冷冻母乳喂养与胎龄<32周或出生体重<1500 g早产儿巨细胞病毒感染的关系

Cytomegalovirus infection in preterm infants of gestational age <32 weeks or birth weight <1 500 g fed by their own mother's frozen breast milk

目的分析冷冻母乳喂养住院早产儿巨细胞病毒(cytomegalovirus,CMV)感染情况。方法回顾性分析2018年1月至2020年12月在我院出生且住院并接受母乳喂养的胎龄<32周或出生体重<1500 g的早产儿及其母亲的相关临床资料,包括母乳及早产儿尿液标本CMV-DNA检测情况。采用荧光定量聚合酶链反应技术检测母乳及早产儿尿液标本中的CMV DNA。采用χ2检验(或Fisher精确概率法)、两独立样本t检验及Mann-Whitney U检验等统计学方法对数据进行统计学分析。结果共纳入94例产妇的103例早产儿(含9对双胎)。母乳CMV-DNA阳性早产儿75例(包括8对双胎),阴性28例(包括1对双胎)。母乳CMV DNA阳性的75例早产儿中,67例(包括8对双胎)早产儿改为冷冻母乳(-20℃,72 h)喂养,其中6例发生CMV感染(9.0%),均未治疗。冷冻母乳喂养的67例患儿中,母乳CMV DNA阳性分布在产后2~10周,其中第8周拷贝数达到高峰,早产儿根据尿CMV DNA情况分为CMV感染组(6例)和非感染组(61例),感染组母乳CMV DNA平均拷贝数[22.7(3.0~95.7)×103拷贝/ml与5.0(0.5~89.5)×103拷贝/ml,Z=-2.218]及最高拷贝数[45.9(5.9~261.0)×103拷贝/ml与9.8(1.2~766.0)×103拷贝/ml,Z=-2.218]均高于非感染组(P值均<0.05)。根据母乳喂养方式将103例早产儿分为冷冻母乳喂养组(67例)和新鲜母乳喂养组(36例),2组早产儿在喂养不耐受[37.3%(25/67)与50.0%(18/36),χ2=1.550]、新生儿坏死性小肠结肠炎[0.7%(1/67)与0.0%(0/36)]、支气管肺发育不良[28.4%(19/67)与27.8%(10/36),χ2=0.004]、早产儿视网膜病[20.9%(14/67)与8.3%(3/36),χ2=2.682]及晚发败血症[22.4%(15/67)与30.6%(11/36),χ2=0.828]发生率比较,差异均无统计学意义(P值均>0.05)。结论冷冻母乳喂养早产儿母乳获得性CMV感染发生率低,感染后临床表现不明显,且相关并发症的发生率也并未增加。冷冻母乳或可作为胎龄<32周或出生体重<1500 g早产儿母乳CMV DNA阳性的有效处理方式。

Objective To understand cytomegalovirus(CMV)infection status in hospitalized preterm infants who were fed by their own mother's frozen breast milk.Methods This retrospective study enrolled breastfed neonates with gestational age less than 32 weeks or birth weight less than 1500 g who were born and admitted to Gynecology and Obstetrics Hospital of Fudan University from January 2018 to December 2020.Clinical data of the babies and their mothers were collected and analyzed,including CMV DNA results of breast milk and urine samples of the subjects by fluorescence quantitative polymerase chain reaction.Chi-square test(or Fisher's exact probability test),two independent samples t test,and Mann-Whitney U test were used for the statistical analysis.Results A total of 94 parturients and their 103 premature infants(including nine pairs of twins)were included.CMV DNA of breast milk was noted for positive in 75 cases(including eight pairs of twins)and for negative in 28 cases(including one pair of twins).Out of the 75 preterm infants born to mothers with positive CMV DNA breast milk,67(including eight pairs of twins)were switched to frozen breast milk(-20℃for 72 h),and six of them were infected by CMV(9.0%)without any treatment.All of the 103 infants were divided into two groups:the frozen milk fed group(n=67)or fresh milk fed group(n=36).In the frozen milk fed group,the CMV DNA was mainly detected during 2-8 weeks postpartum with copy number reaching the peak at 8th week.And those infants in the frozen milk fed group,whose mother's breast milk CMV DNA was positive,was further divided into CMV infected(n=6)or CMV non-infected groups(n=61)according to the urine test results.Moreover,compared with the non-infected group,the average[22.7(3.0-95.7)×103 copies/ml vs 5.0(0.5-89.5)×103 copies/ml,Z=-2.218)and the highest[45.9(5.9-261.0)×103 copies/ml vs 9.8(1.2-766.0)×103 copies/ml,Z=-2.218]copy number of CMV DNA in the breast milk were higher in the CMV infected group(both P<0.05).The incidence of feeding intolerance[37.3%(25/67)vs 50.0%(18/36),χ2=1.550],neonatal necrotizing enterocolitis[0.7%(1/67)vs 0.0%(0/36)],bronchopulmonary dysplasia[28.4%(19/67)vs 27.8%(10/36),χ2=0.004],retinopathy of prematurity[20.9%(14/67)vs 8.3%(3/36),χ2=2.682],and late-onset sepsis[22.4%(15/67)and 30.6%(11/36),χ2=0.828]did not differ significantly between the frozen or fresh milk fed groups(all P>0.05).Conclusions The incidence of breast milk-related CMV infection in those fed with frozen breast milk was low and does not increase the without increasing risks of related complications or leading to obvious clinical manifestations after infection.For preterm infants with gestational age<32 weeks or birth weight<1500 g,frozen breast milk can be an alternative for mothers with CMV DNA positive breast milk.