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1.
AIDS Care ; : 1-8, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38500011

ABSTRACT

Despite success in managing HIV during pregnancy, challenges remain around sustained adherence with antiretroviral therapy (ART), and the suboptimal viral load (VL) suppression during the postpartum period. The objective of this study was to compare VL levels at delivery and during the postpartum period and assess factors associated with lack of viral suppression during the postpartum period in Canada. We combined data from two Canadian prospective cohorts, which included 286 HIV-positive women (352 pregnancies) who delivered between 2012 and 2020. Delivery VL, postpartum VL, and potential factors associated with an undetectable VL (<50 copies/mL), 2-18 weeks after delivery were assessed. To account for the correlation between multiple pregnancies from the same woman, generalized estimating equations were used to assess bivariate associations. Ninety-nine per cent of pregnant women were on ART during pregnancy compared to 93% during the postpartum period. Of those with available VL results (n = 214 pregnancies), 94% of women achieved an undetectable VL at delivery compared to 87% during the postpartum period. The postpartum period is a challenging time for ART use and VL control. Qualitative studies are needed to better understand these challenges and guide us in designing adequate interventions.

2.
Dev Neurosci ; 45(4): 210-222, 2023.
Article in English | MEDLINE | ID: mdl-36822171

ABSTRACT

Macrocephaly has been associated with neurodevelopmental disorders; however, it has been mainly studied in the context of pathological or high-risk populations and little is known about its impact, as an isolated trait, on brain development in general population. Electroencephalographic (EEG) power spectral density (PSD) and signal complexity have shown to be sensitive to neurodevelopment and its alterations. We aimed to investigate the impact of macrocephaly, as an isolated trait, on EEG signal as measured by PSD and multiscale entropy during the first year of life. We recorded high-density EEG resting-state activity of 74 healthy full-term infants, 50 control (26 girls), and 24 macrocephalic (12 girls) aged between 3 and 11 months. We used linear regression models to assess group and age effects on EEG PSD and signal complexity. Sex and brain volume measures, obtained via a 3D transfontanellar ultrasound, were also included into the models to evaluate their contribution. Our results showed lower PSD of the low alpha (8-10 Hz) frequency band and lower complexity in the macrocephalic group compared to the control group. In addition, we found an increase in low alpha (8.5-10 Hz) PSD and in the complexity index with age. These findings suggest that macrocephaly as an isolated trait has a significant impact on brain activity during the first year of life.


Subject(s)
Electroencephalography , Megalencephaly , Female , Humans , Infant , Entropy , Electroencephalography/methods , Brain
3.
Int J STD AIDS ; 34(3): 175-182, 2023 03.
Article in English | MEDLINE | ID: mdl-36529684

ABSTRACT

BACKGROUND: Limited data is available on raltegravir (RAL) pharmacokinetics during pregnancy and the value of therapeutic drug monitoring (TDM) in pregnancy is unknown. This study aims to describe RAL trough plasma concentrations (Ctrough) during pregnancy and review the impact of RAL TDM on outcomes. METHODS: Women from the prospective mother-infant HIV cohort of Mother and Children's Infectious Diseases Center who received RAL during their pregnancy between 2011-2020 were included. TDM reports were reviewed and Ctrough values estimated when possible, using historical RAL half-lives. RESULTS: We included 76 pregnant women of which 47 underwent TDM. We observed a significant association between virological response and Ctrough (p-value .034) with an increase of 0.1 mg/L corresponding to a 2.96 reduction in the risk of having a detectable viral load. The results indicated that in pregnant women a RAL Ctrough threshold of 0.04 mg/L has a higher specificity (75%) as compared to our current Ctrough target value of 0.02 mg/L (25%) and an acceptable sensitivity (77%). No significant differences were observed between Ctrough at each trimester. When comparing pregnancies with and without TDM, no statistically significant differences were observed in the virologic response during pregnancy and at delivery, or with the need for triple antiretroviral prophylaxis in newborns. CONCLUSIONS: An association between RAL Ctrough and viral load was observed and achieving a RAL Ctrough of 0.04 mg/L or greater is a predictor of virologic response in pregnant women. The impact of TDM in pregnancy, however, could not be demonstrated.


