The hidden pandemic: COVID-19-related stress, SLC6A4 methylation, and infants’ temperament at 3 months

Background: The COVID-19 pandemic represents a collective trauma that may have enduring stress effects during sensitive periods, such as pregnancy. Prenatal stress may result in epigenetic signatures of stress-related genes (e.g., the serotonin transporter gene, SLC6A4) that may in turn influence infants’ behavioral development. Methods: In April 2020, we launched a longitudinal cohort study to assess the behavioral and epigenetic vestiges of COVID-19-related prenatal stress exposure in mothers and infants. COVID-19-related prenatal stress was retrospectively assessed at birth. SLC6A4 methylation was assessed in infants’ buccal cells. Infants’ temperament was assessed at 3-month-age. Results: Complete data were available from 108 mother-infant dyads. Greater COVID-19-related prenatal stress was significantly associated with higher infants’ SLC6A4 methylation (RR =.07, p =.007, B =.16 [.05;.29]). SLC6A4 methylation at these sites predicted infants’ temperament at 3 months (RR =.05, p =.027, B = -.45 [-.92;-.06]). Conclusion: Indirect effects of the pandemic may alter the trajectories of behavioral development infants. Appropriate prevention and care acts need to be adopted by healthcare systems.

First wave of COVID-19 pandemic and caesarean delivery rate in Italy

INTRODUCTION When COVID-19 first spread in Europe, it was unclear if the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be transmitted from mother to fetus. Hence, doubts arose as the best way to deliver considering that caesarean delivery (CD) indeed could prevent vertical transmission. METHODS We calculated CD rate in 5 Italian regions (Lombardy, Emilia-Romagna, Tuscany, Umbria, Sardinia) differently affected by the first wave of the pandemic. Data were retrospectively obtained from each birth center and aggregated by areas (provinces). Data related to March-April 2020, corresponding to first COVID-19 peak in Italy, were compared with the March-April 2019 as well with November-December 2019, and odds ratio (ORs) were calculated. RESULTS A total of 24 provinces were included, covering 21.8% of the Italian population. Overall CD rate did not differ in the three examined periods: neither in the comparison of March-April 2019 (reference period) versus November-December 2019 (OR: 0.98 95% CI 0.93-1.05) nor in the comparison of the reference period versus March-April 2020 (OR: 1.03;95 % CI 0.98-1.09). CD rate did not change even in areas with the highest incidence of COVID-19. Only 17 out of 3.257 CDs was due to direct COVID-19 complications (0.5%;95% CI 0.3-0.8). No pregnant women with COVID-19 proven infection died. CONCLUSIONS The first wave of COVID-19 pandemic did not significantly affect delivery mode in Italy, even in areas with the highest infection rates.

Childbirth Care among SARS-CoV-2 Positive Women in Italy

The new coronavirus emergency spread to Italy when little was known about the infection's impact on mothers and newborns. This study aims to describe the extent to which clinical practice has protected childbirth physiology and preserved the mother-child bond during the first wave of the pandemic in Italy. A national population-based prospective cohort study was performed enrolling women with confirmed SARS-CoV-2 infection admitted for childbirth to any Italian hospital from 25 February to 31 July 2020. All cases were prospectively notified, and information on peripartum care (mother-newborn separation, skin-to-skin contact, breastfeeding, and rooming-in) and maternal and perinatal outcomes were collected in a structured form and entered in a web-based secure system. The paper describes a cohort of 525 SARS-CoV-2 positive women who gave birth. At hospital admission, 44.8% of the cohort was asymptomatic. At delivery, 51.9% of the mothers had a birth support person in the delivery room;the average caesarean section rate of 33.7% remained stable compared to the national figure. On average, 39.0% of mothers were separated from their newborns at birth, 26.6% practised skin-to-skin, 72.1% roomed in with their babies, and 79.6% of the infants received their mother's milk. The infants separated and not separated from their SARS-CoV-2 positive mothers both had good outcomes. At the beginning of the pandemic, childbirth raised awareness and concern due to limited available evidence and led to "better safe than sorry" care choices. An improvement of the peripartum care indicators was observed over time.

The MOM-COPE research project: Measuring the outcomes of maternal COVID19-related prenatal exposure

Background: The coronavirus disease of 2019 (Covid-19) represents an unprecedented threat for human health worldwide that may have profound stress effects. Pregnancy is a sensitive period for adverse parenting effects on infants’ development and epigenetic mechanisms (DNA methylation) may play a pivotal role. Here we present the study protocol of the MOM-COPE project. Methods: Mothers and infants will be enrolled in twelve neonatal units in Northern Italy, a dramatic hotspot for Covid-19 contagion in Europe. Maternal covid-related stress will be assessed with an ad-hoc questionnaire. At birth, newborns and mothers’ salivary samples will be obtained to estimate target genes’ methylation (BDNF, FKBP5, NR3C1, SLC6A4, and OXTR). Post-natal bonding and infants’ temperament will be assessed through maternal reports at 3, 6 and 12 months. Maternal sensitivity and infants’ emotional regulation will be assessed during remote videotaped mother-infant interaction at 12 months. Results: The study has obtained approval of the Ethics Committee and is going to start by May 15th. Hypotheses and anticipated results will be discussed according to the available behavioral epigenetic literature on parenting, pregnancy and large-scale disasters. Discussion: This multi-centric study will provide evidence about the effect of pandemic-related prenatal stress exposure on the health and well-being of mothers and infants from birth to 12 months of age. Moreover, the longitudinal nature of the study will allow to assess the relative role of epigenetic regulation of specific target genes in mediating the effect of this precocious adverse exposure on short- and long-term outcomes.

Vaginal delivery in SARS-CoV-2-infected pregnant women in Northern Italy: a retrospective analysis.

OBJECTIVE: To report mode of delivery and immediate neonatal outcome in women infected with COVID-19. DESIGN: Retrospective study. SETTING: Twelve hospitals in northern Italy. PARTICIPANTS: Pregnant women with COVID-19-confirmed infection who delivered. EXPOSURE: COVID 19 infection in pregnancy. METHODS: SARS-CoV-2-infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. MAIN OUTCOME AND MEASURES: Data on mode of delivery and neonatal outcome. RESULTS: In all, 42 women with COVID-19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0-72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7-59.0) cases: in eight cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8-61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3-61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1-45.6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS-Cov-2 infection. In one case, a newborn had a positive test after a vaginal operative delivery. CONCLUSIONS: Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn. TWEETABLE ABSTRACT: This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn.