Multi‐Organ Phenotypes of Offspring Born Following Hypertensive Disorders of Pregnancy: A Systematic Review

Background Hypertensive pregnancies are associated with an increased risk of cardiovascular and neurological diseases in the offspring during later life. However, less is known about the potential impact on multi‐organ phenotypes in offspring before disease symptoms occur. The objective of this systematic review was to determine the associations of fetal exposure to maternal hypertensive pregnancy with multi‐organ phenotypes across developmental stages. Methods and Results Ovid MEDLINE, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), WoS, Scopus, CINAHL, and ClinicalTrials.gov were systematically searched until February 2024. Records were independently screened by 2 authors. Studies reporting on the structure or function of the heart, blood vessels, brain, liver, and kidneys in offspring of hypertensive pregnancies compared with a normotensive control population were included. Risk of bias was assessed using the Newcastle‐Ottawa Scale. Extracted data were presented using harvest plots. Seventy‐three studies including 7091 offspring of hypertensive pregnancies and 42 164 controls were identified that met the inclusion criteria. Thirty‐two studies were investigations in fetuses, 24 in neonates and infants, 12 in children, 2 in adolescents, and 3 in adults. Offspring of hypertensive pregnancies had structural and functional changes in the heart compared with controls in some studies across developmental stages. Offspring of hypertensive pregnancies also had smaller occipital and parietal vessels, higher aortic intima‐media thickness, and lower retinal arteriolar‐to‐venular ratio. Some conflicting evidence existed for other phenotypical alterations. Conclusions There is still inconsistent evidence of multi‐organ structural and functional differences in offspring of hypertensive pregnancies. The evidence base could therefore be further strengthened through well‐designed and conducted prospective studies. Registration Information www.crd.york.ac.uk . Unique Identifier: CRD42023387550.