Subject(s)
Anti-HIV Agents , HIV Infections , Pregnancy Complications, Infectious , Child , Female , Humans , Infant, Newborn , Pregnancy , Raltegravir Potassium/therapeutic use , HIV Infections/drug therapy , Prospective Studies , Drug Monitoring , Pregnancy Complications, Infectious/drug therapy , Viral Load , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/pharmacokinetics
4.
Front Hum Neurosci ; 16: 928543, 2022.
Article in English | MEDLINE | ID: mdl-35927999

ABSTRACT

Macrocephaly is present in about 2-5% of the general population. It can be found as an isolated benign trait or as part of a syndromic condition. Brain overgrowth has been associated with neurodevelopmental disorders such as autism during the first year of life, however, evidence remains inconclusive. Furthermore, most of the studies have involved pathological or high-risk populations, but little is known about the effects of brain overgrowth on neurodevelopment in otherwise neurotypical infants. We investigated the impact of brain overgrowth on basic perceptual learning processes (repetition effects and change detection response) during the first year of life. We recorded high density electroencephalograms (EEG) in 116 full-term healthy infants aged between 3 and 11 months, 35 macrocephalic (14 girls) and 81 normocephalic (39 girls) classified according to the WHO head circumference norms. We used an adapted oddball paradigm, time-frequency analyses, and auditory event-related brain potentials (ERPs) to investigate differences between groups. We show that brain overgrowth has a significant impact on repetition effects and change detection response in the 10-20 Hz frequency band, and in N450 latency, suggesting that these correlates of sensorial learning processes are sensitive to brain overgrowth during the first year of life.

5.
Int J STD AIDS ; 32(7): 654-661, 2021 06.
Article in English | MEDLINE | ID: mdl-33612017

ABSTRACT

We wished to evaluate the efficacy, safety, and acceptability of cabergoline for lactation inhibition in women who live with HIV. In this multicenter prospective observational study, cabergoline was offered as a single oral dose of 1 mg within the first 48 h postpartum. Women were recruited if they delivered a live infant after 35 weeks of gestational age. Participants filled out a questionnaire regarding symptoms of lactation and cabergoline adverse effects on day 2 and day 14 postpartum. On day 14, they also completed a questionnaire about their satisfaction with cabergoline treatment. Prolactin serum level was measured on both visits. Among 68 participants, all but one received cabergoline. The overall effectiveness defined by partial or complete success at day 14 was 98.3% (confidence intervals: 89.5-99.9). At day 14, 67.4% of women who received cabergoline had prolactin serum levels <25 mcg/L (threshold necessary for galactopoiesis). Mild nonspecific adverse effects were experienced by 24 (29.9%) women on day 2 and 24 (41.4%) on day 14, and lasted 48 h or less. Overall, 96% of women were satisfied with cabergoline's ability to prevent postpartum lactation symptoms. In conclusion, cabergoline is an effective, well-accepted, and well-tolerated medication for lactation inhibition in WLWH.


Subject(s)
Ergolines , HIV Infections , Cabergoline , Ergolines/therapeutic use , Female , HIV Infections/drug therapy , Humans , Lactation , Prolactin
6.
Eur J Obstet Gynecol Reprod Biol ; 258: 409-413, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33548895

ABSTRACT

OBJECTIVE: To assess the choice and attitude of pregnant women regarding CMV serological screening and CMV prevention behaviors in pregnancy. STUDY DESIGN: In this cross-sectional study, pregnant women were recruited in a single center during routine prenatal screening tests at 11-16 weeks. Participants filled out a questionnaire assessing knowledge about congenital CMV (cCMV) infection, risk perception and willingness to have CMV serological screening as well as their attitude toward CMV prevention behaviors. RESULTS: Among 234 pregnant women, 74.4 % (95 % confidence interval: 68.8-80.0 %) wanted CMV serological screening in pregnancy. The factors significantly associated with the desire for screening were perceived risk and perceived severity of cCMV. An informed choice regarding CMV screening (value-consistent, based on good knowledge and deliberated) was performed by 54 % of women who chose the screening and 30 % of women who declined the screening (p = 0.039). The median scores regarding attitudes toward CMV prevention behaviors were 3.7/5 for avoiding sharing behaviors and 4.0/5 for not kissing a child on the lips. CONCLUSION: The majority of pregnant women want to have CMV serological screening once informed about congenital CMV infection. New tools need to be developed to allow for informed choice regarding CMV serological screening in pregnancy.


