Clinical trial NCT04540029: Measuring Outcomes of Maternal COVID-19-related Prenatal Exposure
Official title: Measuring Outcomes of Maternal COVID-19-related Prenatal Exposure
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Prenatal Stress
Keywords: COVID-19
Epigenetics
Prenatal stress
Stress regulation
Maternal sensitivity
Pandemics
Serotonin transporter
Glucocorticoid receptor
Oxytocin receptor
Brain-derived neutropic factor
Lead sponsor: IRCCS National Neurological Institute "C. Mondino" Foundation
Sponsor class: OTHER
First posted: 2020-09-07
Enrollment: 350
Sex: ALL
Minimum age (years): 0
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Infant negative emotionality
timeFrame: At 12 months of infants' age
Secondary outcomes:
measure: Infants' target gene methylation status
timeFrame: At birth
Other outcomes:
measure: Maternal target gene methylation status
timeFrame: At delivery
measure: Maternal mental health
timeFrame: At 3, 6, and 12 months of infants' age
measure: Maternal sensitivity
timeFrame: At 12 months of infants' age
Locations:
city: Pavia
country: Italy
facility: IRCCS Mondino Foundation
state: PV
Study officials:
affiliation: University of Pavia
name: Livio Provenzi, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.