HIV Infection, HBV Infection, HDV Infection, HCV Infection, Arbovirus Infections
Conditions
Keywords
Pregnancy, HIV, HBV, HCV, Arbovirus, National health data system, Neurocognitive disorders, Quality of life, Pregnancy viral infections, Mother-to-child transmission, Social epidemiology, Hepatitis
Brief summary
The VIROPREG study is a French prospective multicenter cohort study that aims to assess the impact of viral infections and antiviral treatments received during pregnancy on maternal and child health. The study focuses on both chronic viral infections: human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV)\] and on arbovirus infections. This study aims at investigating the following research questions: * What is the rate of mother-to-child transmission for each virus? * What are the effects of maternal infection on (i) pregnancy outcomes, (ii) the mother's physical and psychological health, and (iii) the fetus' health and development, with a focus on long-term psychomotor development in children born to women living with HIV? * What is the impact of antiretroviral and/or antiviral prophylactic and/or therapeutic treatments administered during pregnancy on maternal and fetal health? Mother-child pairs will be followed from pregnancy through delivery and from birth until the child reaches 7 years of age. Each mother-child pair will be enrolled into one of four cohort groups based on the maternal infection. HIV Cohort: Pregnant women living with HIV who participate in the research will: * Be followed according to the routine care schedule from enrollment to post-natal visit usually scheduled in maternity after delivery (6-8 weeks post-partum) * Participate in additional follow-up by phone call or videoconference at 4- and 7-years post-partum for research purposes * Complete questionnaires at inclusion, delivery, 4- and 7- years postpartum * In case of breastfeeding, receive follow-up care aligned with routine schedules for up to 2 years postpartum, including 2 additional visits specifically for research at 2- and 3- months postpartum. * In selected cases: provide blood, umbilical cord blood, colostrum and breast milk samples during follow-up visits for research purposes (pharmacological and virological analyses). Children born to mothers living with HIV and who participate in the research will: * Be followed according to the routine care schedule from birth until 2 years of age * Participate in additional follow-up by phone call or videoconference, addressed to mothers, at 4- and 7- years of age for research purposes. HBV Cohort: Pregnant HBV-infected women who participate in the research will: * Be followed according to the routine care schedule from enrollment to post-natal visit usually scheduled in maternity after delivery (6- 8 weeks post-partum) * Complete questionnaires at inclusion and delivery * Provide blood samples during follow-up visits for research purposes. Children born to HBV-infected mothers and who participate in the research will: * Be followed according to the routine care schedule from birth to 2 years of age * Participate in additional follow-up for research purposes at 3 months and 18-24 months of age. HCV Cohort: Pregnant HCV-infected women who participate in the research will: * Be followed according to the routine care schedule from enrollment to post-natal visit usually scheduled in maternity after delivery (6 - 8 weeks post-partum) * Complete questionnaires at inclusion and delivery * Provide blood samples during follow-up visits for research purposes. Children born to HCV-infected mothers and who participate in the research will: * Be followed according to the routine care schedule from birth until 2 years of age * Attend additional follow-up visits scheduled at 3 and 9 months of age for research purposes. Arbovirus Cohort: Pregnant women infected with arbovirus who participate in the research will: * Be followed according to the routine care schedule from enrollment to delivery * Participate in additional follow-up for research purposes at 4 years after delivery. * In case of breastfeeding, women will be monitored for research purposes at Day 7 and Day 30 postpartum * Complete questionnaires at inclusion, Day 7-10 from the inclusion, delivery and 4 years after delivery * Provide blood, amniotic fluid, placenta, umbilical cord blood, colostrum and breast milk samples during follow-up visits for research purposes. Children born to mothers infected with arbovirus and who participate in the research will: * Be followed according to the routine care schedule from birth until 2 years of age. * Participate in additional follow-up for research purposes at inclusion, Day 7 and Day 30 after inclusion * Participate in additional follow-up by phone call or videoconference, addressed to mothers, at 4- and 7- years of age for research purposes.