Subject(s)
Cytomegalovirus Infections , Pregnancy Complications, Infectious , Child , Cross-Sectional Studies , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/prevention & control , Female , Humans , Mass Screening , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/prevention & control , Pregnant Women
7.
J Matern Fetal Neonatal Med ; 34(5): 683-689, 2021 Mar.
Article in English | MEDLINE | ID: mdl-31092068

ABSTRACT

Objective: To evaluate the association of antiretroviral therapy (ART) type and duration of exposure with early placental function using biomarkers of aneuploidy screening.Study design: Three hundred thirty-eight pregnant women living with HIV were enrolled in two Canadian centers. Multiple linear regressions were performed adjusting for confounding factors (race, age, gestational age, body mass index, parity, smoking, and fetal sex).Results: Women receiving ART had significantly increased second trimester alpha-fetoprotein (AFP) levels (ß = 0.147, 95% CI = [0.067-0.227] for protease inhibitor-based ART and ß = 0.176, 95% CI = [0.080-0.272] for ART without protease inhibitor) compared to women who received no treatment. However, there was no significant association between ART type and the levels of free ß-human chorionic gonadotrophin (ß-hCG), pregnancy-associated plasma protein-A (first trimester), unconjugated estriol, total hCG, and inhibin A (second trimester). No significant association was shown between biomarker levels and duration of ART exposure.Conclusion: Early placental function does not appear to be significantly affected by ART, except for AFP.


Subject(s)
HIV Infections , Placenta , Biomarkers , Canada , Chorionic Gonadotropin, beta Subunit, Human , Cohort Studies , Female , HIV Infections/drug therapy , Humans , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, Second , Pregnancy-Associated Plasma Protein-A , Prenatal Diagnosis , alpha-Fetoproteins
8.
J Perinat Med ; 48(3): 234-241, 2020 Mar 26.
Article in English | MEDLINE | ID: mdl-32031981

ABSTRACT

Background Outcome of congenital cytomegalovirus (cCMV) infection in the absence of routine CMV screening and third-trimester scan in North America is scarcely documented. The aim of this study was to assess the severe outcomes related to cCMV according to the indication for screening. Methods This was a retrospective study of 84 mother-child pairs followed for cCMV between 2003 and 2017 at CHU Sainte-Justine in Montreal, Canada. Prenatal ultrasound, neonatal symptoms, neuroimaging and severe outcomes (cerebral palsy, severe cognitive impairment, bilateral hearing loss or neonatal death) were reviewed. Results Among 38 cases with abnormal prenatal ultrasound, 41.9% of live-born infants developed severe outcomes. Sixteen (42.1%) were detected in the third trimester. Among 16 cases diagnosed prenatally because of maternal history, all had normal prenatal ultrasound, and none developed severe outcomes. Among cases diagnosed postnatally because of neonatal symptoms, 25% developed severe outcomes. All infants who developed severe outcomes had moderate/severe neonatal symptoms. Conclusion Outcome of cCMV infection varies according to the reason for screening and timing of diagnosis. Any prenatal ultrasound anomaly might indicate a risk of severe outcome, and warrants a detailed ultrasound scan. However, late detection, or postnatal diagnosis, represented more than half of the cases, and awareness of this will help ensuring optimal management.


