Efficacy of Different Regimens of Vitamin D Supplementation in Preterm Infants- A Randomized Double Blind Trial

Adequatedose of vitamin D needed for supplementation in preterm babies is stillcontroversial with different recommendations by different bodies. Theserecommendations are mainly based on consensus opinion and from the resultswhich are extrapolated from the studies done on adults. AAP recommends 400 IU per day whileESPGHAN recommends 800-1000 IU per day. There are no Indian studies on vitaminD supplementation in preterm babies. These recommendations have to be tested inour conditions as serum vitamin D levels are determined by maternal vitamin Dlevels, sunlight exposure, and skin pigmentation to identify whether they areeffective in attaining vitamin D sufficiency. Hence a randomized trialaddressing two different doses (400 IU per day vs. 800 IU per day) of vitamin D3would help in identifying the appropriate dosage of vitamin D to besupplemented to maintain serum vitamin D levels in the sufficiency range.Babies would be randomized to receive400 IU or 800 IU per day of vitamin D3 drops orally. The preparations would beprepared in such a way that the volume, color, appearance of the drug in boththe group would remain the same. Mother would be advised to administer the drugin home by mixing it in 5 ml of expressed breast milk in a paladay. Compliancewill be ensured by asking the mother to produce the empty vials of the vitaminD3 drops while attending the high risk clinic on follow up. Mother also wouldbe asked to maintain record of the number of doses missed. Mothers would be counseled forexclusive breast feeding during enrollment. Babies would be fed on expressedbreast milk (EBM) fortified with human milk fortifier (HMF) once the baby is on100 ml/kg feeds as per the existing unit protocol. One sachet (2g) of theavailable HMF (Lactodex-HMF) will be mixed with 50 ml of expressed breast milkand ½ sachet for 25 ml of EBM. Total number of HMF sachets used per day perbaby would be recorded so that daily vitamin D intake through HMF can becalculated. Babies who are on both formula and expressed breast milk would beadvised to add HMF only to the EBM feeds but not formula.

At discharge the mother would beadvised to continue HMF till the baby weighs at least 2000g. Mother will beadvised to keep record of the total number of HMF sachets consumed per day andalso would be advised to produce the empty HMF sachets on follow up so that theamount of vitamin D available through HMF per day can be calculated. Once thebaby is more than 2000g mother will be advised to continue only breast milk.Maximum vitamin D intake through HMF will be 304 IU per day if the baby is on200 ml/ kg day which is the accepted upper limit of feed volume per day in theunit. Mother will be advised to decrease the dose of vitamin D3 supplement by0.1 ml per every 2 sachets of HMF used.

Blood samples (2ml) would be taken atenrollment, at term age(±2 weeks) and at 3 months (±2 weeks) corrected age in a  plain vial and the serum would be separatedand stored at -20o C for analysis as a batch for 25(OH)D3 and PTHevery week. Serum Calcium, Phosphorus and alkaline phosphatase will be analyzedfrom the side lab on the day of sampling.Babies would be monitored for adverseeffects. Serum calcium, phosphorus and alkaline phosphatase would be doneduring follow up visits. Urine calcium creatinine ratio will be done in thespot sample to look for hypercalciuria monthly. Ultrasound abdomen also will bedone at term age and at 3 months corrected age to look for nephrocalcinosis.

Wholebody bone mineral content and bone mineral density would be measured at 3months (±2 weeks) corrected age through dual energy x rayabsorptiometry (DEXA) using the Discovery QDR series, Hologic, USA machine.