Observational cohort study of use of caffeine in preterm infants and association between early caffeine use and neonatal outcomes

Szatkowski, Lisa; Fateh, Sheeza; Abramson, Janine; Kwok, T'ng Chang; Sharkey, Don; Budge, Helen; Ojha, Shalini

doi:10.1136/archdischild-2022-324919

Cited by 10 publications

(7 citation statements)

References 27 publications

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“…In the Caffeine for Apnea of Prematurity Trial (CAP trial) [1], there was no significant difference in mortality between the caffeine group and the non-caffeine group. Otherwise, in studies conducted by Dobson et al [16], Patel et al [18], Shenk et al [23], Szatkowski et al [21], and Yun et al [14] as well as in this current meta-analysis, there was a significantly higher rate of mortality in the early caffeine group. Given the improvement in other outcomes, these results may potentially be due to survival bias favoring the late caffeine initiation group.…”

Section: Discussioncontrasting

confidence: 40%

“…After removing duplicate records and studies that did not meet the eligibility criteria, 21 studies remained. Following the application of our inclusion and exclusion criteria, a total of 11 studies were included in the final review [3,[14][15][16][17][18][19][20][21][22][23]. Among the patients included in these 11 studies, 78,332 received early caffeine administration, while 44,237 received late caffeine administration.…”

Section: Resultsmentioning

confidence: 99%

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Early versus Late Caffeine Therapy Administration in Preterm Neonates: An Updated Systematic Review and Meta-Analysis

Karlinski Vizentin,

Madeira de Sá Pacheco,

Fahel Vilas Bôas Azevêdo

et al. 2023

Neonatology

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Background: Caffeine is commonly used as therapy for apnea of prematurity and has shown potential in preventing other conditions in preterm neonates. However, the optimal timing for caffeine therapy remains uncertain. Objective: This study aimed to compare the outcomes of early versus late administration of caffeine in preterm neonates. Methods: PubMed, Embase, and Cochrane Library were searched for studies comparing 0–2 days to ≥3 days caffeine introduction in preterm neonates. Outcomes included were mortality, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), late-onset sepsis, length of hospital stay, and the composite of BPD or death. RevMan 5.4.1 was used for statistical analysis. Results: A total of 122,579 patients from 11 studies were included, 2 were randomized controlled trials (RCTs), and 63.9% of the neonates received early caffeine administration. The rates of BPD (OR: 0.70; 95% CI: [0.60–0.81]; p < 0.0001), IVH (OR: 0.86; 95% CI: [0.82–0.90]; p < 0.0001), ROP (OR: 0.80; 95% CI: [0.74–0.86]; p < 0.0001), late-onset sepsis (OR: 0.84; 95% CI: [0.79–0.89]; p < 0.00001), and PDA (OR: 0.60; 95% CI: [0.47–0.78]; p < 0.0001) were significantly reduced in the early caffeine group. The composite outcome of BPD or death was also lower in the early caffeine group (OR: 0.76; 95% CI: [0.66–0.88]; p < 0.0003). Mortality rate was higher in the early caffeine group (OR: 1.20; 95% CI: 1.12–1.29; p < 0.001). Conclusion: As compared with late caffeine administration, early caffeine is associated with a reduction in BPD, IVH, ROP, late-onset sepsis, and PDA in preterm neonates, albeit increased mortality. Additional RCTs are warranted to confirm these findings and evaluate whether the effect on mortality may be related to survival bias in observational studies favoring the late treatment group.

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Section: Discussioncontrasting

confidence: 40%

Section: Resultsmentioning

confidence: 99%

Early versus Late Caffeine Therapy Administration in Preterm Neonates: An Updated Systematic Review and Meta-Analysis

Karlinski Vizentin,

Madeira de Sá Pacheco,

Fahel Vilas Bôas Azevêdo

et al. 2023

Neonatology

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“… 26 This observation has some support from our recent report on the increasing use of early caffeine especially in extremely preterm infants during the same period. 27 The increasing popularity of less invasive surfactant administration 28 in more recent years may alter these patterns in the future, making these data useful for comparison.…”

Section: Discussionmentioning

confidence: 99%

Respiratory management and outcomes in high-risk preterm infants with development of a population outcome dashboard

