Abstract
ObjectivePreterm birth is the main reason for neonatal deaths worldwide. We investigate whether maternal gut microbiota may play a previously overlooked role.MethodsThe Norwegian Microbiota Study (NoMIC) is a case control study on preterm birth (<259 days of gestation, calculated primarily based on the last menstrual period), including two consecutively born term infants per infant born prematurely. Eligible mothers were fluent in Norwegian and recruited from the maternity ward at a county hospital in Eastern Norway in the period 2002–2005. Fecal samples were collected at day 4 postpartum, and analyzed using 16S ribosomal RNA gene sequencing. We used samples from 121 mothers giving birth vaginally. Measures of alpha diversity (Shannon, Phylogenetic Diversity and Observed Operational Taxonomic Units) and microbiome composition were combined with information from the Medical Birth Registry, pregnancy journals, and questionnaires.ResultsThe association between maternal gut diversity and preterm delivery was examined using logistic regression. One IQR increase in Shannon diversity was significantly associated with 38% lower odds of spontaneous preterm birth, (95% confident interval (CI): 1%, 61%), and the association was stronger when adjusting for maternal age, marital status, ethnicity, parity, BMI, education, antibiotic use, pets in the household, income and smoking (48% lower odds, 95% CI: 4.2%, 72%). Mothers delivering prematurely also had lower abundance of OTUs belonging to Bifidobacterium and Streptococcus, and of the Clostridiales order.ConclusionAnalysis of maternal gut microbiota using next-generation sequencing shows that low gut diversity, with a distinct microbial composition, is associated with spontaneous preterm delivery.
Highlights
Preterm delivery, defined as birth before 37 weeks of pregnancy, is the cause of many neonatal deaths worldwide[1], but the underlying etiology is not well understood [2, 3]
One interquartile range (IQR) increase in Shannon diversity index (Shannon) diversity was significantly associated with 38% lower odds of spontaneous preterm birth, (95% confident interval (CI): 1%, 61%), and the association was stronger when adjusting for maternal age, marital status, ethnicity, parity, Body Mass Index (BMI), education, antibiotic use, pets in the household, income and smoking
High quality Illumina results (>1,000 Number of observed operational Taxonomic Units (OTUs)) from sequencing the V4 16S rRNA region were available in 183 mothers, but only 121 mothers (102 term/19 preterm) who had delivered vaginally, and who had not reported antibiotic use on or after the day of delivery were used in the main analysis
Summary
Preterm delivery, defined as birth before 37 weeks of pregnancy, is the cause of many neonatal deaths worldwide[1], but the underlying etiology is not well understood [2, 3]. Many maternal factors are associated with spontaneous preterm delivery, including previous premature birth, age and parity, low socioeconomic status, non-Caucasian origin and smoking before conception [3]. Intrauterine inflammation due to vaginal infections or imbalance in the vaginal flora, with potential pathogens ascending into a near sterile intrauterine environment, is the cause of many spontaneous preterm deliveries [5,6,7]. The risk of spontaneous preterm delivery is highest in IBD mothers with flaring disease during pregnancy, indicating a strong relation with inflammation [10]
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