早产儿口服补充DHA和ARA制剂对坏死性小肠结肠炎影响的Meta分析

doi:10.13481/j.1671-587X.20260420

Abstract

Abstract:

Objective To systematically evaluate the effect of oral supplementation of docosahexaenoic acid （DHA） and arachidonic acid （ARA） on the incidence of necrotizing enterocolitis （NEC） in the preterm infants， and to clarify the correlation. Methods Seven Chinese and English databases including PubMed， CNKI， and Wanfang were searched for studies on the association between oral DHA and ARA supplementation and NEC in the preterm infants from inception to October 2025. Two researchers independently completed literature screening and data extraction. The publication bias was assessed using funnel plots and Egger’s test. Relative risk （RR） and 95% confidence interval （CI） were used as effect indicators， and Meta analysis was performed. Results A total of 10 studies were included， including 6 studies with low risk of bias and 4 studies with unclear risk. The Meta-analysis results showed that oral DHA and ARA supplementation had no significant effect on the incidence of NEC （RR=1.01， 95%CI： 0.72-1.43， P=0.94）. The subgroup and sensitivity analyses results indicated that the form of supplementation （DHA combined with ARA or DHA alone）， the dose level （high or low dose）， and different gestational ages of the preterm infants didn’t significantly affect the incidence of NEC； no significant effect was observed on the NEC incidence of preterm infants with Bell stage≥Ⅱ grade. Conclusion Oral supplementation of DHA and ARA in the preterm infants has not been shown to have a significant protective effect on the incidence of NEC， and its clinical value in the prevention and treatment of NEC still needs to be further verified by research.

Key words: Docosahexaenoic acid, Arachidonic acid, Necrotizing enterocolitis, Preterm infant, Meta-analysis

CLC Number:

Zhongyu GAO,Dan DANG,Chuan ZHANG,Bingbing ZOU,Chenghao WU,Jiaxu YANG,Hui WU. Effect of oral DHA and ARA supplementation on necrotizing enterocolitis in preterm infants: A Meta-analysis[J].Journal of Jilin University(Medicine Edition), 2026, 52(4): 1077-1085.

Figures/Tables 6

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References 35

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Study	Intervention/Control	Gestational ageWeight	Start of intervention	Duration	Dosage	Definition of NEC
HELLSTR?M et al. 2021^[16]	101/105	<28 weeks	Within 3 d after birth	Until 40 weeks	ARA 100 mg·kg^-1·d^-1+DHA 50 mg·kg^-1·d^-1	NEC stage≥ Ⅱa or higher^[30]
MOLT et al.2024^[17]	60/60	<29 weeks	The second day after birth	Until 36 weeks	ARA 100 mg·kg^-1+DHA 50 mg·kg^-1	NEC stage≥Ⅱa
FROST et al.2021^[18]	24/6	<28 weeks, <1 500 g	Within 72 h after birth	Until 8 weeks ordischarge	①ARA 80 mg·kg^-1+DHA 40 mg·kg^-1 ②ARA 240 mg·kg^-1+DHA 120 mg·kg^-1·d^-1	Not specified
ROBINSON et al. 2021^[19]	18/10	<34 weeks, <1 000 g	Not mentioned	Until 8 weeks ordischarge	①DHA 20 mg·kg^-1·d^-1+ARA 40 mg·kg^-1·d^-1 ②DHA 60 mg·kg^-1·d^-1+ARA 120 mg/kg/d	Not specified
COLLINS et al. 2015^[20]	31/11	<33 weeks	Not mentioned	28 d	DHA 40 g·L^-1, DHA 80 g·L^-1, DHA 120 g·L^-1	Australian and New Zealand Neonatal Network^[31]
BAACK et al.2017^[21]	31/29	24-34 weeks	1 week after birth	Discharge or until 37 weeks	DHA 50 mg·d^-1	Not specified
COLLINS et al.2017^[28]	601/619	<29 weeks	Within 3 d after their first enteral feeding	Until 36 weeks	DHA 60 mg·kg^-1	Australian and New Zealand Neonatal Network^[31]
MARC et al.2020^[29]	260/231	23-28 weeks	Within 72 h after birth	Until 36 weeks	DHA 1.2 g·d^-1	NEC stage≥Ⅱ
BERNABE-GARCíA et al.2021^[23]	100/100	<32 weeks 1 000-1 500 g	Not mentioned	14 d of life	DHA 75 mg·kg^-1	NEC stage≥Ⅱa
FADL et al.2021^[24]	30/30	≤32 weeks，≤1 500 g	Not mentioned	14 d of life	DHA 100 mg·d^-1	Not specified

Group	No. of study	Participant	RR (95%CI)	I²(%)/P value	Grade	Comment
DHA	6	2 073	0.79(0.36-1.77)	54/0.07	Low certainty	CI wide and includes adverse lines, high inconsistency
DHA&ARA	4	384	0.96(0.45-2.05)	0/0.91	Moderate certainty	CI wide and includes adverse lines
High dose of DHA (>60 mg·kg^-1·d^-1)	5	800	0.44(0.10-1.97)	65/0.03	Low certainty	CI wide and includes adverse lines, high inconsistency
Low dose of DHA (≤60 mg·kg^-1·d^-1)	7	1 674	1.14(0.79-1.64)	0/1.00	Moderate certainty	CI wide and includes adverse lines
GA≤28 weeks	3	727	1.28（0.68-2.40）	0/0.45	Moderate certainty	CI wide and includes adverse lines
GA>28 weeks	7	1 730	0.69（0.32-1.40）	32/0.34	Low certainty	CI wide and includes adverse lines, high inconsistency
Bell stage≥Ⅱ grade	4	1 017	0.96(0.38-2.41)	45/0.92	Moderate certainty	CI wide and includes adverse lines

Effect of oral DHA and ARA supplementation on necrotizing enterocolitis in preterm infants: A Meta-analysis

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