Non-typeable Haemophilus influenzae-associated early pregnancy loss: an emerging neonatal and maternal pathogen

Abstract

Objectives There is increasing evidence indicating an association between invasive non-typeable Haemophilus influenzae (NTHi) infection in pregnancy and early pregnancy loss. As the diagnosis relies on microbiological investigation of postmortem placental and foetal samples, a significant proportion of NTHi-related pregnancy loss remains unrecognised. To better characterise NTHi in septic abortion, we report NTHi cases associated with early pregnancy loss. Methods We reviewed all post-mortems at <24 weeks gestation with histologically proven acute chorioamnionitis on placental histology and enrolled cases with at least one matched foetal and placental sample culture positive for NTHi. The study was approved by the NHS Lothian Caldicott Guardian. Results In our cohort, invasive NTHi has accounted for 20% of infections associated with early pregnancy loss prior to 24 weeks gestation. All patients were young and healthy pregnant women at < 20 weeks' gestation who presented with abdominal pain, PV bleed /discharge and were septic at the time of presentation. One patient with previous history of miscarriage who presented with cervical incompetence had more severe pathology suggestive of early intrauterine pneumonia. Conclusion The burden of invasive NTHi disease in early pregnancy loss is likely to be much larger than currently recognised. NTHi should be considered in pregnant women presenting with abdominal pain and PV bleed/discharge in whom clinical signs of sepsis are present. Active surveillance should be considered in this patient group including septic abortion to capture the true prevalence of this emerging pathogen to inform preventative and therapeutic approaches.

Invasive Haemophilus influenzae Infections after 3 Decades of Hib Protein Conjugate Vaccine Use

“…Early-onset neonatal NTHi infections are well described in studies from Europe (197)(198)(199), the United States (200), and Australia (201), with an incidence of 0.9/100,000 (95% CI, 0.9 to 1.6) in infants born at term rising to 342/100,000 (95% CI, 234 to 483) in infants born at ,28 weeks gestation (104,197,199,202) accounting for approximately 5% of all neonatal sepsis episodes (104). The European EU-IBIS study reported a 10-foldhigher incidence of invasive NTHi disease than with Hib in neonates, with 81% of cases occurring in the first 7 days of life (9).…”

“…Each additional gestational week reduced the CFR by 21% (OR, 0.79; 95% CI, 0.69 to 0.90). NTHi can colonize the female genital tract, and an ascending infection can cause both maternal and fetal infection, with maternal sepsis, septic abortion, preterm delivery, and increased complications during labor as possible consequences (196,198,203). In the EU-IBIS study, for example, NTHi caused more infections in women than in men aged 25 to 44 years, and there may be an increased risk of invasive NTHi infection in women of childbearing age.…”

“…There is increasing evidence that NTHi invasive infection in early pregnancy may be associated with fetal loss, but as this diagnosis relies on postmortem placental and fetal samples, it is likely to be underrecognized. In a retrospective survey of all postmortem samples at ,24 weeks gestation, NTHi was identified in 20% of cases with histologically confirmed chorioamnionitis and matched fetal and placental samples (198).…”

Genome Characterisation of Invasive Haemophilus influenzae in Pregnancy: The Noticeable Placental Tissue Tropism Is Distributed across the Species Rather Than Linked with Capsulation or Particular Clones

“…The diagnosis relies on the microbiological investigation of placental and foetal samples, and a significant proportion of Haemophilus-related preterm delivery or pregnancy loss may go unrecognised. A study from Scotland in 2017-2018 reviewed all post-mortems at <24 weeks gestation with histologically proven acute chorioamnionitis on placental histology; H. influenzae accounted for 20% of infections associated with early pregnancy loss prior to week 24 [28]. The inconsistent definition, or reporting, of invasive H. influenza infections in pregnancy is apparent from the contrasting numbers of bacteraemia, from 100% in the US ABC catchment areas 2008-2019 [7] to 34% in the New Zealand study [8].…”

Fetal Loss and Preterm Birth Caused by Intraamniotic Haemophilus influenzae Infection, New Zealand

“…Historically, H. influenzae has not been recognized as a leading cause of intraamniotic infection (IAI) ( 12 ). However, recent case reports describe IAI that showed histologic evidence of acute necrotizing chorioamnionitis, suggesting that maternal H. influenzae infection can involve the amniotic cavity and the fetus ( 13 ).…”