Study: Folate status in early pregnancy and hyperactivity in childhood

reference

Schlotz W, Jones A, Phillips DI, Gale CR, Robinson SM, Godfrey KM. Low maternal folate status in early pregnancy is associated with hyperactivity in childhood and peer problems in offspring.J Child Psychiatry. 2010;51(5):594-602.

design

Prospective cohort study

Participant

The authors tested 100 mothers for red blood cell folate levels at the end of the first trimester, and folate intake was assessed throughout the participants' pregnancy. Head circumference of the newborns was measured and weight was measured at birth and at 9 months of age. When the children were 8.7 years old, mothers were asked to complete a questionnaire about their children's behavior, which included hyperactivity, emotional symptoms, behavioral problems, and peer problems. The authors controlled for maternal smoking, alcohol consumption, and gender.

Key findings

The mothers of these children, who were later reported to have high levels of hyperactivity and peer problems, were found to have lower levels of folate in red blood cells as well as total folate intake. The range of folate intake for mothers was 328.5–624.4 µg in early pregnancy and 269.9–410 µg in late pregnancy. Controlling for mothers' smoking and alcohol consumption during pregnancy did not change the results.

Effects on practice

This study is the first to show an association between mothers' folate status and their children's behavioral outcomes. Additionally, they found that reduced head growth speed was also associated with lower folate levels during pregnancy. It should be noted that head growth is a rough indicator of brain growth.

However, there was a connection here suggesting that folate status in utero influences neurological development and reduced fetal brain growth is one of the results.

However, there was a connection here suggesting that folate status in utero influences neurological development and reduced fetal brain growth is one of the results. Inadequate prenatal folate intake is known to affect other aspects of nervous system development, as evidenced by its association with spina bifida and other spinal dysraphisms. This study also provides information about when folate status may be more important. In this case, the evidence points to the first trimester. In fact, other studies have shown that nutritional status has a greater impact early in pregnancy than later in pregnancy.¹

It is concerning that nutrition could play such an important role in the growing fetus, at a time when many mothers may not even know they are pregnant or believe that prenatal nutrition is not particularly important. Even more concerning, mothers' folate intake in this study did not deviate far from the recommended minimum prenatal dose of 400 mcg. It is possible that other confounding factors affect folate status and usable folate intake, such as: E.g. tobacco smoke, oral contraceptives, trimethoprim, methotrexate or sulfasalazine. Therefore, the use of these substances by mothers before pregnancy may cause another disadvantage compared to other women who do not take these substances.

Folate deficiency is known to reduce fetal cell replication.²especially in the brain,^3.4resulting in smaller brain size⁵and behavioral problems.⁶It is possible that prenatal folate deficiency influences the risk of later hyperactivity through its influence on the development of the dopaminergic system.⁷but this still needs to be investigated. Other research establishes a fairly clear link between folate and attention deficit hyperactivity disorder (ADHD). Pediatric leukemia survivors who have mutations in 5,10-methylenetetrahydroreductase (MTHFR), a crucial enzyme that provides usable folate for DNA synthesis, exhibit ADHD symptoms later in life.⁸This could be further compromised by chemotherapeutic folate antagonists (particularly methotrexate), which are commonly used in these patients.

The authors themselves state that there are many disruptive factors, especially after the birth of the child. However, looking at the previous literature, it makes sense that behavior is influenced. This may not be the only factor, but it is certainly an important factor to consider when advising mothers on their family planning. This may be even more important for mothers who themselves suffer from attention deficit disorder (ADD), ADHD or depression. Additionally, it is important to note that mothers who have given birth to a child with a neural tube defect in the past are at significantly increased risk of neural tube defects in subsequent births. Therefore, starting one month before pregnancy, these mothers require a much higher folate intake, up to 4 mg.