血清褪黑素、前列腺素2水平与早产儿坏死性小肠结肠炎病情及预后的关系

doi:10.3969/j.issn.1006-5725.2025.21.014

Abstract

Abstract:

Objective To investigate the relationship between serum melatonin and prostaglandin E₂（PGE2） levels with disease severity and prognosis of necrotizing enterocolitis （NEC） in premature infants. Methods A total of 215 premature infants diagnosed with NEC （NEC group） admitted to our hospital between January 2022 and February 2025 and 80 healthy premature infants （control group） were prospectively enrolled. NEC cases were stratified by Bell′s staging divided into mild （n = 67）， moderate （n = 90）， and severe （n = 58） subgroups. Serum levels of melatonin and PGE2 were measured by enzyme-linked immunosorbent assay. Spearman correlation analysis was used to assess the relationship between serum melatonin， PGE2 levels and Bell staging. According to the 28-day prognosis assessment， NEC infants were divided into a poor prognosis group and a good prognosis group. Multivariate logistic regression and ROC analysis were used to explore the association and predictive value of serum melatonin and PGE2 levels in NEC prognosis， and decision curve analysis （DCA） was used to evaluate clinical net benefit. Results Compared with the control group， the NEC group had significantly lower serum melatonin levels and higher PGE2 levels （P < 0.05）. Among the NEC subgroups， serum melatonin levels decreased and PGE2 levels increased progressively from mild to severe NEC （P < 0.05）. Serum melatonin was negatively correlated with Bell stage， while PGE2 was positively correlated （P < 0.05）. The 28-day poor prognosis rate in NEC infants was 18.60% （40/215）. Severe disease and elevated PGE2 were independent risk factors for poor prognosis， while higher birth weight and increased melatonin were independent protective factors （P < 0.05）. The area under the ROC curve （AUC） for predicting prognosis using melatonin， PGE2， and their combination was 0.797， 0.780， and 0.880， respectively， with the combined prediction performing significantly better than either biomarker alone （P < 0.05）. DCA indicated that when the threshold probability exceeded 0.1， the net benefit of the combined model was greater than that of either marker alone. Conclusion In premature infants with NEC， reduced serum melatonin and elevated PGE2 levels are associated with increased disease severity and poor prognosis. The combination of serum melatonin and PGE2 levels provides high predictive value for prognosis.

Key words: premature infant, necrotizing enterocolitis, melatonin, prostaglandin E2, disease severity, prognosis

CLC Number:

R726.5

Yunxia MA,Ying ZHANG,Dan. LIU. Relationship between serum melatonin， prostaglandin E2 levels and disease severity and prognosis in premature infants with necrotizing enterocolitis[J]. The Journal of Practical Medicine, 2025, 41(21): 3392-3397.

