Being born to term with a weight lower than 3.5 kilos is related to a higher risk of developing neurodevelopmental problems

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UiB research shows that being born to term with a weight lower than 3.5 kilos is related to a higher risk of developing neurodevelopmental problems such as cerebral palsy and autism.

In medical research it is well known that being born preterm gives you a higher risk of health issues later in life, including neurodevelopmental disorders such as ADHD and autism. However, most babies that develop neurodevelopmental disabilities are born to term.

Marianna Cortese at the Department of Clinical Medicine wanted to find out if being born at term but with a lower weight, affected the risk of developing these disabilities.

They looked at 1.8 million births from the Medical Birth Registry in Norway. By using the unique personal identifiers assigned at birth they linked the data to other mandatory health and administrative registries. This way they could follow the babies’ health into adulthood.

They adjusted for factors such as maternal smoking, marital status of the mother and immigrant status. Those factors had only a trivial impact of the result:

“Compared to babies born with a weight in the range of 3.5–3.9 kg, lower birth weight was associated with an increased likelihood of developing one of the above neurodevelopmental disabilities.

We conclude that lower birth weight can be a marker of neurodevelopmental (ND) disabilities independent of preterm delivery,” says Cortese.

Up to 25-fold higher risk

The strongest association was for cerebral palsy, with 25-fold increased odds for the lowest birth weights. This was followed by 16-fold for vision/hearing disabilities, 11-fold for intellectual impairment and 7-fold for schizophrenia. For epilepsy the risk was 5.4-fold and for autism spectrum disorder and other behavioral disorders (including ADHD) it was 3.5-fold.

Cortese adds:

“Despite these large associations and risk increases, low birth weight only explains a smaller proportion of term ND disabilities (the largest proportion was for intellectual disability with 21%), meaning that these are complex multifactorial diseases.”

They excluded all the babies with malformations from the study:

“Malformations can be part of syndromes and are associated with neurodevelopmental disabilities. Therefore, we excluded babies with malformations to minimize the possibility that our results could be due to babies with malformations,” says Cortese.

The only factor they adjusted for that made an impact on the result was year of birth:

“Year of birth could be capturing trends that are going on related to other risk factors, the occurrence of ND disorders, changes in care, et cetera,” Cortese explains.

‘Could be a marker of some prenatal problem’

Despite the strong connection between low birth weight and neurodevelopmental disabilities, the researchers don’t think that low birth weight is an independent risk factor:

“We believe that lower birth weight indicates that something may have happened during the pregnancy that led to a slower growth and consequently to a lower birth weight, and this event predisposes or increases at the same time the risk of certain ND disabilities. Low birth weight could thus be a marker of some prenatal insult or problem,” she says.

Babies born with a higher weight than normal have also an increased risk for the same disabilities.

As to what are the potential clinical outcomes of this study, Cortese says:

“Hopefully these findings will motivate further research on potential prenatal insults, events, problems, pathologies that could be the underlying cause of some ND disabilities. If these are causes that could be intervened on that means we one day maybe would be able to prevent the occurrence of ND disabilities in some children.”


Previous research has explored multiple factors contributing to the development of neurodevelopmental disorders, including gender, perinatal risks, and family history. These will be discussed and correlated to our findings in the following section.

Based on worldwide research exploring the gender ratio in mental disorders, it was noted that the prevalence of males: females was 4:1.9,10 This is in line with our findings. Females probably present less often to mental health services due to multiple reasons.

One of the possible reasons could be the hypothesis of the difference in spatial development of the brain, which allows the female brain to take advantage of certain “protective factors.” 11 Another possible explanation is the reporting bias that is encountered with female patient intake, where females tend to seek medical help on a higher level of severity. 11

The World Health Organization (WHO) defines low birth weight as a weight at birth being less than 2500 g (5.5 lb). A birth weight of below 1500 g (3.3 lb) is classified as “very low birth weight” while a birth weight of above 4000 g (8.8 lb) is defined as “high birth weight.” 12

The overall prevalence of low birth weight in the Gulf Cooperation Council (GCC) countries has been found to be 8.5% with the United Arab Emirates at a prevalence of 6% of the country’s population. 13 Low birth weight can drastically affect the quality of life and make the newborn prone to an increased risk of hypothermia, impaired nutrition, ophthalmological complications, immune disorders, hearing defects as well as long term cognitive and motor impairments.14-16

The prevalence of low birth weight in the general population in the United Arab Emirates was estimated to be 6%. 13 Our study concluded a prevalence of 16% for children born low birth weight. This is significantly higher than the prevalence in the GCC being 8.5% for babies born low birth weight, 13 as well as the worldwide estimate of preterm births being 9.5%. 17 However, this could possibly be due to our sample not being representative of the general population, where the population was selected based on patients presenting to mental health services in a tertiary care institution. This could have added to a selection bias, which lead to an increased prevalence in low birth weights.

