Tuesday, May 31, 2022

Psychological distress in pregnant women during the COVID-19 pandemic and measures of the structure of the foetal brain

Psychological distress in pregnant women

A study published in Communications Medicine looks at maternal psychological distress during the COVID-19 pandemic and structural changes of the human foetal brain.

Prof Ciara McCabe, Professor of Neuroscience, Psychopharmacology and Mental Health, University of Reading, said:

“This small preliminary study is an extension of the authors’ previous work linking fetal brain development and maternal stress.  The study shows brain differences between pre-pandemic and pandemic fetal development.  However the authors acknowledge that the developmental differences related to stress did not remain after multiple correction, suggesting other pandemic factors may be at play, for e.g., unknown exposure to covid-19.  However the long term implications of this type of work is yet unknown.  Follow up longer term studies are needed for this.  As the human brain develops rapidly in early childhood with many further changes in adolescence it will be interesting to see how pandemic fetal development affects these later developmental processes going forward.

Does the press release accurately reflect the science?


Is this good quality research?  Are the conclusions backed up by solid data?


How does this work fit with the existing evidence?

“Yes, this is an extension of work by the same group looking at stress and fetal brain development.

Maternal stress and fetal brain development.

Have the authors accounted for confounders?  Are there important limitations to be aware of?

“The brain developmental differences related to stress did not remain after multiple correction, suggesting other pandemic factors may be at play.  Plus any brain changes between groups may have been due unknown exposure to covid-19.

What are the implications in the real world?  Is there any overspeculation?

“The long term implications are unknown.

Should new mothers or pregnant women be worried?

“No, as the long term implications are unknown plus the human brain continues to develop a lot in childhoods early years and right through to adulthood.  Then more slowly from then on.

Is this study able to show what effects there might be of any observed brain structural differences, or don’t we know that from this

“No as they are fetal – you can see brain differences but this study can’t directly tell you how this might affect behaviour later on.

Does this study have long-term data or is it preliminary?

“No – it is preliminary.” 

Dr Nadja Reissland, Senior Lecturer in Psychology, Durham University, said:

“The study was well conducted with a good sample of pregnant women during COVID compared with a Pre-Covid sample.  In the literature however there are now also quite a few studies which show that the pandemic itself was perhaps not the main factor, rather social support plays a big role in how pregnant women fared during the pandemic.  Women who were supported coped well whereas women who were left on their own (e.g. to decide whether or not to take the vaccine, with reduced care, worries about partner being allowed to be present at the birth) fared worse.  One study published in Pregnancy and Childbirth (2022) reported a negative experience when they had to give birth during the pandemic especially during the first lockdown.  Given that COVID was present in the second lockdown the difference between first and second lockdown are of interest.  These results emphasise that the context of being pregnant and giving birth is of prime importance.  It is something the authors mention themselves in the limitations to their study.

“Another limitation is that maternal COVID status was not assessed independently.  Hence it is unclear if at least some of the women were COVID positive which might have influenced the results.  Nevertheless, this is an important study showing that stress and depression seem to play a role in brain formation.

Maternal COVID status

“These findings makes sense and could explain what we have found in many of our fetal studies showing that maternal stress, depression and anxiety affect fetal behaviour.  For example in our paper on fetal vision (Reissland et al 2020) we found that In contrast to other studies examining fetal reactions to prenatal light stimulation, without controlling for maternal factors (importantly maternal stress, depression and anxiety) that in fetuses at 33 weeks gestation, maternal anxiety and depression, and fetal growth factors (femur length) all had a significant effect on fetal reactivity to face-like compared to a non-face-like control light stimulus.  This calls into question some previously published results.

“In another study (Reissland et al 2018) we found that fetuses in the third trimester reacted differentially to sound and light stimulation depending on maternal mental health status with a 20% increase in fetal eyeblink for each unit increase in anxiety score and a 21% decrease in fetal eyeblink for each unit increase in depression score indicating that fetuses are affected differentially by maternal anxiety and depression.

“The current study makes clear that in fact maternal stress measured using PSS and depression measured using EPDS, two measures used in many of our studies, have an effect on fetal brain development and this goes someway to explaining our findings of differential behaviours by the fetus depending on maternal mental health status.”


Reissland, N., Froggatt, S., Reames, E., & Girkin, J. (2018). Effects of maternal anxiety and depression on fetal neuro-development. Journal of Affective Disorders. 241, 460-474.

Reissland, N., Wood, R., Einbeck, J. & Lane, A. (2020). The effects of maternal mental health and prenatal attachment on fetal reactions to face-like light stimulation. EarlyHumanDevelopment151:105227 https://doi.org/10.1016/j.earlhumdev.2020.105227

Prof Carmine Pariante, Professor of Biological Psychiatry, Institute of Psychiatry Psychology & Neuroscience, King’s College London (IoPPN), said:

“The paper by Lu et al. presents some interesting findings of changes in the size of brain structures of developing foetus during the COVID pandemic, compared with a historical cohort the previous year. The sample size is relatively small, but these studies are difficult to complete and thus the authors should be commended for such an effort. Although the paper includes a multitude of statistical analyses, thus risking the occurrence of chance findings, in reality the findings are to be considered robust: the neuroimaging analyses uses advanced methods, and the described brain changes are consistent with what we already know about the effects of stress and mental disorders on the brain, including the effects of maternal stress or depression on the infant brains (although interestingly they cannot replicate well-known differences in the male and female infant brains).

“There are two main limitations that are worth considering. First, studies across historical cohorts are very difficult to interpret, especially when major social events occur, like in this study. The authors acknowledge that they do not measure “social isolation, financial insecurity, and nutritional changes”, which were massive factors during the pandemic. My opinion is that these factors will have had a more direct role in explaining these brain changes than just the subjective levels of mothers’ anxiety, and indeed some of the association between brain changes and maternal anxiety are statistically weak.

“The second limitation is that the paper does not present any neurological or behavioural assessment of the babies, which could have been easily carried out in the first few days or weeks after birth. These would have offered a clear interpretation of the true relevance of these brain size changes for babies’ mental life. So we don’t know from this study what impact, if any, these brain size changes might have on babies.”

‘Maternal psychological distress during the COVID-19 pandemic and structural changes of the human fetal brain’ by Yuan-Chiao Lu et al. was published in Communications Medicine at 16:00 UK time on Thursday 26 May 2022.

DOI: 10.1038/s43856-022-00111-w

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