Recent research published in translational psychiatry The chemical composition of blood in newborn babies’ umbilical cords may provide early clues about their likelihood of developing diseases such as autism and ADHD, the researchers suggest. By analyzing specific molecules related to cholesterol and amino acids, scientists discovered patterns that evidence increased risk due to these developmental differences years before symptoms typically appear. The findings point to a future in which a simple blood test at birth could help identify children who may benefit from early support and intervention.
Childhood-onset neurodevelopmental disorders affect up to one in five children worldwide. These conditions include various differences in brain development and function. The most common examples include attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and certain delays in language, learning, or motor coordination.
Diagnosing these conditions usually requires observing a child’s behavior and developmental milestones over time. The average age of first diagnosis is about 5 1/2 years, but many children are diagnosed much later.
Polina Girchenko, a researcher at the University of Oulu and the University of Helsinki in Finland, said this timeline misses a very sensitive developmental window. “Most neurodevelopmental disorders are only diagnosed when symptoms appear, often during school age, by which time the most important stages of brain development have already passed,” says Girchenko. “We wanted to know whether the risk of these diseases can already be detected at birth.”
The time spent in the womb is a period that deeply influences the development of the fetal brain. The environment in the womb can shape how the nervous system forms and how it is wired. The scientific framework of this concept suggests that health and disease outcomes in childhood and adulthood are often attributable to prenatal exposures.
To better understand this prenatal environment, scientists can examine umbilical cord blood at the moment of birth. Umbilical cord blood contains substances produced by the fetus itself as well as substances carried from the mother across the placenta. Some of these substances are metabolites.
Metabolites are small molecules left behind when the body builds tissues, breaks down food, and processes chemicals. Studying the complete set of these small molecules is known as metabolomics. Because cord blood serves as a chemical snapshot of the newborn’s physiological state, metabolomics reveals detailed information about the biological processes occurring immediately before birth.
Previous studies examining umbilical cord blood for signs of neurodevelopmental conditions have yielded mixed and sometimes contradictory results. Many previous studies have considered only a handful of specific metabolites. Other projects have focused solely on autism or ADHD, missing the wide range of childhood developmental differences that often overlap.
To address these gaps, the authors of the current paper designed a broader approach. They wanted to see whether different metabolic markers could predict all kinds of neurodevelopmental disorders. They also wanted to know whether analyzing these molecules could provide evidence beyond what is already known from standard early life risk factors such as maternal health and birth weight.
To explore this link, researchers analyzed data from an existing project called the PREDO study. The project initially followed a cohort of pregnant women and their children born in Finland between 2006 and 2010. The researchers followed the 858 children included in this particular analysis from birth until they became teenagers, reaching a median age of about 14 years.
At the birth of each child, medical staff drew blood from the umbilical vein. Scientists stored this plasma and then tested it using a high-throughput technique that uses magnetic resonance to identify and measure specific molecules. They looked at a targeted panel of 110 different metabolic measurements.
These 110 measures covered key biological functions such as fluid balance, inflammation, and fat and sugar processing. Over the next years, researchers tracked the children using reliable national health care registries to see who received formal neurodevelopmental diagnoses. Of the 858 children, 120 met criteria for at least one neurodevelopmental disorder.
The authors then used statistical modeling to compare cord blood from children who were later diagnosed with blood from 738 children who were not diagnosed. They identified a specific combination of 12 metabolic indicators that collectively were associated with a higher likelihood of developing neurodevelopmental disorders.
Seven of these 12 molecules were associated with high-density lipoprotein, commonly known as HDL. In adult health, HDL is often referred to as “good cholesterol” for its role in heart health. However, in the fetus, HDL cholesterol is a necessary building block for cell membranes and the production of hormones that support optimal brain function.
The remaining five markers include the total concentration of all fat-containing particles, two types of fatty acids, and two amino acids in the blood. Amino acids are the basic chemical units that form proteins. Two specific amino acids identified in this pattern were alanine and histidine. Fatty acids included measurements of omega-6 fatty acids and fat unsaturation, which are involved in brain growth and signaling.
Scientists found that levels of all 12 of these specific metabolites were consistently lower in the cord blood of children who later developed neurodevelopmental disorders. This pattern of hypometabolic markers existed across a variety of specific diagnostic categories. It has occurred in children with ADHD, language disorders, learning disabilities, and autism.
