探讨新生儿微小脲原体(Up)脑膜炎患儿的临床表现、并发症、诊断、治疗及预后等。

选择2023年10月31日徐州市中心医院收治的1例早发型Up脑膜炎早产儿(患儿1)为研究对象。采用回顾性分析方法，对患儿1病史、入院体格检查、相关辅助检查结果及诊疗过程等临床资料进行分析。以"微小脲原体/细小脲原体""脑膜炎/脑炎""新生儿""早产"及"Ureaplasma parvum""meningitis""neonate/newborn""preterm/premature"为检索词，在国内数据库(万方数据知识服务平台、中国知网、维普数据库)及国外数据库(PubMed、Embase、Web of Science)中，检索自建库至2025年4月收录的关于新生儿Up脑膜炎患儿研究相关文献，对Up脑膜炎新生儿的临床表现、并发症、诊断、治疗及预后进行综合分析。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。

①患儿1为女性早发型Up脑膜炎早产儿，出生胎龄为34^＋1周，因"生后呻吟吐沫30 min"，生后当天于本院住院治疗。患儿1母亲孕期阴道拭子及患儿1鼻拭子检查结果显示，均为解脲脲原体(UU)核酸呈阳性。入院后第6天，患儿1开始反复低热伴呼吸暂停，结合脑脊液检查结果[白细胞计数(WBC)为62×10⁶/L、葡萄糖浓度为0.55 mmol/L、蛋白质水平为1.29 g/L]，以及脑脊液宏基因组学二代测序技术(mNGS)检测结果(脑脊液中检测出Up，序列数为154、相对丰度为32.25%)，被诊断为Up脑膜炎。入院第7天，对其采取大剂量阿奇霉素静脉滴注治疗，具体剂量为20 mg/(kg·d)×1次/d，入院后第10天减量为5 mg/(kg·d)×1次/d。入院后第18天，患儿1因"脑室内出血、重度阻塞性幕上脑积水"，予以每天穿刺放脑脊液10 mL/kg治疗，并动态监测脑脊液，9 d后(入院后第27天)脑脊液各项指标逐渐恢复正常，停用阿奇霉素，但是脑积水未见明显减轻，入院后第29天转诊至外院进行Ommaya囊植入术，生后第3~6个月无需再抽脑积水，脑积水症状好转。校正月龄为6个月时，患儿1各项发育指标基本正常。②文献复习结果：共计检索出关于新生儿Up脑膜炎相关研究文献为15篇，纳入的Up脑膜炎新生儿为16例(患儿2~17)，加上患儿1，共计17例Up脑膜炎新生儿被纳入进行以下综合分析。这17例患儿中，除1例未报道性别、1例未报道出生胎龄、1例未报道出生体重外，其余16例患儿中，男、女性别为6、10例，出生胎龄中位数为31.5周(27.3，39.8周)，早产儿(出生胎龄<37周)为10例，出生体重中位数为1 860 g(997，3 355 g)，低出生体重儿(出生体重<2 500 g)为9例。17例患儿发病日龄中位数为生后7 d(3.0，10.5 d)，早发型(生后7 d内)Up脑膜炎为9例；12例表现为发热，6例表现为神经系统异常，4例为呼吸系统异常；10例并发脑积水，3例并发颅内出血；脑脊液检查结果显示，WBC均增高(中位数为608×10⁶/L)，蛋白质水平均显著增高，为(3.7±2.0)g/L，葡萄糖浓度均显著降低(中位数为0.5 mmol/L)。10例仅用mNGS检测进行脑脊液Up进行诊断。17例Up脑膜炎患儿治疗采用的药物为红霉素、阿奇霉素[常用剂量为20 mg/(kg·d)]及喹诺酮类抗菌药物，疗程为3~10周；4例单用Ommaya囊植入治疗脑积水。经治疗后，除1例未随访外，其余16例患儿中，14例随访结果显示智力、运动发育正常。

新生儿Up脑膜炎多见于早产儿，以早发型为主，大多表现为发热，神经系统异常发生率相对较低，部分患儿可能伴有呼吸系统异常，常伴有脑积水和颅内出血等并发症。脑脊液检查结果显示，WBC增高，蛋白质水平显著增高，葡萄糖浓度显著降低，Up检测常用mNGS。该病患儿的治疗药物多选择大环内酯类及喹诺酮类抗菌药物，脑积水治疗首选单用Ommaya囊植入术。绝大部分该病患儿经治疗后预后良好。

To explore the clinical manifestations, complications, diagnosis, treatment and prognosis in neonatal Ureaplasma parvum (Up) meningitis.

