Table 4.
Comparison of prior studies of caffeine citrate reporting necrotizing enterocolitis frequency. No studies have shown a significant caffeine-related increase in NEC.
| N caffeine | Sites | Population | NEC, n/N (%) | Median duration of therapy (days) | |
|---|---|---|---|---|---|
| FDA labela | 46 | 9 | 28 to <33 wk GA | 2/46 (4.3%) | 10 |
| CAP trialb | 1006 | 35 | 500–1250 g | 63/1006 (6.3%)c | 37 |
| NICHD NRNd | 9575 | 20 | 22–28 wk GA, BW 401–1500 g |
11% | Not reported |
| VONd | 38,017 | 669 | BW 501–1500 g | 2015/38,017 (5.3%) | Not reported |
| Current studyd | 410 | 4 | 22–28 wk GA | 35/410 (8.5%) | 60 |
BW: body weight; CAP trial: Caffeine for Apnea of Prematurity Trial (9); FDA: U.S. Food and Drug Administration (10); GA: gestational age; NICHD NRN: The National Institute of Child Health and Human Development Neonatal Research Network study from 2003 to 2007 (28); VON: The Vermont Oxford Network study from 2009 (29).
Randomized controlled trial, post-hoc analysis with no significant increase in NEC with caffeine treatment compared with placebo;
Randomized controlled trial with no significant increase in NEC with caffeine treatment compared with placebo (p=0.63);
Placebo group reported NEC in 67/1000 (6.7%);
Retrospective analysis.