Severe Infection and Mortality in Kenyan Newborns

This dissertation addresses severe neonatal infection and neonatal mortality in high-burden settings. Worldwide, almost half of all deaths in children under 5 years of age occur in the neonatal period (days 0-27 of life). Complications of prematurity, intrapartum events and severe infections cause the majority of these deaths, despite known effective interventions. The risk of neonatal mortality in Kenya is more than 23 times as high as the risk in the lowest mortality countries. We conducted a prospective cohort study of 380 pairs of mothers and newborns identified from two referral-level facilities in rural Western Kenya within 96 hours of life. Pairs were eligible if either the mother had an intrapartum risk factors for peripartum infection, or the newborn had a clinical signs of possible severe illness (pSBI), or both. Among high-risk newborns with risk factors for or clinical signs of severe illness [Early-onset neonatal sepsis (EOS) study population], we: 1) Determined prevalence and correlates of neonatal bacteremia; 2) Determined incidence and risk factors for 7-day mortality; and 3) Determined the performance of World Health Organization (WHO) empiric illness algorithms in predicting mortality and identified a novel set of prognostic factors to improve mortality prediction. The prevalence of bacterial blood stream infection as identified by blood culture was low, but antibiotic treatment coverage was high. Despite low prevalence of bacteremia, high coverage of WHO-recommended antimicrobial therapy, and receipt of hospital care, 7-day mortality risk was high. Signs of probable severe bacterial infection (pSBI) in the WHO Integrated Management of Childhood Illness (IMCI) were strongly associated with mortality, and WHO empiric algorithms for identifying and classifying severe illness in young infants performed well in predicting mortality. Among high-risk newborns who were not exclusively low birthweight, in addition to 4 of the 7 IMCI signs (poor feeding, fast breathing, only moves when stimulated, fever), least area shrinkage and selection operator regression determined that apnea and low birthweight were important prognostic factors for mortality. Strategies to prevent mortality among a population of high-risk newborns for whom currently-recommended interventions are insufficient to prevent death are urgently needed.