Stage- and sex-specific associations of prenatal individual and mixed metals exposure with adiposity peak and adiposity rebound among children: a prospective birth cohort study.

Prenatal exposure to aluminum, manganese, cobalt, barium, thallium, and mercury was positively associated with both the age and BMI at adiposity peak and negatively associated with the age of adiposity rebound.

• Associations were identified across 2718 mother-infant dyads from a prospective birth cohort
• Individual BMI trajectories from birth to 7 years old were fitted to estimate adiposity peak and adiposity rebound in offspring
• Linear mixed models were used to identify relevant metal elements associated with AP or AR
• 17 serum metal elements were measured across three trimesters and in cord blood

First trimester exposure to barium and thallium was significantly associated with advanced adiposity rebound phase.

• Barium in the first trimester: OR = 1.20, 95% CI 1.03–1.39, P = 0.02
• Thallium in the first trimester: OR = 1.36, 95% CI 1.04–1.78, P = 0.03
• Advanced adiposity rebound is considered a risk indicator for later obesity and metabolic abnormalities
• Stage-specific associations were identified with the first trimester as a critical exposure window for AR timing

Sex-specific differences were observed, with boys being more susceptible to mercury exposure and girls being more susceptible to manganese exposure in relation to adiposity outcomes.

• Sex-stratified analyses revealed differential susceptibility to specific metals
• Mercury showed stronger associations with adiposity peak and rebound parameters in boys
• Manganese showed stronger associations with adiposity peak and rebound parameters in girls
• Sex-specific associations were identified using multiple informant models and mixture methods

The second trimester was identified as a sensitive window for prenatal metal mixture exposure effects on adiposity peak and rebound, with manganese, cobalt, and thallium identified as key metals in mixtures.

• Multiple mixture analysis methods were applied: Bayesian kernel machine regression, quantile-based g-computation, and weighted quantile sums
• Manganese, cobalt, and thallium were the key contributing metals in prenatal metal mixtures
• Stage-specific analyses across three trimesters and cord blood identified the second trimester as a sensitive window
• Multiple informant models were used alongside mixture approaches to assess associations

Adiposity peak and adiposity rebound are key indicators of early childhood growth closely related to obesity, premature puberty, and metabolic abnormalities.

• Individual BMI trajectories from birth to 7 years old were fitted to estimate AP and AR in offspring
• Epidemiological studies have shown that prenatal metal exposure is linked to obesity in children
• Studies concerning the association of metals during pregnancy with AP and AR in children were described as scarce prior to this work
• This study presents the 'initial epidemiological evidence of the associations between prenatal metal exposure and AP and AR in children'

The study measured 17 serum metal elements across three trimesters and cord blood in a cohort of 2718 mother-infant dyads.

• Metals measured included aluminum, vanadium, manganese, iron, cobalt, nickel, copper, zinc, selenium, cadmium, barium, thallium, lead, calcium, magnesium, mercury, and molybdenum
• Measurements were taken across three trimesters and in cord blood
• The cohort comprised 2718 mother-infant dyads
• The study was designed as a prospective birth cohort study