Incidence, Outcome and Prevention of Congenital Human Cytomegalovirus (HCMV) Infection in HCMV-seropositive Pregnant Women
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 23,500
- 试验地点
- 23
- 主要终点
- Part 1. Epidemiology study. Incidence and clinical outcome of congenital HCMV infection in pregnant women with preconception immunity.
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Unreliable women as judged by the investigator
- •Women not willing to give written consent
研究组 & 干预措施
Epidemiology
HCMV-seropositive pregnant women receiving standard care
Prevention
HCMV-seropositive pregnant women receiving hygienic information
干预措施: Hygienic recommendations (Behavioral)
结局指标
主要结局
Part 1. Epidemiology study. Incidence and clinical outcome of congenital HCMV infection in pregnant women with preconception immunity.
时间窗: Within 21 days of life
Number of infants with ascertained congenital infection.
Part 2. Prevention study. Efficacy of hygiene counseling in reducing congenital HCMV infection in pregnant women with preconception immunity.
时间窗: Within 21 days of life
Number of infants with ascertained congenital infection born to HCMV seropositive women informed about hygiene measures compared to the number of newborns with congenital infection diagnosed in Part 1.
次要结局
- Frequency of HCMV re-infections vs re-activations during pregnancy (Nested study)(10, 20, 30, 40 gestation weeks)
- Antigen-specific IgM levels in non-primary infection during pregnancy (Nested study)(10, 20, 30, 40 gestation weeks)
- Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Contact with young children(Delivery)
- Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Twin pregnancy(Delivery)
- Frequency of non-primary infections during pregnancy (Nested study)(10, 20, 30, 40 gestation weeks)
- Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Age(Delivery)
- Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Concomitant pathologies(Delivery)
- Neutralizing antibody titers in non-primary infection during pregnancy (Nested study)(10, 20, 30, 40 gestation weeks)
- Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Occupation(Delivery)
- Antigen-specific IgG levels in non-primary infection during pregnancy (Nested study)(10, 20, 30, 40 gestation weeks)
- Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Country of origin(Delivery)
研究者
Daniele Lilleri
Principal Investigator
Fondazione IRCCS Policlinico San Matteo di Pavia