Researchers found link between early maternal anemia and intellectual disability – ADHD and autism

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The timing of anemia, a common condition in late pregnancy, can make a big difference for the developing fetus, according to research at Karolinska Institutet published in JAMA Psychiatry.

The researchers found a link between early anemia and increased risk of autism, ADHD and intellectual disability in children.

Anemia discovered toward the end of pregnancy did not have the same correlation.

The findings underscore the importance of early screening for iron status and nutritional counseling.

An estimated 15-20 percent of pregnant women worldwide suffer from iron deficiency anemia, a lowered ability of the blood to carry oxygen that is often caused by a lack of iron.

The vast majority of anemia diagnoses are made toward the end of pregnancy when the rapidly growing fetus takes up a lot of iron from the mother.

In the current study, the researchers examined what impact the timing of an anemia diagnosis had on the fetus’ neurodevelopment, in particular, if there was an association between an earlier diagnosis in the mother and the risk of intellectual disability (ID), autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in the child.

Overall, very few women are diagnosed with anemia early in pregnancy. In this study of nearly 300,000 mothers and more than half a million children born in Sweden between 1987-2010, less than 1 percent of all mothers were diagnosed with anemia before the 31st week of pregnancy.

Among the 5.8 percent of mothers who were diagnosed with anemia, only 5 percent received their diagnosis early on.

The researchers found that children born to mothers with anemia diagnosed before the 31st week of pregnancy had a somewhat higher risk of developing autism and ADHD and a significantly higher risk of intellectual disability compared to healthy mothers and mothers diagnosed with anemia later in pregnancy.

Among the early anemic mothers, 4.9 percent of the children were diagnosed with autism compared to 3.5 percent of children born to healthy mothers, 9.3 percent were diagnosed with ADHD compared to 7.1 percent, and 3.1 percent were diagnosed with intellectual disability compared to 1.3 percent of children to non-anemic mothers.

After considering other factors such as income level and maternal age, the researchers concluded that the risk of autism in children born to mothers with early anemia was 44 percent higher compared to children with non-anemic mothers, the risk of ADHD was 37 percent higher and the risk of intellectual disability was 120 percent higher.

Even when compared to their siblings, children exposed to early maternal anemia were at higher risk of autism and intellectual disability. Importantly, anemia diagnosed after the 30th week of pregnancy was not associated with a higher risk for any of these conditions.

“A diagnosis of anemia earlier in pregnancy might represent a more severe and long-lasting nutrition deficiency for the fetus,” says Renee Gardner, project coordinator at the Department of Public Health Sciences at Karolinska Institutet and the study’s lead researcher.

“Different parts of the brain and nervous system develop at different times during pregnancy, so an earlier exposure to anemia might affect the brain differently compared to a later exposure.”

The researchers also noted that early anemia diagnoses were associated with infants being born small for gestational age while later anemia diagnoses were associated with infants being born large for gestational age. Babies born to mothers with late-stage anemia are typically born with a good iron supply unlike babies born to mothers with early anemia.

An estimated 15-20 percent of pregnant women worldwide suffer from iron deficiency anemia, a lowered ability of the blood to carry oxygen that is often caused by a lack of iron.

Although the researchers couldn’t disentangle anemia caused by iron deficiency from anemia caused by other factors, iron deficiency is by far the most common cause of anemia.

The researchers say the findings could be the result of iron deficiency in the developing brain and may thus support a protective role for iron supplementation in maternity care. The researchers emphasize the importance of early screening for iron status and nutritional counselling but note that more research is needed to find out if early maternal iron supplementation could help reduce the risk of neurodevelopmental disorders in children.

Adult women typically need 15 mg of iron per day, though needs may increase later in pregnancy. Since excessive iron intake can be toxic, pregnant women should discuss their iron intake with their midwife or doctor.

Funding: The research was supported by grants from the Swedish Research Council and from the Strategic Research Area Neuroscience at Karolinska Institutet.


Attention deficit hyperactivity disorder (ADHD) is shown as one of the most common disorders in school-aged children.[1,2,3,4,5,6] ADHD has widespread effects on the functioning and development of affected children as well as having considerable impact on others including family members, peers, and teachers. It can lead to other disorders and academic difficulties and relationship and social functioning problems.[1,2,3,6] ADHD has also been shown to have long-term adverse effects on social-emotional development, vocational success and academic performance.[1,2,3,5,7,8,9] ADHD is the most prevalent neuropsychiatric disorder worldwide, in both developed and developing countries, affecting between 5% and 15% of school-aged children. The underlying pathophysiology of ADHD remains complex and not clearly understood.[8,9]

Several studies[8,9,10,11,12,13,14,15] have attempted to understand the role of serum ferritin levels as a reliable measure of iron stores in body tissues, including the brain, in the absence of anemia in children with ADHD. Sever et al.,[11] studied the correlation between iron deficiency and ADHD and reported that supplementation of 5 mg/kg of iron to 14 ADHD children for 30 days resulted in increased serum ferritin level and reduced levels of ADHD on Conner’s Rating Scale using standardized assessment tools.[4,5,6] It has been argued that ADHD is primarily caused by reduced serum iron concentration in view of significantly reduced serum iron levels in ADHD children.[9,10,11,12,13,14,15,16] Furthermore, genetic factors are known to be the dominant cause of ADHD,[5,8,9,10,17,18] and their interactions with environmental, and socioeconomical factors[9,10,11,12] produce a complex picture.

Iron deficiency is reported to be the most prevalent problem in the world today[19,20,21,22,23] and nutritional problem among children and there is there is considerable evidence iron is important for neurological functioning and development.[19] According to the World Health Organization, iron deficiency is the most prevalent nutritional deficiency. A 30% prevalence of iron deficiency anemia (IDA) at a minimum, has been noted among children, adolescents, and women in nonindustrialized countries, and iron deficiency is also the most prevalent nutritional deficiency in industrialized countries.[20,21] More recently study showed that the iron deficiency increased risk of psychiatric disorders, and attention deficit hyperactivity disorder, and developmental disorders.[20,21,22,23]

This is the first study to investigate the association between circulating iron serum, ferritin and vitamin D levels and ADHD and associated risk factors. This study, using a nationwide population-based database with a case-control method and the largest sample size, attempted to clarify the association between iron deficiency anemia and ADHD among children. We hypothesized that children with IDA exhibited the higher risk of having ADHD psychiatric disorder.

Conclusions

The association between lower serum levels of various factors needs to be explored further in longitudinal studies. This study indicates that low serum iron, ferritin levels and vitamin D deficiency may be associated with ADHD pathophysiology and therefore must be assessed. Furthermore in addition, education for the parents, teachers, families, and society at large is absolutely vital if the burden of disease related to ADHD is to be reduced. It may also be that various chemicals in the diet may be interfering with the absorption of various protectors and this must be explored as a matter of urgency.

What this study adds?

The correlation between iron, ferritin, vitamin D deficiency, and ADHD in young children has previously not been reported in the literature. However, data is lacking regarding the association between iron deficiency and ADHD. This study reveals that those deficiencies were higher in ADHD children compared with healthy children. Supplementing infants with iron and vitamin D might be a safe and effective strategy for reducing the risk of ADHD.


Source:
Karolinska Institute
Media Contacts:
Press Office – Karolinska Institute
Image Source:
The image is in the public domain.

Original Research: Open access
“Association of Prenatal Maternal Anemia With Neurodevelopmental Disorders”. Aline Marileen Wiegersma, Christina Dalman, Brian K. Lee, Håkan Karlsson, Renee M. Gardner.
JAMA Psychiatry doi:10.1001/jamapsychiatry.2019.2309.

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