Q & A with Drs. de Vrijer and Eastabrook

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Extended question and answer with Drs. Barbra De Vrijer and Genevieve Eastabrook of the Pregnancy Research Group in London

1. Do we know why obesity is considered such a high risk in pregnancy and for baby?

We actually know very little about how obesity affects the placenta. Most research is centered around abnormal transport and metabolism of nutrients (glucose, amino acids) by the placenta, abnormal storage of fatty acids, abnormal blood flow to and in the placenta, and chronic inflammation and release of factors affecting blood pressure and endothelial function in the mother. 

The likely answer is that complications occur when many systems fail, but this remains difficult to study since labour changes all these markers and once we get our hands on a placenta, it's no longer connected to the mother and a functioning metabolic organ. 

2. What do you see as the main issues with using age and obesity alone as risk markers for pregnancy? 

Recognition that age and BMI alone are very poor indicators of the person's health has led to the non-pregnant medical literature and clinical care moving away from using these as sole determinants for clinical decision making. You can be elderly and obese and in better cardiometabolic health than someone younger and leaner, and this knowledge has resulted in concepts such as 'healthy obesity' and 'unhealthy obesity.’

We see the same for our pregnant women with obesity. However, markers of poor cardiometabolic health that have been studied in non-pregnant men and women have not been extensively studied or are not expected to work well in pregnancy. The changed immune system, changes in metabolism driven by placental hormones and contribution of the placenta itself to plasma markers makes pregnancy a unique situation.

3. Looking at an ideal situation, what markers could be identified and tested so that you could thoroughly assess every Mom’s health and the risk factors for pregnancy and baby?

There are some newer technologies that may prove of value, providing information about the placental metabolic health. Novel imaging techniques using MRI can be used to detect function, for instance blood flow patterns, pH, and oxygenation or can trace metabolism within the placenta or fetus. 

Placental exosomes are small packages of cell content from the placenta that circulate in the mother, and can provide information about the placenta without contamination by the mother’s vascular, oxidative, metabolic or inflammatory markers. 

We can also use more direct measurements of the mother’s cardiometabolic health from early in pregnancy, for example metabolite assessment. 

4. Could you explain more about placental exosomes?

Exosomes are small, extracellular vesicles that are formed within cells and, therefore, their contents represent the state of the cell in which they were produced. They contain a variety of signaling molecules such as protein, mRNA, microRNA, and noncoding RNA, and are released into the maternal circulation by placental cells in response to environmental changes. 

They can be released as early as six weeks gestation making it possible to analyze placental composition over the entire course of the pregnancy which may provide new insights into placental function and dysfunction.
5. What MRI tool is being developed for studying brain development? 

Together with Dr. Sandrine de Ribaupierre, Pediatric Neurosurgeon, and Dr. Roy Eagleson and Dr. Charles McKenzie at Robarts and Western, we are testing methods currently used to image brain function in newborn and premature infants for use during pregnancy. For this type of research, the fetal brain needs to be imaged in exact angles and planes, and fetal motion is a problem in this situation as well. 

Our group currently is trialing software to adequately image brain anatomy during fetal development and has demonstrated that having the mother hum or sing for blocks of time, one can activate and image the auditory network of the fetus, similar to what is seen in preterm neonates. The development of techniques that allow for fast 3D acquisition of images of the prenatal brain will help clinicians in counseling about consequences of abnormal brain development earlier in pregnancy and infancy.