Subject(s)
Cytomegalovirus Infections/congenital , Neurodevelopmental Disorders/virology , Adult , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/diagnostic imaging , Cytomegalovirus Infections/epidemiology , Female , Humans , Infant, Newborn , Neuroimaging , Pregnancy , Quebec/epidemiology , Retrospective Studies , Ultrasonography, Prenatal , Young Adult
9.
J Obstet Gynaecol Can ; 42(4): 446-452, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31882286

ABSTRACT

OBJECTIVE: Little is known about pregnancy outcomes among women who have acquired human immunodeficiency virus (HIV) through perinatal infection and survived into adulthood. The objectives of this study were to describe pregnancy outcomes among women with perinatal HIV infection (PHIV) in Canada and to identify potential challenges in the prevention of perinatal HIV transmission in this population. METHODS: A retrospective review of all pregnancies among women with PHIV who were previously followed as children at two tertiary care centres in Montréal, Québec, was conducted. Data were extracted from pediatric and obstetrical records. RESULTS: There were 21 pregnancies among 11 women, and 18 of these pregnancies were unintentional. Mean age at first pregnancy was 19.5 years (range 15-29 years). At the first prenatal visit, 79% had a detectable viral load, 36% were immunosuppressed (CD4 T cell count <200 mm3), and only 36% were receiving antiretroviral therapy (ART). At the time of delivery, although all were prescribed ART, 50% of these women still had a detectable viral load, and 36% remained immunosuppressed. All of the women harboured mutations conferring drug resistance to zidovudine and lamivudine, and the majority (73%) were also resistant to nevirapine. None of the infants were HIV infected, although all received prophylaxis with agents to which their mother's virus was resistant. CONCLUSION: Unplanned pregnancies, difficulties with adherence to ART, and drug resistance were identified challenges in the management of pregnancies among women with PHIV. This study highlights a gap in the reproductive counselling of adolescents with PHIV and the need for close follow-up and adherence support during pregnancy in this population.


Subject(s)
Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , HIV Infections/drug therapy , HIV Long-Term Survivors/psychology , Pregnancy Complications, Infectious/drug therapy , Pregnancy, Unplanned , Adolescent , Adult , Canada/epidemiology , Female , HIV Infections/epidemiology , HIV Infections/transmission , HIV Long-Term Survivors/statistics & numerical data , Humans , Infant , Infectious Disease Transmission, Vertical/prevention & control , Medication Adherence/psychology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Quebec/epidemiology , Retrospective Studies , Viral Load , Young Adult , Zidovudine/therapeutic use
10.
BMC Pregnancy Childbirth ; 19(1): 482, 2019 Dec 09.
Article in English | MEDLINE | ID: mdl-31815612

ABSTRACT

BACKGROUND: Early antiretroviral therapy (ART) during pregnancy has dramatically reduced the risk of perinatal HIV transmission. However, studies have shown an association between premature delivery and the use of ART during pregnancy (particularly protease inhibitor (PI)-based therapies), which could be explained by placental dysfunction. The objective of this study was to evaluate the association of ART (class, duration of exposure and time of initiation) with placental function by using angiogenic factors placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) as biomarkers. METHODS: Clinical and biological data from 159 pregnant women living with HIV were analyzed. Levels of each biomarker were measured in the first and second trimester of pregnancy. After logarithmic transformation, we compared these using generalized estimating equations according to (a) the type of ART; (b) the duration of exposure to ART; and (c) the time of initiation of ART. RESULTS: After adjusting for variables such as ethnicity, maternal age, gestational age, body mass index, parity, smoking status, and sex of the fetus, we found no significant association between the class of ART (PI-based or not) and serum concentrations of PlGF or sFlt-1. Furthermore, no significant association was found between biomarker levels and the duration of ART exposure or the timing of ART initiation (pre- or post-conception). CONCLUSIONS: This study suggests that first and second trimester angiogenic factor levels are not significantly associated with ART, regardless of the duration or type (with or without PI). These observations seem reassuring when considering the use of ART during early pregnancy.


Subject(s)
Anti-Retroviral Agents/adverse effects , HIV Infections/drug therapy , Placenta Growth Factor/blood , Pregnancy Complications, Infectious/blood , Vascular Endothelial Growth Factor Receptor-1/blood , Adult , Biomarkers/blood , Cohort Studies , Female , HIV Infections/transmission , Humans , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/virology , Pregnancy Trimesters/blood , Premature Birth/chemically induced
11.
J Infect Dis ; 219(5): 760-771, 2019 02 15.
Article in English | MEDLINE | ID: mdl-30365007

