Brain Development, Drugs and Disease Edexcel A

When we are born, our brains contain a load of neurones which begin to form connections (synapses) or are removed, making the brain more organised and allowing our visual system to develop. This all happens very early in life and relies on both of our eyes receiving visual input. The period of early life when our brains are developing is called the critical period.

If 100 women take a valproate medicine during pregnancy about 10 of their babies will be born with physical birth abnormalities. And about 30 to 40 of the 100 children will go on to have disorders affecting their learning and thinking abilities, including autism. All doses of valproate carry a risk but the data support that the higher the dose of valproate, the higher the risks of birth abnormalities and effects on the child’s brain development. Two smaller epidemiological studies (Hunt et al 2008 and Wade, 2015) did not show an increased relative risk of small for gestational age but these studies may not have been adequately powered to detect an increase in risk.

• For the majority of these drugs the data relating to safety of use during pregnancy remains limited or very limited.
• The available clinical studies (Fujii et al 2013, Killic et al 2014, Hernandez-Diaz et al 2017) do not allow for firm conclusions to be reached.
• The behaviours can be very similar to autism, and either milder, or without the other behaviours.See also, Autism, above.
• Randomised controlled clinical trials are usually considered the best evidence to support a causal association.
• Pregabalin (brand name Lyrica) is indicated as adjunctive therapy in adults with partial seizures with or without secondary generalisation.
• The cause is not known, the purpose is not known, and whether the person has any control over the behaviour is not known.

Non-clinical studies

Non-clinical data from studies in rats have reported developmental toxicity (embryolethality, growth retardation) in the offspring exposed to either oxcarbazepine or its active 10-hydroxy metabolite during pregnancy at doses relevant to human therapeutic doses. The largest studies are those by Christensen et al 2013 (386 children exposed to carbamazepine) and 2019 (423 children exposed to carbamazepine), which examined the risk of autism spectrum disorders and ADHD, respectively. The studies by Christensen et al and the meta-analyses do not suggest an increased risk of symptoms or diagnoses of autism spectrum disorders or ADHD following carbamazepine exposure during pregnancy. Where studies have examined effects on intelligence quotient (IQ), there are conflicting results from some of the individual studies compared with the findings of the meta-analyses.

What is CVI?

Similar findings were not seen in the meta-analyses (Banach et al 2010 (83 children in the carbamazepine group) and Bromley et al 2014 (150 children in the carbamazepine group)) that included other prospective observational studies. These differences may reflect the different methodologies and designs in the individual studies and limitations such as the potential for residual confounding and lack of a comparison to women with epilepsy in some studies. During cerebrumiq its clinical development a drug is tested on a range of people in clinical trials in order to generate information on safety and efficacy. However pregnant women are generally excluded from participation in these trials for ethical reasons. Studies in pregnant animal models (non-clinical studies) are used as a surrogate to investigate the effects of a drug in pregnancy.

CerebrumIQ reviews spark deeper questions about what intelligence really means

The information and analyses contained in this report reflect evidence that was available at the time of the review in 2020. The MHRA will continue to monitor the safety of all medicines, however the information in this report will not be actively updated with new data or studies. Due to the serious harms that can happen to the unborn baby, a number of restrictions have been made to prevent women with epilepsy from taking valproate during pregnancy. This report presents our review of studies in animals and in women who are pregnant to assess the safety of epilepsy medicines use during pregnancy.