Flexible modelling of risk factors on the incidence of pneumonia in young children in South Africa using piece-wise exponential additive mixed modelling

• Published in: BMC medical research methodology Vol. 21; no. 1; p. 17
• Main Authors: Ramjith, Jordache, Roes, Kit C B, Zar, Heather J, Jonker, Marianne A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.01.2021; BioMed Central; BMC
• Subjects: Additive model; Air pollution; Children & youth; Childrens health; Cox model; Development and progression; Etiology; Frailty; Immunization; Indoor air quality; Medical research; Mortality; Parent educational background; Pediatric research; Piece-wise exponential model; Pneumonia; Pneumonia in children; Premature birth; Proportional hazards; Recurrent events; Research methodology; Risk factors; Socioeconomic factors; Survival analysis; Time-varying effects; Vaccines; South Africa; Piece-wise exponential model; Survival analysis; Cox model; Proportional hazards; Time-varying effects; Additive model; Recurrent events
• ISSN: 1471-2288; 1471-2288
• DOI: 10.1186/s12874-020-01194-6

Recurrent episodes of pneumonia are frequently modeled using extensions of the Cox proportional hazards model with the underlying assumption of time-constant relative risks measured by the hazard ratio. We aim to relax this assumption in a study on the effect of factors on the evolution of pneumonia incidence over time based on data from a South African birth cohort study, the Drakenstein child health study. We describe and apply two models: a time-constant and a time-varying relative effects model in a piece-wise exponential additive mixed model's framework for recurrent events. A more complex model that fits in the same framework is applied to study the continuously measured seasonal effects. We find that several risk factors (male sex, preterm birth, low birthweight, lower socioeconomic status, lower maternal education and maternal cigarette smoking) have strong relative effects that are persistent across time. When time-varying effects are allowed in the model, HIV exposure status (HIV exposed & uninfected versus HIV unexposed) shows a strong relative effect for younger children, but this effect weakens as children grow older, with a null effect reached from about 15 months. Weight-for-length at birth shows a time increasing relative effect. We also find that children born in the summer have a much higher risk of pneumonia in the 3-to-8-month age period compared with children born in winter. This work highlights the usefulness of flexible modelling tools in recurrent events models. It avoids stringent assumptions and allows estimation and visualization of absolute and relative risks over time of key factors associated with incidence of pneumonia in young children, providing new perspectives on the role of risk factors such HIV exposure.