Higher daily doses of caffeine lowered the incidence of moderate to severe neurodevelopmental disabilities in very low birth weight infants

Ravichandran, Saranya; Chouthai, Nitin; Patel, Bhavyata; Sharma, Amit; Gupte, Avanti; Michelle, Mia; Mamilla, Divya; Lulic-Botica, Mirjana; Thomas, Ronald; Kamat, Deepak

doi:10.1111/apa.14465

Cited by 12 publications

(7 citation statements)

References 33 publications

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“…NLRC4 dependent mechanisms can also contribute to brain injury induced by cerebral ischemia, as has recently been described in a rodent‐based model of stroke [37]. Interestingly, caffeine therapy for the apnea of prematurity, which reduces the incidence of moderate to severe neurodevelopmental disabilities in very low birth weight infants [38], can also reduce NLRC4‐inflammasome activation [39].…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide postnatal changes in immunity following fetal inflammatory response

et al. 2020

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The exposure to a fetal inflammatory response (FIR) is often followed by a postnatal systemic inflammation, increasing the risk of perinatal brain injury. We profiled the transcriptome and proteome in neonatal dried blood spots from extremely preterm newborns (< 28 weeks of gestation), affected and unaffected by FIR. The observed molecular changes confirm the activation of the innate immune system in FIR‐affected neonates and reveal an impairment of their adaptive immunity.

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Section: Discussionmentioning

confidence: 99%

Genome‐wide postnatal changes in immunity following fetal inflammatory response

et al. 2020

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“…which reduces the incidence of moderate to severe neurodevelopmental disabilities in very low birth weight infants 37 , can also reduce NLRC4-inflammasome activation 38 . 6 7The resolution of inflammation requires neutrophil arrest, death and removal 39 .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide postnatal changes in immunity following fetal inflammatory response

Costa

Bonet

Solé

et al. 2019

Preprint

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The fetal inflammatory response (FIR) increases the risk of perinatal brain injury, particularly in extremely low gestational age newborns (ELGANs, < 28 weeks of gestation). One of the mechanisms contributing to such a risk is a postnatal intermittent or sustained systemic inflammation (ISSI) following FIR. The link between prenatal and postnatal systemic inflammation is supported by the presence of well-established inflammatory biomarkers in the umbilical cord and peripheral blood. However, the extent of molecular changes contributing to this association is unknown. Using RNA sequencing and mass spectrometry proteomics, we profiled the transcriptome and proteome of archived neonatal dried blood spot (DBS) specimens from 21 ELGANs. Comparing FIR-affected and unaffected ELGANs, we identified 783 gene and 27 protein expression changes of 50% magnitude or more, and an experiment-wide significance level below 5% false discovery rate. These expression changes confirm the robust postnatal activation of the innate immune system in FIR-affected ELGANs and reveal an impairment of their adaptive immunity. In turn, the altered pathways provide clues about the molecular mechanisms triggering ISSI after FIR, and the onset of perinatal brain injury.

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“…Several findings also revealed the benefits of higher doses of caffeine for VLBW preterm infants. A retrospective analysis suggested that a higher average daily dose of caffeine citrate was associated with better neurodevelopmental outcomes in VLBW infants ( Ravichandran et al, 2019 ). Another RCT trial found that a maintenance dose as high as 10 mg/kg better reduced the duration of apnea and caffeine treatment in this population ( Zhang et al, 2019 ).…”

Section: Dosage Of Caffeine In Preterm Infantsmentioning

confidence: 99%

“…Recently, it has also been proposed that individualized caffeine medication can be administered with the help of a physiologic based pharmacokinetics (PBPK) model ( Abduljalil et al, 2020 ; Aranda and Beharry, 2020 ; Verscheijden et al, 2020 ). On the other hand, the clinical response is specific to each individual and influenced by many factors such as gestational age, birth weight and genetic variability ( Gal, 2007 ; Bloch-Salisbury et al, 2010 ; Francart et al, 2013 ; Ravichandran et al, 2019 ; He et al, 2020 ). Although increasing evidence has proven that the higher dose of caffeine is beneficial for newborns, there are also potential toxic risks and unknown long-term safety problems.…”

Section: Therapeutic Drug Monitoring Of Caffeinementioning

confidence: 99%

Caffeine for the Pharmacological Treatment of Apnea of Prematurity in the NICU: Dose Selection Conundrum, Therapeutic Drug Monitoring and Genetic Factors

Long

Guo

et al. 2021

Front. Pharmacol.

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Caffeine citrate is the drug of choice for the pharmacological treatment of apnea of prematurity. Factors such as maturity and genetic variation contribute to the interindividual variability in the clinical response to caffeine therapy in preterm infants, making the optimal dose administered controversial. Moreover, the necessity for therapeutic drug monitoring (TDM) of caffeine is still worth discussing due to the need to achieve the desired target concentrations as well as concerns about the safety of higher doses. Therefore, we reviewed the pharmacokinetic profile of caffeine in preterm infants, evidence of the safety and efficacy of different doses of caffeine, therapeutic concentration ranges of caffeine and impact of genetic variability on caffeine therapy. Whereas the safety and efficacy of standard-dose caffeine have been demonstrated, evidence for the safety of higher administered doses is insufficient. Thus, preterm infants who lack clinical response to standard-dose caffeine therapy are of interest for TDM when dose optimization is performed. Polymorphisms in pharmacodynamics-related genes, but not in pharmacokinetics-related genes, have a significant impact on the interindividual variability in clinical response to caffeine therapy. For preterm infants lacking clinical response, how to develop individualized medication regimens for caffeine remains to be explored.

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Higher daily doses of caffeine lowered the incidence of moderate to severe neurodevelopmental disabilities in very low birth weight infants

Abstract: A higher average daily dose of caffeine citrate was associated with better neurodevelopmental outcomes of VLBW infants. However, the cumulative dose did not have an impact on their short-term or long-term outcomes. Further research is needed to confirm our findings.

Cited by 12 publications

References 33 publications

Genome‐wide postnatal changes in immunity following fetal inflammatory response

Genome‐wide postnatal changes in immunity following fetal inflammatory response

Genome-wide postnatal changes in immunity following fetal inflammatory response

Caffeine for the Pharmacological Treatment of Apnea of Prematurity in the NICU: Dose Selection Conundrum, Therapeutic Drug Monitoring and Genetic Factors

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