Interventions
BIOLOGICALBlood sampling
Blood sampling will be done to perform pharmacological and virological analysis.
BIOLOGICALUmbilical cord blood sampling
Umbilical cord blood will be sampled to perform pharmacological analysis.
Questionnaires will be administered to the participant at different times during the study.
BIOLOGICALBreast milk sampling
If breastfeeding, breast milk will be collected to perform pharmacological analysis.
BIOLOGICALAmniotic fluid sampling
Amniotic fluid will be sampled for virological and immunological analysis and biobanquing
BIOLOGICALUrine sampling
Urine will be sampled for biobanquing
BIOLOGICALVaginal swab
Vaginal swab will be sampled for biobanquing
BIOLOGICALPlacenta sampling
Placenta will be sampled for virological and immunological analysis
Sponsors
ANRS, Emerging Infectious Diseases
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Pregnant women : * Cis-gender pregnant woman wishing to carry her pregnancy to term and give birth in one of the maternity units participating in the research, whatever the term of pregnancy (inclusion as soon as possible after conception, whatever the outcome); * Age ≥18 years; * Viral infection studied known before pregnancy or diagnosed during pregnancy; * Signed, free, informed and written consent; * Be cared for in one of the maternity units taking part in the study Newborns/children: \- Free, informed, written and signed consent of parental guardians.
Exclusion criteria
Pregnant women : * Planned delivery in a non-study center; * Planned absence that could hinder participation in the research; * Vulnerable population (minors, persons under guardianship or trusteeship, or persons deprived of their liberty by judicial or administrative decision); * Level of French oral comprehension insufficient according to the investigator for the research process understanding Newborns/children: * Refusal of parental authority to allow newborn/child to participate in study * Follow-up of the child planned in a center not participating in the study * Scheduled absence of parents that could hinder the child's participation in the study;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| HIV-1/HIV-2 Cohort: Scores assessing gross and fine motor skills and social-emotional development at 4 years of age | From enrollment to the end of follow-up at the age of 4 |
| Hepatitis B Cohort: HBV infection at 9 months of age | From enrollment of the child to 9 months of age |
| Hepatitis C Cohort: HCV infection between 18 and 24 months of age | From enrollment of the child to between 18 and 24 months of age |
| Arbovirus Cohort: For each arbovirus, occurrence of one of the following events defining an unfavourable pregnancy outcome, from among: o Maternal/fetal: spontaneous miscarriage, fetal death in utero, medical abortion; o Neonatal: neonatal death | From enrollment up to 28 days of newborn's life |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HIV-1/HIV-2 cohort : Social determinants in children born to mothers living with HIV-1/HIV-2 | From enrollment of the children to the age of 7 years old | Social determinants will be collected with the social deprivation during pregnancy index (SDI). The contribution of social determinants will be assessed on the health and development indicators at 4 and 7 years old |
| HIV-1/HIV-2 cohort : Post-natal antiretroviral prophylaxis in children born to mothers living with HIV-1/HIV-2 | From enrollement of children to the age of 2 years old | — |
| HIV-1/HIV-2 Cohort: Obstetrical pathologies, hospitalizations and adverse pregnancy outcomes in pregnant women living with HIV-1/HIV-2 | From enrollment of pregnant women to delivery | — |
| HIV-1/HIV-2 Cohort: Social determinants in pregnant women living with HIV-1/HIV-2 | From enrollment of pregnant women up to the children's 7 years old | Social determinants will be collected using the SDI and the augmented PRECAR score. |
| HCV Cohort: HCV antiviral treatment during pregnancy | From enrollment of pregnant women to delivery | — |
