Researcher in Focus: Dr. Lyudmyla Zakharchenko

Our Researcher in Focus for February is Dr. Lyudmyla Zakharchenko. Lyudmyla is a National Children’s Research Centre funded Clinical Research Fellow based in the Children’s Heart Centre at Children’s Health Ireland, Crumlin, working under the supervision of Prof. Afif El-Khuffash and Dr. Orla Mary Franklin, and in collaboration with co-investigator, Prof. Eleanor Molloy. Lyudmyla is working on her study “Post-Operative Myocardial Performance and Pulmonary Hypertension in Infants with Down Syndrome: The Role of Inflammation”.

As Lyudmyla explains “Down syndrome (DS for short) is a condition where there is an extra chromosome 21 and this is the commonest chromosomal condition in the world. Ireland has the highest incidence of DS in Europe, 1 in 546 births”.

It is a multi-systemic disorder and children with Down Syndrome are at increased risk of a wide variety of health complications Including congenital heart disease and pulmonary hypertension. Lyudmyla explains further “Half of the babies born with DS also have problems with the structure of the heart (called congenital heart disease or CHD for short) and the risk of high pressure in the blood vessels of their lungs (called Pulmonary hypertension or PH for short). Pulmonary hypertension can cause babies with an abnormal heart to become very sick after corrective cardiac surgery and increase the risk of death after surgery”.

A large body of research has shown that children with Down Syndrome show signs of chronic inflammation, for example, altered immune cell activity and increased levels of inflammatory biomarkers in their blood. “Babies with this condition also have an abnormal immune system that favours inflammation (or an overactive immune system)” said Lyudmyla.

Lyudmyla is interested in how this inflammatory state may increase pulmonary hypertension and contribute to poorer outcomes in children with Down Syndrome following surgery.

In her study, Lyudmyla sought to explore how inflammation may increase pulmonary hypertension and contribute to poorer outcomes.  “The interaction between this overactive immune system, PH and how well babies with DS do after corrective surgery needs further study. We think that babies with DS and CHD have an overactive immune system that will determine how well they do after surgery. We think that this overactive immune system will negatively affect heart function and PH after surgery and delay recovery after surgery” said Lyudmyla.

At the Children’s Heart Centre at Children’s Health Ireland, Crumlin and in collaboration with Prof. Molloy’s laboratory, Lyudmyla compared post-surgical outcomes, heart function (using echocardiography) and markers of inflammation in children with and without Down Syndrome. This allowed her to look at the association between inflammation, heart function, and outcomes following surgery. “We performed blood test to test how active the immune system is in babies that need heart corrective surgery. We performed this before surgery, just after surgery and before discharge from the hospital. We also performed an ultrasound of the heart to look at heart function at the same time as the blood tests. We related the findings with how the baby behaves after surgery to see if we could predict which babies will become unwell after surgery” explained Lyudmyla.

Analysis of the study results provided a number of interesting findings. Lyudmyla said “We demonstrated that infants with Down syndrome (DS) and congenital heart disease undergoing corrective surgery have an increased rate of adverse post-operative outcomes when compared with infants with similar congenital heart disease but without DS”.

Her results also showed that certain types of adverse post-operative outcomes are exclusively seen in children with Down Syndrome “Some of those outcomes occurred predominantly in infants with DS/CHD. Whereas other adverse outcomes such as abnormal drainage, we called this chylothorax [leakage of lymphatic fluid into the space between the lung and chest wall], occurred exclusively in infants with DS/CHD”.

The results also suggested that preterm birth was a major contributing factor to the increased risk of post-surgery complications in children with Down Syndrome “Our analysis showed that within the DS/CHD group the complications ware increased due to preterm gestation of the DS group rather that the chromosome anomaly itself. A lower gestational age at birth was the most common determinant of post-operative inotrope use, duration of ventilation and longer intensive care stay. This novel information should be taken into consideration when planning delivery. Where possible avoidance of premature delivery should be the goal in infants prenatally diagnosed with CHD”.

Functional assessments of the heart showed that “Children who have Down syndrome and congenital heart disease were identified as the most vulnerable group with impairments of both sides of the heart. Recovery of children with DS and CHD was longer with more significant support for the heart with inotropes [medications that can increase/decrease the contractility of the heart]”.

The assessment of markers of inflammation showed that “Children with Down syndrome and CHD have significant alteration in pro-inflammatory and anti-inflammatory immune responses peri-operatively versus children with the same cardiac lesions but without DS. These findings should be taken into the consideration during the peri-operative period, as it possibly can add more explanation to the associated pulmonary hypertension, complications post-operatively, especially the high incidences of chylothorax in the DS/CHD population” explained Lyudmyla.

On completion of the study, Lyudmyla said “A better knowledge in this area will hopefully lead to improvement in monitoring and management for children with DS including parental counselling. This study provides the caregivers and parents of children with DS/CHD with more information about possible complications after surgical intervention and duration of hospital stays. Also, these findings can inform surgical team and intensive care unit of early recognition of complications of the DS/CHD group and may result in earlier consider of therapies and medications to support heart and health to improve recovery and reduce numbers of hospital stay. In addition, these immune responses could act as biomarkers of severity and further analysis to assess correlation with heart function and complications such as pulmonary hypertension.  In the future, possible consideration to use newer methods of the therapy in this population”.