Importance: Unencapsulated Haemophilus influenzae frequently causes noninvasive upper respiratory tract infections in children but can also cause invasive disease, especially in older adults. A number of studies have reported an increased incidence in neonates and suggested that pregnant women may have an increased susceptibility to invasive unencapsulated H influenzae disease.

Objective: To describe the epidemiology, clinical characteristics, and outcomes of invasive H influenzae disease in women of reproductive age during a 4-year period.

Design, Setting, and Participants: Public Health England conducts enhanced national surveillance of invasive H influenzae disease in England and Wales. Clinical questionnaires were sent prospectively to general practitioners caring for all women aged 15 to 44 years with laboratory-confirmed invasive H influenzae disease during 2009-2012, encompassing 45 215 800 woman-years of follow-up. The final outcome was assessed in June 2013.

Exposures: Invasive H influenzae disease confirmed by positive culture from a normally sterile site.

Main Outcomes and Measures: The primary outcome was H influenzae infection and the secondary outcomes were pregnancy-related outcomes.

Results: In total, 171 women had laboratory-confirmed invasive H influenzae infection, which included 144 (84.2%; 95% CI, 77.9%-89.3%) with unencapsulated, 11 (6.4%; 95% CI, 3.3%-11.2%) with serotype b, and 16 (9.4%; 95% CI, 5.4%-14.7%) with other encapsulated serotypes. Questionnaire response rate was 100%. Overall, 75 of 171 women (43.9%; 95% CI, 36.3%-51.6%) were pregnant at the time of infection, most of whom were previously healthy and presented with unencapsulated H influenzae bacteremia. The incidence rate of invasive unencapsulated H influenzae disease was 17.2 (95% CI, 12.2-24.1; P < .001) times greater among pregnant women (2.98/100 000 woman-years) compared with nonpregnant women (0.17/100 000 woman-years). Unencapsulated H influenzae infection during the first 24 weeks of pregnancy was associated with fetal loss (44/47; 93.6% [95% CI, 82.5%-98.7%]) and extremely premature birth (3/47; 6.4% [95% CI, 1.3%-17.5%]). Unencapsulated H influenzae infection during the second half of pregnancy was associated with premature birth in 8 of 28 cases (28.6%; 95% CI, 13.2%-48.7%) and stillbirth in 2 of 28 cases (7.1%; 95% CI, 0.9%-23.5%). The incidence rate ratio for pregnancy loss was 2.91 (95% CI, 2.13-3.88) for all serotypes of H influenzae and 2.90 (95% CI, 2.11-3.89) for unencapsulated H influenzae compared with the background rate for pregnant women.

Conclusions and Relevance: Among women in England and Wales, pregnancy was associated with a greater risk of invasive H influenzae infection. These infections were associated with poor pregnancy outcomes.