Thursday, June 8, 2023
| Variable | Maternal cases | Neonatal cases | Total pregnancies |
|---|---|---|---|
| Total | 38 | 16 | 52† |
| Maternal ethnicity | |||
| European | 4 (10.5) | 5 (31.3) | 8 (15.4) |
| Māori | 17 (44.7) | 4 (25) | 20 (38.5) |
| Pacific | 14 (36.8) | 6 (37.5) | 20 (38.5) |
| Other | 3 (7.9) | 1 (6.3) | 4 (7.7) |
| Median maternal age, y (range)‡ | 25 (15–44) | 29.5 (18–43) | 25 (15–44) |
| Socioeconomic deprivation‡ | |||
| Quintile 5 | 22 (59.5) | 6 (46.1) | 26 (54.2) |
| Quintile 4 | 10 (27.0) | 2 (15.4) | 12 (25.0) |
| Quintile ≤3 | 5 (13.5) | 5 (38.5) | 10 (20.8) |
| Median gestation,‡ wk (range) | 32 (8–40) | 34 (26–41) | 32 (8–41) |
| Pregnancy outcomes | |||
| Intrauterine death <24 weeks’ gestation | 13 (34.2) | 0 | 13 (25.0) |
| Intrauterine death ≥24 weeks’ gestation | 3 (7.9) | 1 (6.3) | 4 (7.7) |
| Live preterm birth | 13 (34.2) | 10 (62.5) | 21 (40.4) |
| Live birth at term | 6 (15.8) | 4 (25) | 10 (19.2) |
| Pregnancy outcome unclear | 3 (7.9) | 1 (6.3) | 4 (7.7) |
| Clinical diagnosis | |||
| Intraamniotic infection§ | 34 (89.5) | 2 (12.5) | 36 (69.2) |
| Primary bacteremia | 4 (10.5) | 12 (75.0) | 14 (26.9) |
| Pneumonia | 0 | 1 (6.3) | 1 (1.9) |
| Meningitis | 0 | 1 (6.3) | 1 (1.9) |
| Other | 0 | 0 | 0 |
| Specimens culturing H. influenzae¶ | |||
| Maternal blood culture | 13 | 1 | 14 |
| Neonatal blood culture | 2 | 15 | 17 |
| Placental tissue or products of conception | 30 | 3 | 33 |
| High vaginal swab specimens§ | 17 | 0 | 17 |
| Cerebrospinal fluid | 0 | 1 | 1 |
Table 1. Pregnancy-associated invasive Haemophilus influenzae case demographic and clinical data, New Zealand*
*Values are no. (%) unless otherwise indicated. †In 2 pregnancies, invasive H. influenzae infection occurred in the mother and the neonate. Thus, the 38 maternal cases and 16 neonatal cases occurred in 52 unique pregnancies.
‡Data for gestational duration were unavailable for 2 neonatal cases and 1 maternal case; maternal age data were unavailable for 2 cases; 2013 area-level New Zealand deprivation index (NZDep2013) data were unavailable for 2 cases. NZDep2013 quintile 5 is the most deprived socioeconomic area, and quintile 1 is the least deprived socioeconomic area.
§Intraamniotic infection was defined as H. influenzae isolated from placental samples or products of conception (with or without maternal/neonatal H. influenzae bacteremia) or maternal H. influenzae bacteremia with H. influenzae concurrently isolated from high vaginal swab specimens. Isolation of H. influenzae from a high vaginal swab specimen alone, without isolation from another site, was insufficient to meet the case definition for invasive H. influenzae disease. Invasive disease was diagnosed in 9 cases with associated maternal bacteremia, 1 case with associated neonatal bacteremia, and 7 cases with documented infection of placental tissue.
¶The total number of positive culture results exceeds the number of cases because in some cases H. influenzae was isolated from ≥1 site.