ABSTRACT

BACKGROUND: Vertical transmission is the major cause of pediatric hepatitis C virus (HCV) infection. The objective of this study was to better understand HCV pathogenesis in pregnant women and provide insights into risk factors and mechanisms involved in vertical transmission. METHODS: Evolutionary dynamics of HCV variant spectra and HCV-specific neutralizing antibody responses were examined using high-throughput sequencing and pseudoparticle-based assays in pregnant women monoinfected with HCV (n = 17) or coinfected with HCV and human immunodeficiency virus (HIV)-1 (n = 15). RESULTS: Overall, statistically significant associations were found between HCV quasispecies diversity, selective pressure exerted on the HCV E2 envelope protein, and neutralizing activity of maternal immunoglobulins. Women with low quasispecies diversity displayed significantly higher mean aspartate aminotransferase and alanine aminotransferase levels throughout pregnancy, but this difference was restricted to monoinfected participants. Low quasispecies diversity and inefficient neutralizing activity were also significantly associated with vertical transmission, but only in the monoinfected group. CONCLUSIONS: These results indicate that maternal neutralizing antibody responses play a role in the prevention of vertical HCV transmission, but not in presence of HIV-1 coinfection, and suggest that the mechanism of vertical transmission may be different between monoinfected and coinfected women. These findings could inform management strategies for the prevention of vertical HCV transmission.


Subject(s)
Genetic Variation , Hepacivirus/classification , Hepatitis C/transmission , Hepatitis C/virology , Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious/virology , Quasispecies , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Female , HIV Infections/complications , Hepacivirus/genetics , High-Throughput Nucleotide Sequencing , Humans , Infant , Infant, Newborn , Male , Pregnancy , Risk Factors , Young Adult
12.
Phys Med Biol ; 63(22): 225012, 2018 11 12.
Article in English | MEDLINE | ID: mdl-30418939

ABSTRACT

For newborns and neonates, ultrasound (US) is the most common imaging modality used for examinations due to its accessibility and ease of use. However, precise volume measurements remain limited in 2D, while MRI in newborns is typically avoided because of immobilization issues which may require sedation. The objective of this study is to assess and validate the lateral ventricular and total brain volumes obtained with an automatic segmentation method using cerebral trans-fontanelle 3D US. Infants aged between 2 and 8.5 months old were recruited, with both MRI and 3D US acquired on the same day was used to validate ventricular and brain volume measurements in comparison to MRI. Lateral ventricles were segmented on both the US (manually and with a proposed automatic fusion-based approach) and MRI, while brain volumes were estimated with an automatic segmentation method. Volumetric 3D US measurements were then evaluated with respect to age distribution. For the comparison between MRI and 3D US, strong inter-class correlations (ICC) were found for the ventricle volumes (manual: 5.9% ± 2.5% difference (ICC = 0.99); automatic: 6.0% ± 2.6% difference (ICC = 0.98)), as well as the total brain size, with a 3.0% ± 1.3% difference (ICC = 0.98). There was no statistically significant difference based on t-test and f-test for the lateral ventricles volume (t-test: p = 0.542) and (f-test: p = 0.738) and for the total brain volume (t-test: p = 0.412) and (f-test: p = 0.685) between MRI and 3D US. This study demonstrates that 3D US can be used to automatically assess lateral ventricular and total brain volumes with no significant difference to the MRI acquisitions. The highest correlations were obtained for infants under 8 months when the fontanelle is open.


Subject(s)
Imaging, Three-Dimensional/methods , Lateral Ventricles/diagnostic imaging , Ultrasonography/methods , Female , Humans , Imaging, Three-Dimensional/standards , Infant , Infant, Newborn , Lateral Ventricles/growth & development , Male , Reproducibility of Results , Ultrasonography/standards
13.
Clin Infect Dis ; 67(7): 1063-1071, 2018 09 14.
Article in English | MEDLINE | ID: mdl-30010773

ABSTRACT

Background: Immunization of pregnant women with tetanus-diphtheria-acellular pertussis vaccine (Tdap) provides protection against pertussis to the newborn infant. Methods: In a randomized, controlled, observer-blind, multicenter clinical trial, we measured the safety and immunogenicity of Tdap during pregnancy and the effect on the infant's immune response to primary vaccination at 2, 4, and 6 months and booster vaccination at 12 months of age. A total of 273 women received either Tdap or tetanus-diphtheria (Td) vaccine in the third trimester and provided information for the safety analysis and samples for the immunogenicity analyses; 261 infants provided serum for the immunogenicity analyses. Results: Rates of adverse events were similar in both groups. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM. Conclusions: This study demonstrated that Tdap during pregnancy results in higher levels of antibodies early in infancy but lower levels after the primary vaccine series. Clinical Trials Registration: NCT00553228.


