Placental Streptococcus agalactiae DNA is associated with neonatal unit admission and foetal pro-inflammatory cytokines in term infants

Abstract

We previously reported that DNA from Streptococcus agalactiae (Group B Streptococcus, GBS) was present in the placenta in ~5% of women prior to the onset of labour but the clinical significance of this finding is unknown. We re-analysed our previous study as a case control study of neonatal unit (NNU) admission. Of 436 infants born at term, 7/30 with placental GBS and 34/406 without placental GBS were cases (OR=3.3, 95% CI=1.3-7.8). We then performed a validation study of a further 239 cases of term NNU admission and 686 term controls: 16/36 with placental GBS and 223/889 without GBS were admitted to the NNU (OR=2.4, 95% CI=1.2-4.6). Of the 36 infants with placental GBS, 10 were admitted to the neonatal unit with evidence of probable but culture negative sepsis (OR=4.8, 95% CI=2.2-10.3), 2 were admitted with proven GBS sepsis (OR=66.6, 95% CI=7.3-963.7), 6 were admitted and had chorioamnionitis (OR=5.3, 95% CI=2.0-13.4), and 5 were admitted and had funisitis (OR=6.7, 95% CI=12.5-17.7). Very similar results were obtained when GBS positivity was additionally defined by RT-qPCR of GBS specific ribosomal RNA extracted from separate samples from the same placentas. Fetal cytokine storm (two or more pro-inflammatory cytokines >10 times median control levels in umbilical cord blood) was present in 36% of infants with placental GBS DNA and 4% of cases where the placenta was negative (OR=14.2, 95% CI=3.6-60.8). Overall, ~1 in 200 term births had GBS detected in the placenta and the infant experienced neonatal morbidity. Hence we show that occult perinatal sepsis due to GBS is relatively common and that infection may occur through placental transmission and cause fetal cytokine storm.