Umbilical Cord Blood May Offer Early FH Diagnosis

Liam Davenport

May 09, 2018

LISBON, Portugal — Familial hypercholesterolemia (FH) could eventually be diagnosed in umbilical cord blood samples taken at birth, potentially allowing people with the disease to be treated long before the damaging effects of high blood cholesterol levels begin, preliminary results from a Danish study suggest.

An interim analysis of 200 children, presented here at the European Atherosclerosis Society (EAS) 2018 meeting, showed that on five key lipid measures, there was a high degree of correlation between cord and neonatal blood samples, although absolute levels were lower in cord blood.

Nina Strandkjaer, a medical student at the University Hospital of Copenhagen and Herlev Hospital, Denmark, told | Medscape Cardiology that "these are quite new findings" and are correlations, "so we don't know for sure yet whether we can use this for screening for FH."

"We still need to verify that the cholesterol levels at birth correlate with levels later on in life," she added.

Strandkjaer nevertheless said that if they are able to clarify whether cutoff levels for cord blood cholesterol can be established, then it may be possible to use cord blood in the future to do screening and genetic testing in the children with higher cholesterol levels.

In this way, she said, they could identify children with FH or children with higher risk who need to be examined further.

COMPARE Substudy

Presenting the study, Strandkjaer pointed out that FH, which is characterized by increased plasma low-density lipoprotein (LDL) cholesterol levels and is seen in 1 in 225 of the population, leads to early atherosclerosis and premature cardiovascular disease if left untreated.

Because early detection and treatment of FH from childhood are therefore recommended in international guidelines, the researchers examined whether assessing cholesterol levels in umbilical cord blood would correlate with levels in neonatal venous blood and thus point to the possibility of early screening for the disease.

They therefore conducted COMPARE, a substudy of the Copenhagen Baby Heart study, to collect cord and neonatal venous blood simultaneously at birth in 300 randomly selected full-term neonates and measure various lipid levels.

The current analysis includes data on 215 to 231 paired blood samples, depending on the parameter being assessed, revealing a high degree of correlation between cord and venous blood.

The R2 value was 0.69 for total cholesterol, 0.82 for LDL cholesterol, 0.84 for high-density lipoprotein (HDL) cholesterol, 0.59 for triglycerides, and 0.74 for apolipoprotein B (P = 10–4 for all).

Interestingly, cholesterol levels were significantly lower in cord blood than in neonatal venous blood at birth on all five measures, at a mean difference of 0.31 mmol/L for total cholesterol, 0.11 mmol/L for LDL cholesterol, 0.12 mmol/L for HDL cholesterol, 0.32 mmol/L for triglycerides, and 0.06 mmol/L for apolipoprotein B (P = 10–5 for all comparisons).

The researchers conclude that the good correlation between cord blood and venous neonatal blood on all five measures suggests "that measurements of cholesterol levels in cord blood may have a role in future FH diagnostics."

FH Diagnosis Often Random

Strandkjaer explained that this is particularly important because the way in which people are diagnosed with FH "is very random at the moment."

"If you are heterozygous, you don't have symptoms until later on in life. If you are homozygous, you'll have symptoms earlier on in life," she told | Medscape Cardiology.

However, "in Denmark, for example, we don't do any screening for FH, so normally FH individuals are identified when they have a cardiac event or symptoms of hypercholesterolemia," or if their doctor tests their blood for another reason.

Paolo Parini, MD, PhD, EAS treasurer and director of research and development at the Karolinska Institutet, Stockholm, Sweden, who was not involved in the study, agreed with the picture painted by Strandkjaer.

Speaking to | Medscape Cardiology, he explained that only the week before he had seen a 15-year-old girl who was diagnosed with FH after she had a blood test while being investigated for acne, and "it turned out she had very high cholesterol levels."

He pointed out that as a result, "she had already lost many years of therapy, and today we are all aware that it is the total life exposure to cholesterol that is important."

Turning to the current analysis, Parini therefore said that to "start screening for FH as soon as possible is very important." However, it is difficult to take blood from a newborn baby, "so if you can use cord blood, that would be wonderful."

"There is not much information about how the cord in the blood reflects the blood in children, and this is one of the first attempts to define that," he added. "That is what is very nice about the study."

Parini noted that "as expected, there are differences between the cholesterol in the blood and the cord, which is slightly lower, but the correlation is very strong, meaning that, independently of the absolute value, these measurements have the potential to be used in screening every newborn child."

One of the outstanding questions, which was also acknowledged by Strandkjaer in the postpresentation discussion, is that "there is still much to learn about how it correlates with later blood levels," he pointed out.

It's known that cholesterol levels take 1 year or more to reach higher levels, "so we, with time, will have a more precise algorithm to define the criteria of how to use the absolute values of cholesterol in the cord."

"But the importance of the message here, independently of the absolute values of cholesterol, is the correlation of those values with what is seen later on in the peripheral venous blood of the children," Parini concluded.

No funding was reported. Parini declares equity interests in Galmed Pharmaceuticals and Triple Crown AB and being a consultant for Akcea Therapeutics UK.

European Atherosclerosis Society (EAS) 2018. Presented May 7, 2018.


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