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

Foundation IRCCS San Matteo Hospital

Status: Unknown

Conditions: Congenital Cytomegalovirus Infection; Maternal Cytomegalovirus Infection

Treatments: Behavioral: Hygienic recommendations

Study type: Interventional

Funder types: Other

Identifiers

NCT03973359

20170011101

Details and patient eligibility

About

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.

Full 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).

Enrollment: 23,500 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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23,500 participants in 2 patient groups

Epidemiology

No Intervention group

Description:

HCMV-seropositive pregnant women receiving standard care

Prevention

Experimental group

Description:

HCMV-seropositive pregnant women receiving hygienic information

Treatment:

Behavioral: Hygienic recommendations