During the study period of 10 months from October 2020 to July 2021, 78 babies ≤ 32 weeks or with birth weight ≤ 1250 g were eligible for MBD screen at 4 weeks in our NICU. Of these, 57 babies developed MBD and were stratified into three groups based on their gestation (≤ 28 weeks, 29–30 weeks, 31–32 weeks). Their baseline demographic characteristics are given in Table 1, and feeding details are given in Table 2.

Among the baseline nutritional characteristics, there was a significantly longer duration of parenteral nutrition in ≤ 28 weeks and 29–30 weeks as compared to 31–32 weeks (Table 2). The time to reach full feeds, initiation of fortification, and number of days of fortification prior to the first evaluation of MBD was significantly prolonged in the lower gestations. However, the maximum feed volume and calorie received, type of milk fed, and feed intolerance episodes were comparable among the three groups.

The overall incidence of MBD in the present study population was 73%, while 100% of ≤ 28 weeks babies had MBD at discharge (Table 3). Fifty-four percent of babies was available for at least 1 follow-up post discharge.

Seventeen babies of ≤ 30 weeks required inorganic phosphorus supplementation in addition to calcium phosphate supplementation in order to correct the MBD. All infants required almost the same average doses of calcium, phosphorus, or vitamin D supplementation with no significant difference in the average dosage in the three groups (Fig. 1).

Average supplementation of calcium, phosphorus, and vitamin D

There was no significant difference found in the serum calcium and serum phosphorus of the three groups at the varied postnatal age (PNA) of estimation and also at follow-up when they received optimum supplementation. The serum calcium level was maintained throughout in all the three groups. USG KUB was done in 51 infants prior to discharge to look for nephrocalcinosis due to calcium supplementation. None of them had evidence of nephrocalcinosis. The serum phosphorus level improved to > 5.5 mg/dl by 14 weeks in ≤ 28 weeks babies, by 12 weeks in 29–30 weeks babies, and by 12 weeks in 31–32 weeks babies when optimally supplemented. Serum phosphorus level normalized in all the babies by 42–44 weeks PMA. However, no significant difference was found in the serum ALP level of the three groups at the varied PNA of estimation except at 12 weeks PNA as the serum ALP level normalized by this time, i.e., 42–44 weeks PMA. The serum ALP level did not normalize till the last follow-up, i.e., 1.5 month corrected age in ≤ 28 weeks, which indicates that a longer time is required for normalization of this biochemical parameter in this subgroup (Table 4).

Methylxanthines, diuretics, and corticosteroids are known to increase the chance of development of metabolic bone disease. Infants who received caffeine with or without steroids or diuretics had a significantly higher incidence of hypophosphatemia and higher alkaline phosphatase levels at 4 weeks of age and also at discharge (Table 5).

The time to reach full feeds with fortification had no statistically significant effect on the incidence of metabolic bone disease as detected by serum phosphorus level and serum alkaline phosphatase level (Table 6).

The mean duration of hospital stay was 10 weeks in ≤ 28 weeks, 8 weeks in 29–30 weeks, and 6 weeks in 31–32 weeks of babies. Thus, the duration of hospital stay was higher in ≤ 28 weeks as compared to the other two groups due to obvious reasons of prematurity-related complications and the longer time required by the extremely preterm babies to reach suck-swallow-breathing coordination.