Confounding biases in studies on early- versus late-caffeine in preterm infants: a systematic review

Vujovic, Sandra Nylander; Nava, Chiara; Johansson, Minna; Bruschettini, Matteo

doi:10.1038/s41390-020-0757-1

Cited by 14 publications

(10 citation statements)

References 48 publications

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“…However, all observational studies, including ours, have inherent limitations 26. Nylander et al conducted a systematic review of studies comparing early versus late caffeine but were unable to draw conclusions from 12 cohort studies due to methodological problems 26. We attempted to minimise these.…”

Section: Discussionmentioning

confidence: 98%

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

Szatkowski

Fateh

Abramson

et al. 2023

Arch Dis Child Fetal Neonatal Ed

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ObjectiveTo quantify trends in caffeine use in infants born at <32 weeks’ gestational age (GA), and to investigate the effects of early vs late caffeine on neonatal outcomes.Study designRetrospective propensity score matched cohort study using routinely recorded data from the National Neonatal Research Database of infants born at <32 weeks’ GA admitted to neonatal units in England and Wales (2012–2020).Results89% (58 913/66 081) of infants received caffeine. In 70%, caffeine was started early (on the day of birth or the day after), increasing from 55% in 2012 to 83% in 2020. Caffeine was given for a median (IQR) of 28 (17–43) days starting on day 2 (1–3) and continued up to 34 (33–34) weeks postmenstrual age.In the propensity score matched cohort of 13 045 pairs of infants, the odds of preterm brain injury (early caffeine, 2306/13 045 (17.7%) vs late caffeine, 2528/13 045 (19.4%), OR=0.89 (95% CI 0.84 to 0.95)) and bronchopulmonary dysplasia (BPD) (early caffeine, 4020/13 045 (32.8%) vs late caffeine, 4694/13 045 (37.7%), OR=0.81 (95% CI 0.76 to 0.85)) were lower in the group that received early caffeine compared with those who received it later.ConclusionsEarly use of caffeine has increased in England and Wales. This is associated with reduced risks of BPD and preterm brain injury. Randomised trials are needed to find the optimal timing of caffeine use and the groups of infants who will benefit most from early administration of caffeine.

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Section: Discussionmentioning

confidence: 98%

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

Szatkowski

Fateh

Abramson

et al. 2023

Arch Dis Child Fetal Neonatal Ed

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“…Sub-DOI: 10.1159/000528914 group analysis from the CAP trial showed better outcomes with earlier treatment [150]. Caffeine prophylaxis has become widespread based on cohort studies, despite the risk of bias, since earlier treatment is associated with better outcomes [150,151]. Randomised trials of caffeine prophylaxis for extremely preterm infants are scarce and show conflicting results [152,153], and further studies combining caffeine prophylaxis with LISA are currently underway.…”

Section: Strategiesmentioning

confidence: 99%

European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update

et al. 2023

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Respiratory distress syndrome (RDS) care pathways evolve slowly as new evidence emerges. We report the sixth version of “European Guidelines for the Management of RDS” by a panel of experienced European neonatologists and an expert perinatal obstetrician based on available literature up to end of 2022. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, appropriate maternal transfer to a perinatal centre, and appropriate and timely use of antenatal steroids. Evidence-based lung-protective management includes initiation of non-invasive respiratory support from birth, judicious use of oxygen, early surfactant administration, caffeine therapy, and avoidance of intubation and mechanical ventilation where possible. Methods of ongoing non-invasive respiratory support have been further refined and may help reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation by targeted use of postnatal corticosteroids remains essential. The general care of infants with RDS is also reviewed, including emphasis on appropriate cardiovascular support and judicious use of antibiotics as being important determinants of best outcome. We would like to dedicate this guideline to the memory of Professor Henry Halliday who died on November 12<sup>,</sup> 2022.These updated guidelines contain evidence from recent Cochrane reviews and medical literature since 2019. Strength of evidence supporting recommendations has been evaluated using the GRADE system. There are changes to some of the previous recommendations as well as some changes to the strength of evidence supporting recommendations that have not changed. This guideline has been endorsed by the European Society for Paediatric Research (ESPR) and the Union of European Neonatal and Perinatal Societies (UENPS).

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“…Other large retrospective studies and systematic reviews have reported similar beneficial outcomes with early initiation of caffeine, including a reduction in rates of death or broncho‐pulmonary dysplasia (BPD), and better neuro‐developmental outcomes at 18–24 months corrected age 6–9 . Conversely, some studies have reported adverse outcomes, such as increases in mortality and/or inconclusive results for the benefits of early initiation of caffeine 10,11 . A randomised controlled trial (RCT) has previously been conducted to evaluate the effect of early caffeine treatment (in the first 5 days) in ventilated pre‐term infants (<30 weeks) compared to prescribing caffeine prior to extubation 12 .…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8][9] Conversely, some studies have reported adverse outcomes, such as increases in mortality and/or inconclusive results for the benefits of early initiation of caffeine. 10,11 A randomised controlled trial (RCT) has previously been conducted to evaluate the effect of early caffeine treatment (in the first 5 days) in ventilated pre-term infants (<30 weeks) compared to prescribing caffeine prior to extubation. 12 This trial was terminated prematurely with a non-significant increase in mortality in the early caffeine group, with no 5 m difference in age at first extubation (primary outcome) and other outcomes.…”

Section: Discussionmentioning

confidence: 99%

National survey on caffeine use in neonatal units across the United Kingdom

2022

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AimTo understand the variations in practice for caffeine use among neonatal units in the United Kingdom.MethodsAn online survey was sent to every neonatal unit in the United Kingdom.ResultsWe received a response from 92 neonatal units (47%) with the proportion of response from special care, Local neonatal units, neonatal intensive care units and neonatal surgical units were 23%, 34%, 23% and 21% respectively. All the units reported the use of caffeine, and 40 units (46%) initiated caffeine within 24 h of birth. Fifty‐nine units (64%) reported routine use of caffeine for pre‐term infants <32 weeks. Seventy‐one units (77%) reported that they continue caffeine for infants needing mechanical ventilation. Thirty‐one units (34%) discontinued caffeine at 34 weeks post‐menstrual age, irrespective of the respiratory support. Ten units (11%) reported discontinuation of caffeine only after weaning off all respiratory support, and 40% of units had a variable practice of discontinuing caffeine depending on the individual baby. Seventy‐nine units (86%) reported they would regularly optimise caffeine dose based on weight checks.ConclusionOur survey showed some variation in practice with regards to the timing of caffeine initiation, gestational age cut‐off for routine caffeine prescription and discontinuation.

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Confounding biases in studies on early- versus late-caffeine in preterm infants: a systematic review

Cited by 14 publications

References 48 publications

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

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

European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update

National survey on caffeine use in neonatal units across the United Kingdom

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