Prenatal exposure to antipsychotic drugs not associated with school test scores

Health and Wellness 13. okt 2022 3 min Senior Researcher Julie Werenberg Dreier, Senior Researcher Xiaoqin Liu Written by Morten Busch

When women who use antipsychotic drugs become pregnant, concerns often arise about whether the medication is safe for the unborn child. Antipsychotic drugs are used for treating people with a spectrum of mental disorders such as schizophrenia and bipolar disorder, and discontinuing treatment can have severe consequences for both the mother and the child in the perinatal period. This puts pregnant women in a quandary when they have to decide whether to continue with antipsychotic treatment during and after pregnancy. A new study of children born to mothers who filled prescriptions for antipsychotic drugs during pregnancy therefore brings good news. The children’s test scores in the subjects Danish and mathematics were not associated with whether the mother used antipsychotic drugs in pregnancy or not.

Schizophrenia and bipolar disorder often emerge in late adolescence or young adulthood and therefore coincide with childbearing age. Antipsychotic drugs are the first-line pharmacotherapy for these disorders but are also prescribed for treating depression and anxiety. The number of women taking antipsychotics during pregnancy is increasing in most countries, and in some countries, as many as 5% of all pregnant women take them. Because these drugs are not normally tested on pregnant women, there has been concern that they could harm the development of the fetal brain. This concern can now be alleviated slightly.

“We conducted a very large registry-based study and found no association between children’s performance on standardised school tests and whether their mothers used antipsychotic drugs during pregnancy or not. These results are very reassuring because they indicate that such exposure does not negatively affect the child’s cognitive abilities,” explains first author Xiaoqin Liu, Senior Researcher, National Centre for Register-based Research, Aarhus University.

The spectre of old scandals

The new study is based on the fact that some medications, including antipsychotic drugs, can cross the placenta. The concern has been that antipsychotic drugs can potentially reduce dopaminergic neurotransmission, an important signal that enables nerve cells to communicate with each other. The concern has therefore been that any limited transfer could negatively impact the significant development that takes place in the brain during the embryonic stage.

Further, the spectre of old scandals may continue to haunt us. For example, in the 1950s, thalidomide, an apparently harmless sedative and antinausea drug, caused many birth defects as well as miscarriages and stillbirths. However, investigating how medication use in pregnancy potentially affects child health is difficult because pregnant women are often excluded from clinical trials of medicines for ethical reasons.

“Retrospective and observational studies of pregnant women who use various kinds of medications are therefore very important, since this is one of our only opportunities to determine whether they are safe for the children in the short and long term. We are therefore pleased to provide some results that may help reassure pregnant women who need to take antipsychotic medication,” adds Julie Werenberg Dreier, who was also involved in the study and is a Senior Researcher at the National Centre for Register-based Research, Aarhus University.

Apparent differences disappear when adjusted

Four recent studies have shown little or no increased risk of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder and autism among children exposed to antipsychotic drugs prenatally. However, most studies have been limited to children aged 5 years or younger, and no studies have been performed to investigate whether the children’s cognitive abilities or academic performance are impaired.

Using the Danish prescription and health registries, the researchers obtained data on 667,517 children born in Denmark between 1997 and 2009 attending public primary and lower-secondary schools.

“All children had completed at least one Danish or mathematics test at 9–15 years old as part of the Danish national test programme in public primary and lower-secondary schools. The mean test scores were 50 for the exposed children versus 55 for the unexposed children for Danish and 48 for the exposed children versus 56 for the unexposed children for mathematics, but when we adjusted for such factors as parental educational background, maternal underlying disorders and other social circumstances, the differences disappeared,” explains Xiaoqin Liu.

Although the new results are positive because the drugs do not seem to be associated with the children’s test scores, the researchers still think that the children of parents with severe mental disorders requiring treatment may need support.

“The children of mothers who used antipsychotic drugs in pregnancy did have lower test scores than other children based on the unadjusted numbers. While this difference is not related to the mother’s use of antipsychotic drugs, these children may still benefit from educational support for other reasons,” says Xiaoqin Liu.

Implementing knowledge

Julie Werenberg Dreier thinks that the new results are important to consider when risks and benefits are discussed as part of the process of finding the right treatment for pregnant women with schizophrenia or bipolar disorder.

“In pregnancy, the potential beneficial and harmful effects of treatment for the mother and the unborn child must be balanced when deciding whether to initiate or continue treatment and when choosing between different types of drugs with varying efficacy and side-effects. This balancing act is often extremely difficult because knowledge of how each specific drug could affect the child is often so limited,” explains Julie Werenberg Dreier.

According to Julie Werenberg Dreier, disseminating null results like this is therefore just as important as the other results that gain far more attention.

“Researchers and the media often prefer to write about new and surprising associations, but conveying no apparent association is just as important here. Implementing this knowledge requires reaching out to both clinicians and the women who are taking antipsychotic drugs and are either already pregnant or are considering it,” concludes Julie Werenberg Dreier.

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