Journal of inborn errors of metabolism and screening, 2023
Screening newborns for genetic and other diseases is one of the most effective ways to improve he... more Screening newborns for genetic and other diseases is one of the most effective ways to improve health and reduce disease in a population. In developed countries, newborn screening has been a cornerstone of public health for decades. In many developing countries, however, newborn screening is still in its infancy. Many countries still lack screening programs. When a program is available, it generally lacks well-defined criteria on which decision-makers can justify the choice of diseases screened for and the methods used. One of the reasons put forward to understand this observation is the fact that little consideration is given by decision-makers to economic evaluations as a pillar of decision-making, as is the case in industrialized countries. This article provides a brief description of the challenges of using economic evaluation of newborn screening in developing countries. This will be illustrated by the example of the national newborn screening program in Vietnam.
Diabetes Research and Clinical Practice, Jun 1, 2018
Gestational diabetes mellitus (GDM) affects between 5 and 10% of all pregnancies in Canada and ca... more Gestational diabetes mellitus (GDM) affects between 5 and 10% of all pregnancies in Canada and can lead to adverse health outcomes in both the mother and fetus. Amino acids (AA) and acylcarnitines (AC) have been identified as early biomarkers of type 2 diabetes but their usefulness in screening for GDM has yet to be demonstrated. We conducted a nested case-control study involving 50 controls and 50 GDM cases diagnosed between the 24th and 28th week of gestation. Heparinized plasma samples were obtained during the first and early second trimester of pregnancy. Case and controls were matched according to date of recruitment, maternal age, gestational age at blood sampling as well as pre-pregnancy body mass index. Eight AA and eight AC were quantified using an ultra-high pressure liquid-chromatography quadrupole time-of-flight mass spectrometry platform. Conditional regression analyses adjusted for matching factors and smoking habits during pregnancy were performed to identify plasma metabolites associated with GDM risk. Odds ratio (OR) and 95% confidence interval (CI) for the prediction of GDM per one standard deviation increase of AA or AC in plasma levels were 0.25 (0.08-0.79) for butyrylcarnitine, 0.31 (0.12-0.79) for glutamic acid, 2.5 (1.2-5.3) for acetylcarnitine, 2.9 (1.3-6.8) for isobutyrylcarnitine and 5.3 (1.7-17.0) for leucine. These five metabolites were selected by stepwise conditional logistic regression to create a predictive model with an OR of 2.7 (1.5-4.9). Whether the identified metabolites can predict the risk of developing GDM requires additional studies in a larger sample of pregnant women.
Bjog: An International Journal Of Obstetrics And Gynaecology, Sep 1, 2014
Objectives: To evaluate the diagnostic value of urine microscopy in addition to dipstick analysis... more Objectives: To evaluate the diagnostic value of urine microscopy in addition to dipstick analysis for urinary tract infection (UTI). Methods: Results of 203 consecutive urine specimens submitted over a two-week period for culture, dipstick analysis and microscopy (done for leukocyte esterase and/or nitrite positive specimens; n = 147) were compared. Positive results were defined as follows: leukocyte esterase≥ trace, WBC count ≥ 5 cells/HPF and for culture ≥ 10 4 CFU/mL. Sensitivities and specificities of dipstick and microscopy were calculated against culture. Pre-test probability was based on a prevalence of UTI of 23%. Results: Conclusions: The addition of subsequent microscopic testing is most useful when used in cases in which the esterase alone is positive. In our setting, this occurs in 69% of submitted specimens. Application to different settings of practice with different pre-test probabilities may improve accuracy of diagnosis of urinary tract infection.
