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Maternal early-pregnancy body mass index-associated metabolomic component and mental and behavioral disorders in

Polina Girchenko¹, Marius Lahti-Pulkkinen^2,3,4, Jari Lipsanen²

¹Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland. polina.girchenko@helsinki.fi.

Molecular Psychiatry

|August 10, 2022

Insights

Maternal obesity and associated metabolic changes during pregnancy increase children's risk for mental and behavioral disorders. Identifying these metabolic patterns may enable personalized interventions for healthier child development.

Area of Science:

Perinatal Medicine
Metabolomics
Child Neurodevelopment

Background:

Maternal pre-pregnancy obesity is linked to adverse child neurodevelopment and mental health.
Existing research often overlooks the complex interplay of multiple metabolites and their correlation with maternal Body Mass Index (BMI).

Purpose of the Study:

To identify a maternal early-pregnancy BMI-associated metabolomic component.
To assess this component's association with child mental and behavioral disorders.
To determine if this component improves prediction and mediates the effect of maternal BMI on child outcomes.

Main Methods:

Utilized multivariate supervised analytical methods on metabolomic data from 425 mothers in the PREDO study.
Measured 68 targeted metabolites from maternal blood samples during pregnancy.
Linked metabolomic data with child mental and behavioral disorder diagnoses from healthcare registers.

Main Results:

Identified a maternal early-pregnancy BMI-associated metabolomic component explaining 55.4% of variance (52.0% predictive ability).
This component significantly increased the hazard of any mental/behavioral disorder (HR 1.45) and the risk of comorbid disorders (RR 1.43) in children.
The metabolomic component improved model fit by 37.7-65.6% over maternal BMI and mediated 60.8-75.8% of maternal BMI's effect.

Conclusions:

Maternal BMI-related metabolic alterations during pregnancy are significantly associated with increased risk of mental and behavioral disorders in offspring.
These findings highlight the potential of metabolomic profiling for early identification and personalized interventions.
The identified metabolomic component serves as a potential biomarker for mediating maternal BMI effects on child mental health.

Read full analysis

Abstract:

Maternal pre-pregnancy obesity and/or higher body mass index (BMI) have been associated with neurodevelopmental and mental health adversities in children. While maternal metabolomic perturbations during pregnancy may underpin these associations, the existing evidence is limited to studying individual metabolites, not capturing metabolic variation specific to maternal BMI, and not accounting for the correlated nature of the metabolomic measures. By using multivariate supervised analytical methods, we first identified maternal early-pregnancy BMI-associated metabolomic component during pregnancy. We then examined whether this component was associated with mental and behavioral disorders in children, improved the prediction of the child outcomes over maternal BMI, and what proportion of the effect of maternal BMI on the child outcomes this component mediated. Early-pregnancy BMI of 425 mothers participating in the PREDO study was extracted from the national Medical Birth Register. During pregnancy, mothers donated up to three blood samples, from which a targeted panel of 68 metabolites were measured. Mental and behavioral disorders in children followed-up from birth until 8.4-12.8 years came from the Care Register for Health Care. Of the 68 metabolites averaged across the three sampling points, 43 associated significantly with maternal early-pregnancy BMI yielding a maternal early-pregnancy BMI-associated metabolomic component (total variance explained, 55.4%; predictive ability, 52.0%). This metabolomic component was significantly associated with higher hazard of any mental and behavioral disorder [HR 1.45, 95%CI(1.15, 1.84)] and relative risk of having a higher number of co-morbid disorders [RR 1.43, 95%CI(1.12, 1.69)] in children. It improved the goodness-of-model-fit over maternal BMI by 37.7-65.6%, and hence the predictive significance of the model, and mediated 60.8-75.8% of the effect of maternal BMI on the child outcomes. Maternal BMI-related metabolomic perturbations during pregnancy are associated with a higher risk of mental and behavioral disorders in children. These findings may allow identifying metabolomic targets for personalized interventions.

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