Kwok,

Poulter,

Algarni

et al. 2023

Thorax

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IntroductionBronchopulmonary dysplasia (BPD) is associated with adverse long-term respiratory and neurodevelopmental outcomes. No recent studies examined the changing respiratory management and outcomes, particularly severe BPD, across a whole population.PurposeEvaluate the temporal trends in the respiratory management and outcomes of preterm infants born below 32 weeks gestational age and develop an individualised dashboard of the incidence of neonatal outcome.MethodsUsing the National Neonatal Research Database, we determined changes in respiratory management, BPD rates, postdischarge respiratory support and mortality in 83 463 preterm infants in England and Wales from 2010 to 2020.ResultsBetween 2010 and 2020, antenatal corticosteroids use increased (88%–93%, p<0.0001) and neonatal surfactant use decreased (65%–60%, p<0.0001). Postnatal corticosteroid use increased, especially dexamethasone (4%–6%, p<0.0001). More recently, hydrocortisone and budesonide use increased from 2% in 2017 to 4% and 3%, respectively, in 2020 (p<0.0001). Over the study period, mortality decreased (10.1%–8.5%), with increases in BPD (28%–33%), severe BPD (12%–17%), composite BPD/death (35%–39%) and composite severe BPD/death (21%–24%) (all p<0.0001). Overall, 11 684 infants required postdischarge respiratory support, increasing from 13% to 17% (p<0.0001), with 1843 infants requiring respiratory pressure support at discharge. A population dashboard (https://premoutcome.github.io/) depicting the incidence of mortality and respiratory outcomes, based on gestation, sex and birthweight centile, was developed.ConclusionMore preterm infants are surviving with worse respiratory outcomes, particularly severe BPD requiring postdischarge respiratory support. Ultimately, these survivors will develop chronic respiratory diseases requiring greater healthcare resources.

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“…For workstream 1, we will include infants who: were born at <32 weeks' GA; survived at least 48 hours from birth; and were admitted for neonatal care from 1 January 2016 to 30 September 2023 to a neonatal unit contributing data to the NNRD. In line with previous work, 18 19 we will exclude infants with missing data on key characteristics (eg, sex, GA, final discharge destination) as well as infants admitted >12 hours after birth and those missing data for one or more episodes of care.…”

Section: Eligibility Criteriamentioning

confidence: 99%

Effects of implementation of a care bundle on rates of necrotising enterocolitis and own mother’s milk feeding in the East Midlands: protocol for a mixed methods impact and process evaluation study

Abramson,

Szatkowski,

Bains

et al. 2024

BMJ Open

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IntroductionPrevention of necrotising enterocolitis (NEC) is vital for improving neonatal outcomes. Feeding own mother’s milk helps prevent NEC. Rates of own mother’s milk feeding in the East Midlands are lower than the national average and the incidence of NEC is higher. The East Midlands Neonatal Operational Delivery Network (EMNODN) has created a care bundle to improve these in babies born at <32 weeks’ gestation, the group at the highest risk of NEC. The bundle was introduced in September 2022 and embedded by December 2022. We will evaluate its effectiveness and conduct a process evaluation to understand barriers and facilitators to implementation.Methods and analysisWe will conduct a retrospective cohort study (workstream 1) using data from the National Neonatal Research Database (NNRD). We will identify infants receiving any own mother’s milk on day 14 and at discharge, and cases of severe NEC. We will aggregate outcomes by birth month and use interrupted time series analysis to estimate an incidence rate ratio for changes after the care bundle was embedded, relative to pre-implementation. We will model data from all other NNRD units and assess whether there are any concurrent changes to exclude confounding due to other events.We will apply the RE-AIM framework (workstream 2), supplemented by the Consolidated Framework for Implementation Research and Framework for Implementation Fidelity, to conduct a mixed methods evaluation in EMNODN units. We will triangulate data from several sources, including questionnaires and semistructured interviews with parents and healthcare professionals, and data from patient records.Ethics and disseminationThe study has approval from the South East Scotland Research Ethics Committee 01 and the Health Research Authority and Health and Care Research Wales (IRAS 323099). Results will be disseminated via scientific journals and conferences, to neonatal service commissioners and through public-facing infographics.Trial registration numberNCT05934123.

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Observational cohort study of use of caffeine in preterm infants and association between early caffeine use and neonatal outcomes

Cited by 10 publications

References 27 publications

Early versus Late Caffeine Therapy Administration in Preterm Neonates: An Updated Systematic Review and Meta-Analysis

Early versus Late Caffeine Therapy Administration in Preterm Neonates: An Updated Systematic Review and Meta-Analysis

Respiratory management and outcomes in high-risk preterm infants with development of a population outcome dashboard

Effects of implementation of a care bundle on rates of necrotising enterocolitis and own mother’s milk feeding in the East Midlands: protocol for a mixed methods impact and process evaluation study

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