A preterm infant with early-onset Up meningitis (infant 1), who was admitted to Xuzhou Central Hospital on October 31, 2023 was included into this study. A retrospective analysis was conducted on the clinical data of infant 1, including medical history, physical examination findings at admission, relevant auxiliary examination results, and the diagnosis and treatment process. Using the search terms " Ureaplasma parvum" " meningitis" " neonate/newborn" " preterm/premature" both in Chinese and English, literature related to neonatal Up meningitis indexed in domestic databases (Wanfang Data Knowledge Service Platform, CNKI, and VIP Database) and international databases (PubMed, Embase, and Web of Science) from the inception of each database to April 2025 was searched. A comprehensive analysis of the clinical manifestations, complications, diagnosis, treatment, and prognosis of Up meningitis in newborns was conducted on the related literature. This study was in line with World Medical Association Declaration of Helsinki revised in 2013.

①Infant 1: a female preterm infant with early-onset Up meningitis born at a gestational age of 34^{+ 1} weeks, was admitted to our hospital on the day of birth due to " moaning and frothing for 30 minutes" after delivery. Antenatal vaginal swab from the mother and a postnatal nasal swab from the infant 1 both tested positive for Ureaplasma Urealyticum (UU) nucleic acid. On day 6 after admission, the infant 1 began to experience recurrent low-grade fevers accompanied by apnea. Combined with a cerebrospinal fluid white blood cell count (WBC) of 62×10⁶/L, a glucose concentration of 0.55 mmol/L, and a protein level of 1.29 g/L, metagenomic next-generation sequencing (mNGS) detected Up in the cerebrospinal fluid, with a sequence count of 154 and a relative abundance of 32.25%, Up meningitis was diagnosed. On day 7 after admission, high-dose intravenous azithromycin was initiated at 20 mg/(kg·d) once daily. The dose was reduced to 5 mg/(kg·d) once daily on day 10 after admission. From day 18 to 27 after admission, due to " intraventricular hemorrhage and severe obstructive supratentorial hydrocephalus", daily therapeutic cerebrospinal fluid aspiration (10 mL/kg) was performed. The cerebrospinal fluid parameters gradually normalized, and azithromycin was discontinued on day 27 after admission. However, the hydrocephalus did not significantly improve. On day 29 after admission, the infant 1 was transferred to another hospital for Ommaya reservoir placement. From 3 to 6 months after birth, there was no longer any need to withdraw hydrocephalus fluid, and the symptoms of hydrocephalus improved. At a corrected age of 6 months, the development of infant 1 was assessed as essentially normal. ②Literature review results: A literature search identified 15 relevant articles on neonatal Up meningitis, reporting on 16 affected neonates (infants 2-17). Including infant 1, a total of 17 neonates with Up meningitis were analyzed. Among these 17 cases, excluding one case whose gender was not reported, there were 6 males and 10 females; gestational age was not reported in one case, but the median gestational age of the remaining 16 cases was 31.5 weeks (27.3, 39.8 weeks), with 10 cases being preterm (gestational age at birth < 37 weeks); birth weight was not reported in one case, but the median birth weight of the remaining 16 cases was 1 860 g (997, 3 355 g), with 9 cases having low birth weight (birth weight < 2 500 g); the median age at onset was 7 days after birth (3.0, 10.5 days), and 9 cases were classified as early-onset (within 7 days after birth) Up meningitis. Clinically, 12 cases presented with fever, 6 with neurological abnormalities, and 4 with respiratory abnormalities. Complications included hydrocephalus in 10 cases and intracranial hemorrhage in 3 cases. The cerebrospinal fluid examination results showed an elevated WBC count (median: 608×10⁶/L), a significantly increased protein level (3.7±2.0) g/L, and a significantly decreased glucose concentration (median: 0.5 mmol/L). In 10 cases, mNGS was the sole method used to detect Up in the cerebrospinal fluid. Commonly used antibiotics for Up meningitis included erythromycin, azithromycin [often at a dose of 20 mg/(kg·d)], and quinolones, with treatment courses ranging from 3 to 10 weeks. Hydrocephalus was managed with Ommaya reservoir insertion alone in 4 cases. Regarding outcomes, follow-up information was unavailable for one infant. Of the remaining 16 cases, follow-up assessments indicated normal intellectual and motor development in 14 infants.

Neonatal Up meningitis predominantly occurs in preterm infants, with early-onset cases being the most common. The primary clinical manifestation is fever, while the incidence of neurological abnormalities is relatively low. Some infants may present with respiratory abnormalities, and the condition is frequently associated with complications such as hydrocephalus and intracranial hemorrhage. Cerebrospinal fluid analysis typically reveals an elevated WBC count, significantly increased protein levels, and markedly decreased glucose concentrations. mNGS is commonly used for the detection of Up. Macrolides and quinolones are the antibiotics of choice for treatment, while Ommaya reservoir implantation alone is the preferred approach for managing hydrocephalus. The prognosis is favorable for the vast majority of infants following treatment.