The hidden pandemic: prenatal maternal stress during the COVID-19 emergency and epigenetic and behavioural effects on the development of the infant at three months

COVID-19 is a highly viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in Wuhan in 2019. It has spread rapidly as a worldwide pandemic, with a primary hotspot in Northern Italy. Becoming a collective trauma, it may have enduring risk for relevant psychological stress in citizens and, in particular, during sensitive periods as pregnancy. Prenatal stress exposures associate with less-than-optimal child development outcomes through some epigenetic mechanisms (e.g., DNA methylation) of stress-related genes (e.g., the serotonin transporter gene, SLC6A4). In April 2020, the longitudinal cohort study Measuring the Outcomes of Maternal COVID-19-related Prenatal Exposure (MOM-COPE) was launched in Northern Italy to assess the behavioral and epigenetic effects of COVID-19-related prenatal stress exposure in 108 mother-infant dyads. At birth, mothers provided retrospective quantitative measures of prenatal COVID-19-related stress during pregnancy. SLC6A4 methylation was assessed in thirteen CpG sites in mothers’ and infants’ buccal cells. At 3 months of age of the infant, mothers also provided data on their own psychological status (stress, depressive and anxious symptoms) and coping strategies, and on child’s temperament. Greater COVID-19-related stress during pregnancy was significantly associated with SLC6A4 methylation in seven CpG sites in infants, but not in mothers. This SLC6A4 methylation was significantly and negatively associated with infants’ temperament, in particular with the infants’ positive affect at 3 months. Thus, prenatal COVID-19-related stress during pregnancy has relevant psychobiological and behavioral effects on infants. Its outcomes get under the skin, resulting in a significant hidden pandemic.