Association of birthweight with all-cause and cause-specific premature mortality in the UK: A prospective cohort study

Abstract

Purpose

We investigated the association between birthweight and all-cause and cause-specific premature mortality, and evaluated the effect modification by lifestyle factors.

Methods

This prospective cohort study used data of participants aged 39–71 years from the UK Biobank in 2006–2010 and followed up till the end of 2022. Birthweight was classified into < 1.0 kg, 1.0–<1.5 kg, 1.5–<2.5 kg, 2.5–<4.0 kg, and ≥ 4.0 kg. Cox proportional-hazards models were used to estimate adjusted hazard ratios (aHR) and 95 % confidence intervals (CI) for premature mortality.

Results

Of 221 848 participants, there were 6336 premature deaths (2148 cardiovascular, 624 respiratory, 3040 cancers, 524 other causes). Birthweight was nonlinearly associated with risks of all-cause, cardiovascular, and cancer-related mortality but the association was linear for respiratory and other-cause mortality. Compared to birthweight of 2.5–<4.0 kg, birthweight< 1.0 kg (aHR 1.36, 95 %CI 1.00–1.85) and ≥ 4.0 kg (1.10, 1.02–1.17) were associated with increased risks of all-cause mortality. A similar pattern was observed for cardiovascular mortality, with corresponding aHRs of 1.54 (1.02–2.49) and 1.16 (1.03–1.31) for birthweight of 2.5–<4.0 kg, and ≥ 4.0 kg, respectively. Birthweight≥ 4.0 kg was associated with increased risk of cancer-related mortality (1.11, 1.00–1.22). The mortality risks did not differ significantly across lifestyle scores (all P-interaction>0.05).

Conclusions

Both lower and higher birthweight were associated with increased risks of premature mortality from all causes and cardiovascular diseases, and higher birthweight was associated with increased risk of cancer-related mortality.