Evaluation of the Safety and Efficacy of Standard Intravenous Immunoglobulins in Pregnant Women With Primary Cytomegalovirus Infection

Study Overview
=================
Brief Summary
-----------------
Because the potential benefit of standard intravenous immunoglobulins (IVIG) - obtained from unselected donor pools including a varying proportion of donors previously exposed to CMV - has not yet been explored in pregnant women, the investigators performed a longitudinal prospective study on the possible efficacy of IVIG for prevention or therapy of fetal CMV infection.

Detailed Description
-----------------
Human IVIG are offered monthly to consecutive enrolled pregnant women with confirmed primary CMV infection at any stage, for the prevention and treatment of fetal CMV infection. Primary infection is defined by positive CMV IgM antibodies with absent or low titres of CMV IgG antibodies, and either low (<40%) CMV IgG avidity indexes with positive CMV IgM AND IgG antibodies. In addition women with indefinite avidity index and positive CMV DNA detection in urine and/or blood samples are also considered for treatment. Standard human intravenous immunoglobulins were chosen for their safety and efficacy, well documented in other settings. IVIGs were used to perform all of the infusions in the study, undiluted after reconstitution, in accordance with instructions of the manufacturer. We chose to perform IVIG infusions using 0.5 g/Kg of body weight, to make sure that a dose of specific CMV IgG at least comparable with that carried by HIG were infused at each time point. Infusions last 4 to 5 hours, using a double lumen line to infuse approximately 1500 mL of either 5% glucose or saline solution in parallel with the undiluted IVIG preparation, to reduce the risk of infusion reactions. CMV IgG and IgM antibodies and IgG avidity indexes are assayed before and after each IVIG infusion, within 15 minutes. Quantitative CMV DNA is amplified from whole blood and urine samples from pregnant women and neonates, using the Real-Time PCR, and on samples of amniotic fluid from women who required amniocentesis. The newborns will be followed for five years after delivery.

Official Title
-----------------
Evaluation of the Safety and Efficacy of Standard Intravenous Immunoglobulins in Pregnant Women With Primary Cytomegalovirus Infection

Conditions
-----------------
Cytomegalovirus Congenital Infection

Intervention / Treatment
-----------------
* Biological: standard intravenous immunoglobulin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant women with confirmed primary CMV infection at any stage of gestation. Exclusion Criteria: Pregnant women with falsely positive CMV IgM antibodies or high (>40%) CMV IgG avidity indexes
Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: standard intravenous immunoglobulin<br>Single arm evaluation of neurological consequences of congenital CMV infection in comparison with historical untreated controls. | Biological: standard intravenous immunoglobulin<br>* Human standard intravenous immunoglobulin (IVIG), 0.5 g/Kg of body weight, monthly after confirmation of primary gestational CMV infection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevention of neurological damage due to Cytomegalovirus congenital infection | Number of infected newborns with neurological deficits divided by the total number of infected newborns | Neonates will be followed for 5 years, that is the estimated period of time over which late neurological manifestations may ensue | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety of aspecific immunoglobulins in pregnant women with primary CMV infection | Number of women with symptoms or adverse events during infusions divided by the total number of treated women | Participants are followed during the infusion period, an expected average of 5 hours; possible minor side-effects are searched for at each follow up visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
congenital CMV infection, standard immunoglobulins, immunoglobulin therapy, IgG CMV avidity index, Cytomegalovirus