Epidemiology and Prevention of Congenital HCMV in Immune Mothers. Congenital HCMV Infection Lombardy

NCT ID: NCT03973359

Last Updated: 2019-06-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 23500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-04
• Study Completion Date: 2020-12-31

Brief Summary

Human cytomegalovirus (HCMV) is the leading infectious agent causing congenital disabilities such as mental retardation, psychomotor delay, hearing loss, speech and language disabilities, behavioural disorders and visual impairment. About 0.6% newborns are HCMV-congenitally infected and, among these, about 20% are symptomatic at birth or will develop long-term sequelae. The public health impact of congenital HCMV is substantial although greatly unrecognized. In Italy, estimated direct costs per affected child exceed €100.000 for a total of €60-70M. HCMV is also a significant cause of infection/disease in the immunocompromised host.

Epidemiological studies and population-based models have preliminarily documented that most of the burden associated to congenital HCMV would be due to non-primary maternal infection. Presently, reinfections are believed to be responsible for the great majority of infected fetuses born to immune mothers.

This study addresses incidence, outcome and prevention of congenital HCMV infection in seropositive pregnant women.The study includes 2 parts: part 1 in which the incidence and outcome of congenital HCMV is investigated in a large population of HCMV seropositive pregnant women and HCMV shedding and immune response is closely monitored in a subset of participants (nested study); part 2 in which the efficacy of an hygiene intervention is assessed.

Detailed Description

Part 1. Epidemiologic study. To investigate incidence and outcome of congenital infection in immune mothers, clinical records of pregnant women are reviewed for HCMV serostatus at ≤ 13 weeks' gestation. Women with HCMV serology compatible with a remote infection are asked to participate in the study. Consenting women are given a pre-stamped, pre-addressed envelope containing a swab to collect newborn's saliva. Envelopes are sent by courier to a centralized diagnostic facility for HCMV testing.

Women can also be enrolled at delivery, provided that the woman has records of presence of virus-specific IgG and absence of IgM early during gestation(or in a previous pregnancy) or, in case of unknown serostatus, a sample of serum/plasma stored at ≤ 13 weeks' gestation is available for retrospective antibody testing (retrospective part of the epidemiology study).

Part 1. Nested study. A subset of IgG pos IgM neg women selected among those enrolled at ≤13 weeks' gestation in the epidemiology study are included in a nested study. These women are monitored at enrolment, 20, 30 weeks of gestation and at delivery by prospective determination of HCMV DNA excretion in different bodily fluids. In DNA-positive specimens selected HCMV genes will be sequenced.

Part 2. Prevention study. To assess the effectiveness of hygiene measures for prevention of congenital infection HCMV seropositive pregnant women are enrolled at ≤ 13 weeks' gestation. Part 2 starts when enrolment of Part 1 is completed. In practice, part 2 is a continuation of part 1 with the only addition of delivering hygiene information at enrolment.

Part 2 will not be performed in case congenital infection rate in Part 1 is <0.4% and clear maternal risk factor for intrauterine transmission cannot be identified at interim analysis (i.e. after examination of 5000 newborns).

In case HCMV DNA is detected in newborn's saliva, a urine sample is obtained for confirmation of congenital infection. Infants with documented congenital infection are clinically assessed at the time of diagnosis (for Part 1 and 2) and at one year of age (Part 1 only).

Conditions

Congenital Cytomegalovirus Infection; Maternal Cytomegalovirus Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Epidemiology

HCMV-seropositive pregnant women receiving standard care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Prevention

HCMV-seropositive pregnant women receiving hygienic information

Group Type: EXPERIMENTAL

Hygienic recommendations

Intervention Type: BEHAVIORAL

Recommendation of protective behaviours such as frequent hand washing and avoiding risky behaviours such as kissing young children on the mouth or cheeks and sharing utensils, foods etc.

