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Scientific Frontline: Extended "At a Glance" Summary: Maternal 12-HETE and Childhood Asthma
The Core Concept: The absence of a specific fatty acid molecule known as 12-HETE in the blood of pregnant women significantly increases the risk of their children developing childhood asthma and early respiratory infections.
Key Distinction/Mechanism: While prenatal omega-3 supplementation (like fish oil) is commonly thought to prevent childhood asthma, this research reveals a critical dependency: omega-3 only offers protective benefits if the mother has measurable levels of 12-HETE. A lack of 12-HETE during early pregnancy leads to poor immune maturation and an altered lung microbiome in the child.
Major Frameworks/Components:
- Biomarker Identification: Measurement of 12-HETE levels in maternal blood at week 24 of pregnancy.
- Microbiome Analysis: Evaluation of the child's airway bacterial composition and immune response as early as one month of age.
- Longitudinal Tracking: Monitoring of respiratory infections and asthma development in children over their first ten years.
- Supplement Efficacy Testing: Randomized trials determining that the efficacy of omega-3 intervention depends entirely on maternal 12-HETE baseline levels.
Branch of Science: Pediatrics, Immunology, Pulmonology, and Public Health.
Future Application: 12-HETE levels could serve as a clinical biomarker to provide personalized, targeted prenatal care, allowing physicians to precisely identify which pregnant women will genuinely benefit from omega-3 supplementation to prevent childhood asthma.
Why It Matters: Childhood asthma is one of the most prevalent chronic pediatric diseases worldwide. Understanding its prenatal biological origins paves the way for precise, early preventative strategies rather than relying on generalized, one-size-fits-all maternal supplementation.
Shortness of breath, coughing, and respiratory infections.
Childhood asthma, also known as asthmatic bronchitis, is one of the most common chronic diseases in children worldwide.
But why does the disease develop? Research shows that conditions in the very early phase of life—already during pregnancy—are likely to be decisive.
In a new study, researchers from the University of Copenhagen and the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) at the Danish Pediatric Asthma Center at Herlev and Gentofte Hospital in Denmark investigated the link between a specific fatty acid in the blood of pregnant women and the risk of their children developing childhood asthma.
“For the first time, we show that a specific fatty acid molecule in pregnant women is linked to the child’s risk of developing asthmatic bronchitis. If the mothers do not have a measurable amount of this molecule in their blood during pregnancy, there is a higher occurrence of childhood asthma in the child’s first year of life,” says asthma researcher and clinical professor Bo Chawes from the Department of Clinical Medicine and COPSAC.
The researchers found that the occurrence of childhood asthma during the first ten years of life was 62 percent higher if the mother did not have measurable amounts of the fatty acid molecule 12-HETE in her blood, compared with mothers in whom the researchers were able to measure it.
The researchers emphasize that this is a statistical association and that the study cannot determine whether a lack of 12-HETE directly causes asthma.
More respiratory infections
At the same time, the study also shows that children of mothers without measurable 12-HETE in their blood during pregnancy more often have multiple respiratory infections and an altered bacterial composition in their airways. This supports the idea that the fatty acid molecule likely plays a significant role in the development of asthma, the researchers believe.
“As early as when the child is one month old, we can see a completely different bacterial composition and immune response in their airways if we cannot measure 12-HETE in the mothers’ blood. And we know that these factors are crucial for the risk of developing asthma,” says Bo Chawes. He adds:
It appears that 12-HETE is crucial in the early maturation of the child’s immune system “It appears that 12-HETE is crucial in the early maturation of the child’s immune system. If the child very early—already in the womb—has too low levels of these fatty acids, this likely leads to an immune system that does not function well enough and consequently results in an altered lung microbiome. This can increase susceptibility to respiratory infections and the development of asthma.”
To reach their results, the researchers followed several hundred mothers and their children over a ten-year period by collecting and analyzing blood samples from the mothers, examining the bacterial composition in the children’s airways, and diagnosing childhood asthma.
Nuancing the need for supplements
Previous studies have shown that supplementation with omega-3—found, among other sources, in fish oil—during pregnancy can in some cases have a protective effect against children developing asthma. In the new study, the researchers therefore also examined whether 12-HETE could play a role in this context.
To investigate this, the researchers conducted a randomized trial and found that omega-3 supplementation apparently only reduces the occurrence of asthma in children of mothers in whom 12-HETE could be measured.
In this group, the occurrence of early childhood asthma was 58 percent lower compared with the group that received a placebo. The researchers found no difference when the fatty acid could not be measured in the mothers.
“We show that 12-HETE is crucial for whether omega-3 supplementation during pregnancy has a protective effect against childhood asthma. In other words, it is not certain that all pregnant women will benefit from the same supplements, but in the future, we may be able to identify those who will gain the greatest benefit,” says Bo Chawes.
About the study
The study is based on data from two large mother–child cohorts: the Danish COPSAC2010 cohort and the American VDAART cohort. COPSAC2010 consists of 738 mothers and 700 children. VDAART consists of 881 women and 810 children.
In the Danish cohort, the researchers measured levels of the fatty acid 12-HETE in blood samples from pregnant women at week 24 of pregnancy and followed the children’s health over ten years, with a focus on asthma and respiratory infections.
The study shows a higher occurrence of early childhood asthma in children of mothers without measurable amounts of 12-HETE in the blood but cannot determine a causal relationship—that is, whether a lack of 12-HETE causes asthma.
The researchers subsequently validated the results in the American cohort.
“It is in itself a major strength that we follow more than 700 women and their children intensively with biological samples and symptom monitoring, all the way until the children are ten years old. We do not demonstrate a causal relationship, but the study is strengthened by the fact that we can replicate our findings in an American cohort with a fairly identical design,” says Bo Chawes.
The researchers also conducted a randomized trial in the Danish cohort, in which pregnant women received either omega-3 supplementation or a placebo. This made it possible to investigate whether the effect of omega-3 supplementation on childhood asthma depends on the mother’s level of 12-HETE.
The researchers tested the randomized trial in the American cohort by estimating the mothers’ omega-3 intake based on their diet.
A more precise prevention?
It is still too early to use the results clinically, for example, to advise on the need for omega-3 supplementation, the researchers emphasize.
Among other things, there is a need to identify more concrete measurement values for 12-HETE that can be used to guide pregnant women.
“Childhood asthma is extremely common, and therefore it is crucial to find out what drives it and how we can prevent it. With our study, we have shown that 12-HETE could potentially function as a biomarker and thus represent the first step toward a more personal and precise prevention of childhood asthma,” says Bo Chawes.
Published in journal: Cell Reports Medicine
Authors: Liang Chen, Nicklas Brustad, Jonathan Thorsen, Tingting Wang, Mina Ali, Julie N. Kyvsgaard, Mario Lovric, Parvaneh Ebrahimi, Yang Luo, Casper-Emil T. Pedersen, Nicole Prince, Rachel S. Kelly, Ann-Marie M. Schoos, Nilo Vahman, Morten A. Rasmussen, Susanne Brix, Augusto A. Litonjua, Scott T. Weiss, Craig E. Wheelock, Jessica Lasky-Su, and Bo Chawes
Source/Credit: University of Copenhagen
Reference Number: med050126_01