Impacts that last a lifetime

The first 1,000 days life, between conception and a child’s second birthday, are a critical and unique window of opportunity to support optimal health, growth and brain development. The impacts last a lifetime.

A child’s healthy development can be threatened during pregnancy by stressors like maternal obesity, inflammation, and abnormal placental development and function.

The placenta is a key organ in fetal growth and development because it controls maternal-to-fetal exchanges of essential nutrients and hormones. Attacks on metabolic function due to stressors are associated with future life risks for the infant, such as obesity, diabetes and cardiovascular disease.

“Clinicians are still not able to identify which pregnancies or infants are at risk, nor are they able to diagnose abnormalities early enough to suggest interventions or therapies that could help prevent future disease from developing,” remarks Dr. Barbra de Vrijer, Lawson Associate Scientist.

As maternal-fetal medicine specialists who noticed this gap, Drs. de Vrijer and Genevieve Eastabrook, Lawson Associate Scientist, formed the Pregnancy Research Group. They collaborate with expert researchers from a variety of fields to promote maternal, fetal and infant health.

Drs. Barbra de Vrijer and Genevieve Eastabrook

Drs. Barbra de Vrijer and Genevieve Eastabrook

Marking chronic inflammation

When a woman becomes pregnant, her immune system responds by allowing – and not rejecting as it would in any other circumstance – the placenta to invade and redirect the mother’s blood supply.

“It’s quite amazing, considering that a large portion of the pregnancy is not a part of the mom’s body itself. Most people would not survive an eight-pound tumour or 40 week-long infection, yet a woman’s body deals with pregnancy quite well,” says Dr. de Vrijer.

Pregnancy-related suppression of the immune system is often strong enough to protect the placenta against the type of immune response that any other ‘stressor’ could cause.

But when there is chronic inflammation, the placenta can no longer keep up. Inflammatory markers are found to be increased in early pregnancies that later develop preeclampsia or growth restriction.

As Dr. Eastabrook notes, “the performance of these markers as predictors of future development of pregnancy complications is not good enough to be of any clinical use. In fact, the ‘best’ predictors for pregnancy complications we currently have are pre-pregnancy BMI (Body Mass Index), mean arterial blood pressure and the mother’s age.”

Despite tremendous progress in neonatal outcomes for preterm births, there have been only modest improvements in the management of at-risk pregnancies. Low-dose Aspirin is advised to all women at risk of preeclampsia, but overall there is no treatment other than to induce labour. Preeclampsia is a complication characterized by high blood pressure and signs of damage to other organ systems.

If the complication occurs early in pregnancy, management is fairly straightforward: wait as long as possible to deliver the baby, and closely monitor placental blood flow and wellbeing of the fetus using ultrasound.

When the placenta is affected by chronic inflammation and preeclampsia develops in the third trimester of pregnancy, ultrasound fails because changes in fetal growth and placental function are often too subtle to detect.

“In order to prevent late onset growth restriction, preeclampsia and stillbirth, we need more reliable tools to identify at-risk patients,” says Dr. Eastabrook.

A promising assessment technique is Pulse Wave Velocity (PWV). This portable and non-invasive test measures arterial stiffness, a measure of cardiovascular health that is strongly correlated with inflammation. Arterial stiffness is measured through the velocity of the blood pressure wave travelling through the arteries over time.

Arterial stiffness should decrease very early in pregnancy as part of normal adaptation. These changes are not seen in pregnancies destined to develop late onset complications.

By indirectly measuring the effects of obesity, metabolic changes and inflammation, the team is assessing the cardiovascular system’s adaptation to pregnancy. In addition, PWV is a more accurate assessment of cardiovascular health than blood pressure alone, especially for patients with extremely high BMI.

Imaging fetal and placental metabolism

While ultrasound is limited to assessing the baby’s size, anatomical structures and umbilical blood flow, the team is now using MRI to study the content of cells, oxygen levels and metabolism.

Imaging of a fetus inside a placenta

Lawson researchers are using a revolutionary new way of imaging the growing fetus, including its internal organs, fat and other tissues. The placenta and umbilical cord are also highly visible.

A recent study looked at the fetal fat content as a marker for metabolic health and found that the normal fetus rapidly accumulates fat during the third trimester.

The research team is now studying whether there are different compartments of fat that are more predictive of abnormal fetal growth and development, and if they can find these differences during pregnancy.

Innovative work is also being done by collaborators Dr. Charles McKenzie and Dr. Timothy Regnault, Lawson Scientists, who are investigating an MRI technique to accurately track placental and fetal metabolism by imaging how sugars are metabolized during pregnancy.

MRI has one disadvantage compared to ultrasound: greater difficulty dealing with motion. During pregnancy it is not only the fetus that moves, but uterine contractions cause the placenta to shift and it is much more difficult for pregnant women to hold their breath for prolonged periods of time.

The team is one of the first in the world that is working on adapting computer algorithms to correct for this motion.

“We’re really gaining momentum,” shared Dr. de Vrijer. “As clinician scientists, we are driven by the goal of providing the best pregnancy care to women, and a healthy life for their children.”

‘Seeing inside a person, inside a person.’

Lawson researchers are using a revolutionary new way of imaging the growing fetus, including its internal organs, fat and other tissues. The placenta and umbilical cord are also highly visible. This MRI technique can track placental and fetal metabolism during pregnancy. Learn more about this technique by watching this video:

 

 

Dr. Barbra de Vrijer is Division Head for Maternal-Fetal Medicine in Obstetrics & Gynaecology at London Health Sciences Centre; Associate Professor at
Western University; and, Associate Scientist at Children’s Health Research Institute (CHRI), a Lawson Program.

Dr. Genevieve Eastabrook is Assistant Professor at Western University and Associate Scientist at Children’s Health Research Institute (CHRI), a Lawson program.