Maternal Hypertensive Disorders and Neurodevelopmental Outcomes

Maternal hypertensive disorders of pregnancy—including chronic hypertension, gestational hypertension and pre-eclampsia—affect up to 10 per cent of pregnancies worldwide and are increasingly recognised as risk factors for a spectrum of offspring neurodevelopmental impairments. Epidemiological studies have linked these conditions to higher incidences of attention-deficit/hyperactivity disorder, autism spectrum disorder and intellectual disability, even after accounting for familial confounders. Pathophysiological mechanisms centre on placental insufficiency, systemic inflammation, oxidative stress and dysregulated angiogenic factors, which together disrupt fetal cerebral blood flow, neurogenesis and synaptogenesis. Neuroimaging in school-age children reveals altered white matter microstructure and regional brain volumes, while animal models confirm deficits in neuronal proliferation, myelination and cognitive performance. These insights underscore the importance of early identification of at-risk pregnancies, optimisation of blood pressure control, and development of targeted interventions to preserve long-term cognitive and behavioural outcomes.

Research from Nature Portfolio

One large nationwide study examined extremely and very preterm infants (22–31 weeks’ gestation) born to mothers with hypertensive disorders, using a stratified matched-pair design controlling for maternal age, parity, gestational age and year of delivery. Initial analyses showed higher in-hospital mortality among infants exposed to maternal hypertension, but after adjustment for birth weight and other covariates this association inverted: these infants exhibited lower adjusted odds of death, severe intraventricular haemorrhage, periventricular leukomalacia, neonatal seizures and cerebral palsy at three years. The findings suggest that, when major perinatal risk factors are equalised, antenatal hypertensive exposure may confer unanticipated neuroprotective effects in the most preterm infants.

Maternal Hypertensive Disorders and Neurodevelopmental Outcomes publication trend

The graph below shows the total number of articles in maternal hypertensive disorders and neurodevelopmental outcomes across all publications each year (not limited to Nature Index journals).

Technical terms

Pre-eclampsia: A multisystem pregnancy-specific disorder defined by new-onset hypertension and end-organ dysfunction after 20 weeks’ gestation.

Gestational hypertension: Elevated blood pressure arising after mid-pregnancy in the absence of proteinuria or other systemic signs.

Blood pressure trajectory: The pattern of systolic and diastolic blood pressure change across sequential antenatal visits, used to identify risk profiles.

Cholinergic Anti-inflammatory Pathway: A neuroimmunological mechanism whereby vagus nerve stimulation inhibits proinflammatory cytokine release.

Neurogenesis: The process by which neural progenitor cells proliferate and differentiate into mature neurons during brain development.

References

1. Associations of prenatal blood pressure trajectory and variability with child neurodevelopment at 2 years old. BMC Medicine (2024).
2. Modulation of vagal activity may help reduce neurodevelopmental damage in the offspring of mothers with pre-eclampsia. Frontiers in Immunology (2023).
3. Maternal hypertensive disorders and neurodevelopmental disorders in offspring: a population-based cohort in two Nordic countries. European Journal of Epidemiology (2021).
4. Impacts of Maternal Preeclampsia Exposure on Offspring Neuronal Development: Recent Insights and Interventional Approaches. International Journal of Molecular Sciences (2024).
5. Diffusion Tensor Imaging of White Matter in Children Born from Preeclamptic Gestations. American Journal of Neuroradiology (2017).
6. Developmental and Functional Brain Impairment in Offspring from Preeclampsia-Like Rats. Molecular Neurobiology (2015).
7. Mortality and neurological outcomes in extremely and very preterm infants born to mothers with hypertensive disorders of pregnancy. Scientific Reports (2021).