Researchers even found that lower levels of these molecules correlated with milder subclinical symptoms of developmental delay. These mild symptoms were reported by mothers on screening questionnaires when their children were infants.
The authors then determined whether this metabolic pattern provided new predictive information. They compared the predictive power of the metabolites to established early-life risk factors. These standard risk factors include the mother’s age, education level, pre-pregnancy BMI, and mental health during pregnancy. The baby’s birth weight and gestational age were also included.
Interestingly, many maternal risk factors, such as high BMI and prenatal depression, were correlated with exactly the same pattern of lower cord blood metabolites. This suggests that maternal health and environment may influence the availability of essential fats and amino acids to the developing fetus.
Standard risk factors alone explain about 12.2 percent of the variance in whether a child develops a neurodevelopmental disorder. When the researchers added 12 cord blood metabolites to the statistical model, prediction accuracy improved. The combined model accounted for 16.6% of the variance.
The researchers also looked at a smaller group of 737 mothers for whom genetic data was available. They calculated a genetic risk score to estimate a mother’s genetic chance of having ADHD and autism. Even when this maternal genetic risk was taken into account, cord blood metabolites provided a small improvement in predicting the child’s future diagnosis.
“Umbilical cord blood contains chemical signals that may indicate a child’s risk for future neurodevelopmental disorders, and these signals add information beyond what standard clinical and newborn screening data provide,” Girchenko told PsyPost. “This means that one day blood tests linked to clinical information could help identify children who would benefit from early prevention.”
This kind of proactive approach can ultimately change a child’s developmental trajectory, she added. “The first years of life are when the brain is most responsive to intervention, so even modest improvements in early detection can have significant public health implications,” Girchenko explained. “Identifying risks at birth is the first step. The larger goal is to translate that knowledge into preventive measures that reduce the burden on children, families, schools, and health systems.”
Although the findings of this project provide interesting biological relevance, there are several limitations that should be considered before using these markers in the clinic. The authors emphasize that this study is at an early stage of scientific discovery.
“This is a proof-of-concept study,” Girchenko said. “While we have shown that risk signals are present in umbilical cord blood and can be measured, biomarkers must be independently validated before use in clinical screening programs. This is not a diagnostic test.”
The initial group of mothers in the PREDO study was recruited primarily because of their increased clinical risk for pregnancy complications such as preeclampsia. This means that our sample had a higher rate of prenatal difficulties than the general population, which could skew the typical metabolic profile.
Statistical analyzes involved both identifying metabolic markers and testing their predictive power based on the same group of children. In scientific research, testing a newly discovered pattern on a completely different group of people helps confirm its accuracy. Future projects will need to replicate these findings in different populations to verify that these 12 molecules are reliable predictors.
The study was conducted in a resource-rich Nordic country. This limits the extent to which the findings can be applied to people from different geographic or economic settings. Finland’s health care system, diet, and environmental exposures may not reflect the everyday realities of people in other parts of the world.
It is important to note that these predictive models do not establish direct cause and effect. Low levels of these metabolites do not necessarily mean that a child will develop a neurodevelopmental disorder. Rather, it may simply serve as a biological footprint for other processes that occur during pregnancy, such as maternal stress, immune system activity, and nutritional deficiencies.
The researchers analyzed only a specific panel of 110 metabolic measurements. Although this panel covered many major biological pathways, human blood contains thousands of different molecules. A more comprehensive metabolomic analysis may reveal additional patterns and even stronger predictors that this limited panel missed.
Looking ahead, the research team aims to test the model in new settings. Girchenko said next steps include “validating in independent cohorts, ideally across different populations, and combining these metabolic biomarkers with other molecular and clinical data.”
Scientists may also investigate whether changes in a mother’s nutrition or lifestyle during pregnancy can safely alter these metabolic markers. The authors note that previous clinical trials have tested whether supplementing children’s diets with certain fatty acids can reduce ADHD symptoms, suggesting that some metabolic pathways may respond to targeted interventions.
“The long-term goal is validated newborn screening for neurodevelopmental risk, combined with targeted primary prevention strategies that can be provided before symptoms appear,” Girchenko said.
The study, “Umbilical cord blood metabolomic changes improve prediction of childhood-onset neurodevelopmental disorders,” was authored by Polina Girchenko, Marius Lahti-Pulkkinen, Chenyao Ni, Jari Lahti, Li Tian, Aino Airikka, Eero Kajantie, and Katri Räikkönen.
