Gender-based differences in children with sepsis and ARDS: The ESPNIC ARDS Database Group

Abstract

Male gender predisposes to severe sepsis and septic shock. This effect has been ascribed to higher levels of testosterone. The ESPNIC ARDS database was searched, to determine if there was evidence of a similar male preponderance in severe sepsis in prepubertal patients in spite of low levels of male sex hormones at this age. A total of 72 patients beyond neonatal age up to 8 years of age with sepsis were identified. The male/female (M/F) ratio was 1.7 (1.0;2.7) and differed significantly from non-septic ARDS patients in this age group [n = 209; M/F = 1.0 (0.8;1.3)]. The highest M/F-ratio was observed in the first year of life. The gender-ratio was the same as reported in adult patients with sepsis. In infants between 1 month and 12 months of age, the ratio was 2.8 (1.2;6.1) (Chi2= 5.6; P< 0.01), in children from 1 year to 8 years of age it was 1.2 (0.7;2.2) (n.s.). In a subgroup of patients with severe sepsis or septic shock, caused by other bacteria than Neisseria meningitidis, the M/F-ratio was 2.1 (1.2;3.6) (Chi2= 4.9; P<0.05), while in patients with meningococcal sepsis (n=20) the M/F-ratio was 1.0 (0.4;2.3). In prepubertal ARDS patients with sepsis an increased frequency of male patients is found, comparable to adults. No male preponderance exists in patients with ARDS due to meningococcal septic shock. Since levels of testosterone and other sex hormones are extremely low at this age, we conclude that factors others than testosterone are involved in the male preponderance in severe sepsis.

Longitudinal studies of inter-alpha inhibitor proteins in severely septic patients: A potential clinical marker and mediator of severe sepsis*

“…In some studies, women do no better or may actually do worse than men after septic shock develops (23,27,28). The impact of genderrelated differences in I␣Ip levels on prognosis of sepsis in women will require further study.…”

The role of infection and comorbidity: Factors that influence disparities in sepsis

“…Estrogen levels in combination with plasma cytokine imbalance may contribute to the differences in the inflammatory response and the development of sepsis (39,40), whereas hormonal manipulation in animal models has been shown to reduce the risk of death with sepsis for males compared with females (41). However, gender disparities also exist in the neonatal and pediatric sepsis populations (14)(15)(16), making hormonal differences an incomplete explanation. Furthermore, the observed increased risk specifically for Gram-positive infections among males compared with females after controlling for the site of infection suggests other contributing factors in the differential risk for sepsis.…”

“…Even greater differences in the risk for sepsis exist among African Americans, where incidence rates are twice as high compared with Caucasians (RR 1.90, 95% CI 1.81-2.00). Both racial and gender disparities have been found to also exist in the pediatric sepsis population (14)(15)(16)), yet the reasons for these disparities remain to be determined.…”

Pediatric Acute Lung Injury

“…Data from the ESPNIC ARDS database (www.meb.uni-bonn.de/ards) showed that more boys than girls developed ARDS (45 vs.27) in the age group 0 < 12 months [53]. Therefore, it was concluded that factors other than testosterone might be involved in the male preponderance (low levels of male sex hormones at this age).…”