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Babies, pre-eclamptic mothers and grandparents: a three-generation phenotyping study
Insights
Paternal history of essential hypertension increases offspring risk of developing hypertension. This risk is higher in daughters and may be exacerbated during pregnancy, suggesting an underlying endothelial vulnerability.
Area of Science:
- Cardiovascular epidemiology
- Obstetrics and Gynecology
- Genetics and Genomics
Background:
- Pre-eclampsia (PE) is linked to future cardiovascular disease.
- Offspring of mothers with PE have an elevated risk of cardiovascular disease.
- Paternal lineage may also contribute to PE risk.
Purpose of the Study:
- To investigate the association between grandparental essential hypertension and maternal pre-eclampsia.
- To determine the influence of parental hypertension on offspring blood pressure.
Main Methods:
- Collected medical and obstetric histories from 673 women with pre-eclampsia and their families.
- Recorded blood pressure and essential hypertension (EHT) status in participating grandmothers and grandfathers.
- Analyzed the relationship between grandparental EHT and maternal blood pressure during pregnancy.
Main Results:
- Grandparental systolic blood pressure and EHT status significantly predicted maternal systolic pressure during pregnancy.
- Maternal body mass index had a lesser effect on maternal blood pressure.
- Grandmaternal EHT did not influence her daughter's blood pressure.
Conclusions:
- A paternal history of essential hypertension is associated with increased risk of non-pregnant hypertension in offspring.
- The risk of hypertension is greater in daughters than sons.
- Pregnancy may reveal or worsen this hypertensive risk, possibly due to endothelial factors.
Objectives:
Pre-eclampsia (PE) is associated with an increased incidence of cardiovascular disease in later life. Daughters of PE mothers have an increased risk of developing the disease; recent epidemiological data suggest a (grand)paternal contribution. We have directly studied the parents of 673 women with stringently defined PE in relation to their daughters' disease.
Methods:
(Grand)parental medical history, current medication and blood pressure (using an Omron 705 automated monitor) were recorded, with obstetric history for the grandmother, including directly verified pregnancy hypertension.
Results:
The age of the 649 participating grandmothers was 55.5 +/- 7.5 years (mean +/- SD) and that of the 542 participating grandfathers was 58.0 +/- 7.3 years. Essential hypertension (EHT) requiring therapy was present in 23.4% of the grandmothers and 22.8% of the grandfathers. Patients had moderate to severe PE; a quarter were delivered before 34 weeks' gestation. A third of the babies had birthweights below the third centile; the perinatal mortality rate was 2.1%. Grandparental absolute systolic pressures and EHT status were highly significant determinants of maternal systolic pressure during gestation (F = 11.8, P < 0.001; F = 8.91, P = 0.003, respectively); maternal body mass index (BMI) had less effect. A similar, less marked, pattern was seen for diastolic pressure (F = 6.01, P = 0.014; F = 11.50, P < 0.0001). Grandmaternal EHT did not influence her daughter's systolic or diastolic pressure (P > 0.2 for both).
Conclusions:
A paternal, but not maternal, history of EHT is associated with increased risks of non-pregnant hypertension in the children, the risk being greater in daughters than sons. Pregnancy may unveil or exacerbate this effect, possibly reflecting underlying endothelial vulnerability.
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