Babies, pre-eclamptic mothers and grandparents: a three-generation phenotyping study.
OBJECTIVE
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.
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001724:Birth Weight; D001794:Blood Pressure / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D007226:Infant Mortality; D007231:Infant, Newborn; D008875:Middle Aged; D010290:Parents; D010641:Phenotype; D049590:Postpartum Period; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000235:genetics / Q000503:physiopathology; D011256:Pregnancy Outcome; D012720:Severity of Illness Index; D006113:United Kingdom
D000959:Antihypertensive Agents