Interventions

Hygienic recommendations

Recommendation of protective behaviours such as frequent hand washing and avoiding risky behaviours such as kissing young children on the mouth or cheeks and sharing utensils, foods etc.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Adult (≥ 18 years old) pregnant women at ≤13 weeks gestation
• Presence of HCMV IgG and absence of IgM or presence of high avidity IgG with or without IgM
• Presence of HCMV-specific IgG and absence of IgM or presence of high avidity IgG in case of positive IgM at ≤13 weeks gestation documented by medical report or by retrospective antibody determination on samples stored at ≤13 weeks (for women enrolled at delivery)
• Willingness to participate in the study
• Ability to understand information material
• Written informed consent

Exclusion Criteria

• Unreliable women as judged by the investigator
• Women not willing to give written consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Regionale per la Ricerca Biomedica

OTHER

Sponsor Role: collaborator

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role: lead

Responsible Party

Daniele Lilleri

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniele Lilleri, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Policlinico San Matteo

Locations

ASST Spedali Civili di Brescia

Brescia, , Italy

Site Status: RECRUITING

Poliambulanza Brescia

Brescia, , Italy

Site Status: RECRUITING

ASST Vimercate (Ospedale di Carate Brianza)

Carate Brianza, , Italy

Site Status: RECRUITING

ASST Monza (presidio di Desio)

Desio, , Italy

Site Status: RECRUITING

Fondazione IRCCS Ospedale Maggiore Policlinico

Milan, , Italy

Site Status: RECRUITING

Ospedale Macedonio Melloni (ASST FBF-Sacco)

Milan, , Italy

Site Status: RECRUITING

Ospedale San Raffaele

Milan, , Italy

Site Status: RECRUITING

Ospedale Buzzi (ASST FBF-Sacco)

Milan, , Italy

Site Status: RECRUITING

Ospedale Sacco (ASST FBF-Sacco)

Milan, , Italy

Site Status: RECRUITING

Fondazione Monza Brianza per il Bambino e la sua Mamma

Monza, , Italy

Site Status: RECRUITING

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status: RECRUITING

ASST dei Sette Laghi (Ospedale Filippo Del Ponte)

Varese, , Italy

Site Status: ACTIVE_NOT_RECRUITING

Countries

Italy

Central Contacts

Daniele Lilleri, MD

Role: CONTACT

d.lilleri@smatteo.pv.it

+39 0382 501501

Gabriela Cassinelli, PhD

Role: CONTACT

g.cassinelli@smatteo.pv.it

+39 0382 502682

Facility Contacts

Federico Prefumo, MD

Role: primary

Giorgio Pagani, MD

Role: primary

Anna Locatelli, MD

Role: primary

Simona Rutolo, MD

Role: primary

Beatrice Tassis, MD

Role: primary

Michele Vignali, MD

Role: primary

Paolo Cavoretto, MD

Role: primary

Irene Cetin, MD

Role: primary

Valeria Savasi, MD

Role: primary

Patrizia Vergani, MD

Role: primary

Arsenio Spinillo, MD

Role: primary

References

Lilleri D, Tassis B, Pugni L, Ronchi A, Pietrasanta C, Spinillo A, Arossa A, Achille C, Vergani P, Ornaghi S, Riboni S, Cavoretto P, Candiani M, Gaeta G, Prefumo F, Fratelli N, Fichera A, Vignali M, Barbasetti Di Prun A, Fabbri E, Cetin I, Locatelli A, Consonni S, Rutolo S, Miotto E, Savasi V, Di Giminiani M, Cromi A, Binda S, Fiorina L, Furione M, Cassinelli G, Klersy C; CHILd Study Group. Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study). Clin Infect Dis. 2023 Feb 8;76(3):513-520. doi: 10.1093/cid/ciac482.

Reference Type: DERIVED

PMID: 35717635 (View on PubMed)

Other Identifiers

20170011101

Identifier Type: -

Identifier Source: org_study_id