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Pediatrics

Maternal body mass index, offspring body mass index, and blood pressure at 18 years: a causal mediation analysis

Abstract

Objective

Understanding the natural history of hypertension is key to identifying prevention strategies. Previous work suggests that in utero exposures and offspring anthropometrics may play a role. This study examined the relationship between maternal pre-pregnancy body mass index (BMI) and the mediating role of childhood and adolescent BMI on offspring blood pressure at 18 years.

Methods

We performed multivariable regression and causal mediation analyses within 3217 mother - offspring pairs from the Avon Longitudinal Study of Parents and Children prospective birth cohort. The main exposure was maternal pre-pregnancy BMI, and the outcome was offspring blood pressure at 18 years of age categorized as normal or elevated. Latent trajectory analysis was used to quantify the mediator, offspring BMI trajectories, derived from multiple measurements throughout childhood and adolescence. Mediation analyses were repeated using current offspring BMI at 18 years as a continuous variable.

Results

Multivariable logistic regression revealed that for every 1 unit increase in maternal BMI, the risk of elevated blood pressure at 18 years of age increased by 5% (aOR: 1.05, 95% CI: 1.03–1.07; p < 0.001). The strength of this association was reduced after adjusting for offspring BMI trajectory (aOR: 1.03, 95% CI: 1.00–1.05; p = 0.017) and eliminated after adjusting for offspring BMI at 18 years (aOR: 1.00; 95% CI: 0.98–1.03; p = 0.70). Causal mediation analysis confirmed offspring BMI at 18 years as a mediator, where BMI trajectory accounted for 46% of the total effect of maternal BMI on elevated offspring blood pressure and current BMI account for nearly the entire effect.

Conclusions

Maternal pre-pregnancy BMI is associated with an increased risk of elevated blood pressure in offspring at 18 years of age although it appears to be entirely mediated by offspring BMI.

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Fig. 1: Directed acyclic graph (DAG) describing possible pathways through which exposure to maternal obesity may lead to elevated blood pressure in adolescence.
Fig. 2: Results from latent trajectory analysis.
Fig. 3: Simplified DAG showing results from causal mediation analyses stratified by mediator.

Code availability

All R code used to generate latent trajectory analysis and causal mediation analyses are available in Appendix B.

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Acknowledgements

We are extremely grateful to all the families who took part in the ALSPAC study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses.

Funding

The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). JMM was supported by a Canadian Institutes of Health Research (CIHR) Applied Public Health Chair, MBA holds a Tier 2 Canada Research Chair (CRC) in the Developmental Origins of Chronic Disease. JMM holds grants from the CIHR, Diabetes Canada, the Heart and Stroke Foundation of Canada (HSFC), the Cosmopolitan Foundation, and the Lawson Foundation. AD currently has research funding from CIHR, Research Manitoba and CHRIM. MBA holds grants from the CIHR, The Bill and Melinda Gates Foundation, the Canada Foundation for Innovation, the Garfield G. Weston Foundation, Prolacta Biosciences, Mitacs, the Canadian Institutes for Advanced Research, the Children’s Hospital Foundation of Manitoba, and Research Manitoba; NB and JMM, MBA and AD were also supported by a Research Manitoba grant to the DEVOTION research cluster. None of the cited agencies were involved in the design, conduct, or approval of this manuscript.

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NB, BD and JMM: Designed and conceptualized the study. BD and NB performed the analyses. MA: Designed and conceptualized the study, was involved in securing funding, reviewed and revised the manuscript. AD: Designed and conceptualized the study was involved in securing funding, reviewed and revised the manuscript. JMC and NB take full responsibility for the analyses and content presented in this manuscript.

Corresponding author

Correspondence to Jonathan M. McGavock.

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Brunton, N.M., Dufault, B., Dart, A. et al. Maternal body mass index, offspring body mass index, and blood pressure at 18 years: a causal mediation analysis. Int J Obes 45, 2532–2538 (2021). https://doi.org/10.1038/s41366-021-00930-2

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