American Journal of Obstetrics and Gynecology, 2017
cervical ripening or pitocin. Results were also examined by gestational age (GA) at the initiatio... more cervical ripening or pitocin. Results were also examined by gestational age (GA) at the initiation of delivery: 24-28 vs. 29-32 weeks. RESULTS: 471 pregnancies were analyzed; 200 (42%) had a pre-labor CD and 271 had IOL. The frequency of the MC (10.2% vs 21.1%) was significantly lower with IOL (aOR 0.46[0.24-0.88])(Table 2). The NC rates were not significantly different. The median duration of IOL was 13.9 hrs and the successful VD rate was 53%. VD success rate was lower at 24-28 weeks compared to 29-32 weeks (adjusted p¼0.01) (Table 1). Factors associated with an increased rate of VD were epidural (aOR 5.3 [2.6-11.1]), prior delivery (aOR 4.6 [2.2-9.4]), and Hispanic ethnicity (aOR 3.0 [1.0-8.5]); SGA infants were associated with a decreased rate of VD (aOR 0.3 [0.1-0.7]). CONCLUSION: In women with PAH requiring early preterm delivery, IOL is associated with a significantly lower risk of maternal but not neonatal morbidity compared with pre-labor CD. About half of women who undergo IOL have a successful VD and a median duration of IOL of 13.9 hours.
As per the Ministry of Health's mandate, newborn screening (NBS) for hemoglobinopathies started o... more As per the Ministry of Health's mandate, newborn screening (NBS) for hemoglobinopathies started on November 4th 2013 in Quebec, initially for the Greater Montreal area. The NBS laboratory is equipped with two high-performance liquid chromatography (HPLC) instruments for 1st tier testing, and abnormal results (2nd tier) are repeated using capillary electrophoresis (CE). To our knowledge, we are the first in America to implement a HPLC-CE design for newborn screening. Objectives: To illustrate the complementarity of HPLC and CE in the interpretation of results for hemoglobinopathy newborn screening. Methods: Newborn blood specimens from filter paper dried spots were first analyzed with the Biorad VARIANT™nbs System. Abnormal or indeterminate results were repeated using Sebia Capillarys 2 Neonatal Fast. Results: Analytical correlation between these technologies showed excellent results (n = 56). Three months after implementation, 18621 samples have been tested using HPLC, while 450 samples were retested using CE as 2nd tier. We identified 5 samples (0.03% of all samples, 1.1% of 2nd tier tests) for which initial interpretation by instruments software was not similar and needed further comparison of spectra to identify the appropriate hemoglobin variant. Conclusions: Despite a good correlation, we observed rare discrepancies in hemoglobin variant calls between both technologies, which have complementary strengths and limitations. Implementation of NBS using both HPLC and CE by the Quebec Newborn Blood Screening Program should help to improve sensitivity and specificity, and thus the overall performance of newborn screening for hemoglobinopathies.
Background: By 2050, an estimated 152 million people will be living with dementia. Prospective st... more Background: By 2050, an estimated 152 million people will be living with dementia. Prospective studies suggest that exposure to psychosocial stressors at work could be associated with a higher risk of mild cognitive impairment or dementia, but the evidence is still not clear. Method: This study aimed to evaluate the effect of cumulative exposure to psychosocial stressors at work on global cognitive function in a cohort followed for over 25 years. At baseline in 1991-1993 (T1), 9,188 white-collar workers were recruited. Two follow-ups were carried out in 1999-2001 (T2) and 2015-2019 (T3). This analysis was done among 5,728 participants working in T2, which participated in T3. Global cognitive function was evaluated with the validated Montreal Cognitive Assessment test (Nasreddine, 2005) and categorized in three groups according to standardized cutoffs. Psychosocial stressors at work were evaluated with the validated Job Content Questionnaire (Karasek, 1979) at each time. The effect of cumulative exposure to psychosocial stressors at work at T1 and T2 on cognitive function categories at T3 was estimated with marginal structural models using inverse probability of treatment and censoring weights. Each observation was weighted for the inverse of the probability of death and lost to follow-up and adjusted for potential confounders measured at T1 (age, sex, education, number of years in the same job, comorbidities, and lifestyle habits). Multiple imputation of missing data was performed. Result: Workers exposed to low job demand and those exposed to a passive job (low job demand combined with low job control) at both T1 and T2 were at higher risk of moderate to severe cognitive impairment than non-exposed workers (prevalence ratios (PR) and 95% confidence intervals (CI) of 1.34 (1.10;1.63), p=0.003, and 1.27 (1.05;1.54), p=0.012 respectively). Men, but not women, exposed to low job control at both T1 and T2 were at higher risk of moderate to severe cognitive impairment than non-exposed workers (PR and 95% CI: 1.38 (1.07;1.79), p=0.015). No statistically significant associations were observed with the risk of mild cognitive impairment. Conclusion: Primary prevention of cognitive impairment could be possible with the reduction of these frequent and modifiable psychosocial stressors at work.
