Research Projects

1. Screening for risk for pregnancy complications and applying results of basic research to clinical problems

We were funded by Government of South Australia to develop predictive tests for couples' risks for complications of late pregnancy, specifically preeclampsia, IUGR, preterm birth and gestational diabetes. This is the Adelaide arm of the SCOPE (SCreening fOr Pregnancy Endpoints) project. SCOPE is an international consortium of clinicians and scientists who by the end of 2011 had assembled a biobank and detailed clinical and lifestyle database for 5,628 women pregnant for the first time and their partners. Recruiting has ceased in all SCOPE centres.  In Adelaide we initially undertook a targeted gene approach and aimed to identify maternal and paternal genes that determine a couple's risk prior to the development of symptoms. These genes have already been shown to be important in the control of placental development, cardiovascular disease, inflammation and cancer. We have a particular interest in how the father imparts risk for pregnancy complications in the mother and baby.

We have recently developed 3-tiered algorithms to predict risk in early pregnancy for subsequent preeclampsia, preterm birth, IUGR and gestational diabetes using combinations of genetic, clinical, family history and lifestyle factors.

We began recruiting women to the Screening Tests to Predict Poor Outcomes of Pregnancy (STOP) study in March 2015. We aim to validate our risk prediction algorithms in this cohort. We expect to have recruited 1,400 women to this cohort by the end of 2017. We will utilise our new software designed to provide an individualised probability of risk for each couple in the STOP Study. We will also continue to collect important clinical and lifestyle data about each pregnancy and health of both mother and child to answer new questions in obstetric research including effects of maternal diet and micronutrient supplementation on pregnancy outcome.

We have another cohort Predicting Adverse Pregnancy Outcomes (PAPO) in whom women suffer recurrent pregnancy complications but primarily recurrent spontaneous miscarriage (RSM). It appears that RSM is in the continuum of pregnancy complications associated with poor placentation. We aim to elucidate molecular mediators in RSM and identify potential therapeutic targets for subsequent development and testing.

2. The role of Vitamin D in the placenta and pregnancy success

In recent years, vitamin D has emerged as a micronutrient important for optimal pregnancy outcome. In women, vitamin D deficiency has been associated with complications of pregnancy including preeclampsia, intrauterine growth restriction, gestational diabetes, preterm birth and a greater need for caesarean section but the data are conflicting. Although our understanding of the specific functions of vitamin D in pregnancy is scant, it seems likely that vitamin D deficiency may play a role in complicated pregnancies because robust regulation of vitamin D activation and degradation occurs locally in the placenta. Animal studies have shown that maternal vitamin D deficiency is associated with excessive inflammation in the uterus underlying the placenta (decidua) that impacts fetal growth and health.

Perhaps the best known function of vitamin D is in the maintenance of calcium balance. Indeed, calcium supplementation in women with low dietary calcium has been shown to prevent preeclampsia. However, little is known of the mechanisms by which vitamin D and calcium act in the placenta and in maternal adaptation to pregnancy. We are working to elucidate the molecular mechanisms by which vitamin D and calcium affect placentation and pregnancy outcome.

3. Developing omic profiles in maternal blood that reflect those in the placenta

We have been funded by NIH NICHD to develop a non-invasive method to assess placental function across gestation in real time. Using our biobank of placental samples obtained right across gestation with matched maternal blood samples we have been using genome and epigenome wide sequencing technologies to profile placental health. These will be integrated with other data we hold about these pregnancies that indicate aspects of placental function. 

4. Epigenetic programming of placental and fetal development

The placenta is derived from the conceptus and is therefore genetically identical to the fetus. Perhaps the best known function of the placenta is to transport gases, nutrients and wastes between mother and fetus. However, the placenta also plays a major role in orchestrating maternal adaptation to pregnancy by secreting a variety of steroid and peptide hormones. These placental hormones stimulate maternal physiological changes that are essential for pregnancy success. To facilitate these functions the placenta invades the decidua, colonizing and transforming the uterine spiral arterioles to sequester a maternal blood supply for efficient maternal-fetal exchange. Invading placental extravillous cytotrophoblasts employ molecular mechanisms that closely match those of a metastatic tumor but unlike cancer this process is strictly controlled both spatially and temporally in the placenta. Such mechanisms are not fully understood but include complex interactions between both extravillous cytotrophoblasts and maternal endothelium and leukocytes.

Emerging evidence suggests that epigenetic regulation of the placental transcriptome is important for the molecular control of placental growth and differentiation. However, the epigenetic landscape affecting placental gene expression may be different to that in other healthy tissues and the role of epigenetic modifications, and particularly DNA methylation, in placental development remains largely unknown. Of particular interest is the fact that the placenta is the most hypomethylated human tissue and is characterized by the presence of large partially methylated domains (PMDs) containing silenced genes. We are working to understand how and why the placenta is hypomethylated and what role DNA methylation plays in regulating placental gene expression across gestation.

5. Interactions between maternal micronutrient status, obesity and metabolic health in disadvantaged women 

Large numbers of pregnant women supplement with folic acid in Australia to prevent neural tube defects. This has been shown to be effective for this purpose. However, many supplement formulations that target pregnant women also include a number of other micronutrients with or without good evidence for their benefits. There are some data suggesting positive effects on maternal health and others showing that deficiencies affect child health and well being. There are some data that show that some groups of women benefit such as those who are obese but not all. We aim to determine how maternal status for various micronutrients interacts with obesity, placental genetics and epigenetics to affect maternal and child outcomes.