YL Wong, EEH Chan, M Watson

Dear Editor,

We were intrigued by the results of the 2013 paper by Mutlu et al which demonstrated a significant correlation between hyperbilirubinaemia and vitamin D deficiency in full-term neonates.¹ Vitamin D deficiency is a significant problem worldwide, with an estimated 12-40% of United Kingdom children found to be deficient.² The St Mary's Hospital, London paediatric department runs a neonatal prolonged jaundice clinic to screen for sinister causes of hyperbilirubinaemia. Whilst majority of neonates had benign unconjugated hyperbilirubinaemia, a coincidental finding of low vitamin D levels was often reported in the full blood workup. In light of this, we collected patients' data from December 2012 to December 2014 to ascertain if a trend between hyperbilirubinaemia and vitamin D deficiency was found in our London population, similar to that found by Mutlu.

A retrospective analysis of 229 neonates showed no correlation between vitamin D and bilirubin levels (Figure 1, correlation coefficient -0.083). The babies presented between 14-30 days post-partum with total bilirubin levels ranging from 9 to 333 μmol/l (average=164.38±64.01 μmol/l) whilst serum 25-OH vitamin D levels ranged from <10 ng/ml to 88.7 ng/ml (average = 20.28±15.61 ng/ml). In addition, we split the data into those with normal or high bilirubin levels (above 200 μmol/l), and found a non-significant difference in their mean vitamin D levels (normal group = 20.89±15.59 ng/ml; high bilirubin group = 18.70±15.67 ng/ml, p=0.341) (Figure 2).

Figure 1 Scatter-plot graph of vitamin D against total bilirubin levels.

Figure 2 Vitamin D levels grouped by normobilirubinaemia vs. hyperbilirubinaemia.

Our results seem to contradict the findings of Mutlu et al's paper; however we propose several reasons for the differences in our results. Firstly, the post-natal age of the study population differed. In our study, we collected blood results from full-term neonates (>14 days) who had prolonged jaundice, however the former study took measurements from newborns between day 3 and day 10 post-partum. Secondly, as vitamin D is largely derived from the sun, seasonal variations may act as a potential confounder. Whilst Mutlu's prospective study spanned over 4 months through the winter to spring period, our study looked at data from 2 years covering all seasons. Finally, it is worth noting that the ethnically diverse multicultural population of London may contribute to the differing results.

Vitamin D is a prohormone that regulates blood calcium levels to promote skeletal bone growth. Low levels of vitamin D can result in hypocalcaemia and its related symptoms of non-specific muscle pain, whilst severe vitamin D deficiency could result in seizures, cardiomyopathy and the softening of bones associated with nutritional rickets.² In addition, a recent paper reported an increased susceptibility to early onset sepsis in neonates with lower vitamin D levels.³ However we have shown that even in a relatively healthy group of neonates, vitamin D levels were suboptimal and this might be associated with breastfed infants who are more likely to present with prolonged hyperbilirubinaemia. Whilst serum 25-OH vitamin D is not a routine test for neonates, we hope that in light of our study and ongoing research in this field, there will be greater awareness and readiness of paediatricians to prescribe vitamin D supplements to their patients.

We would like to acknowledge the help of Lee, Cheng Wei (BSc Mathematics) for his assistance with the statistical analysis of the data.

No conflicts of interest declared.

References

1. Mutlu M, Cayir A, Cayir Y Ozkan B, Aslan Y. Vitamin D and Hyperbilirubinaemia in Neonates. HK J Paediatr (new series)2013;18:77-81.

2. Bentley J. The role of vitamin D in infants, children and young people. Nurs Child Young People 2015;27:28-35.

3. Cetinkaya M, Cekmez F, Buyukkale G, et al. Lower vitamin D levels are associated with increased risk of early-onset neonatal sepsis in term infants. J Perinatol 2015;35:39-45.