| HIV-1/HIV-2 Cohort:Therapeutic sequences,viral load and CD4 count during pregnancy and at delivery; clinical and biological tolerance of treatments;plasma ARV assays;ARV resistance genotypes performed in routine in pregnant women living with HIV-1/HIV-2 | From enrollment of pregnant women to delivery | — |
| HIV-1/HIV-2 Cohort: Quality of life in pregnant women living with HIV-1/HIV-2 | Delivery stay | Quality of life will be assessed by the WHOQOL-BREF during the delivery stay |
| HIV-1/HIV-2 Cohort: Adherence of women in pregnant women living with HIV-1/HIV-2 | Delivery stay | Adherence of women will be assessed through HIV-related literacy with the FCCHL (Functional, Communicative and Critical Health Literacy scale) during the delivery stay. |
| HIV-1/HIV-2 Cohort: Experienced discrimination and care-giver interactions in pregnant women living with HIV-1/HIV-2 | During the delivery stay and during the telephone visit at child's 4 years old | — |
| HIV-1/HIV-2 Cohort: Sharing of virological status in pregnant women living with HIV-1/HIV-2 | During the delivery stay and during the telephone visit at child's 4 years of age | — |
| HIV-1/HIV-2 Cohort: Presence of anxiety-depressive symptoms in pregnant women living with HIV-1/HIV-2 | Delivery stay | Presence of anxiety-depressive symptoms using the EPDS questionnaire |
| HIV-1/HIV-2 Cohort: Non-optimal access to care during pregnancy; comparison of care consumption with HAS recommendations for pregnancy monitoring | From enrollment of pregnant women to delivery | — |
| HIV-1/HIV-2 Cohort: Breast-feeding practices: in the event of breast-feeding | During the breast-feeding period, up to 24 months after delivery | — |
| HIV-1/HIV-2 Cohort: Measurement of drug concentration in plasma in pregnant women treated with certains targeted drugs | From enrollment of pregnant women to delivery | Targeted drugs are: tenofovir alafenamide, etravirine, doravirine, rilpivirine, bictegravir,dolutegravir, cabotegravir, raltegravir, fostemsavir, lenacapavir, any new ARV not yet marketed in 2023 (islatravir, ibalizumab...) |
| HIV-1/HIV-2 Cohort: Monthly measurements of ARV drug concentration in breast milk (if breast-feeding) | During the breast-feeding | — |
| HIV-1/HIV-2 Cohort: In breast-fed newborns, monthly measurements of plasma concentrations of the same ARVs | During the breast-feeding | — |
| HBV Cohort: Delay between diagnosis of HBV infection and date of onset of pregnancy in HBV-infected pregnant women | From enrollment of pregnant women to delivery | — |
| HBV Cohort: Therapeutic prophylaxis practices in HBV-infected pregnant women | From enrollment of pregnant women to delivery | — |
| HBV Cohort: HBV viral load during obstetrical follow-up and at delivery in HBV-infected pregnant women | From enrollment of pregnant women to delivery | — |
| HBV Cohort: Plasma concentrations of HBV antivirals in treated women | At inclusion and at delivery | — |
| HBV Cohort: Maternal morbidity and mortality | From enrollment of pregnant women to delivery | — |
| HBV Cohort: Initiation or resumption of follow-up by a hepatologist of postpartum HBV-infected women | During the post-partum period, up to 2 months after delivery | — |
| HBV Cohort: Screening practices among close contacts of infected women | From enrollment of pregnant women to delivery | — |
| HBV Cohort: Seroprevalence of HDV in HBV-infected pregnant women | From enrollment of pregnant women to delivery | — |
| HBV Cohort: Active HDV infection (in women with positive HDV serology) | From enrollment of pregnant women to delivery | — |
| HBV Cohort: Liver disease at fibrosis, cirrhosis and/or hepatic carcinoma stage during pregnancy in HBV-infected pregnant women (+/- HDV) | From enrollment of pregnant women to delivery | — |
| HBV Cohort: Social determinants in HBV-infected pregnant women | At inclusion and during the delivery stay | Social determinants will be assessed by the social deprivation during pregnancy index (SDI) and the augmented PRECAR score |
| HBV Cohort: Adherence of HBV-infected pregnant women | During the delivery stay | — |
| HBV Cohort: Presence of anxiety-depressive symptoms in women living with HBV | During the delivery stay | — |
