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Original Investigation |

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

Sarah Collins, MPH1; Mary Ramsay, FFPHM1; Mary P. E. Slack, FRCPath2; Helen Campbell, MSc1; Sally Flynn, FIBMS2; David Litt, PhD2; Shamez N. Ladhani, MRCPCH, PhD1,3
[+] Author Affiliations
1Immunisation, Hepatitis, and Blood Safety Department, Public Health England, London, England
2Respiratory and Vaccine Preventable Bacterial Reference Unit, Public Health England, London, England
3Paediatric Infectious Diseases Research Group, St George’s University of London, London, England
JAMA. 2014;311(11):1125-1132. doi:10.1001/jama.2014.1878.
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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.

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Timing of Haemophilus influenzae Infection by Week of Gestation and Subsequent Fetal Outcome

Most (96.1%; 74/77) infections were unencapsulated H influenzae. Twenty-six (35.1%) of unencapsulated H influenzae infections occurred during the first trimester, 23 (31.1%) during the second trimester, and 25 (33.8%) during the third trimester. Of the 2 H influenzae serotype f infections, 1 occurred during the first trimester and 1 during the second trimester. The only case of H influenzae serotype b infection occurred during the third trimester. Infection in all but 2 cases ended in miscarriage, stillbirth, or birth of the infant at the time of infection. Two women developed invasive unencapsulated H influenzae disease at 12 weeks’ gestation and delivered their infants (who survived) at 25 weeks’ and 28 weeks’ gestation.aDenotes a case in which an encapsulated serotype was isolated.

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