Abstract
Preterm birth (PTB) is the leading cause of infant morbidity and mortality. Genitourinary infection is implicated in the initiation of spontaneous PTB; however, examination of the urinary microbiota in relation to preterm delivery using next-generation sequencing technologies is lacking. In a case-control study nested within the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study, we examined associations between the urinary microbiota and PTB. A total of 49 cases (delivery < 37 weeks gestation) and 48 controls (delivery ≥ 37 weeks gestation) balanced on health insurance type were included in the present analysis. Illumina sequencing of the 16S rRNA gene V4 region was performed on urine samples collected during the second trimester. We observed no difference in taxa richness, evenness, or community composition between cases and controls or for gestational age modeled as a continuous variable. Operational taxonomic units (OTUs) classified to Prevotella, Sutterella, L. iners, Blautia, Kocuria, Lachnospiraceae, and S.marcescens were enriched among cases (FDR corrected p≤ 0.05). A urinary microbiota clustering partition dominated by S. marcescens was also associated with PTB (OR = 3.97, 95% CI: 1.19–13.24). These data suggest a limited role for the urinary microbiota in PTB when measured during the second trimester by 16S rRNA gene sequencing. The enrichment among cases in several organisms previously reported to be associated with genitourinary pathology requires confirmation in future studies to rule out the potential for false positive findings.
Highlights
Preterm birth (PTB) is the leading cause of infant morbidity and mortality [1], [2] and occurs in approximately 11% of all live births.[2,3,4] Microbial infection of the genitourinary and reproductive tract during pregnancy is thought to be an initiating factor in spontaneous PTB
For the present nested case-control study, we examined whether bacterial diversity and community composition identified from 16S rRNA gene sequencing of urine collected during the second trimester were associated with the risk of PTB among women participating in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study
We examined whether specific Operational taxonomic units (OTUs) generated from percent similarity and entropy-based partitioning methods or the inferred metagenome were associated with delivery status
Summary
Preterm birth (PTB) is the leading cause of infant morbidity and mortality [1], [2] and occurs in approximately 11% of all live births.[2,3,4] Microbial infection of the genitourinary and reproductive tract during pregnancy is thought to be an initiating factor in spontaneous PTB. Intrauterine infections, bacterial vaginosis (BV), urinary tract infections (UTI), and maternal systemic infections have been associated with preterm delivery.[5,6,7,8] A prevailing theory postulates that pathogenic organisms of the lower genital tract migrate to the fetal membranes, and subsequently into the amniotic fluid, invoking an inflammatory response that results in the initiation of preterm labor.[9,10,11] recent reports have suggested hematogenus transmission of microbes to the amniotic fluid providing a plausible mechanism for systematic infection in PTB.[12,13,14,15]. Culture-independent investigations of the cervicovaginal microbiota have reported PTB to be associated with increased α-diversity, as well as a high diversity, Lactobacillus poor community state type; results have been inconsistent.[11, 18,19,20,21]
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