Objective: To probe into the clinical efficacy and safety of caffeine at different starting times on prevention and treatment of apnea in very low birth weight preterm infants. Methods: PubMed

the Cochrane Library

EMBase

CNKI

Wanfang

CMB and VIP database were retrieved to collect the case-control study of caffeine at different starting times on prevention and treatment of apnea in very low birth weight preterm infants. The retrieval time was from the establishment of the database to Apr. 2020. Quality of different types of studies was evaluated by using Cochrane Handbook 5.1.0 and Newcastle Ottawa scale (NOS)

RevMan 5.3 was used for Meta-analysis. Results: A total of 10 studies were enrolled

including 5 randomized controlled trials (RCT) and 5 retrospective cohort studies. Results of the literature quality evaluation showed that 5 RCT were of grade B

and 5 retrospective cohort studies had the NOS score from 7 to 9 points. A total of 2

665 children were included

with 1

515 cases in the early administration group and 1

150 cases in the late administration group. Meta-analysis showed that the incidence of apnea (AOP) (RR=0.48

95%CI from 0.38 to 0.60

P<0.01)

duration of oxygen inhalation (SMD=-0.97

95%CI from -1.13 to -0.80

P<0.01)

mechanical ventilation time (SMD=-0.82

95%CI from -1.06 to -0.58

P<0.01)

caffeine administration time (SMD=-0.42

95%CI from -0.56 to -0.28

P<0.01)

incidence of bronchopulmonary dysplasia (BPD) (RR=0.50

95%CI from 0.41 to 0.60

P<0.01)

incidence of patent ductus arteriosus (PDA) (RR=0.56

95%CI from 0.44 to 0.70

P<0.01)

incidence of retinopathy of prematurity (ROP) (RR=0.59

95%CI from 0.47 to 0.74

P<0.01)

incidence of intraventricular hemorrhage (IVH) (RR=0.66

95%CI from 0.54 to 0.81

P<0.01) and incidence of necrotizing enterocolitis (NEC) (RR=0.70

95%CI from 0.55 to 0.91

P<0.01) in early administration group were significantly lower than that those in late administration group

while the mortality (RR=1.15

95%CI from 0.73 to 1.81

P=0.55) was not significantly different. Conclusion: Early administration of caffeine in very low birth weight preterm infants can significantly reduce the incidence of AOP

BPD

ROP

PDA

IVH and NEC

and shorten the mechanical ventilation time

duration of oxygen inhalation and caffeine administration time

which has no effect on mortality.