Effect of prophylactic caffeine in the treatment of apnea in very low birth weight infants: a meta-analysis

Figures & data

Figure 1. Flow chart of study selection process.

Table 1. Characteristics of included studies.

Study	Year	Number	Gestation age (weeks)		Intervention		Outcomes
			prophylactic caffeine group	therapeutic caffeine group	prophylactic caffeine group	therapeutic caffeine group
Iranpour	2022	45/45	31.37 (1.55)	31.50 (1.50)	Caffeine citrate was given as a loading dose of 10 mg/kg and a daily dose of 10 mg/kg of caffeine was used after birth, iv	use caffeine when AOP exists or infants required mechanical ventilation	①⑤⑥⑦⑧
Elmowafi	2021	90/91	28.6 ± 2.1	28.8 ± 1.8	Caffeine citrate was given as a loading dose of 20 mg/kg/d and a maintenance dose of 10 mg/kg/d within the first 72 h of life, iv	not receive any placebo or similar drugs before apnea	①②③④⑤⑥⑦⑧⑨
Chen K	2020	26/30	30.44 ± 1.09	29.91 ± 1.29	20 mg/kg caffeine citrate each time within 8–12 h after birth, a dose of 5 mg/kg/d was given after 24 h, iv	started on caffeine therapy when AOP exists.	②④
Fakoor	2019	50/50	29.04 ± 1.30	29.38 ± 1.0	20 mg/kg of venous caffeine was injected to infants in the 2nd day of birth (24–48 h), a maintenance dose was injected 24 h after the first injection with the daily dose of 5 mg/kg	not receive caffeine before apnea	⑤⑧⑨
Ke H	2018	539/557	29.7 ± 4.5	30.1 ± 3.9	Give caffeine citrate immediately after admission, the first dose was 20 mg/kg intravenously for 30 min, and the maintenance dose was 10 mg/(kg·d) 24h late	use caffeine when AOP exists	②③④⑥⑦
Amaro	2018	41/42	25.7 (24.3-27.0)	26.1 (24.2–28.4)	A loading dose of caffeine citrate 20 mg/kg from 24h after birth followed by a maintenance dose of 5 mg/kg/d, iv	received an equivalent volume of normal saline bolus before apnea	②③④⑨
Zhao Y	2017	66/66	29.15 ± 1.67	29.67 ± 1.65	Intravenously for 30 min from 24 h after birth, the first dose was 20 mg/kg, and maintained at 5 mg/kg 24 h later, every 24 h, until the gestational age reached 34 weeks	not receive caffeine before apnea	①④⑤⑦
Zhao Z	2017	65/61	31.4 ± 2.7	31.9 ± 2.5	Caffeine citrate was administered within 2 h after birth. The first load dose was 20 mg/kg, pumped intravenously at 30 min, and the maintenance dose was 5 mg/kg intravenously at 24 h	use caffeine citrate after apnea appears	①②③④⑥⑦⑧⑨
Armanian	2016	26/26	28.7 ± 1.95	28.57 ± 2.06	Caffeine 20 mg/kg was administered as the initial dose on the 1st day of life, and then 5 mg/kg daily was used as the maintenance dose for the first 10 d of life, iv	Not receive caffeine before apnea	①④⑦⑧⑨
Davis	2010	233/220	27.3(1.84)	27.8(1.76)	A loading dose of 20 mg of caffeine citrate per kilogram of body weight from 24 h after birth was followed by a daily maintenance dose of 5 mg/kg, iv	Not receive caffeine before apnea	②⑤⑨
Schmidt	2006	1006/1000	27 ± 2	27 ± 2	A loading dose of either 20 mg of caffeine citrate per kilogram of body weight from 24 h after birth and followed by a daily maintenance dose of 5 mg/kg, iv	use caffeine therapy three days after birth	④⑤⑥

①AOP; ②Duration of mechanical ventilation; ③Duration of oxygen therapy; ④BPD; ⑤PDA; ⑥ROP; ⑦NEC; ⑧IVH; ⑨Death before hospital discharge.

Figure 2. Assessment of risk of bias. (A) Risk of bias graph about each risk of bias item presented as percentages across all included studies. (B) Summary of risk of bias for each trial. Plus sign: low risk of bias; minus sign: high risk of bias; question mark: unclear risk of bias.

Figure 3. Forest plots for the primary outcomes. The length of the line segment indicates the 95% confidence interval in each study. The red vertical lines represent the effect size. The black vertical lines represent invalid line. (A) AOP; (B) duration of mechanical ventilation; (C) duration of oxygen therapy.

Figure 4. Forest plots for the secondary outcomes. (A) BPD; (B) PDA; (C) ROP; (D) NEC; (E) IVH; (F) death before hospital discharge.