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Risk for Invasive Haemophilus influenzae Infection During Pregnancy and Association With Adverse Fetal Outcomes

Collins, Sarah; Ramsay, Mary; Slack, Mary P.E.; Campbell, Helen; Flynn, Sally; Litt, David; Ladhani, Shamez N.

Obstetrical & Gynecological Survey:
doi: 10.1097/01.ogx.0000452700.51556.d3
Obstetrics: Medical Complications of Pregnancy

ABSTRACT: Haemophilus influenzae is a gram-negative coccobacillus with 6 serotypes (a-f), categorized by the polysaccharide capsule. The most invasive is serotype b, and the organism can also remain unencapsulated. Routine vaccination against serotype b has decreased the incidence of the disease in all age groups. Invasive infections caused by unencapsulated H. influenzae are now relatively more common. An increased risk for invasive H. influenzae disease during pregnancy can cause serious illness in pregnant women, as well as lead to fetal death and premature delivery. This national surveillance study was undertaken to determine the epidemiology, clinical characteristics, and outcomes of invasive H. influenzae in women of reproductive age during 2009 to 2012 in England and Wales.

Public Health England performs national surveillance for invasive H. influenzae disease by a combination of isolate submission, routine laboratory reporting, and clinical reporting protocols. Standardized questionnaires were sent prospectively to clinicians ∼3 months after the patients’ infections were reported. The women were aged 15 to 44 years with laboratory-confirmed invasive H. influenzae disease.

From 45,215,800 woman-years of follow-up, 2568 cases of invasive infection were recorded; 1906 isolates (74.2%) were serotyped. Women of reproductive age accounted for 224 cases (8.7%) and 171 cases (9.0%) with serotyped isolates. Questionnaires were completed for all 171 cases; 144 cases (94.2%) had unencapsulated H. influenzae infection, 11 (6.4%) had serotype b, and 16 (9.4%) had other encapsulated serotypes. Sixty-five (38.4%) of the 171 women had at least 1 concurrent condition, most commonly chronic respiratory disease, malignancy, or immunosuppression; this was not associated with age at infection or serotype. Bacteremia was present in 53.8%; and pneumonia, in 29.2%, and 4% of women had meningitis. Nine women with unencapsulated H. influenzae had pelvic inflammatory disease. Four of 12 deaths were associated with H. influenzae. The case-fatality rate was 2.3%, and the strains were unencapsulated in 2 and serotype b and f in 1 each. Of the 75 women (43.9%) pregnant at diagnosis, 72 (96.0%) had unencapsulated H. influenzae; 73 (97.3%) miscarried or delivered the infant at the time of infection. The incidence rate ratio of invasive H. influenzae disease was 13 times higher in parturients compared with nonpregnant women and 17 times higher for women with unencapsulated H. influenzae (P < 0.001 for both). No women had concurrent conditions at the time of infections, and all pregnant women survived the infection. Outcomes for 75 pregnancies (77 fetuses), including 72 cases (74 fetuses) with unencapsulated disease, were recorded. Among the unencapsulated H. influenzae pregnancies, 43 (58.1%) of 74 fetuses were miscarried, 2 were stillborn (2.7%), and 29 were liveborn (39.2%), including 11 at less than 37 weeks. Unencapsulated H. influenzae infection during the first 24 weeks was associated with fetal loss (44/47; 93.6%) and extremely premature birth (3/47; 6.4%). During the second half of pregnancy, unencapsulated H. influenzae infection in 28 cases was associated with premature birth and stillbirth in 8 (28.6%) and 2 (7.1%) cases, respectively. The incidence of pregnancy loss was 61.0 of 100 pregnancies for women with invasive disease and 60.8 of 100 for those with unencapsulated H. influenzae. Crude incidence rate ratios for pregnancy loss were 2.91 and 2.90 for all serotypes and unencapsulated H. influenzae, respectively.

For suspected intrapartum sepsis, intrauterine death, septic abortion, or premature rupture of membranes, vaginal and placental samples should be tested for H. influenzae. A joint medical record for mothers and their infants would assist with developing evidence-based standards to reducing maternal and neonatal morbidity and mortality resulting from H. influenzae infection.

Author Information

Immunisation, Hepatitis, and Blood Safety Department (S.C., M.R., H.C., S.N.L.), and Respiratory and Vaccine Preventable Bacterial Reference Unit (M.P.E.S., S.F., D.L.), Public Health England, London, England; and Paediatric Infectious Diseases Research Group, St George’s University of London, London, England (S.N.L.)

© 2014 by Lippincott Williams & Wilkins.