Some of the maternal factors that put the fetus and the mother at risk of complications during pregnancy include smoking, alcohol intake, and drug abuse. 5 Although a large component of our data on maternal social history was classified as missing, this further highlights the challenges of conducting research in a background of cultural sensitivity and under-reporting of information on this topic.

Research has also shown that gestational age, and particularly preterm birth, increases the rates of complications in the newborn. 18 Preterm birth is defined by the World Health Organization as infants born alive before the completion of 37 weeks (term) of pregnancy. 19 Family history is also known to have a significant impact on the occurrence of neurodevelopmental disorders.6,7

Studies have also shown that individuals who were born very preterm have higher rates of psychiatric diagnoses compared to term-born controls. 20 This also highlights the factors included in this study, such as preterm births playing a vital part in the increase in prevalence of low birth weight which has been previously reported. 21 Our sample demonstrated a 15% prevalence of preterm births in children and adolescents with neurodevelopmental disorders. This supports the current trends of high prevalence of neurodevelopmental disorders and preterm births seen in studies with larger sample sizes worldwide.22-24 Further research is needed to explore the specific risk factor(s) involved in affecting the birth weight status.

In the context of ADHD and ASD being the most prevalent neurodevelopmental disorders, there has been extensive research done in identifying a familial component often found in ASD and ADHD between siblings in twin studies as well as first degree relatives. 8 Our study observed that 27% of the patients diagnosed with mental disorders had a positive family history for ASD or ADHD present. On exploring further, we also noticed that 30% of these patients who had a positive family history were also diagnosed with ADHD or ASD. This might contribute to the significant genetic component established in previous studies conducted on these 2 neurodevelopmental disorders and encourages further research into identifying their heritability. 8

However, it was difficult to determine an association in this study with regards to family history because we expect under-diagnosis of mental health conditions in the previous generations in this region due to the lack of mental health awareness and services. The information on family history used in this study was obtained from health intake forms that were completed by parents, which probably was influenced by information bias as well.

Interestingly, high birth weight seemed to show a significant association with neurodevelopmental disorders. Previous studies have revealed that risk factors leading to high birth weight includes post term birth. 25 Additionally, research has proposed that infants born post term are exposed to decreased blood flow to the brain due to the changes that affect the placenta in the post term period. 26 The finding in our study as well as previous research probably highlights that further study needs to be done in understanding this pathophysiology on a more clinically relevant level.

Regarding the strengths of this study, we made sure to include all the patients in the set time frame from August 30, 2017 to September 9, 2018. This helped reducing selection bias in the study. Another positive aspect to this study was the variety of mental disorders that were looked at with regards to low birth weight in the pediatric population. In terms of limitations, there was no statistical association observed between infants born low birth weight and developing neurodevelopmental disorders, however, due to the study design it aimed to describe the prevalence rather than assess an association between these variables.

The reliability of this non-association is also questionable due to the selection bias in this sample. Another limitation to this study could have been in the form of a recall bias due to missing information encountered in various parts of the intake form during the data collection phase. Gestational age was classified to be “less than 36 weeks” as “1,” indicating preterm births, and “36 or greater” as “0” for babies born at term. This limited the scope of the study for exploring gestational age even further and warrants further research on this topic.

In conclusion, we found a high prevalence of low birth weight, and preterm birth in children and adolescents presenting to a tertiary care institution and being diagnosed with a neurodevelopmental disorder. The presence of low birth weight was not statistically significant in our sample as a correlation with development of neurodevelopmental disorders. Furthermore, family history of ADHD as well as ASD was high in the sample included in our study which probes the need for future research on statistically relevant correlations on these most common neurodevelopmental disorders.

This is the first study to our knowledge that has explored risk factors for neurodevelopmental disorders in Dubai, United Arab Emirates. Future research, using other methodologies, for instance a case-control design that includes a healthy population control group as well as larger sample size in the form of a longitudinal study, along with exploring potential correlations between the rate of low birth weights and patients with 2 or more neurodevelopmental disorders is warranted. This will probably help in better understanding of potential modifiable risk factors for these neurodevelopmental conditions that have a long-term significant functional impact.

reference link : https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8274076/


More information: Marianna Cortese et al, Term Birth Weight and Neurodevelopmental Outcomes, Epidemiology (2021). DOI: 10.1097/EDE.0000000000001350

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