Association between lower birthweight and neurodevelopmental difficulties may not be causal

Breaking new ground 4. feb 2024 2 min Professor and Director Alexandra Havdahl Written by Kristian Sjøgren

Lower birthweight has long been linked to an increased risk of developing neurodevelopmental difficulties, including difficulties in attention, hyperactivity, communication and social interaction. However, a new study shows that lower birthweight and intrauterine growth restriction do not cause these neurodevelopmental difficulties. According to a researcher, the association between birthweight and neurodevelopmental traits may be explained by the child’s genetics.

Researchers have long known that lower birthweight is clearly associated with increased risk of neurodevelopmental diagnoses, such as attention-deficit/hyperactivity disorder (ADHD) and autism.

In this context, thinking that intrauterine growth restriction may be the underlying cause has been reasonable , since a fetus growing atypically could be predisposed to neurodevelopmental divergence.

However, a new study shows that intrauterine growth restriction does not explain children’s increased likelihood of neurodevelopmental difficulties such as inattention, hyperactivity-impulsivity, social communication difficulties and repetitive behaviour.

Instead, the child’s genes are likely part of the cause, predisposing to both neurodevelopmental difficulties and intrauterine growth restriction.

“Previous studies have generally assumed that intrauterine growth restriction causes the association between lower birthweight and children’s neurodevelopmental difficulties. However, several alternative explanations, such as the socioeconomic status of the parents or the child’s genetics, may cause birthweight to be associated with neurodevelopment,” explains a researcher behind the study, Alexandra Havdahl, Professor and Director, PsychGen Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo.

The research has been published in JAMA Psychiatry.

Data for 114,500 children and their parents

The researchers wanted to determine whether intrauterine growth restriction causes the increased risk of children with lower birthweight developing neurodevelopmental difficulties.

They obtained data for 114,500 children and their parents from the Norwegian Mother, Father and Child Cohort Study (MoBa).

The data included the children’s birthweight and their later scores on measures of neurodevelopmental difficulties such as language, motor, social, attention and activity regulation.

They also had access to considerable relevant data for the parents, including weight, education and the like.

Finally, the researchers also used data from genetic profiling of the parents and children.

The researchers examined the associations between data for birthweight and neurodevelopment difficulties. They also used a Mendelian randomisation approach to investigate a possible causal relationship derived from maternal genetic variants associated with lower birthweight.

Alexandra Havdahl explains that the researchers investigated whether the same maternal genetic variants also contributed to children’s neurodevelopmental difficulties, which would be expected if intrauterine growth restriction causes neurodevelopmental difficulties.

“Many studies have investigated this association, but this is the first time that it has been investigated in such a large and comprehensive data set,” she adds.

The child’s genes may cause the association

The study revealed, as expected, that birthweight as a proxy for fetal growth or development is associated with neurodevelopmental difficulties.

The researchers sought a causal link but found that the maternal genes associated with lower birthweight do not affect the child’s neurodevelopment and produce traits of ADHD and autism.

Thus, intrauterine growth restriction did not cause the neurodevelopmental difficulties among children with lower birthweight.

Nevertheless, the researchers identified an association between a child’s genetic predisposition and both intrauterine growth restriction and neurodevelopmental difficulties.

“This supports our hypothesis that common genetic factors influencing birthweight and neurodevelopment are a more likely explanation for the association – rather than environmental factors that inhibit intrauterine growth,” explains Alexandra Havdahl.

More studies in the wings

According to Alexandra Havdahl, the discovery is important for understanding the causes of differences in neurodevelopment and for considering the information that is given to pregnant women and to parents. The mother’s lifestyle habits and health conditions affecting intrauterine growth do not appear to strongly affect whether the unborn child later develops neurodevelopmental difficulties.

However, the study opens up a need for more investigations into the shared genetics behind low intrauterine growth and neurodevelopment, and the researchers want to continue their studies.

“We will now examine data from several cohorts to determine exactly how the genetic predisposition for neurodevelopmental diagnoses such as ADHD and autism is expressed during intrauterine growth and throughout childhood. When we have determined the genetic factors for this association, it is possible to consider potential measures to support growth among children predisposed to neurodevelopmental conditions,” concludes Alexandra Havdahl.

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