB (Pediatrics). Fellowship in Neonatology from National Neonatology Forum India. Fellow in Neonatal-Perinatal Medicine at the University of British Columbia. Areas of interest: Neonatal nutrition, Fluid and Electrolyte Management, Inborn Errors, Neurodevelopmental follow-up of preterm infants. Dr. Todurkar is a volunteer blogger at CPBF.




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