Study of the Transmission of Cytomegalovirus (CMV) Infection From Mother to Foetus

Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 15 ED50.

Time frame: At Month 0

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 10 ED50.

Time frame: At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 15 ED50.

Time frame: At Month 6

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 15 ED50.

Time frame: At Month 4

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 15 ED50.

Time frame: At Month 2

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 10 ED50.

Time frame: At Month 0

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 10 ED50.

Time frame: At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 10 ED50.

Time frame: At Month 6

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 10 ED50.

Time frame: At Month 4

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Antibody titers were expressed as Geometric Mean Titers (GMTs), for the seropositivity cut-off of ≥ 10 ED50.

Time frame: At Month 2

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay \[ELISA\], with respect to positive and negative subjects.

Time frame: At Month 6

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

Time frame: At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (≥) 0.668 U/mL.

Time frame: At Month 6

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection, with available CMV infection status of the newborn, foetus or stillbirth and with available results.

Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (≥) 0.668 U/mL.

Time frame: At Month 2

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection, with available CMV infection status of the newborn, foetus or stillbirth and with available results.

Anti-gB IgG concentrations were assessed by ELISA, presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EU/mL). The cut-off value was greater than or equal to (≥) 54 EU/mL.

Time frame: At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection, with available CMV infection status of the newborn, foetus or stillbirth and with available results.

Anti-gB IgG concentrations were assessed by ELISA, presented as geometric mean concentrations (GMCs) and expressed in ELISA units per milliliter (EU/mL). The cut-off value was greater than or equal to (≥) 54 EU/mL.

Time frame: At Month 0

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection, with available CMV infection status of the newborn, foetus or stillbirth and with available results.

Descriptive statistics of the frequency of CMV-specific CD4 T cells expressing at least two markers among CD40L, IL-2, IFNg, TNFa, as assessed by Intracellular Cytokine Staining \[ICS\], by stimulating agent (among immediate-early gene \[IE1\] antigen, glicoprotein B \[gB\] antigen, CMV lysate antigen and CMV pp65 antigen).

Time frame: At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection, with available CMV infection status of the newborn, foetus or stillbirth and with available results.

Descriptive statistics of the frequency of CMV-specific CD8 T cells expressing at least two markers among CD40L, IL-2, IFNg, TNFa, as assessed by Intracellular Cytokine Staining \[ICS\], by stimulating agent (among immediate-early gene \[IE1\] antigen, glicoprotein B \[gB\] antigen, CMV lysate antigen and CMV pp65 antigen).

Time frame: At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection, with available CMV infection status of the newborn, foetus or stillbirth and with available results.

Descriptive statistics of the frequency of CMV-specific CD4 T cells expressing at least two markers among: cluster of differentiation 40 ligand (CD40L), interleukin-2 (IL-2), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), as assessed by Intracellular Cytokine Staining \[ICS\], by stimulating agent (among Human Cytomegalovirus \[HCMV\] immediate-early gene \[IE1\] antigen, HCMV glicoprotein B \[gB\] antigen, HCMV lysate antigen and HCMV pp65 antigen).

Time frame: At Month 0

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection, with available CMV infection status of the newborn, foetus or stillbirth and with available results.

Descriptive statistics of the frequency of CMV-specific CD8 T cells expressing at least two markers among CD40L, IL-2, IFNg, TNFa, as assessed by Intracellular Cytokine Staining \[ICS\], by stimulating agent (among immediate-early gene \[IE1\] antigen, glicoprotein B \[gB\] antigen, CMV lysate antigen and CMV pp65 antigen).

Time frame: At Month 0

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection, with available CMV infection status of the newborn, foetus or stillbirth and with available results.

Labelled cells were quantified by flow cytometry, by stimulating agent (among immediate-early gene \[IE1\] antigen, glicoprotein B \[gB\] antigen, CMV lysate antigen and CMV pp65 antigen). Note: Results were retrieved by subtracting the background without imputing the negative and zero values, this generated negative values.

Time frame: At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection, with available CMV infection status of the newborn, foetus or stillbirth and with available results.

Labelled cells were quantified by flow cytometry, by stimulating agent (among immediate-early gene \[IE1\] antigen, glicoprotein B \[gB\] antigen, CMV lysate antigen and CMV pp65 antigen).

