Abstract
Observational epidemiological studies have reported that higher maternal blood pressure (BP) during pregnancy is associated with increased future risk of offspring cardiometabolic disease. However, it is unclear whether this association represents a causal relationship through intrauterine mechanisms. We used a Mendelian randomization (MR) framework to examine the relationship between unweighted maternal genetic scores for systolic BP and diastolic BP and a range of cardiometabolic risk factors in the offspring of up to 29 708 genotyped mother-offspring pairs from the UKB study (UK Biobank) and the HUNT study (Trøndelag Health). We conducted similar analyses in up to 21 423 father-offspring pairs from the same cohorts. We confirmed that the BP-associated genetic variants from the general population sample also had similar effects on maternal BP during pregnancy in independent cohorts. We did not detect any association between maternal (or paternal) unweighted genetic scores and cardiometabolic offspring outcomes in the meta-analysis of UKB and HUNT after adjusting for offspring genotypes at the same loci. We find little evidence to support the notion that maternal BP is a major causal risk factor for adverse offspring cardiometabolic outcomes in later life.
Highlights
Observational epidemiological studies have reported that higher maternal blood pressure (BP) during pregnancy is associated with increased future risk of offspring cardiometabolic disease
Observational epidemiological studies using multivariable regression have shown that gestational hypertensive disorders are associated with increased risk of offspring cardiometabolic diseases in later life, including cardiovascular diseases and type 2 diabetes.[1,2,3,4,5]
Maternal blood pressure (BP) during pregnancy is associated with offspring cardiometabolic risk factors, in particular offspring BP,[7] sibling studies have indicated that the associations could be explained by confounding due to postnatal environmental factors or inherited genetic variants instead of intrauterine programming.[8,9,10]
Summary
Observational epidemiological studies have reported that higher maternal blood pressure (BP) during pregnancy is associated with increased future risk of offspring cardiometabolic disease. Observational epidemiological studies using multivariable regression have shown that gestational hypertensive disorders are associated with increased risk of offspring cardiometabolic diseases in later life, including cardiovascular diseases and type 2 diabetes.[1,2,3,4,5] These associations could be due to intrauterine effects (ie, developmental programming), in which case intervening to prevent gestational hypertensive disorders could lower cardiometabolic risk in the offspring.[6] maternal blood pressure (BP) during pregnancy is associated with offspring cardiometabolic risk factors, in particular offspring BP,[7] sibling studies have indicated that the associations could be explained by confounding due to postnatal environmental factors or inherited genetic variants instead of intrauterine programming.[8,9,10] definitive evidence as to whether increased maternal BP during pregnancy has long-term impacts on offspring cardiometabolic health in human populations is lacking Understanding this relationship will help determine whether intervening on maternal BP during pregnancy will combat the rising incidence of offspring cardiometabolic diseases in adulthood. Maternal blood pressure during pregnancy is unlikely to cause large increases in the risk of offspring cardiometabolic diseases in later life, including hypertension. Understanding this relationship will help determine whether intervening on high maternal blood pressure during pregnancy will combat the rising incidence of offspring cardiometabolic diseases in adulthood
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