Limited assessment and lack of focus on low abundance
organisms
The above results indicate that reporting strategies, rather than
methodology, may contribute to the underreporting of less abundant
pathogens in metagenomic vaginal microbiome studies during pregnancy. As
the majority of studies in our review explored the compositional
variation of vaginal microbiome during pregnancy, underreporting can be
a serious issue because known pathogens may not be analyzed as potential
contributors to pregnancy complications, which can lead to limited
clinical treatment.
We observed differences in threshold determinants for analysis or
reporting. Among the 32 studies that did not report GBS, 24 analyzed the
microbiome at the species level, but only reported the most prevalent
genus (i.e., Lactobacillus species). This may lead to a
misclassification error, in which only the most abundant bacteria or
species is associated with the outcome of interest. Additionally, 20
studies reported Streptococcus at the genus level, but did not
conduct further species-level analysis. It is possible that studies that
did not specify Streptococcus had GBS present within their
population, a result which could be re-evaluated if raw sequencing data
is made available.
Moreover, four studies that did not report GBS in their results or
microbiome data identified GBS-positive women in their study based on
culture-based clinical testing.8–11 This suggests
that there may be a benefit to using both sequence-based and
culture-based methods to verify presence or absence of low abundance
microbes within vaginal microbiome communities. Previous studies have
shown discordance in culture-based GBS colonization results between
antenatal screening and culture on admission for
delivery.5,18 In a study by McCoy and colleagues, that
rate was about 40%.5 Alternatively, Hussain et al.
reported a discordance rate of 11%.18 While the
transient nature of GBS colonization is known, factors that contribute
to loss or gain of maternal GBS colonization remain
uncertain.6
Evaluation of culture-based GBS screening determined that GBS
transmission to neonates is more likely when maternal colonization is
heavy, as determined by the number of colonies grown at the time of
screening.19,20 However, it is unclear how well
clinical culture-based microbial assessments correlate with the
detection of clinically relevant pathogens in sequencing-based vaginal
microbiome studies. Furthermore, much of the research investigating risk
of neonatal GBS infection related to maternal bacterial load was
completed in the 1980s and has not been evaluated relative to
sequencing-based methods.20 Future studies that
concurrently evaluate the accuracy of GBS reporting within microbial
communities via metagenomic sequencing approaches and culture-based
methods are needed.