Both parents' pre-pregnancy BMI predicts MASLD in offspring at 24

Design

prospective birth cohort study with causal mediation analysis

Population

1,933 offspring in the UK ALSPAC cohort assessed at age 24

Primary outcome

MASLD at 24, defined by transient elastography steatosis plus a cardiometabolic risk factor

Effect

maternal BMI odds ratio 1.10 (95% CI 1.06-1.14) and paternal 1.09 (1.04-1.13) per kg/m2; biparental overweight or obesity 3.73 (2.43-5.73); 67% mediated by cumulative childhood BMI

The ALSPAC UK birth cohort followed 1,933 offspring to age 24, when MASLD was defined by hepatic steatosis on transient elastography plus at least one cardiometabolic risk factor. Prevalence at 24 was 10.4%.

Both parents' pre-pregnancy body mass index mattered, and by almost the same amount: each 1 kg/m2 of maternal BMI raised the odds of offspring MASLD by 10% (odds ratio 1.10, 95% CI 1.06 to 1.14) and each 1 kg/m2 of paternal BMI by 9% (1.09, 1.04 to 1.13). Where both parents were overweight or obese, the odds were 3.73 times those of two normal-weight parents (2.43 to 5.73). Causal mediation analysis attributed 67% of that association to cumulative excess childhood BMI between ages 7 and 17.

The paternal finding is the interesting one. A maternal effect can be explained by the intrauterine environment; a nearly identical paternal effect cannot, and points instead to shared genetics, shared household diet and activity, or paternal epigenetic contributions. The mediation figure is the practical one: two-thirds of the risk passed through childhood adiposity, which is modifiable in a way that parental pre-pregnancy BMI is not by the time a paediatric or hepatology clinic sees the child.

• Ask about family weight history when a young adult presents with steatosis - both parents, not only the mother
• Treat childhood and adolescent adiposity as the intervenable step; two-thirds of the association ran through it
• Consider elastography in young adults with obesity and a strong family history rather than waiting for abnormal enzymes
• Frame advice to families rather than to individuals; the household is the shared exposure
• Note MASLD was present in one in ten 24-year-olds in this cohort - this is not a middle-aged diagnosis

Why it matters

A paternal effect as large as the maternal one rules out the intrauterine explanation as the whole story.

Don't overread it

An observational birth cohort - it cannot show that changing parental weight before pregnancy would reduce offspring MASLD.

The statistics, in plain English

Mediation analysis estimates how much of an association travels through an intermediate step, and its 67% figure rests on assumptions - chiefly that there is no unmeasured confounding between childhood BMI and adult MASLD - that cannot be verified. Treat it as an informative estimate, not a measured quantity. The odds ratio of 3.73 with an interval from 2.43 to 5.73 is robust in direction but imprecise in size. And this is one UK birth cohort: the absolute prevalence of 10.4% at 24 will differ elsewhere, though the direction of the parental effect is unlikely to.

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