Subject(s)
Antibodies, Bacterial/blood , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Diphtheria-Tetanus-acellular Pertussis Vaccines/immunology , Adult , Diphtheria/prevention & control , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Diphtheria-Tetanus-Pertussis Vaccine/adverse effects , Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Diphtheria-Tetanus-acellular Pertussis Vaccines/adverse effects , Female , Humans , Infant, Newborn , Pregnancy , Tetanus/prevention & control , Whooping Cough/prevention & control , Young Adult
14.
J Obstet Gynaecol Can ; 40(11): 1409-1416, 2018 11.
Article in English | MEDLINE | ID: mdl-29937136

ABSTRACT

OBJECTIVE: There is no consensus on the use of cytomegalovirus (CMV)-specific hyperimmunoglobulins (CSHIGs) for suspected congenital CMV infections during pregnancy, but this therapy is currently used in some countries. The objectives of this study were to describe tolerability and pregnancy outcome following treatment with monthly intravenous CSHIG and compare rates of positive PCR and postnatal symptoms according to whether CSHIGs were given or not. METHODS: This retrospective cohort study included all pregnant women who were diagnosed with primary CMV infection or congenital CMV infection at the Centre Hospitalier Universitaire Sainte-Justine (Montreal, QC) between 2005 and 2016. CSHIG was discussed with pregnant women who received positive CMV PCR results from amniotic fluid or if ultrasound anomalies suggested congenital infection and there was serologic evidence of maternal primary infection (therapeutic group). CSHIG was also offered as prophylaxis in pregnant women without fetal ultrasound anomalies but with evidence of maternal primary infection, when amniocentesis either had negative results or was not performed (prophylactic group). A matched analysis was performed to control for timing of maternal infection, amniocentesis, and type and timing of ultrasound anomaly. RESULTS: Sixteen women received CSHIG, and 55 had no CMV-specific treatment. CSHIG treatment was well-tolerated. In bivariate analyses, the risk of congenital CMV infection and postnatal symptoms did not significantly decrease with CSHIG treatment, in both the therapeutic and the prophylactic groups. After matching, there was still no difference in outcomes between CSHIG-treated and untreated women. CONCLUSION: The effectiveness of CSHIG in preventing congenital CMV infection and its clinical manifestations could not be demonstrated.


Subject(s)
Antibodies, Viral/therapeutic use , Cytomegalovirus Infections , Immunoglobulins/therapeutic use , Pregnancy Complications, Infectious , Amniocentesis , Antibodies, Viral/adverse effects , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/prevention & control , Female , Humans , Immunoglobulins/adverse effects , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Outcome/epidemiology , Retrospective Studies
15.
Infect Genet Evol ; 62: 141-150, 2018 08.
Article in English | MEDLINE | ID: mdl-29678797

ABSTRACT

Pregnancy is associated with modulations of maternal immunity that contribute to foeto-maternal tolerance. To understand whether and how these alterations impact antiviral immunity, a detailed cross-sectional analysis of selective pressures exerted on HIV-1 envelope amino-acid sequences was performed in a group of pregnant (n = 32) and non-pregnant (n = 44) HIV-infected women in absence of treatment with antiretroviral therapy (ART). Independent of HIV-1 subtype, p-distance, dN and dS were all strongly correlated with one another but were not significantly different in pregnant as compared to non-pregnant patients. Differential levels of selective pressure applied on different Env subdomains displayed similar yet non-identical patterns between the two groups, with pressure applied on C1 being significantly lower in constant regions C1 and C2 than in V1, V2, V3 and C3. To draw a general picture of the selection applied on the envelope and compensate for inter-individual variations, we performed a binomial test on selection frequency data pooled from pregnant and non-pregnant women. This analysis uncovered 42 positions, present in both groups, exhibiting statistically-significant frequency of selection that invariably mapped to the surface of the Env protein, with the great majority located within epitopes recognized by Env-specific antibodies or sites associated with the development of cross-reactive neutralizing activity. The median frequency of occurrence of positive selection per site was significantly lower in pregnant versus non-pregnant women. Furthermore, examination of the distribution of positively selected sites using a hypergeometric test revealed that only 2 positions (D137 and S142) significantly differed between the 2 groups. Taken together, these result indicate that pregnancy is associated with subtle yet distinctive changes in selective pressures exerted on the HIV-1 Env protein that are compatible with transient modulations of maternal immunity.


