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关于极低和/或超低出生体重儿通过母乳喂养获得产后巨细胞病毒感染的文献综述及一家意大利医院的经验

Literature Review and an Italian Hospital Experience about Post-Natal CMV Infection Acquired by Breast-Feeding in Very Low and/or Extremely Low Birth Weight Infants.

作者信息

Garofoli Francesca, Civardi Elisa, Zanette Simona, Angelini Micol, Perotti Gianfranco, Zecca Marco, Lombardi Giuseppina

机构信息

Neonatal and Intensive Care Unit (NICU), Fondazione IRCCS Policlinico San Matteo, Italy.

出版信息

Nutrients. 2021 Feb 18;13(2):660. doi: 10.3390/nu13020660.

Abstract

Breastfeeding is recommended for all neonates due to a known variety of beneficial effects, but infants can be infected by cell-associated bacteria and viruses from breast milk, such as cytomegalovirus (CMV). The majority of CMV-seropositive breastfeeding women have a viral, self-restricted reactivation, can shed the virus in the milk for about 12 weeks after delivery, and can transmit the infection to their offspring. Post-natal CMV-infected term infants are mainly asymptomatic, while very low birth weight (VLBW, <1500 g) and extremely low birth weight (ELBW, <1000 g) infants may present with severe disease, short-term sequelae ranging from abnormalities in laboratory indexes to sepsis-like syndrome, and long-term sequelae such as developmental problems. Thus, the use of thermally treated maternal milk for VLBW/ELBW infants may be indicated to prevent/reduce the risk of CMV transmission. Different techniques, with varying efficacy in eradicating CMV and maintaining the activity of biological compounds in milk are available: long/short pasteurization, freeze-thawing, the use of microwaves, and ultraviolet-C irradiation. In our NICU, the use of maternal raw milk is always strongly recommended for term/preterm infants, but to reduce risk of CMV transmission, freeze-thawing mother's own milk is used in neonates with GA ≤ 30 weeks or/and weight ≤ 1000 g, usually regardless of serological maternal condition, as CMV screening is not routinely offered to pregnant women and the milk of seroimmune mothers is not evaluated for CMV reactivation, as its rate is similar to seroprevalence. Over the last 4 years, we had 10 VLBW/ELBW newborns in our NICU with late-onset sepsis and negative cultures. In these cases, the research of CMV DNA in neonatal urine or saliva, for the diagnosis of post-natal symptomatic infection (once congenital transmission has been excluded) may be useful and not invasive. The take-home message we would like to share is that acquired CMV infection should be considered in VLBW/ELBW infants breastfed by seropositive mothers and presenting severe symptoms-particularly sepsis with negative cultures. This could allow pediatricians to make better-quality diagnoses, perform supportive therapy, provide antiviral treatment if needed, or establish a "pre-emptive" therapy for these high-risk neonates.

摘要

由于已知母乳喂养具有多种有益效果,因此建议所有新生儿都进行母乳喂养,但婴儿可能会被母乳中与细胞相关的细菌和病毒感染,如巨细胞病毒(CMV)。大多数CMV血清反应阳性的母乳喂养女性会出现病毒的自我限制再激活,分娩后可在乳汁中排出病毒约12周,并可将感染传播给其后代。产后感染CMV的足月儿主要无症状,而极低出生体重(VLBW,<1500 g)和超低出生体重(ELBW,<1000 g)的婴儿可能会出现严重疾病,短期后遗症从实验室指标异常到败血症样综合征不等,长期后遗症如发育问题。因此,对于VLBW/ELBW婴儿,可能需要使用经过热处理的母乳来预防/降低CMV传播的风险。有不同的技术,在根除CMV和维持乳汁中生物化合物活性方面具有不同的效果:长/短巴氏杀菌、冻融、微波使用和紫外线-C照射。在我们的新生儿重症监护病房(NICU),始终强烈建议足月儿/早产儿使用母乳,但为了降低CMV传播风险,对于胎龄≤30周或/和体重≤1000 g的新生儿,使用冻融后的母乳,通常不考虑母亲的血清学状况,因为未对孕妇进行常规CMV筛查,且未评估血清免疫母亲的乳汁中CMV再激活情况,因为其发生率与血清阳性率相似。在过去4年中,我们的NICU有10例VLBW/ELBW新生儿发生迟发性败血症且培养结果为阴性。在这些情况下,检测新生儿尿液或唾液中的CMV DNA以诊断产后有症状感染(一旦排除先天性传播)可能有用且无创。我们想分享的关键信息是,对于由血清反应阳性母亲母乳喂养且出现严重症状(特别是培养结果为阴性的败血症)的VLBW/ELBW婴儿,应考虑获得性CMV感染。这可以使儿科医生做出质量更高的诊断,进行支持性治疗,在需要时提供抗病毒治疗,或为这些高危新生儿建立“抢先”治疗方案。

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本文引用的文献

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Do Neonatal Infections Require a Positive Blood Culture?新生儿感染是否需要血培养阳性?
Am J Perinatol. 2020 Sep;37(S 02):S18-S21. doi: 10.1055/s-0040-1714079. Epub 2020 Sep 8.
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Enabling Breastfeeding to Support Lifelong Health for Mother and Child.促进母乳喂养,保障母婴终生健康。
Obstet Gynecol Clin North Am. 2020 Sep;47(3):363-381. doi: 10.1016/j.ogc.2020.04.001. Epub 2020 Jul 2.
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Postnatally acquired cytomegalovirus infection in extremely premature infants: how best to manage?极早产儿获得性巨细胞病毒感染:如何最佳治疗?
Arch Dis Child Fetal Neonatal Ed. 2020 May;105(3):334-339. doi: 10.1136/archdischild-2019-317650. Epub 2019 Oct 15.

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