创作:Epi汪 审核:Epi汪 2020年10月02日
  • 纳入577名小于32周早产而进ICU的新生儿,在产后四周采集粪便样本,在2岁时利用量表评估神经发育状况;
  • 肠道菌群聚类分为6类,分别以产气肠杆菌、梭状芽胞杆菌、大肠杆菌、肠球菌、葡萄球菌占主导,第6类因核酸浓度过低而未测出,其中第3类被认为是最好;
  • 在ICU中接受辅助通气者,肠道菌群呈5、6型的风险降低,而接受镇静和低容量肠内营养的,呈5、6型的风险增高;
  • 婴儿期4、5、6型肠道菌型与儿童2年内死亡或发育迟缓存在关联。
JAMA Network Open [IF:5.032]

Assessment of Neonatal Intensive Care Unit Practices and Preterm Newborn Gut Microbiota and 2-Year Neurodevelopmental Outcomes



2020-09-23, Article

Abstract & Authors:展开

Importance : In very preterm newborns, gut microbiota is highly variable with major dysbiosis. Its association with short-term health is widely studied, but the association with long-term outcomes remains unknown.
Objective : To investigate in preterm newborns the associations among practice strategies in neonatal intensive care units (NICUs), gut microbiota, and outcomes at 2 years.
Design, Setting, and Participants: EPIFLORE is a prospective observational cohort study that includes a stool sample collection during the fourth week after birth. Preterm newborns of less than 32 weeks of gestational age (GA) born in 2011 were included from 24 NICUs as part of the French nationwide population-based cohort, EPIPAGE 2. Data were collected from May 2011 to December 2011 and analyzed from September 2016 to December 2018.
Exposures : Eight NICU strategies concerning sedation, ventilation, skin-to-skin practice, antibiotherapy, ductus arteriosus, and breastfeeding were assessed. A NICU was considered favorable to a practice if the percentage of that practice in the NICU was more than the expected percentage.
Main Outcomes and Measures : Gut microbiota was analyzed by 16S ribosomal RNA gene sequencing and characterized by a clustering-based method. The 2-year outcome was defined by death or neurodevelopmental delay using a Global Ages and Stages questionnaire score.
Results : Of 577 newborns included in the study, the mean (SD) GA was 28.3 (2.0) weeks, and 303 (52.5%) were male. Collected gut microbiota was grouped into 5 discrete clusters. A sixth cluster included nonamplifiable samples owing to low bacterial load. Cluster 4 (driven by Enterococcus [n = 63]), cluster 5 (driven by Staphylococcus [n = 52]), and cluster 6 (n = 93) were significantly associated with lower mean (SD) GA (26.7 [1.8] weeks and 26.8 [1.9] weeks, respectively) and cluster 3 (driven by Escherichia/Shigella [n = 61]) with higher mean (SD) GA (29.4 [1.6] weeks; P = .001). Cluster 3 was considered the reference. After adjustment for confounders, no assisted ventilation at day 1 was associated with a decreased risk of belonging to cluster 5 or cluster 6 (adjusted odds ratio [AOR], 0.21 [95% CI, 0.06-0.78] and 0.19 [95% CI, 0.06-0.62], respectively) when sedation (AOR, 10.55 [95% CI, 2.28-48.87] and 4.62 [1.32-16.18], respectively) and low volume of enteral nutrition (AOR, 10.48 [95% CI, 2.48-44.29] and 7.28 [95% CI, 2.03-26.18], respectively) was associated with an increased risk. Skin-to-skin practice was associated with a decreased risk of being in cluster 5 (AOR, 0.14 [95% CI, 0.04-0.48]). Moreover, clusters 4, 5, 6 were significantly associated with 2-year nonoptimal outcome (AOR, 6.17 [95% CI, 1.46-26.0]; AOR, 4.53 [95% CI, 1.02-20.1]; and AOR, 5.42 [95% CI, 1.36-21.6], respectively).
Conclusions and Relevance: Gut microbiota of very preterm newborns at week 4 is associated with NICU practices and 2-year outcomes. Microbiota could be a noninvasive biomarker of immaturity.

First Authors:
Jean-Christophe Rozé

Correspondence Authors:
Jean-Christophe Rozé

All Authors:
Jean-Christophe Rozé,Pierre-Yves Ancel,Laetitia Marchand-Martin,Clotilde Rousseau,Emmanuel Montassier,Céline Monot,Karine Le Roux,Marine Butin,Matthieu Resche-Rigon,Julio Aires,Josef Neu,Patricia Lepage,Marie-José Butel,EPIFLORE Study Group