Subject(s)
HIV Infections/virology , HIV-1/genetics , Pregnancy Complications, Infectious/virology , env Gene Products, Human Immunodeficiency Virus/genetics , Evolution, Molecular , Female , Humans , Models, Molecular , Pregnancy , Protein Conformation , Selection, Genetic
16.
J Virol ; 91(23)2017 12 01.
Article in English | MEDLINE | ID: mdl-28931691

ABSTRACT

Hepatitis C virus (HCV) can be transmitted from mother to child during pregnancy and childbirth. However, the timing and precise biological mechanisms that are involved in this process are incompletely understood, as are the determinants that influence transmission of particular HCV variants. Here we report results of a longitudinal assessment of HCV quasispecies diversity and composition in 5 cases of vertical HCV transmission, including 3 women coinfected with human immunodeficiency virus type 1 (HIV-1). The population structure of HCV variant spectra based on E2 envelope gene sequences (nucleotide positions 1491 to 1787), including hypervariable regions 1 and 2, was characterized using next-generation sequencing and median-joining network analysis. Compatible with a loose transmission bottleneck, larger numbers of shared HCV variants were observed in the presence of maternal coinfection. Coalescent Bayesian Markov chain Monte Carlo simulations revealed median times of transmission between 24.9 weeks and 36.1 weeks of gestation, with some confidence intervals ranging into the 1st trimester, considerably earlier than previously thought. Using recombinant autologous HCV pseudoparticles, differences were uncovered in HCV-specific antibody responses between coinfected mothers and mothers infected with HCV alone, in whom generalized absence of neutralization was observed. Finally, shifts in HCV quasispecies composition were seen in children around 1 year of age, compatible with the disappearance of passively transferred maternal immunoglobulins and/or the development of HCV-specific humoral immunity. Taken together, these results provide insights into the timing, dynamics, and biologic mechanisms involved in vertical HCV transmission and inform preventative strategies.IMPORTANCE Although it is well established that hepatitis C virus (HCV) can be transmitted from mother to child, the manner and the moment at which transmission operates have been the subject of conjecture. By carrying out a detailed examination of viral sequences, we showed that transmission could take place comparatively early in pregnancy. In addition, we showed that when the mother also carried human immunodeficiency virus type 1 (HIV-1), many more HCV variants were shared between her and her child, suggesting that the mechanism and/or the route of transmission of HCV differed in the presence of coinfection with HIV-1. These results could explain why cesarean section is ineffective in preventing vertical HCV transmission and guide the development of interventions to avert pediatric HCV infection.


Subject(s)
Hepacivirus/genetics , Hepatitis C/transmission , Infectious Disease Transmission, Vertical , Adult , Bayes Theorem , Coinfection/virology , Computational Biology , Female , Genetic Variation , HIV Infections/complications , HIV Infections/virology , HIV Seropositivity , HIV-1/genetics , HIV-1/immunology , Hepacivirus/physiology , Hepatitis C/complications , Hepatitis C/immunology , Hepatitis C/virology , Hepatitis C Antibodies/blood , High-Throughput Nucleotide Sequencing , Humans , Immunity, Humoral , Infant , Pregnancy , Pregnancy Complications, Infectious/virology , Quasispecies , Risk Factors , Viral Envelope Proteins/genetics
17.
J Obstet Gynaecol Can ; 39(7): e1-e25, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28625288