Figures/Tables 6

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Tab.5

Fig.1

References 26

[1]	HULSCHER J， IRVINE W， CONFORTI A， et al. European reference network for inherited and congenital anomalies evidence-based guideline on surgical aspects of necrotizing enterocolitis in premature neonates［J］. Neonatology，2025，122（3）：376-384. doi:10.1159/000542540 doi: 10.1159/000542540
[2]	ZHAO S， JIANG H， MIAO Y， et al. Factors influencing necrotizing enterocolitis in premature infants in China： A systematic review and meta-analysis［J］. BMC Pediatr，2024，24（1）：148. doi:10.1186/s12887-024-04607-3 doi: 10.1186/s12887-024-04607-3
[3]	CAO X， ZHANG L， JIANG S， et al. Epidemiology of necrotizing enterocolitis in preterm infants in China： A multicenter cohort study from 2015 to 2018［J］. J Pediatr Surg，2022，57（3）：382-386. doi:10.1016/j.jpedsurg.2021.05.014 doi: 10.1016/j.jpedsurg.2021.05.014
[4]	李冰卉，孟琼. 绒毛膜羊膜炎与新生儿相关疾病的研究进展［J］. 实用医学杂志， 2024， 40（23）： 3411-3418.
[5]	SHENOY P， ETCHEVERRY A， IA J， et al. Melatonin use in pediatrics： a clinical review on indications， multisystem effects， and toxicity［J］. Children （Basel），2024，11（3）：323. doi:10.3390/children11030323 doi: 10.3390/children11030323
[6]	赵铭，姜红，秦苗，等. 褪黑素对坏死性小肠结肠炎新生大鼠NLRP3及相关炎性因子影响的研究［J］. 中华新生儿科杂志，2021，36（2）：53-58.
[7]	KONG D， YU Y. Prostaglandin D2 signaling and cardiovascular homeostasis［J］. J Mol Cell Cardiol，2022，6（167）：97-105.
[8]	MO D， DENG C， CHEN B， et al. The severity of NEC is ameliorated by prostaglandin E2 through regulating intestinal microcirculation［J］. Sci Rep，2023，13（1）：13395. doi:10.1038/s41598-023-39251-x doi: 10.1038/s41598-023-39251-x
[9]	张志波. 新生儿坏死性小肠结肠炎：从Bell分期解读到手术指征的把握［J］. 临床小儿外科杂志，2022，21（4）：306-309.
[10]	中国医师协会新生儿科医师分会循证专业委员会. 新生儿坏死性小肠结肠炎临床诊疗指南（2020）［J］. 中国当代儿科杂志，2021，23（1）：1-11.
[11]	熊小琴，冯伟，李小玉，等. 影响足月和早产儿坏死性小肠结肠炎预后的危险因素分析［J］. 重庆医科大学学报，2020，45（9）：1350-1354.
[12]	WANG D， ZHANG F， PAN J， et al. Influencing factors for surgical treatment in neonatal necrotizing enterocolitis： A systematic review and meta-analysis［J］. BMC Pediatr，2024，24（1）：512. doi:10.1186/s12887-024-04978-7 doi: 10.1186/s12887-024-04978-7
[13]	马媛媛，冯茹清，王媛媛. 新生儿坏死性小肠结肠炎患者血清CCL11和IRF5水平检测对临床诊断及预后价值研究［J］. 现代检验医学杂志，2024，39（5）：146-151.
[14]	STANIKOVA A， JOUZA M， BOHOSOVA J， et al. Role of the microbiome in pathophysiology of necrotising enterocolitis in preterm neonates［J］. BMJ Paediatr Open，2023，7（1）：e002172. doi:10.1136/bmjpo-2023-002172 doi: 10.1136/bmjpo-2023-002172
[15]	LI Y， MA B， WANG Z， et al. The effect mechanism of N6-adenosine methylation （m6A） in melatonin regulated LPS-induced colon inflammation［J］. Int J Biol Sci，2024，20（7）：2491-2506. doi:10.7150/ijbs.95316 doi: 10.7150/ijbs.95316
[16]	GAO T， WANG T， WANG Z， et al. Melatonin-mediated MT2 attenuates colitis induced by dextran sodium sulfate via PI3K/AKT/Nrf2/SIRT1/RORα/NF-κB signaling pathways［J］. Int Immunopharmacol，2021，96：107779. doi:10.1016/j.intimp.2021.107779 doi: 10.1016/j.intimp.2021.107779
[17]	严彩霞，张丙宏. 血清褪黑素检测在早产儿脑损伤中的临床意义［J］. 大连医科大学学报，2018，40（3）：243-246.
[18]	Н PAVLYSHYN， SARAPUK I， KOZAK K. The relationship of melatonin concentration in preterm infants and adverse outcomes in the late neonatal period［J］. Biochem Med （Zagreb），2023，33（1）：010706. doi:10.11613/bm.2023.010706 doi: 10.11613/bm.2023.010706
[19]	GAO X， LIU W， GAO P， et al. Melatonin-induced lncRNA LINC01512 prevents Treg/Th17 imbalance by promoting SIRT1 expression in necrotizing enterocolitis［J］. Int Immunopharmacol，2021，7（96）：107787.
[20]	XIONG X， BAO Z， MI Y， et al. Melatonin alleviates neonatal necrotizing enterocolitis by repressing the activation of the NLRP3 inflammasome［J］. Gastroenterol Res Pract，2022，17（2022）：6920577.
[21]	ELGENIDY A， ATEF ABDELSATTAR IBRAHIM H， ELMOZUGI T， et al. Efficacy of melatonin for treatment and prevention of neonatal necrotizing enterocolitis： A systematic review［J］. Naunyn Schmiedebergs Arch Pharmacol，2025，398（5）：4947-4955. doi:10.1007/s00210-024-03681-9 doi: 10.1007/s00210-024-03681-9
[22]	NA Y R， JUNG D， STAKENBORG M， et al. Prostaglandin E2 receptor PTGER4-expressing macrophages promote intestinal epithelial barrier regeneration upon inflammation［J］. Gut，2021，70（12）：2249-2260. doi:10.1136/gutjnl-2020-322146 doi: 10.1136/gutjnl-2020-322146
[23]	彭小婕，张昌越，周代超，等. 前列腺素E2介导的EP4受体通路通过抑制内质网应激减轻溃疡性结肠炎黏膜损伤的研究［J］. 解放军医学院学报，2024，45（1）：78-83，封3.
[24]	莫丹丹. 前列腺素E2对新生儿坏死性小肠结肠炎的作用及机制研究［D］. 重庆：重庆医科大学，2024.
[25]	PATANKAR J V， MÜLLER T M， KANTHAM S， et al. E-type prostanoid receptor 4 drives resolution of intestinal inflammation by blocking epithelial necroptosis［J］. Nat Cell Biol，2021，23（7）：796-807. doi:10.1038/s41556-021-00708-8 doi: 10.1038/s41556-021-00708-8
[26]	ZHANG H， YANG R， YAO Y. Construction and evaluation of a risk model for adverse outcomes of necrotizing enterocolitis based on LASSO-Cox regression［J］. Front Pediatr，2024，10（12）：1366913.

