Study Identifies Skin Biomarkers That Predict Newborn Eczema Risk

It might be possible to develop a simple test to identify newborn children who are at risk of later developing atopic dermatitis (AD), according to findings from a Danish prospective birth cohort study.

In the study, the Barrier Dysfunction in Atopic Newborns Study (BABY), several biomarkers were found in the skin cells of newborns that were predictive not only for having AD but also for having more severe disease.

"We are able to identify predictive immune biomarkers of atopic dermatitis using a noninvasive method that was not associated with any pain," one of the study's investigators, Anne-Sofie Halling, MD, said at a press briefing at the European Academy of Dermatology and Venereology (EADV) 2022 Annual Meeting.

"Importantly, we were able to predict atopic dermatitis occurring months after [sample] collection," said Halling, who works at Bispebjerg Hospital and is a PhD student at the University of Copenhagen in Denmark.

These findings could hopefully be used to help identify children "so that preventive strategies can target these children...and decrease the incidence of this common disease," she added.

AD is caused "by a complex interplay between skin barrier dysfunction and immune dysregulation," Halling said, and it is "the first step in the so-called atopic march, where children also develop food allergy, asthma, and rhinitis." Almost all cases of AD begin during the first years of life. Approximately 15% to 20% of children can be affected, she noted, emphasizing the high burden of the disease and pointing out that strategies are shifting toward trying to prevent the disease in those at risk.

Copenhagen BABY Cohort

This is where the BABY study comes in, Halling said. The study enrolled 450 children at birth and followed them until age 2 years. Gene mutation testing was performed at enrollment. All children underwent skin examination, and skin samples were taken using tape strips. Tape strips were applied to the back of the hand of children born at term and between the shoulder blades on the back of children who were premature.

Skin examinations were repeated, and skin samples were obtained again at age 2 months. They were taken again only if there were any signs of AD. For those diagnosed with AD, disease severity was assessed using the Eczema Area and Severity Index (EASI) by the treating physician. Children were excluded if they had AD at the time the tape strip testing was due to be performed.

Comparing Term and Preterm Children

Halling noted that analyses were performed separately for the 300 children born at term and for the 150 who were preterm.

The prevalence of AD was higher among children born at term than among the preterm children (34.6% vs 21.2%), and the median time to onset was shorter (6 months vs 8 months). There were also differences in the EASI scores among those who developed AD; median scores were higher in the children born at term than in the preterm children (4.1 vs 1.6).

More children born at term than preterm children had moderate to severe AD (23.3% vs 8%), Halling reported.

TARC, IL-8, and IL-18 Predictive of AD

Multiple immune biomarkers were tested, including various cytokines and filaggrin degradation products. On examination of skin samples collected at birth, no particular biomarkers were found at higher levels among children who developed AD in comparison with those who did not develop AD.

With regard to biomarkers examined in skin samples at 2 months of age, however, the results were different, Halling said. One particular cytokine, thymus and activation-regulated chemokine (TARC), was seen to double the risk of AD in the first 2 years of a child's life.

This doubled risk was seen not only among the children born at term but also among those born preterm, although the data were only significant with regard to the children born at term.

The unadjusted hazard ratios (HRs) and adjusted HRs (adjusted for parental atopy and filaggrin gene mutations) in term children were 2.11 (95% CI, 1.36 – 3.26; P = .0008) and 1.85 (95% CI, 1.18 – 2.89; P = .007), respectively.
For preterm children, the HRs were 2.23 (95% CI, 0.85 – 5.86; P = .1) and 2.60 (95% CI, 0.98 – 6.85; P =.05), respectively

These findings were in line with findings of other studies, Halling said. "It is well recognized that TARC is currently the best biomarker in patients with established atopic dermatitis." Moreover, she reported that TARC was associated with a cumulative increase in the risk for AD and that levels were found to be highest in children in whom onset occurred at a later age than among those diagnosed before 6 months of age.

"This is important, as these findings shows that TARC levels predict atopic dermatitis that occurred many months later," Halling said.

And, in term-born children at least, TARC upped the chances that the severity of AD would be greater than had it not been present (adjusted HR, 4.65; 95% CI, 1.91 – 11.31; P = .0007).

Increased levels of interleukin-8 (IL-8) and IL-18 at 2 months of age were also found to be predictive of having moderate to severe AD. The risk was more than double in comparison with those in whom levels were not increased, again only in term-born children.

"Stimulating and Interesting Findings"

These data are "very stimulating and interesting," Dedee Murrell, MD, professor and head of the Department of Dermatology at St. George Hospital, University of New South Wales, Sydney, Australia, observed at the press briefing.

"You found this significant association mainly in the newborn children born at term, and the association in the preterm babies wasn't as high. Is that anything to do with how they were taken care of in the hospital?," Murrell asked.

"That's a really good question," Halling said. "Maybe they need to be exposed for a month or two before we are actually able to identify which children will develop atopic dermatitis."

The study was funded by the Lundbeck Foundation. Halling has acted as a consultant for Coloplast and as a speaker for Leo Pharma. Murrell has disclosed no relevant financial relationships.

European Academy of Dermatology and Venereology (EADV) 2022 Annual Meeting: Abstract 2567. Presented September 7, 2022.

Sara Freeman is a freelance journalist based in London, England.

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