Maternal obesity before pregnancy predicts offspring blood pressure at 18 years of age: A causal mediation analysis

Abstract

ImportanceHypertension is the second most common pediatric chronic disease in Westernized countries. Understanding the natural history of hypertension is key to identifying prevention strategies.ObjectiveExamine the relationship between maternal pre-pregnancy body mass index (BMI) and offspring blood pressure at 18 years and the mediating role of growth throughout childhood and adolescence.Design, Setting, and ParticipantsWe 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. Latent trajectory analysis (LTA) was used to quantify the mediating variable of offspring BMI from 7 to 18 years of age.ExposuresThe main exposure was maternal pre-pregnancy BMI. Analyses were adjusted for relevant confounders including maternal education, maternal blood pressure, and weeks gestation at delivery.Main Outcomes and MeasuresThe main outcome was offspring blood pressure at 18 years of age categorized as normal (SBP < 120 mmHg or DBP < 80mmHg) or elevated (SBP ≥ 120 mmHg or DBP ≥ 80 mmHg) as per the 2017 American Academy of Pediatrics guidelines.ResultsAt 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. Multivariate 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).Conclusion and RelevanceMaternal BMI prior to pregnancy is associated with an increased risk of elevated blood pressure in offspring at 18 years of age and is mediated, in part, by offspring BMI trajectory throughout childhood and adolescence.

Animal Foetal Models of Obesity and Diabetes – From Laboratory to Clinical Settings

“…Maternal overweight is a risk factor for foetal macrosomia and it increases the risk of development of obesity throughout childhood and adolescence (114)(115)(116)(117). High maternal weight during all three trimesters of pregnancy increases the risk of elevated birth weight of offspring (118,119).…”

“…The meta-analysis of clinical studies showed that excessive gestational weight gain increased the risk of childhood obesity by 33% (120). The proposed mechanisms underlying these associations include abnormal placental transfer, epigenetic mechanisms, and altered peripheral and central metabolic profile in offspring (114,115).…”

“…Multiple observational studies on humans revealed a correlation between maternal obesity before and during pregnancy and an increased risk of cardiovascular anomalies (114,115,212,213). The exposure of the foetus to maternal obesity increased its blood pressure, altered the vascular system (endothelial function), and myocardial function (199,214).…”

“…The exposure of the foetus to maternal obesity increased its blood pressure, altered the vascular system (endothelial function), and myocardial function (199,214). Researchers observed a positive correlation between maternal obesity and/ or gestational weight gain and higher systolic blood pressure in the offspring (114,(215)(216)(217). Moreover, a cohort study showed that a higher maternal BMI increased the risk of hospital admissions of adult offspring due to cardiovascular events (43,213).…”