组别	例数	褪黑素	PGE2
NEC组	215	43.99 ± 8.03	40.43 ± 10.20
对照组	80	66.51 ± 9.53	23.69 ± 4.67
t值		-20.320	19.248
P值		< 0.001	< 0.001

组别	例数	褪黑素	PGE2
轻度NEC组	67	48.08 ± 7.86	34.83 ± 8.95
中度NEC组	90	44.01 ± 7.23^?	39.60 ± 9.24^?
重度NEC组	58	39.24 ± 6.80^?#	48.18 ± 8.06^?#
F_趋势值		45.325	70.702
P值		< 0.001	< 0.001

项目	不良预后组（n = 40）	良好预后组（n = 175）	χ²/t/Z值	P值
性别/［例（%）］			0.364	0.546
男	22（55.00）	87（49.71）
女	18（45.00）	88（50.29）
胎龄（x ± s）/周	32.00 ± 2.55	32.90 ± 2.93	-1.787	0.075
日龄（x ± s）/d	5.53 ± 2.18	5.69 ± 1.99	-0.453	0.651
出生体质量（x ± s）/kg	1.23 ± 0.23	1.36 ± 0.28	-3.224	0.002
病情程度/［例（%）］			-7.221	< 0.001
轻度	0（0.00）	67（38.29）
中度	10（25.00）	80（45.71）
重度	30（75.00）	28（16.00）
剖宫产/［例（%）］	32（80.00）	122（69.71）	1.695	0.193
5 min Apgar评分（x ± s）/分	7.45 ± 0.96	7.81 ± 1.09	-1.932	0.055
机械通气/［例（%）］	27（67.50）	90（51.43）	3.390	0.066
动脉导管未闭/［例（%）］	15（37.50）	53（30.29）	0.784	0.376
宫内窘迫/［例（%）］	16（40.00）	63（36.00）	0.224	0.636
母亲妊娠期糖尿病/［例（%）］	6（15.00）	18（10.29）	0.332	0.565
母亲妊娠期高血压/［例（%）］	3（7.50）	11（63.29）	0.000	1.000
喂养方式/［例（%）］			2.048	0.152
母乳	20（50.00）	109（62.29）
奶粉/其他	20（50.00）	66（37.71）
治疗方式［例（%）］			56.253	< 0.001
保守治疗	12（30.00）	151（86.29）
外科手术	28（70.00）	24（13.71）
褪黑素（x ± s）/（pg/mL）	37.29 ± 4.57	45.53 ± 7.87	-8.802	< 0.001
PGE2（x ± s）/（ng/L）	49.24 ± 8.26	38.41 ± 9.52	7.259	< 0.001

变量	β	SE	Wald χ²	P值	OR	95%CI
病情程度（参考：轻度）	-	-	13.878	0.001	-	-
中度	0.303	0.672	0.203	0.652	1.354	0.363～5.055
重度	2.308	0.695	11.037	0.001	10.054	2.576～39.238
出生体质量升高	-0.336	0.106	9.992	0.002	0.715	0.580～0.880
褪黑升高	-0.226	0.047	23.194	< 0.001	0.797	0.727～0.874
PGE2升高	0.174	0.040	19.148	< 0.001	1.190	1.101～1.286
常量	3.546	2.411	2.163	0.141	34.687	-

指标	曲线下面积	95%CI	P值	截断值	敏感度	特异度	最大约登指数
褪黑素	0.797	0.737 ~ 0.869	< 0.001	41.08 pg/mL	0.875	0.680	0.555
PGE2	0.780	0.718 ~ 0.833	< 0.001	42.12 pg/mL	0.800	0.634	0.434
二者联合	0.880	0.829 ~ 0.920	< 0.001	-	0.775	0.863	0.638

Relationship between serum melatonin， prostaglandin E2 levels and disease severity and prognosis in premature infants with necrotizing enterocolitis

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