Time frame: At Month 0

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection, with available CMV infection status of the newborn, foetus or stillbirth and with available results.

Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (≥) 0.668 U/mL.

Time frame: At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection, with available CMV infection status of the newborn, foetus or stillbirth and with available results.

Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (≥) 0.668 U/mL.

Time frame: At Month 4

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection, with available CMV infection status of the newborn, foetus or stillbirth and with available results.

Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs), measured in units per milliliter (U/mL). Concentrations of antibodies were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) for a cut-off greater than or equal to (≥) 0.668 U/mL.

Time frame: At Day 0 = study entry

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection, with available CMV infection status of the newborn, foetus or stillbirth and with available results.

Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay \[ELISA\], with respect to positive and negative subjects. Grey Zone = optical density zone within 20% of cut-off value. When an optical density is within this grey zone, sample testing is repeated to confirm the result.

Time frame: At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay \[ELISA\], with respect to positive and negative subjects. Grey Zone = optical density zone within 20% of cut-off value. When an optical density is within this grey zone, sample testing is repeated to confirm the result.

Time frame: At Month 2

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay \[ELISA\], with respect to positive and negative subjects. Grey Zone = optical density zone within 20% of cut-off value. When an optical density is within this grey zone, sample testing is repeated to confirm the result.

Time frame: At Month 0

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

Time frame: At Month 4

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

Time frame: At Month 2

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

Time frame: At Month 6

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Avidity of anti-CMV tegument protein gB IgG was assessed by ELISA. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

Time frame: At Day 0 = study entry

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Anti-CMV IgM status was assessed by Enzyme-Linked Immunosorbent Assay \[ELISA\], with respect to positive and negative subjects. Grey Zone = optical density zone within 20% of cut-off value. When an optical density is within this grey zone, sample testing is repeated to confirm the result.

Time frame: At Month 4

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

Time frame: At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

The avidity index was calculated as the mean absorbance of reactions in which the immune complexes were exposed to urea divided by the mean absorbance of reactions in which the immune complexes were not exposed to urea, expressed as a percentage.

Time frame: At Month 0

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

Time frame: Within 10 days post-delivery (Days 0-9)

Population: The diagnosis of CMV in the newborn was done according to the local standard of care and samples were not collected for this analysis.

The assessment focused on the presence of CMV DNA copies (by Quantitative Polymerase Chain Reaction \[qPCR\]) in saliva, urine and blood every month from study entry to, and including, pregnancy conclusion.

Time frame: At pregnancy conclusion (Day 0 to 5, Day 0 = day of delivery, stillbirth or termination)

Population: The analysis was performed on the Total Enrolled cohort, which included all pregnant subjects enrolled in this study, with available CMV infection status for their infants.

The assessment focused on the presence of CMV DNA copies (by Quantitative Polymerase Chain Reaction \[qPCR\]) in saliva, urine, blood and vaginal secretions every month from study entry to, and including, pregnancy conclusion.

Time frame: At Month 0

Population: The analysis was performed on the According-to-Protocol (ATP) cohort, which included all pregnant women with confirmed primary CMV infection and with available CMV infection status of the newborn, foetus or stillbirth.

The CMV congenital infections were assessed in newborns and foetuses of subjects who had a confirmed primary CMV infection during pregnancy.

Time frame: At Month 0

Population: The analysis was performed on the Total Enrolled cohort of Infant subjects, which included the newborns' group diagnosed with CMV infection and who had their medical records reviewed 1 month after birth and every 6 months for 2 years and foetus group, referring to infants that were stillborn or with pregnancy termination.

Evidence of infection in the amniotic fluid was assessed by culture or by Polymerase Chain Reaction (PCR).

Time frame: Within 10 days post-delivery (Days 0-9)

Population: The analysis was performed on the Total Enrolled cohort of Infant subjects, which included the newborns sub-group diagnosed with CMV infection and who had their medical records reviewed 1 month after birth and every 6 months for 2 years and foetus sub-group, referring to infants that were stillborn or with pregnancy termination.

Evidence of infection in urine was assessed by culture or by Polymerase Chain Reaction (PCR).

Time frame: Within 10 days post-delivery (Days 0-9)

Population: The analysis was performed on the newborn sub-group in the Total Enrolled cohort of Infant subjects, which included the subjects diagnosed with CMV infection and who had their medical records reviewed 1 month after birth and every 6 months for 2 years.