From the Journals

Placental bacteria not linked to adverse pregnancy outcomes



The human placenta does not have a microbiome, and bacterial placental infection is not a common cause of adverse pregnancy outcomes such as preeclampsia or spontaneous preterm birth, a study has found.

placenta in delivery room dimarik/Getty Images

Dr. Marcus C. de Goffau, of Wellcome Sanger Institute, Cambridge, England, and coauthors wrote that placental dysfunction is linked to a number of common adverse pregnancy outcomes, but in many cases the cause of that dysfunction is unknown.

“Several studies have used sequencing-based methods for bacterial detection (metagenomics and 16S rRNA gene amplicon sequencing), and have concluded that the placenta is physiologically colonized by a diverse population of bacteria (the ‘placental microbiome’) and that the nature of this colonization may differ between healthy and complicated pregnancies,” they wrote.

In a paper published in the July 31 edition of Nature (doi: 10.1038/s41586-019-1451-5), researchers reported the outcomes of a study involving two cohorts. The first included 80 babies delivered by prelabor caesarean section, of whom 20 were small for gestational age, 20 were delivered to mothers with preeclampsia, and 40 were matched controls. The second cohort comprised 100 patients with preeclampsia, 100 small-for-gestational-age infants, 100 preterm births, and 198 matched controls, with two controls having been used twice.

The bacterial content of the placentas was analyzed via deep metagenomic sequencing of total DNA and 16S rRNA gene amplicon sequencing in cohort 1, and 16S rRNA gene amplicon from two different kits for cohort 2’s samples. In the first cohort, samples were also spiked with Salmonella bongori as a positive control.

For cohort 1, researchers were able to detect the S. bongori in all samples, but all other bacterial signals showed clear links to different batches, which the authors said showed they were the result of contamination. This was further supported by the discovery that the Escherichia coli signal seen in a number of batches was all from the same bacterial strain.

In the second cohort, researchers found Bradyrhizobium in nearly all samples, and Burkholderia – which has been thought to play a role in preterm birth – in some samples.

However in the case of the Burkholderia, significant variation between different runs of tests was found, and both Bradyrhizobium and Burkholderia were also found in negative controls.

Researchers also saw a high prevalence of four “ecologically unexpected” bacterial groups but were able to show that these were likely contaminants from a reagent used to wash the placental samples.

The study found that vaginal organisms such as lactobacilli and vaginosis-associated bacteria were more abundant in the second cohort, where babies were delivered by a mix of vaginal, intrapartum and prelabor caesarean section, compared with the first cohort, who were all prelabor caesarean section deliveries.

The only organism that met all the criteria for a genuine placenta-associated bacterial signal was Streptococcus agalactiae, but the authors found no association between it and pregnancy outcomes.

However, they did sound a warning that the perinatal transmission of S. agalactiae from the mother’s genital tract to the neonate could be a cause of fatal sepsis in the infant.

“Further studies will be required to determine the association between the presence of the organism in the placenta and fetal or neonatal disease,” they wrote.

The researchers also found significant associations between the delivery-associated vaginal bacteria Lactobacillus iners and preeclampsia, and between Streptococcus anginosus and the Ureaplasma genus – both of which are associated with vaginosis – and preterm birth.

“We conclude that bacterial placental infection is not a major cause of placentally related complications of human pregnancy and that the human placenta does not have a resident microbiome,” the authors wrote. “Although we see no evidence of a placental microbiome, the frequency of detection of vaginal bacteria in the placenta increased after intrapartum [cesarean] section, suggesting ascending or haematogenous spread.”

The Medical Research Council and the National Institute for Health Research Cambridge Biomedical Research Centre supported the study. Five authors declared grants and support from private industry outside the submitted work.

SOURCE: de Goffau M et al. Nature. 2019 Jul 31. doi: 10.1038/s41586-019-1451-5.

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