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Summary: Fetal growth restriction (FGR) is a significant health care issue, affecting 20,000 Australian pregnancies every year 1. Undetected FGR is one of the key risk factors for stillbirth, but FGR can also cause significant impairments in short and long-term health outcomes for the child. It is a major risk factor for preterm birth and is a recognised causal pathway to the neurodevelopmental injury underlying cognitive and behavioural impairment and cerebral palsy.

Current obstetric care is focused on the detection of the growth restricted fetus and then ultrasound assessment of fetal wellbeing to guide timing of delivery. This approach seeks to maximize the gestational age of the fetus at delivery to minimise the risks of prematurity, while delivering the fetus in time to reduce the likelihood of stillbirth. Currently, no therapies exist that can maximize fetal wellbeing in the setting of growth restriction and minimise the frequency of antenatally acquired brain injury due to in-utero hypoxia.

This double-blind, randomized, parallel group, placebo controlled trial will administer maternal melatonin or placebo supplementation antenatally in the setting of early-onset severe FGR to determine whether melatonin can PROTECT the fetal brain and lead to improved neurodevelopmental outcomes.

Hypothesis: Improved neurodevelopmental outcomes will be observed in children affected by fetal growth restriction who receive antenatal maternal melatonin supplementation in comparison to those who receive placebo.

Aim Primary: The primary aim is to determine whether neurodevelopment at two years of life is improved among survivors of FGR who receive melatonin antenatally compared with those who receive placebo.

Aim Secondary: 1- To determine the impact of melatonin supplementation on fetal growth and wellbeing. 2- To report the occurrence of any adverse and serious adverse events associated with melatonin use.

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