Caffeine Treatment for Apnea of Prematurity and the Influence on Dose-Dependent Postnatal Weight Gain Observed Over 15 Years

Abstract

Background and Aim: To analyze the influence on weight gain of infants exposed to two dosage regimens of oral caffeine citrate (CC) for apnea of prematurity.Methods: Retrospective descriptive observational study of an eligible very low birth weight cohort over a 15-year period in an Irish University hospital. Data were analyzed between two distinct postnatal ages: 14–28 and 29–56 days.Results: During the 15-year study, 457 infants were prescribed caffeine. Among the 14–28-day group, after applying exclusion criteria, 418 infants qualified. Two hundred forty-eight infants received 5 mg/(kg·day) and 170 received 10 mg/(kg·day) of CC. Among the 29–56-day group, 362 infants were identified and after applying exclusions, 332 fulfilled entry criteria [214 on 5 mg/(kg·day) and 118 on 10 mg/(kg·day) regimen]. Baseline characteristics of infants were comparable between groups without statistically significant differences. Mean daily weight gain (MDWG) in grams from day 14 to 28 showed a higher rate of increase for the 5 mg/(kg·day) group compared with the 10 mg/(kg·day) group (17.2 ± 12 g vs. 13.0 ± 10.2 g [p = 0.04]). From day 29 to 56, also MDWG was higher among infants on 5 mg/(kg·day) of CC compared with 10 mg/(kg·day) group (15.6 ± 10.8 g vs. 10.2 ± 9.8 g [p = 0.011]).Conclusion: While a variety of measures are optimized to promote postnatal weight gain of premature infants close to an ideal intrauterine growth curve, not paying sufficient attention to one of the most widely used catabolic agents in neonatology is questionable and warrants vigilance. Additional nutritional measures could be offered to those with prolonged caffeine exposure.

Antioxidative effects of caffeine in a hyperoxia-based rat model of bronchopulmonary dysplasia

“…Its efficacy and tolerability with a wide therapeutic index and high safety have made it the drug of choice for respiratory instabilities and it is often used for many weeks with potential catabolic effects that could impact the initial weight gain of preterms. The effect of caffeine on weight loss of caffeine-treated newborn rats according to our in vivo results matches observations made in preterm infants [22,40,41]. This can be explained by the increased diuresis in kidneys caused by caffeine.…”

“…However, since this is of a temporary nature, and all treated pups after some time returned to the range of body weight similar to untreated controls, the impact of weight loss (or water loss) seems negligible and in fact could easily be treated in the context of patient medical care. From clinical studies it is known that prolonged caffeine insult may lead to a reduction in weight gain, due to a higher energy expenditure and higher oxygen consumption of the organism [42], and influenced by caffeine concentration [41].…”

Electrical activity of the diaphragm following a loading dose of caffeine citrate in ventilated preterm infants

“…One adult study showed an increase in trans-diaphragmatic pressure post caffeine therapy implying that caffeine does indeed enhance muscle contractility of the diaphragm (17). It has been suggested that caffeine acts centrally by rapidly crossing the blood brain barrier (18) and through transmission of neural impulses has subsequent effects on respiratory function resulting in increased diaphragmatic muscle activity (19). A further possibility is that caffeine increases sarcoplasmic reticulum calcium concentrations (17,20) and hence enhances the activation of contractile proteins by increasing the affinity of calcium activation sites for calcium ions (21).…”

Unprecedented reduction in births of very low birthweight (VLBW) and extremely low birthweight (ELBW) infants during the COVID-19 lockdown in Ireland: a ‘natural experiment’ allowing analysis of data from the prior two decades

“…[12][13][14][15] Recognising the sources of heterogeneity and phenotypic plasticity in VLBW and ELBW births may inform eventual effectiveness of preventive measures. 16 17 Socioenvironmental measures implemented as Ireland's response to the SARS-CoV-2 virus (COVID- 19) pandemic collectively constituted a national lockdown, and may possibly have influenced the health and wellbeing of pregnant women and their unborn infants. In that specific setting there existed an opportunity to compare the trend of VLBW and ELBW rates during the lockdown period with the historical data.…”

“…Perinatal demography and patient characteristics of the study population have been published previously. 19 All VLBW and ELBW live births at UMHL from 1 January 2001 to 30 April 2020 were included in the study. No cases were excluded based on congenital anomalies, multiple gestations or inconsistencies around the accuracy of gestational age (GA) estimation.…”