| HBV Cohort: Experienced discrimination and care-giver interactions in HBV-infected pregnant women | During the delivery stay | — |
| HBV Cohort: Non-optimal access to healthcare during pregnancy; study of healthcare consumption in relation to HAS recommendations for pregnancy monitoring | From enrollment of pregnant women to delivery | — |
| HBV Cohort: Post-natal serovaccination of children and schedule | From enrollement of children to the age of 2 years old | — |
| HBV Cohort: HBV infection in children born to HBV-infected mothers | From birth to the age of 2 years old | — |
| HBV Cohort: Factors associated to mother-to-child transmission of HBV (maternal antiviral prophylaxis, neonatal serotherapy, vaccination, hepatitis B profile, level of viral replication, social determinants) | During the follow-up period, up to 2 months after delivery | — |
| HBV Cohort: Timing of mother-to-child transmission in HBV-infected children | 9 months after delivery | — |
| HBV Cohort: Hospitalizations and chronic illnesses | From enrollement of children to the age of 7 years old | — |
| HBV Cohort: HDV infection in children born to mother co-infected with HBV/HDV | 9 months after delivery | — |
| HCV Cohort: Socio-demographic profile of infected women | At inclusion | — |
| HCV Cohort: Maternal morbidity and mortality events in HCV-infected pregnant women | From enrollment of pregnant women to delivery | — |
| HCV Cohort: Management practices during pregnancy (treatment, date of initiation, dosage, duration of treatment, date of end of treatment and reason for discontinuation, if applicable); and post-partum (follow-up by an hepatologist) | From enrollment of pregnant women up to 2 months after delivery | — |
| HCV Cohort: Liver disease at fibrosis, cirrhosis and/or hepatocellular carcinoma stage during pregnancy in HCV-infected women | From enrollment of pregnant women to delivery | — |
| HCV Cohort: Initiation or resumption of post-partum follow-up by a hepatologist for women infected with HCV during pregnancy | During the post-partum period, up to 2 months after delivery | — |
| HCV Cohort: Presence of anxiety-depressive symptoms in women living with HCV | During the delivery stay | — |
| HCV Cohort: Active HCV infection in children born to HCV-infected mothers | At 3 months of age | — |
| HCV Cohort: Diagnostic performance of PCR at 3 months between 18 and 24 months of age | At child's 3months and 18-24 months | — |
| HCV Cohort: Spontaneous cure rate at 9 months and between 18 and 24 months of age | At child's 9 months and 18-24 months | — |
| HCV Cohort: Morbidity criteria in the first 7 years of life | From enrollement of children to the age of 7 years old | — |
| Arbovirosis Cohort: Occurrence of obstetrical pathologies, hospitalisations/stays in intensive care during pregnancy, other unfavourable pregnancy outcomes (premature delivery, etc.), or maternal death | From enrollment of pregnant women to delivery | — |
| Arbovirosis Cohort: Demographic, clinical, biological, virological, immunological and genetic factors associated with, or predictive of, the occurrence of a severe course (shock, haemorrhage, visceral failure, death) of arbovirosis during pregnancy | From enrollment of pregnant women to delivery | — |
| Arbovirosis Cohort: Quality of life in pregnant women with symptomatic, virologically confirmed arbovirus infection | At day 1 and between day7-10 post-infection and during the delivery stay | Quality of life will be assessed by the EuroQol-5 Dimension (EQ5D) and by the WHOQOL-BREF |
| Arbovirosis Cohort: Effect of social determinants on the occurrence of obstetrical pathologies, hospitalisations/stays in intensive care unit during pregnancy, other adverse pregnancy outcomes (premature delivery, etc.) or maternal death | At inclusion, at 4 years post-delivery and during the delivery stay | — |
| Arbovirosis Cohort: Detection of viral RNA by qualitative or semi-quantitative PCR in the placenta and amniotic fluid | At delivery | — |
