Maternal Obesity Before Pregnancy Predicts Offspring Blood Pressure at 18 Years of Age – A Causal Mediation Analysis

Abstract

Background: Hypertension is the second most common pediatric chronic disease in Westernized countries. Understanding the natural history of hypertension is key to identifying prevention strategies. The present study will examine the relationship between maternal pre-pregnancy body mass index (BMI) and the possible mediating role of growth throughout childhood and adolescence 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 (ALSAPC) prospective birth cohort. The main exposure was maternal pre-pregnancy BMI. Latent trajectory analysis (LTA) was used to quantify the mediating variable of offspring BMI Z scores from 7 to 18 years of age. The main outcome was offspring blood pressure at 18 years of age categorized as normal or elevated as per the 2017 American Academy of Pediatrics guidelines. Findings: At 18 years of age, among 3217 offspring, 676 (21%) were overweight or obese, 865 (27%) had elevated blood pressure, and 510 (16%) were hypertensive. LTA identified five distinct offspring BMI trajectories. 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) and this effect was reduced after adjusting for offspring BMI trajectory (aOR: 1.03, 95% CI: 1.00 – 1.05; p = 0.017). Causal mediation analysis confirmed offspring BMI trajectory as a mediator, accounting for 46% of the total effect of maternal BMI on elevated offspring blood pressure (aOR 1.22; 95% CI: 1.07-1.39). Interpretation: Maternal BMI prior to pregnancy is associated with an increased risk of elevated blood pressure in offspring at 18 years of age and is largely mediated by offspring BMI trajectory throughout childhood and adolescence. Funding Statement: 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 Institute 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 (HSF), 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 Drs JMM, MBA and AD were also supported by a Research Manitoba grant to the DEVOTION research cluster. Declaration of Interests: None of the authors report potential or actual conflicts of interest. All authors have completed and submitted a Conflict of Interest Statement. Ethics Approval Statement: Ethical approval was obtained from the ALSPAC Law and Ethics Committee and the Biomedical Research Ethics Board at the University of Manitoba. Informed consent for the use of data collected via questionnaires and clinics was obtained from participants following the recommendations of the ALSPAC Ethics and Law Committee at the time.