Determinants of lung function development from birth to age 5 years: an interrupted time series analysis of a South African birth cohort

Background Early life is a key period that determines long-term health. Lung development in childhood predicts lung function attained in adulthood and morbidity and mortality across the life course. We aimed to assess the effect of early-life lower respiratory tract infection (LRTI) and associated risk factors on lung development from birth to school age in a South African birth cohort. Methods We prospectively followed children enrolled in a population-based cohort from birth (between March 5, 2012 and March 31, 2015) to age 5 years with annual lung function assessment. Data on multiple early-life exposures, including LRTI, were collected. The effect of early-life risk factors on lung function development from birth to age 5 years was assessed using the Generalised Additive Models for Location, Scale and Shape and Interrupted Time Series approach. Findings 966 children (475 [49<middle dot>2%] female, 491 [50<middle dot>8%] male) had lung function measured with oscillometry, tidal flow volume loops, and multiple breath washout. LRTI occurred in 484 (50<middle dot>1%) children, with a median of 2<middle dot>0 LRTI episodes (IQR 1<middle dot>0-3<middle dot>0) per child. LRTI was independently associated with altered lung function, as evidenced by lower compliance (0<middle dot>959 [95% CI 0<middle dot>941-0<middle dot>978]), higher resistance (1<middle dot>028 [1<middle dot>016-1<middle dot>041]), and higher respiratory rate (1<middle dot>018 [1<middle dot>063-1<middle dot>029]) over 5 years. Additional impact on lung function parameters occurred with each subsequent LRTI. Respiratory syncytial virus (RSV) LRTI was associated with lower expiratory flow ratio (0<middle dot>97 [0<middle dot>95-0<middle dot>99]) compared with non-RSV LRTI. Maternal factors including allergy, smoking, and HIV infection were also associated with altered lung development, as was preterm birth, low birthweight, female sex, and coming from a less wealthy household. Interpretation Public health interventions targeting LRTI prevention, with RSV a priority, are vital, particularly in lowincome and middle-income settings. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.