53: Is Caffeine a Risk Factor for Osteopenia of Prematurity?

Neonatal bone health is a problem of growing interest and concern because of the increasing recognition of its impact upon childhood, adolescence and even adulthood. Osteoporosis in adulthood often has its roots in childhood. Some forms may be prevented by proper attention to neonatal and childhood bone health. A premature infant likely suffers lifelong decreased bone mineral density as a result of its early birth and the lack of adequate mineral stores that are typically present in full-term infants. Caffeine is now one of the most commonly prescribed drugs in the NICU to treat apnea of prematurity. Later studies in preterm infants confirmed the diuretic effect of caffeine, and revealed a significant increase in creatinine clearance and urinary calcium excretion. The effect of caffeine treatment on bone health of premature infants was not studied before. 1) The primary outcome is to study the effect of caffeine, as the most frequently used medication in NICU, on bone of premature infants. The effect on bone density is mainly based on X-ray data, which were taken every two weeks during the hospital stay. This is a quantitative descriptive Cohort. This cohort study started from birth till 12 weeks of age. As a pilot study this research study included 109 infants. Cases were defined as premature infants less than 31 weeks gestational age and birth weight less than 1500 grams. Variables considered in this study include: Demographic Data. gestational age in weeks, gender, birth weight in grams and maternal parity level, which was recorded as categorical data; high if more five, moderate if three or four and low parity if one or two. Vitamin D was included as longitudinal data Laboratory data. serum phosphate levels were collected on biweekly basis plus or minus one week as found in Attachment Reflection Laboratory Data Retrieval System. The phosphate level was recorded as categorical data; high if more than 2.5 mmol/L, normal if ranged between 1.8 to 2.5 mmol/L, low if between 1.3 to 1.8 mmol/L and very low if less than 1.3 mmol/L. This was considered at any time point during the cohort study. The chest radiographs were undertaken to investigate any clinical problems. The radiological data (x rays) were reviewed by pediatric radiologist, who did not know about the patients' data, on a biweekly basis in the first 12 weeks of life at least, using Koo et al., criteria. The ethics approval was obtained from the Health Research Ethics Board at University of Manitoba number# H2013: 231 and The Health Sciences Centre Research Impact Approval was obtained from the Health Science Center. Number# RI2013: 088. The mean gestational age of this cohort was 27 weeks (27±1.6); the cohort includes 54 males and 55 females. The average birth weight of this cohort was 665±229 grams. Of the 109 infants, 85 were born to mothers of low maternal parity (77.9%), 16 (14.6%) of moderate maternal parity and eight of high maternal parity (7.5%). The median duration of TPN were 21 days with 1st and 3rd quantiles of 11 and 32 days respectively. we dichotomize the radiological findings by collapse of categories of grade levels. Grade 1, 2 and 3 were collapsed together as Osteopenia of prematurity because we lack enough events in each of the three grades. In the same time we considered grade 0 as normal. So the mixed model is generalized mixed model for binary outcome. The average dose of caffeine was 425.33±235.2 mg as a cumulative dose and the average duration of caffeine therapy was 60±45.8 days. There were 79 infants who received diuretics (73%). The median diuretic dose was 5.9 mg with 1st and 3rd quantiles of 1, 25.8. There were 79 infants who received diuretics (73%). The median diuretic dose was 5.9 mg with 1st and 3rd quantiles of 1, 25.8. There were 79 infants who received diuretics (73%). The median diuretic dose was 5.9 mg with 1st and 3rd quantiles of 1, 25.8. The results of this study revealed a strong correlation between exposure to caffeine (either cumulative dose or duration) and the presence of OP. About 8% of infants with MBD further developed spontaneous rib fractures secondary to OP. Table 1 indicates that higher cumulative dose of caffeine is associated with an increase in the probability of Osteopenia of Prematurity (OP). The effect of caffeine was true even when we controlled the effect of other variables (average weight, the gestational age steroid and vitamin D). The odds of OP is 1.10 times (95% CI 1.05–1.15) higher for every 5 mg/kg increase in caffeine dose when the effect of steroids, Vitamin, gestational age and average biweekly weight are controlled. The graph demonstrates the difference between the gestational ages, 25 and 30 weeks in regard of OP probability when both are exposed to the same dose of caffeine. The probability of OP is higher in lower gestational age (25 weeks) than the 30 weeks gestational age.

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