ABSTRACT

OBJECTIVE: hepatitis C virus (HCV) is an increasingly important public health problem worldwide. Health care workers providing care to women of childbearing age are uniquely placed in their practices to identify a significant proportion of at-risk patients and to provide appropriate screening and counselling. The primary objective of this guideline is to provide accurate, current information to those offering reproductive care to women living with HCV. This document is also intended to raise awareness of HCV in both the medical and general populations. OPTIONS: the areas of clinical practice considered in formulating this guideline are disease prevention, targeted screening of individuals at risk of contracting HCV, management of identified patients in the context of reproductive care, and the appropriate referral of patients to those with particular expertise. OUTCOMES: implementation of these guidelines should facilitate identification of infected individuals. It should also result in improved physical and mental well-being for patients and their families and reduction in transmission rates. EVIDENCE: the literature between 1966 and 2000, including non- English language publications, was extensively searched utilizing Medline. A multidisciplinary group consisting of experts within the fields of obstetrics and gynaecology, infectious diseases, hepatology, and public health convened in Montreal in February 2000. The working group also included a patient and a representative from the Hepatitis C Society of Canada. The level of evidence for the recommendations has been determined using the criteria described by the Canadian Task Force on Periodic Health Examination. BENEFITS, HARMS AND COSTS: the public health benefits of increased identification of at-risk individuals, diagnosis, treatment, implementation of risk reduction behaviours, and reduced transmission rates, both on an individual and at the community level, are significant. However, it must be remembered that the diagnosis of a chronic disease may have far reaching effects for the individual patient and her family. RECOMMENDATIONS: VALIDATION: references were collected through Medline searches and comparison made to existing current guidelines for assessment of consistency. External reviewers expert in their field were also consulted.


Subject(s)
Hepatitis C , Pregnancy Complications, Infectious , Prenatal Care , Canada , Female , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Hepatitis C/therapy , Humans , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/therapy
20.
BMC Pregnancy Childbirth ; 16: 54, 2016 Mar 15.
Article in English | MEDLINE | ID: mdl-26979058

ABSTRACT

BACKGROUND: Advances in diagnostic and therapeutic modalities for congenital cytomegalovirus (CMV) infection have generated a mounting interest in identifying mothers susceptible to CMV. The objectives of this study were to evaluate the prevalence and socio-demographic determinants of CMV susceptibility and CMV awareness, among pregnant women, in Montreal, Quebec. METHODS: Between April and December 2012, women delivering at Centre Hospitalier Universitaire Sainte Justine were recruited for the study. Stored serum from the first trimester of pregnancy was tested for CMV IgG. Knowledge about CMV and socio-demographic characteristics were collected via standardized questionnaire. RESULTS: Four hundred and ninety one women were enrolled in the study. Overall, 225 mothers (46%) were seronegative for CMV, and 85% (n = 415) were unaware of CMV or the associated risks in pregnancy. Significant risk factors for CMV seronegative status included Canadian vs. foreign born (aOR 6.88, 95% CI 4.33-10.94), and high vs. low family income (aOR 4.68, 95% CI 2.09-10.48). Maternal employment status was the only significant predictor of CMV unawareness, with unemployed mothers at the highest risk (aOR 85.6, 95% CI 17.3-421.3). CONCLUSIONS: Nearly half of pregnant women studied were at risk of primary infection, and yet, the majority was unaware of potential risks associated with CMV. Canadian born mothers and those with a high socioeconomic status were more likely to be CMV seronegative. Increased education about CMV infection, through public health interventions and obstetrician/pediatric counseling, is needed for all pregnant women.


Subject(s)
Cytomegalovirus Infections/epidemiology , Cytomegalovirus , Health Knowledge, Attitudes, Practice , Pregnancy Complications, Infectious/epidemiology , Pregnant Women/psychology , Adolescent , Adult , Cytomegalovirus Infections/psychology , Cytomegalovirus Infections/virology , Female , Humans , Immunoglobulin G/blood , Pregnancy , Pregnancy Complications, Infectious/psychology , Pregnancy Complications, Infectious/virology , Pregnancy Trimester, First/blood , Quebec/epidemiology , Risk Factors , Seroepidemiologic Studies , Young Adult
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