| Variable | Births, no. (%) | Cases, no. (%) | Crude incidence per 100,000 births (95% CI) | Poisson regression relative risk (95% CI) |
| Maternal ethnicity | ||||
| Māori | 37,218 (15.4) | 20 (42) | 53.74 (33.50–80.84) | 3.28 (1.32–8.19) |
| Pacific | 47,655 (19.72) | 16 (33) | 37.58 (19.70–52.81) | 2.07 (0.80–5.37) |
| Other | 68,268 (28.25) | 4 (8) | 5.86 (1.82–13.61) | 0.57 (0.17–1.90) |
| European | 88,512 (36.63) | 8 (17) | 9.04 (4.13–16.82) | Referent |
| Total | 241,653 (100.00) | 48 (100.00) | 19.86 | NA |
| Maternal age, y | ||||
| ≤19 | 10,758 (4.45) | 7 (15) | 65.07 (27.96–125.80) | 3.19 (0.97–10.48) |
| 20–24 | 36,498 (15.1) | 17 (35) | 46.58 (27.80–72.35) | 2.79 (0.99–7.80) |
| 25–29 | 61,917 (25.62) | 9 (19) | 14.54 (6.99–26.20) | 1.28 (0.42–3.86) |
| 30–34 | 75,936 (31.42) | 10 (21) | 13.17 (6.60–23.10) | 1.49 (0.51–4.37) |
| ≥35 | 56,544 (23.4) | 5 (10) | 8.84 (3.17–19.01) | Referent |
| Total | 241,653 (100.00) | 48 (100.00) | 19.86 | NA |
| Socioeconomic deprivation | ||||
| Quintile 5 | 78,822 (32.6) | 26 (54.2) | 32.99 (21.88–47.34) | 1.89 (0.83–4.30) |
| Quintile 4 | 40,440 (16.7) | 12 (25) | 29.67 (15.89–49.76) | 2.52 (1.06–6.02) |
| Quintile ≤3 | 122,391 (50.7) | 10 (20.8) | 8.17 (4.09–14.33) | Referent |
| Total | 241,653 (100.00) | 48 (100.00) | 19.86 | NA |
Table 2. Pregnancy-associated invasive Haemophilus influenzae incidence by maternal ethnicity and age and socioeconomic status, New Zealand*
*Maternal age data were missing for 2 pregnancies, and 2013 area-level New Zealand deprivation index (NZDep2013) socioeconomic deprivation data were missing for 2 additional pregnancies. Therefore, crude incidence rates and relative risks from a multivariable Poisson regression model with ethnicity, age and NZDep2013 quintile in the model were calculated from the 48 cases where complete demographic data were available. The other ethnicity category comprised 3 Asian women and 1 Middle Eastern woman. p<0.0035 for ethnicity, p<0.1115 for age, and p<0.1015 for socioeconomic deprivation. NZDep2013 quintile 5 is the most deprived socioeconomic area, and quintile 1 is the least deprived socioeconomic area. NA, not applicable.
Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™
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This activity is intended for infectious disease clinicians, obstetricians, neonatologists, pediatricians, and other clinicians who treat and manage patients with pregnancy-associated invasive Haemophilus influenzae infection and their offspring.
The goal of this activity is for learners to be better able to describe disease burden and mechanisms of adverse pregnancy outcomes, based on 10-year surveillance of pregnancy-associated invasive Haemophilus influenzae infection in Auckland, New Zealand, between October 1, 2008, and September 30, 2018.
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Invasive Haemophilus influenzae infection during pregnancy can cause preterm birth and fetal loss, but the mechanism is unclear. We investigated 54 cases of pregnancy-associated invasive H. influenzae disease in 52 unique pregnancies in the Auckland region of New Zealand during October 1, 2008‒September 30, 2018. Intraamniotic infection was identified in 36 (66.7%) of 54 cases. Outcome data were available for 48 pregnancies. Adverse pregnancy outcomes, defined as fetal loss, preterm birth, or the birth of an infant requiring intensive/special care unit admission, occurred in 45 (93.8%) of 48 (pregnancies. Fetal loss occurred in 17 (35.4%) of 48 pregnancies, before 24 weeks’ gestation in 13 cases, and at ≥24 weeks’ gestation in 4 cases. The overall incidence of pregnancy-associated invasive H. influenzae disease was 19.9 cases/100,000 births, which exceeded the reported incidence of pregnancy-associated listeriosis in New Zealand. We also observed higher rates in younger women and women of Māori ethnicity.
Haemophilus influenzae serotype B (Hib) causes a range of clinical syndromes, including pneumonia, primary bacteremia, and meningitis[1,2]. Childhood immunization with conjugated Hib vaccines has resulted in dramatic decreases in illness and death attributable to Hib[2–4]. Most invasive H. influenzae disease is now caused by nontypeable H. influenzae (NTHi) which predominantly affects young children and the elderly[2,5,6]. In industrialized countries, deaths caused by NTHi infection are now more common than deaths caused by Hib infection[6].
Pregnancy is associated with a 17-fold increase in the incidence of invasive H. influenzae infection, largely caused by infection with NTHi[7]. Invasive H. influenzae infection during the first 24 weeks of pregnancy is associated with >90% rate of fetal loss[7]. Beyond 24 weeks gestation, premature birth occurred in 8 (28.6%) of 28 case-patients and stillbirth in 2 (7.1%) of 28 case-patients[7]. The burden of NTHi infection extends into the neonatal period, resulting in a high incidence of invasive disease in the first 28 days of life, especially in extremely premature neonate; incidence of invasive NTHi infection is 365-fold higher for neonates at <28 weeks’ gestation than for term neonates (>36 weeks’ gestation)[5,8,9].
Literature describing the burden of pregnancy-associated invasive H. influenzae infection consists largely of case reports and public health surveillance data[7,9‒11]. Studies have been limited by a paucity of genital tract or postmortem microbiologic data. The mechanisms of preterm birth and fetal loss associated with invasive H. influenzae infection are incompletely understood. 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].
We report 10 years of pregnancy-associated invasive H. influenzae infection in Auckland, New Zealand. We focus on the overall disease burden and the mechanisms of adverse pregnancy outcomes.
