Like everyone else, I’m struggling to evaluate the potential impact of the coronavirus outbreak. As I write, precautionary measures are being taken across the globe, with different approaches being adopted by different governments, reflecting the different perceptions of risk and the extent of the pandemic. Scientific and medical advisors, doing their best to anticipate where this pandemic will go, are advising governments, desperately hoping to make the right choices for their people.
One problem they all face is assessing the risk to different groups within society. The elderly are particularly vulnerable, and those with pre-existing medical conditions. The young seem to be less effected, a relief for many parents. But what about the unborn? What precautions should pregnant women be taking?
Guidance has emerged on both sides of the Atlantic for women in pregnancy. The message is that there is no evidence that babies in the womb are at risk. Indeed, evidence suggests that corona-type viruses don’t cross the placenta, and case studies have led the UK Royal College of Obstetricians and Gynaecologists to conclude that, "Expert opinion is that the fetus is unlikely to be exposed during pregnancy." This is reassuring, and the expert advice is that women in pregnancy should adopt approximately the same measures to avoid exposure as the rest of the population, and take similar steps for self-isolation should they suspect that they have become infected.
Neuroscientists working on neurodevelopmental disorders, however, might spot that one issue has been overlooked. There is good evidence that severe exposure to viral infection during the first trimester is associated with an increased risk of neurodevelopmental disorders. Perhaps the clearest evidence relates to autism. In one robust study, the risk of a child being subsequently diagnosed with autism increased almost three-fold following exposure to a severe viral infection during the first trimester.
To be clear, these were not simply mild cases of the sniffles: the infection had to be serious enough to warrant hospitalisation. To be clear also: the risk to the child remained low. The population incidence of autism is roughly 1%, so even if tripled, the overwhelming majority of pregnancies deliver neurotypical children.
But could the same be true for Covid-19, if it doesn’t infect the fetus? It could because the fetus doesn’t need to be exposed to the virus directly. Experimental evidence suggests that the problem isn’t the virus itself, rather it results from the mother’s response. Infection causes the mother’s immune system to produce cytokines – signaling molecules the activate the body’s defences and contribute to the development of the fever. While the virus itself may not cross the placenta, the cytokines do, and they impact the development of the fetus. It is this cytokine storm that seems to raise the risk of developmental disorder in the baby.
Does this mean that the Covid-19 pandemic will be followed by an epidemic of autism? Almost certainly not, the numbers will almost certainly be small. The proportion of the population that will contract Covid-19 is currently unclear. Estimates of 60% have been published but these are just best guesses at this stage. Of these only a small proportion will be severely infected, perhaps 20% judging by the current WHO data, and if the duration of the pandemic is relatively short, perhaps a few months, then the cohort of women at risk will be small.
Nonetheless, women in their first trimester might wish to take note of this risk, and perhaps be more inclined to isolate themselves than the general public. As the official advice states, they themselves are not more at risk, and their babies are not at risk from the virus itself. Nonetheless, a severe infection at this time may have downstream consequences.
As the world emerges from this pandemic, some predict that Covid-19 will become an endemic virus, like influenza: something we can immunize against (hopefully), but otherwise learn to accommodate and avoid if possible. In this context, any increased incidence of neurodevelopmental disorders will quickly merge into the existing baseline risk. We know autism has a strong genetic component, but that environmental factors are also linked. Some toxins are thought to increase the risk, and stressful life events more generally. Covid-19 may end up being another factor on that list.
1. Sonja A Rasmussen MM, John C Smulian MM, John A Lednicky P, Tony S Wen MD, Denise J Jamieson MM. Coronavirus Disease 2019 (COVID-19) and Pregnancy: What obstetricians need to know. American Journal of Obstetrics and Gynecology. Elsevier Inc; 2020;:1–35
2. Estes ML, McAllister AK. Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nature Publishing Group. Nature Publishing Group; 2015;16:469–86.
3. Atladóttir HO, Thorsen P, Østergaard L, Schendel DE, Lemcke S, Abdallah M, et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J Autism Dev Disord. 2010;40:1423–30.
4.Amodeo DA, Lai C-Y, Hassan O, Mukamel EA, Behrens MM, Powell SB. Maternal immune activation impairs cognitive flexibility and alters transcription in frontal cortex. Neurobiology of Disease. Elsevier; 2019;125:211–8.
5. Persico AM, Napolioni V. Urinary p-cresol in autism spectrum disorder. Neurotoxicology and Teratology. 2013;36:82–90.