DO NOT USE FOR CLINICAL PRACTICE
Please use current guidelines available on the UHNM intranet for patient treatment
Please use current guidelines available on the UHNM intranet for patient treatment
RECOGNITION AND ASSESSMENT
Definition
- Decreased mineralisation of bones due to deficient phosphate (PO4), calcium (Ca) or vitamin D in preterm babies
- Also known as osteopenia of prematurity
Causes
- Inadequate postnatal intake or absorption to match intrauterine mineral accretion rate
Risk factors
- <32 weeks’ gestation or <1500 g birth weight
- Male gender
- Delay in establishing enteral feeds/enteral feeds with low mineral content/bioavailability [unfortified expressed breast milk (EBM), term formula]
- PO4/Ca or vitamin D deficiency
- Prolonged parenteral nutrition (PN) (>2 weeks)
- Chronic drug use that increases mineral excretion (diuretics, steroids, sodium bicarbonate)
- Lack of mechanical stimulation e.g. sedation/paralysis
- Chronic lung disease
- Cholestatic jaundice
- Short gut syndrome (malabsorption of vitamin D and Ca)
Symptoms and signs
- ≤6 weeks – most babies are asymptomatic and normal on examination
- Usually presents aged 6–12 weeks
- Poor weight gain or faltering growth
- Respiratory difficulties: failure to extubate due to increased chest wall compliance
- Fractures with minor or no trauma; may manifest as pain on handling
- Craniotabes (softening of skull bones)
Later clinical consequences
- Marked dolicocephaly (long and narrow skull)
- Reduced linear growth
DIAGNOSIS
Serum biomarkers
- Low serum PO4 (<1.8 mmol/L) with elevated alkaline phosphatase (ALP) (>900 IU/L) is 100% sensitive and 70% specific for diagnosing low bone mineral density
- Low serum PO4 concentrations (<1.8 mmol/L) have 96% specificity but only 50% sensitivity. Routine PO4 supplementation in high risk babies could lead to secondary hyperparathyroidism, and thus worsen MBD
- Serum Ca levels may remain normal until late in the disease despite bone losses of Ca
- In suspected MBD with elevated ALP and low PO4, serum parathormone (PTH) measurement will help in establishing if there is underlying Ca or PO4 deficiency to provide correct supplementation
- Ca deficiency causes increased PTH to maintain normocalcaemia
- in PO4 deficiency there is no compensatory mechanism – PTH remains normal
Urinary biomarkers
- Urinary excretion of Ca >1.2 mmol/L and PO4 >0.4 mmol/L signifies slight surplus of supply and correlates with highest bone mineral accretion rate
- phosphaturia can occur due to aminoglycoside, indomethacin and steroid therapy
- calciuria can occur due to diuretics, steroids and theophylline
- Tubular reabsorption percent (TRP) of PO4 is also a guide to adequacy of PO4 supplementation. TRP of >95% indicates inadequate supplementation
- TRP (%TRP) = [1 − (urine PO4/urine creatinine) (plasma creatinine/plasma PO4)] x 100
Radiological
- Low bone density on X-rays (rachitic changes, cortical thinning, periosteal elevation) or fractures of long bones or ribs
- Dual-energy X-ray absorptiometry/qualitative ultrasound to assess bone mineral density
PREVENTION
- Optimal nutritional intake
- early PN with optimised Ca and PO4 content – Parenteral nutrition guideline
- early enteral feeds
- optimal ratio of enteral Ca:PO4 of 1.3:1–≤1.4:1 mmol-to-mmol basis should be targetted to avoid secondary hyperparathyroidism
- adequate Ca (3–5.0 mmol/kg/day) and PO4 (2.2–3.7 mmol/kg/day) intake by using fortified EBM or preterm formula. ≥140 mL/kg/day fortified EBM or preterm formula is needed to provide this
- daily intake of ≥400–700 units/kg/day vitamin D
- Ensure appropriate handling and position using deep boundaries to promote active bone loading
INVESTIGATION AND TREATMENT
For all high risk babies, after at least one week of full enteral feeds (≥140 mL/kg/day fortified EBM or preterm formula), measure serum Ca, PO4 and ALP levels from third week of life and follow this guidance:
MONITORING AND FOLLOW-UP
- Stop additional vitamin D when vitamin D and PTH are normal
- Adjust Ca dose based on serum Ca levels and stop only once PTH levels normalise
- Adjust PO4 dose based on serum PO4 levels, and ALP adjusting Ca dose to maintain ratios
- Continue treatment until biochemical indices are normal and radiographic evidence of healing, usually until term corrected gestation