| Arbovirosis Cohort: Detection of viral RNA by qualitative or semi-quantitative PCR in breast milk in breast-feeding women with history of symptomatic, virologically confirmed arbovirus infection during pregnancy, | At day 1, day 7 and day 30 after delivery | — |
| Arbovirosis Cohort: Prevalence of major congenital malformations; Arbovirus infection; Autism spectrum disorders;Confirmed arbovirus infection/hospitalization related to maternal/infant arbovirosis;Disorders; hospitalizations, chronic illness, death | From enrollement of children to the age of 7 years old | The prevalence will be estimated for: * Major congenital malformations according to the EUROCAT classification diagnosed in the first 3 months of life; * Arbovirus infection confirmed at birth defined by detection of arbovirus by PCR in blood at birth; * Autism spectrum disorders at 18-24 months of age, evaluated by using the Modified Checklist Autism for Toddlers (M-CHAT); * Confirmed arbovirus infection and/or hospitalization related to maternal and/or infant arbovirosis during the first 24 months of life; * Disorders of (i) the gross and fine motor skills, assessed by using the "little Developmental Coordination Disorder Questionnaire-French European" (little DCDQ-FE) and (ii) the socioemotional development assessed by using the "Strengths \& Difficulties questionnaire" (SDQ) at 4 years of age. * Hospitalizations, late-onset congenital malformations (cardiac or cerebral), chronic illnesses and death occurring during the child's first 7 years of life, identified using data from PMSI |
| Arbovirosis Cohort: Clinical progression of the disease in infected children diagnosed with an arbovirus infection at birth, | First 30 days of children life | Clinical progression of the disease will be characterised by symptoms, their severity and duration |
| Arbovirosis Cohort: Plasma viremia progression in infected children diagnosed with an arbovirus infection at birth | At day 1, day 7 and day 30 of life | Plasma viremia progression will be measured by specific RT-PCR |
| Arbovirosis Cohort: Presence of total and neutralising antibodies against the arbovirus in the blood, in infected children diagnosed with an arbovirus infection at birth | At day 1, day 7 and day 30 of life | — |
| Arbovirosis Cohort: Presence of total and neutralising antibodies against the arbovirus in the blood in breast-fed children not infected at birth | At day 1, day 7 and day 30 of life | — |
| HIV-1/HIV-2 Cohort: Obstetrical management during pregnancy, including obstetrical follow-up, invasive procedures during pregnancy (trophoblast biopsy, amniocentesis) and decisions concerning the delivery method in pregnant women living with HIV-1/HIV-2 | From enrollment of pregnant women to delivery | — |
| Arbovirosis Cohort: Confirmed arbovirus infection in breast-fed children not infected at birth | During breastfeeding, at day 7 and day 30 of life | Confirmed arbovirus infection will be defined by detection of arbovirus by PCR in blood |
| HCV Cohort: Plasma concentrations of antivirals during pregnancy in women receiving HCV treatment | From enrollment of pregnant women to delivery | — |
| HCV Cohort: Adherence of HCV-infected pregnant women | During the delivery stay | — |
| HIV-1/HIV-2 cohort :The impact of exposure to HIV-1/HIV-2 and antiretroviral treatment in children born to mothers living with HIV-1/HIV-2 | From enrollement of children to the age of 7 years old | The impact of exposure to HIV-1/HIV-2 and antiretroviral treatment will be assessed on: * Presence of major congenital malformations * HIV-1/HIV-2 infection in children * Autism spectrum disorders between 18 and 24 months old, as measured by the Modified Checklist Autism for Toddlers (M-CHAT) * Growth parameters (weight, height, head circumference) from birth to 2 years old; * Learning and coordination disorders, hyperactivity (ADHD), autistic traits assessed at 7 years old by the "Autism-Tics, ADHD and other Comorbidities" (A-TAC) questionnaire; * Hospitalizations, late-onset congenital malformations (cardiac or cerebral) and chronic illnesses occurring during the child's first 7 years of life, identified using data from:PMSI, DCIR * Death at age 7 |
Countries
France
Outcome results
None listed