A study of the association between hypertension in pregnancy and metabolic and hormonal risk factor profiles in mothers and their offspring later in life
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Introduction and aims: It is established that women who have experienced hypertension in pregnancy are at increased risk of cardiovascular disease (CVD) later in life. This risk may be shared with their offspring. We aimed at studying cardiovascular and metabolic risk factors in mothers who have experienced preeclampsia and their offspring 11-12 years after delivery compared to mothers and offspring with a normotensive pregnancy (paper I). We also examined if exposure to maternal hypertensive disorders was associated with cardiovascular risk factors in offspring in young adulthood, and whether these risk factors differed between siblings discordant to the exposure (paper III). It has been suggested that maternal hormonal profiles during pregnancies complicated by preeclampsia, as well as cord blood after delivery may be predominantly androgenic. Little research has been done to examine if this pattern persists with increasing age, and whether it may impact the initiation of puberty. We therefore aimed at comparing circulating androgen concentrations 11 years after delivery between offspring born after preeclampsia and children born after normotensive pregnancies (paper II). Methods: In papers I and II we studied 611 mother-offspring pairs at follow-up 11 (daughters) and 12 (sons) years after birth. Among these, 228 pairs were exposed to preeclampsia in the index pregnancy and 383 were not. We assessed cardiovascular and metabolic risk profiles by examining serum lipids (total cholesterol, HDL cholesterol, non-HDL cholesterol), insulin related factors (glucose, insulin and HOMA-IR) and blood pressure in both mothers and children, as well as BMI in the mothers. Hormone profiles in the children were assessed by circulating total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor I (IGF-I). In boys we also measured testicular volume. In paper III we studied 15 778 participants (mean age 29 years) from the HUNT Study in Norway, including 210 sibling groups. Their information was linked to the Medical Birth Registry of Norway, and blood pressure, anthropometry, serum lipids and CRP were assessed. Among the participants, 706 were born after exposure to maternal hypertension in pregnancy (gestational hypertension 336, term preeclampsia 343, preterm preeclampsia 27). Results: Compared to normotensive mothers, mothers with mild or moderate preeclampsia had more adverse cardiovascular risk factors (higher levels of glucose, insulin and HOMA-IR, BMI, systolic and diastolic blood pressure, and lower HDL cholesterol). Among offspring entering puberty, we found no clear differences between the groups with regards to cardiovascular risk factors, but we found differences in hormone profiles. Thus, DHEAS was highest in girls born after mild and moderate preeclampsia, and lowest in girls and boys born after severe preeclampsia. Testosterone was highest in girls born after severe preeclampsia, while for boys testosterone was higher in all preeclampsia groups compared to unexposed boys. Testicular volume and IGF-I were higher for boys in the preeclampsia group, except for boys in the clinically severe preeclampsia group. Young adult offspring whose mother had maternal gestational hypertension or term preeclampsia in pregnancy had higher systolic and diastolic blood pressure, higher BMI and wider waist circumference. Term preeclampsia was also associated with higher levels of non-HDL cholesterol and triglycerides. Siblings born after a normotensive pregnancy had nearly identical risk factor levels as siblings born after maternal hypertension. Discussion: Our findings confirm that mothers who have experienced preeclampsia in pregnancy are likely to be at increased risk of CVD. We did not find evidence for increased cardiovascular risk factors in the young offspring, but did identify more adverse cardiovascular risk factors in young adult offspring born after gestational hypertension and term (mild/moderate) preeclampsia. Interestingly, we observed a nearly identical pattern in their siblings who were born after a normotensive pregnancy. This seems to indicate that it is not the exposure to hypertension in pregnancy per se that raises their CVD risk, but rather that the higher long term risk of CVD may be attributed to genetic or environmental factors. The different hormonal patterns in offspring born after mild, moderate and severe preeclampsia, and normotensive pregnancies, may reflect different timing of pubertal development. The results also support the theory that preeclampsia is not a single syndrome of increasing severity, but rather a heterogeneous syndrome, perhaps with different origins between mild and moderate (term), and severe (preterm), preeclampsia.