Post by Fergus McCarthy

The focus of preeclampsia research continues to broaden with an increasing amount of studies focusing on long-term maternal health implications of pre-eclampsia and now the implications of maternal pre-eclampsia on the cardio-metabolic risks of the off-spring.

Groups have demonstrated associations between hypertensive disorders of pregnancy and increased risks of hypertension and cardiovascular disease in the offspring of women with pre-eclampsia.1 Previously, using data from 6343 nine-year-old participants, the Avon Longitudinal Study of Parents and Children demonstrated that both pre-eclampsia and gestational hypertension were associated with systolic and diastolic blood pressures in the 9-year-old offspring,  after adjustment for parental and own adiposity and for other potential confounders. The mean difference in systolic blood pressure was 2.05 mm Hg (95 confidence interval, 0.72 to 3.38) and 2.04 mm Hg (95 confidence interval, 1.42 to 2.67) for pre-eclampsia and gestational hypertension, respectively, compared with those with no hypertensive disorders of pregnancy.2

Recently published In Hypertension, Alsnes et al present their work using data from the Prospective and Sibling Studies in the HUNT Study (Nord-Trøndelag Health Study) in Norway. 3

The authors included data from 15,778 participants, including 210 sibling groups and these were then linked to information from the Medical Birth Registry of Norway. Seven hundred and six participants were born after exposure to maternal hypertensive disorders of pregnancy.  336 mothers had gestational hypertension, 343 had term preeclampsia, and 27 had preterm pre-eclampsia.

Offspring whose mothers had hypertension during pregnancy had 2.7 (95% confidence interval, 1.8–3.5) mm Hg higher systolic blood pressure, 1.5 (0.9–2.1) mm Hg higher diastolic blood pressure, 0.66 (0.31–1.01) kg/m2 higher body mass index, and 1.49 (0.65–2.33) cm wider waist circumference, compared with offspring of normotensive pregnancies. Similar differences were observed for gestational hypertension and term pre-eclampsia. Term pre-eclampsia was also associated with higher concentrations of non–high-density lipoprotein cholesterol (0.14 mmol/L, 0.03–0.25) and triglycerides (0.13 mmol/L, 0.06–0.21).

What this study intriguingly adds to the current body of evidence, is that siblings born after a normotensive pregnancy had similar outcomes compared with their siblings who were born after a hypertensive pregnancy, suggesting that the risk is far more complex than in-utero exposure to hypertension. This study has many strengths including good categorisation of hypertensive disorders of pregnancy, detailed cardiovascular phenotyping including standardized assessment of total cholesterol, high-density lipoprotein, and triglycerides.

The results raise the question as to what is driving the increased risk of cardiovascular disease in the offspring and how much hypertension actually contributes? Whether genetics, parental BMI, diet or other variables play a greater role and whether they may be modified remains to be determined.  These studies highlight the complexities involved in determining long-term risk in the offspring, the importance of sibling linkage and finally, they highlight the importance of appropriate long term follow-up of intervention studies involving women with hypertensive disorders of pregnancy.

References

  1. Staley JR, Bradley J, Silverwood RJ, Howe LD, Tilling K, Lawlor DA, Macdonald-Wallis C. Associations of blood pressure in pregnancy with offspring blood pressure trajectories during childhood and adolescence: findings from a prospective study. Journal of the American Heart Association. May 20 2015;4(5).
  2. Geelhoed JJ, Fraser A, Tilling K, Benfield L, Davey Smith G, Sattar N, Nelson SM, Lawlor DA. Preeclampsia and gestational hypertension are associated with childhood blood pressure independently of family adiposity measures: the Avon Longitudinal Study of Parents and Children. Circulation. Sep 21 2010;122(12):1192-1199.
  3. Alsnes IV, Vatten LJ, Fraser A, Bjorngaard JH, Rich-Edwards J, Romundstad PR, Asvold BO. Hypertension in Pregnancy and Offspring Cardiovascular Risk in Young Adulthood: Prospective and Sibling Studies in the HUNT Study (Nord-Trondelag Health Study) in Norway. Hypertension. Apr 2017;69(4):591-598.