Maternal Hypertension Linked to Increased Risk of Ischemic Heart Disease, Stroke in Offspring

An analysis of data from Danish, Finnish, and Swedish national registries including more than 40 years of information suggests children born to mothers with preeclampsia were at an increased risk of cardiovascular disease and stroke later in life.

Results of the study, which was performed by an international team of investigators from institutions in Europe and Asia, suggest offspring prenatal exposed to maternal preeclampsia had a 33% greater risk of ischemic heart disease and a 34% greater risk of stroke in childhood and young adulthood than their counterparts without such exposure, with results also providing insight into impact of preeclampsia subtype and timing of onset on the aforementioned associations.

“Results of this study suggest that offspring born to individuals with preeclampsia had increased [ischemic heart disease] and stroke risk that were not fully explained by preterm or [small for gestational age] birth, and that the associated risks for stroke were higher for severe forms of preeclampsia,” wrote investigators.

Although maternal preeclampsia is associated with adverse maternal and fetal outcomes, research into the effects of maternal preeclampsia on outcomes in offspring during childhood and young adulthood has not been examined. With this in mind, investigators launched the current research endeavor with 3 specific aims: describe the association between maternal preeclampsia and risks of ischemic heart disease and stroke in the offspring, assess whether the association varies by severity or timing of onset of preeclampsia, and estimate the role of preterm birth and small for gestational age (SGA) birth in these associations.

To do so, investigators designed and conducted a multinational-population-based cohort study using data obtained from Danish, Finnish, and Swedish national birth and death registries. From 1973-2016, a total of 2,668,697 live singleton births were identified for inclusion from the Danish birth registries. From 1987-2014, a total of 1,636,116 live singleton births were identified for inclusion from the Finnish registries. From 1973-2014, a total of 4,171,006 live singleton births were identified for inclusion from the Swedish registries.

Of the 8,475,819 births included in the study, 51.3% were boys and 48.7% were girls. Investigators noted the median follow-up time was 19.3 (IQR, 9.0-28.1) years. Among the overall study cohort, 2.2% were exposed to maternal preeclampsia, 0.5% were exposed to preexisting chronic hypertension, and 1.2% were exposed to gestational hypertension. In assessments by country, results indicated the prevalence of preeclampsia was 2.71% in Denmark, 2.04% in Sweden, and 1.91% in Finland.

Results of the investigators’ analyses indicated an increased risk of ischemic heart disease was observed for offspring with exposure to maternal preeclampsia (aHR, 1.33 [95% CI, 1.12-1.58]), preexisting chronic hypertension (aHR, 1.72 [95% CI, 1.02-2.92]), or gestational hypertension (aHR, 1.44 [95% CI, 1.12-1.84]) compared with offspring of individuals with a normotensive pregnancy. When examining stroke outcomes, results suggested those exposure to maternal preeclampsia had a greater risk of overall stroke (aHR, 1.34 [95% CI, 1.17-1.52]) as well as hemorrhagic stroke (aHR, 1.23 [95% CI, 1.01-1.50]) and ischemic stroke (aHR, 1.44 [95% CI, 1.21-1.72]). Further analysis demonstrated severe forms of preeclampsia were associated with a greater stroke risk than less severe forms:

• Severe vs mild or moderate: aHR, 1.81 [95% CI, 1.41-2.32] vs 1.22 [95% CI, 1.05-1.42]
• Early vs late onset: aHR, 2.55 [95% CI, 1.97-3.28] vs 1.18 [95% CI, 1.01-1.39]
• With vs without SGA birth: aHR, 1.84 [95% CI, 1.44-2.34] vs 1.25 [95% CI, 1.07-1.48]

“This cohort study found that maternal preeclampsia during pregnancy was associated with increased risks of IHD and stroke in the offspring up to early adulthood and that the associated risks in case of stroke were higher for severe than for mild or moderate forms of preeclampsia. These associations were not fully explained by preterm or SGA birth,” investigators concluded. “If these findings are confirmed by future studies, screening for risk factors among offspring born to individuals with preeclampsia and primary preventive measures may be implemented early in life to reduce the burden of CVDs.”

This study, “Association of Maternal Preeclampsia With Offspring Risks of Ischemic Heart Disease and Stroke in Nordic Countries,” was published in JAMA Network Open.