Introduction: The case-mother-control-mother design allows to study fetal and maternal genetic fa... more Introduction: The case-mother-control-mother design allows to study fetal and maternal genetic factors together with environmental exposures on early life outcomes. Mendelian constraints and conditional independence between child genotype and environmental factors enabled semiparametric likelihood methods to estimate logistic models with greater efficiency than standard logistic regression. Difficulties in child genotype collection require methods handling missing child genotype. Methods: We review a stratified retrospective likelihood and two semiparametric likelihood approaches: a prospective one and a modified retrospective one, the latter either modeling the maternal genotype as a function of covariates or leaving their joint distribution unspecified (robust version). We also review software implementing these modeling alternatives, compare their statistical properties in a simulation study, and illustrate their application, focusing on gene-environment interactions and partially missing child genotype. Results: The robust retrospective likelihood provides generally unbiased estimates, with standard errors only slightly larger than when modeling maternal genotype based on exposure. The prospective likelihood encounters maximization problems. In the application to the association of smallfor-gestational-age babies with CYP2E1 and drinking water disinfection by-products, the retrospective likelihood allowed a full array of covariates, while the prospective likelihood was limited to few covariates. Conclusion: We recommend the robust version of the modified retrospective likelihood.
International Journal of Environmental Research and Public Health
The identification of modifiable factors that could maintain cognitive function is a public healt... more The identification of modifiable factors that could maintain cognitive function is a public health priority. It is thought that some work-related psychosocial factors help developing cognitive reserve through high intellectual complexity. However, they also have well-known adverse health effects and are considered to be chronic psychosocial stressors. Indeed, these stressors could increase low-grade inflammation and promote oxidative stress associated with accelerated telomere shortening. Both low-grade inflammation and shorter telomeres have been associated with a cognitive decline. This study aimed to evaluate the total, direct, and indirect effects of work-related psychosocial factors on global cognitive function overall and by sex, through telomere length and an inflammatory index. A random sample of 2219 participants followed over 17 years was included in this study, with blood samples and data with cognitive function drawn from a longitudinal study of 9188 white-collar workers...
Where a licence is displayed above, please note the terms and conditions of the licence govern yo... more Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. Take down policy While the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive.
Using a series of keywords, we reviewed electronic databases (Medline, Embase, all records to May... more Using a series of keywords, we reviewed electronic databases (Medline, Embase, all records to May 2009) reporting the performance of biological and ultrasonographic markers to predict preeclampsia, both single markers and combinations of markers. We analyzed the data according to gestational age and risk levels of the studied populations. We evaluated the methodological quality of included publications using QUADAS (quality assessment of diagnostic accuracy studies). We identified 37 relevant studies that assessed 71 different combinations of biochemical and ultrasonographic markers. Most studies were performed during the second trimester on small-scale high-risk populations with few cases of preeclampsia. Combinations of markers generally led to an increase in sensitivity and/or specificity compared with single markers. In low-risk populations, combinations including placental protein 13 (PP13), pregnancy-associated plasma protein A (PAPP-A), a disintegrin and metalloprotease-12 (ADAM12), activin A, or inhibin Ameasured in first or early second trimester and uterine artery Doppler in second trimester appear promising (sensitivity 60%-80%, specificity > 80%). In high-risk populations, the combination of PP13 and pulsatility index in first trimester showed 90% sensitivity and 90% specificity in a single study limited to severe preeclampsia. Combinations of biochemical and ultrasonographic markers improved the performance of early prediction of preeclampsia. From a perspective of integrative medicine, large population-based studies evaluating algorithms combining multiple markers are needed, if screening approaches are to be eventually implemented.
