Measuring Outcomes of Maternal COVID-19-related Prenatal Exposure (MOM-COPE)

The rapidly spreading coronavirus Covid-19 pandemic is a major concern worldwide and Italy is at the forefront of this emergency. At the present moment, the effects on the offspring of Covid-19 disease in pregnant women and/or the indirect effect of COVID-19-related prenatal maternal stress are poorly understood. Epigenetic mechanisms - and especially DNA methylation - are involved in the embedding of prenatal exposures to large-scale disasters into the epigenome and phenotypic outcomes of the offspring. Specific target genes include SLC6A4, NR3C1, OXTR, BDNF, and FKBP5. The central hypothesis of this project is that the exposure to the COVID-19-related prenatal maternal stress may affect infants' outcomes from birth to 12 months partially through increased methylation of target genes involved in stress regulation. The main goal is to investigate the association between Covid-19 disease in pregnancy or COVID-19-related PMS in women pregnant during the first 9 months of the year 2020 and the emotional, social, and cognitive developmental outcomes in their infants from birth to 12 months. Additionally, the role of target genes methylation in mediating this association will be investigated. Mothers and their infants will be enrolled from the delivery units of eleven neonatal facilities located in Northern Italy's COVID-19 contagion hotspot. One group will be enrolled from April to October 2020 (COVID-Exposure Pregnancy, CEP), a second group will be enrolled from April to October 2021 (Non-Exposure Pregnancy, NEP). Moreover, the CEP group will include mothers positive or exposed to COVID-19-related MPS during different trimesters of pregnancy, allowing within-group comparisons on developmentally sensitive time windows. Within 48 hours from baby delivery, saliva samples will be obtained from CEP and NEP newborns, immediately stored at -20°C and analyzed for epigenetic analyses using Next-Generation Sequencing. At 3 and 6 months, mothers will be asked to fill-in validated and reliable questionnaires on the emotional and social-behavioral development of their infants. At 12 months, infants' stress regulation and maternal sensitivity will be evaluated through video recording of mother-infant interactions. This study will provide unprecedented relevant insights on the biochemical mechanisms underlying the impact of Covid-19 disease and the related PMS on human offspring's developmental outcomes.

Study Overview

• Status: Completed
• Conditions: Prenatal Stress
• Intervention / Treatment: Other: Maternal stress

• Study Type: Observational
• Enrollment (Actual): 350

Contacts and Locations

Study Locations

• Italy
  • PV
    • Pavia, PV, Italy, 27100
      • IRCCS Mondino Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 1 year (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Subjects will be mother-infant dyads as defined in the Eligibility Criteria section. Maternal age equal or greater than 18 years. Infants' will be enrolled at birth and followed-up to 12 month-age.

Description

Inclusion Criteria:

• Italian nationality or full mastery of Italian language to access on-line questionnaires without support
• No prenatal pathologies or perinatal risks
• Maternal age higher than 18 years
• Newborns' gestational age equal or higher than 37 weeks

Exclusion Criteria:

• Single-parent mothers
• Medically assisted conception
• Infants' genetic or metabolic comorbidities
• Perinatal injuries or sensorial deficits

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COVID-19 Exposed Pregnancy (CEP); Women who were pregnant and delivered during the outbreak of COVID-19 pandemic in Italy, and their infants.	Other: Maternal stress; Prenatal COVID-19-related stress retrospectively self-reported by mothers after delivery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant negative emotionality	Measure of infant Negative Emotionality through the Infant Behavior Questionnaire - Revised questionnaire. Negative Emotionality mean score ranges from 1 to 7 and higher scores reflect higher negative emotionality.	At 12 months of infants' age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infants' target gene methylation status	Methylation status of the following target genes: BDNF, FKBP5, NR3C1, OXTR, SLC6A4	At birth

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal target gene methylation status	Methylation status of the following target genes: BDNF, FKBP5, NR3C1, OXTR, SLC6A4	At delivery
Maternal mental health	Measure of maternal mental health obtained through the State dimension of the Stait-Trait Anxiety Inventory. The score ranges from 20 to 80, with a clinical cut-off set at 40. Higher scores reflect higher anxiety.	At 3, 6, and 12 months of infants' age
Maternal sensitivity	Maternal sensitivity measured by behavioral codings of mother-infant videorecorded interactions	At 12 months of infants' age

Collaborators and Investigators

• Sponsor: IRCCS National Neurological Institute "C. Mondino" Foundation
• Investigators: Principal Investigator: Livio Provenzi, PhD, University of Pavia

Publications and helpful links

General Publications

• Provenzi L, Grumi S, Giorda R, Biasucci G, Bonini R, Cavallini A, Decembrino L, Drera B, Falcone R, Fazzi E, Gardella B, Giacchero R, Nacinovich R, Pisoni C, Prefumo F, Scelsa B, Sparta MV, Veggiotti P, Orcesi S, Borgatti R; MOM-COPE Study Group. Measuring the Outcomes of Maternal COVID-19-related Prenatal Exposure (MOM-COPE): study protocol for a multicentric longitudinal project. BMJ Open. 2020 Dec 31;10(12):e044585. doi: 10.1136/bmjopen-2020-044585.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2020
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): May 15, 2024

Study Registration Dates

• First Submitted: September 2, 2020
• First Submitted That Met QC Criteria: September 4, 2020
• First Posted (Actual): September 7, 2020

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 15, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19; Epigenetics; Pandemics; Maternal sensitivity; Glucocorticoid receptor; Stress regulation; Serotonin transporter; Prenatal stress; Oxytocin receptor; Brain-derived neutropic factor
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: MOM-COPE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No