Long-term neurologic and cardiovascular outcome in fetal growth restriction. A longitudinal study from prenatal period to early school age

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Oulu University Hospital, Auditorium 4. Remote access: https://oulu.zoom.us/j/66843714135?pwd=czl0Z1p1NHQ0ZUJucjhiYzlsUXJHdz09

Topic of the dissertation

Long-term neurologic and cardiovascular outcome in fetal growth restriction. A longitudinal study from prenatal period to early school age

Doctoral candidate

Licenciate in Medicine Noora Korkalainen

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, PEDEGO

Subject of study

Obstetrics and Gynecology


Professor Amarnath Bhide, St. George´s University Hospital, London, UK


Professor Kaarin Mäkikallio, Turku University Hospital

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Long-term consequences of fetal growth restriction and the effect of prenatal factors

Fetal growth restriction (FGR) is a major obstetric problem affecting 3–9% of pregnancies worldwide. FGR is associated with increased perinatal mortality and morbidity as well as an increased risk for cardiovascular morbidity and neurocognitive difficulties later in life. However, the mechanisms leading to poor neurodevelopment and poor cardiovascular health in FGR are still widely unknown.

The thesis study evaluated the impact of fetal growth and fetal circulatory changes typical for placental insufficiency on long-term outcome at early school age. Neurologic evaluations included parental questionnaires, clinical examinations, language and communication skill assessments and magnetic resonance imaging (MRI) of the head, including detailed diffusion tensor imaging of the white matter. Cardiovascular health was assessed by examining heart rate variability in 24h holter-study. The findings in children born with FGR were compared to the findings of their gestational age-matched appropriately grown peers (AGA). Furthermore, the impact of prenatal fetoplacental hemodynamic findings on the long-term outcomes was studied.

In this thesis study, clinical evaluations revealed that children born with FGR, who showed abnormal blood flow in umbilical artery, fetal venous circulatory changes and abnormal cardiac function prenatally at any gestational age, are at risk for poor neurocognitive development at early school age. In addition, significant placental insufficiency and blood flow redistribution increases the risk for poor literacy and communication skills compared to children with normal fetal growth.

According to MRI scans, children born with FGR have smaller intracranial volumes at early school age than their AGA peers with no difference in grey and white matter volumes. In addition, they show changes in white matter microstructure in several areas when compared with AGA children. This indicates that poor fetal growth impacts brain white matter maturation. In the evaluation of cardiovascular health at early school age, children born with FGR and prenatally detected cerebral vasodilatation showed decreased heart rate variability, indicating changes in the function of autonomic nervous system and increased risk of later cardiovascular morbidity.

In conclusion, FGR and fetoplacental circulatory changes due to placental insufficiency impact cardiovascular and neurologic health at early school age. FGR children with prenatal signs of severe placental insufficiency and cerebral redistribution should be recognized to be at risk for poor neurodevelopment and later cardiovascular morbidity. Regular follow-up programs and preventive measures should be developed to optimize the long-term outcomes.
Last updated: 1.3.2023