Blood Pressure and Angiogenic Markers in Pregnancy

Author:

Birukov Anna12345,Herse Florian1236,Nielsen Julie H.7,Kyhl Henriette B.89,Golic Michaela1236,Kräker Kristin12346,Haase Nadine12346,Busjahn Andreas10,Bruun Signe9111213,Jensen Boye L.14,Müller Dominik N.12346,Jensen Tina Kold815,Christesen Henrik T.891112,Andersen Marianne Skovsager7,Jørgensen Jan Stener58912,Dechend Ralf12346,Andersen Louise Bjørkholt51216ORCID

Affiliation:

1. From the experimental and Clinical Research Center, a joint cooperation between Max-Delbrück-Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Germany (A. Birukov, F.H., M.G., K.K., N.H., D.N.M., R.D.)

2. Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany (A. Birukov, F.H., M.G., K.K., N.H., D.N.M., R.D.)

3. Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (A. Birukov, F.H., M.G., K.K., N.H., D.N.M., R.D.)

4. DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany (A. Birukov, K.K., N.H., D.N.M., R.D.)

5. Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark (A. Birukov, J.S.J., L.B.A.)

6. Berlin Institute of Health, Germany (F.H., M.G., K.K., N.H., D.N.M., R.D.)

7. Department of Endocrinology and Metabolism, Odense University Hospital, Denmark (J.H.N., M.S.A.)

8. Odense Child Cohort, Hans Christian Andersen Children’s Hospital, Odense University Hospital, Denmark (H.B.K., T.K.J., H.T.C., J.S.J.)

9. OPEN Patient data Explorative Network, Odense University Hospital, Denmark (H.B.K., S.B., H.T.C., J.S.J.)

10. HealthTwist GmbH, Berlin, Germany (A. Busjahn)

11. Hans Christian Andersen Children’s Hospital, Odense University Hospital, Denmark (S.B., H.T.C.)

12. Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark (S.B., H.T.C., J.S.J., L.B.A.)

13. Strategic Business Unit Pediatric, Arla Foods Ingredients Group P/S, Viby J, Denmark (S.B.)

14. Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark (B.L.J.)

15. Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark (T.K.J.)

16. Department of Obstetrics and Gynecology, Herlev Hospital, Denmark (L.B.A.).

Abstract

Pregnancy-induced hypertension is a severe pregnancy complication, increasing risk of long-term cardiovascular disease in mothers and offspring. We hypothesized that maternal blood pressure in pregnancy associated with offspring blood pressure; that the associations were sex-specific; and that maternal circulating placental angiogenic markers (PlGF [placental growth factor] and sFlt-1 [soluble fms-like tyrosine kinase-1]) mediated this relationship. We analyzed data from 2434 women and 2217 children from the Odense Child Cohort, a prospective Danish cohort study. Offspring blood pressure trajectory from 4 months to 5 years was highly associated to maternal first, second, and third trimester blood pressure, and mean blood pressure in pregnancy, independent of maternal and offspring covariates. There were offspring sex-specific associations: Girls from mothers in the highest quartile of first and third trimester blood pressure had significantly higher systolic blood pressure at 5 years than the rest of the cohort (mean difference±SEM: 1.81±0.59 and 2.11±0.59 mm Hg, respectively, all P <0.01); whereas boys had significantly higher diastolic blood pressure at 5 years (mean difference±SEM: 1.11±0.45 and 1.03±0.45, respectively, all P <0.05). Concentrations of PlGF at gestational week 28 correlated inversely to maternal gestational blood pressure trajectory, independent of the diagnosis of pregnancy-induced hypertension, adjusted β coefficients (95% CI) for predicting systolic blood pressure (SBP): −3.18 (−4.66 to −1.70) mm Hg, for predicting diastolic blood pressure (DBP): −2.48 (−3.57 to −1.40) mm Hg. In conclusion, maternal gestational blood pressure predicted offspring blood pressure trajectory until 5 years in a sex-differential manner. Furthermore, subtle alterations in blood pressure in early pregnancy preceded hypertension or preeclampsia, and PlGF was a mediator of cardiovascular health in pregnancy.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Internal Medicine

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