Brain injury in preterm growth restriction

Lead researcher

Atul Malhotra

Main finding

We used a single umbilical artery ligation model to induce growth restriction in mid lamb gestation, and then delivered lambs prematurely and ventilated them for a period of 24 hours. Neonatal ventilation and care induced more brain injury in preterm growth restricted lambs as compared to appropriately grown lambs. This was evident on gross histology, and by using specific markers of brain injury. The main mechanisms by which this injury might have resulted from included break down of the blood brain barrier, neuroinflammation and oxidative stress. Interestingly, carotid blood flow was also reduced in the growth restricted lambs.


The Ritchie Centre

Research group

Neurodevelopment and Neuroprotection


Dr Margie Castillo-Melendez
Dr Beth Allison
Dr Amy Sutherland
Dr Ilias Nitsos
Dr Yen Pham
Dr Anna Rocha
A/Prof Michael Fahey
A/Prof Graeme Polglase
Prof Graham Jenkin
A/Prof Suzie Miller

Journal and article title

Most surprising

This is the first time, preterm growth restricted lambs have been ventilated ex-utero for 24 hours. The ventilation and neonatal care provided was very similar to what happens to preterm infants in the neonatal intensive care unit. The brain injury seen in the growth restricted lambs was greater than that seen in the ventilated appropriately grown lambs,.

Future implications

Fetal growth restriction, which is poor growth of the fetus during gestation impacts 3-9% of all pregnancies, and the impact on neonatal and future adverse outcomes is exaggerated in preterm growth restricted infants. The neurological mechanisms of brain injury discovered in this study in this vulnerable infant group provide us with potential targets for neuroprotective therapies. This may lead to improved long term outcomes (brain injury, including cerebral palsy) for these infants.

Disease/health impact

Neonatal brain injury