Although the results of this pilot study are preliminary and should be interpreted with caution, they are very interesting and deserve attention. The observation that the performance in the item cuddliness has a lower score in infants whose mothers were exposed to SARS-CoV-2, and more specifically in those exposed during the third trimester of pregnancy, is particularly interesting. From birth, newborns recognize and create structures of social interaction with others that are critical for optimal brain development 21,22. Social interactions, especially with their caregivers, are based on face-to-face exchanges and close physical contact that lead to attachment 23. Previous studies have related a less optimal response to cuddliness in infants of depressed mothers, suggesting that those infants were more aroused 24. It is interesting to note that none of the infants whose mothers were exposed to SARS-CoV-2 in the first trimester of pregnancy completed the item response to bell. This item requires that the children be in state 1 (deep sleep) in order to initiate the administration. This could be due to an excess of excitation that is not triggered by the environment but is residual. One possible interpretation of this detail is that the level of arousal of the cases group exposed during the first and second trimester of pregnancy was higher than in those exposed in the third trimester that were similar to controls, impairing a proper state regulation.
Those findings points towards that those infants prenatally exposed to SARS-CoV-2 could present difficulties on state regulation, that in accordance with Belot et al., 25 could be partially explained by physiological alterations in the nervous system. This higher level of arousal could be associated with greater activation of infants’ hypothalamic-pituitary-adrenal (HPA) axis, and relates to stress exposure during critical periods, which in turn increases the risk on psychopathology 26. Noticeably, Provenzi et al. 27 observed alterations in the regulatory capacity of 3-month-old infants whose mothers were pregnant during the COVID-19 pandemic compared to infants whose mother were pregnant previous to this period. This finding highlights the importance of psychosocial stress for regulating children’s HPA axis functioning, especially in the third trimester of pregnancy when this system has already been formed. These results are in line with findings from Shuffrey et al. 28, who observed social and motor developmental alterations in children born from mothers pregnant during COVID-19 pandemic period, but not in those exposed prenatally to SARS-CoV-2. Biological data, such as cortisol levels obtained from saliva samples in those infants, will be very useful to explore the functioning of their HPA axis.
Another result that worth considering is that of the poorer performance on pull-to-sit item, which is related to head control, in infants whose mothers were exposed to SARS-CoV-2. Vulnerabilities in infants’ fine and gross motor skills may have significant consequences for later motor development 29. Specifically, poor postural control during pull-to-sit has been suggested as a predictor of developmental disruption 30. Previous studies have linked childhood motor deficits with the risk of developing autism-like disorders 31 and adult schizophrenia spectrum disorders 29. Lower scores in our cases could be indicating a certain motor immaturity or what have been termed neurological soft signs (NSS). NSS entail minor motor and sensory differences, a common feature in children with neuropsychiatric disorders 15,32, that could be considered a proxy marker for underlying neuropsychological deficits.
This study has several limitations. First, since it is a pilot study, the sample is relatively small (only 21 exposed and 21 unexposed). However, as it is an ongoing project, more participants have being recruited, adding to the current sample in later analyses. It should be noted, however, that sample sizes found in the literature related to the NBAS scale are not much larger than our current sample. This is possibly due to the extensive training required to administer the NBAS scale. Second, none of the cases in the study presented with severe COVID-19 symptoms. This circumstance may either be due to a lack of serious cases in our community at the time, or that the few severe cases that might have occurred suffered too much to be enrolled in a research study of this kind. Finally, pairing was not optimal for years of education since, in line with results reported by Shuffrey et al., 28, significantly differed between exposed and unexposed women. A possible interpretation is that voluntary participation was related to higher education in the unexposed group while negatively related to enroll in the exposed group.