Clinical Chemistry and Laboratory Medicine, Mar 29, 2023
Objectives Placental growth factor (PlGF) is used for first-trimester preeclampsia screening and ... more Objectives Placental growth factor (PlGF) is used for first-trimester preeclampsia screening and could be combined with other biochemical markers for Down syndrome screening. We aim to estimate the predictive value of the combination of pregnancy-associated plasma protein (PAPP-A), free β-human chorionic gonadotropin (free β-hCG), placental growth factor (PlGF) and α-fetoprotein (AFP) with and without nuchal translucency. Methods Singleton pregnancies recruited at 11–14 weeks and followed until delivery. The four maternal markers were measured using Kryptor (ThermoFisher-BRAHMS) and adjusted for gestational age and maternal characteristics. The risk of Down syndrome was calculated using the Fetal Medicine Foundation algorithm and multivariate linear regression analyses in all cases and in 2,200 controls. Receiver-operator characteristic (ROC) curves were used to calculate the detection and false-positive rates. Results Twenty-six (0.2%) cases of Down syndrome were diagnosed among 13,386 participants. The combination of the four biomarkers could have detected 88% (95% CI: 72–97%) of the cases at a false-positive rate of 13% (95% CI: 12–15%). The addition of nuchal translucency would have increased the detection rate to 96% (95% CI: 82–99%) at a false-positive rate of 4% (95% CI: 4–5%) using a 1:300 cut-off and to 100% (95% CI: 89–100%) at a false-positive rate of 6% (95% CI: 5–8%) using a 1:500 cut-off. Conclusions First-trimester screening using biochemical markers allows the identification of approximately 88% of Down syndrome cases for a false-positive rate of 13%. The addition of nuchal translucency raises the detection rate above 95% with a false-positive rate below 5%.
Journal of obstetrics and gynaecology Canada, Dec 1, 2009
Objective: To evaluate the reproducibility of first-trimester, three-dimensional placental volume... more Objective: To evaluate the reproducibility of first-trimester, three-dimensional placental volume and vasculature evaluation by ultrasound in correlation with uterine artery Doppler flow studies. Method: We performed a prospective study of a cohort of pregnant women undergoing first-trimester ultrasound examination. Uterine artery Doppler and 3-D power Doppler angiography was performed. Placental volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were calculated three times by two independent observers using the virtual organ computer-aided analysis (VOCAL) software. Intra-and interobserver reproducibility was evaluated by Spearman's correlation test. All parameters between women with low (< 1.5 multiple of median) (MoM) and high (> 1.5 MoM) uterine artery Pourcelot index (PI) were compared by the Mann-Whitney test. Results: A total of 35 women between 11 and 14 weeks' gestation were recruited, including 26 who underwent uterine artery Doppler and six with elevated uterine artery PI. We found excellent intraand interobserver reproducibility (R 2 > 0.85) for all parameters. Women with elevated uterine artery PI had smaller placental volume, VI, FI, and VFI (P < 0.05). Conclusion: 3-D placental volume and vasculature evaluations during the first trimester are reproducible measures that inversely correlate with uterine artery PI.
Background: This study aims to evaluate the performance of the soluble Fms-like tyrosine kinase-1... more Background: This study aims to evaluate the performance of the soluble Fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio to predict early-onset, preterm and severe preeclampsia at mid-pregnancy in asymptomatic women. Methods: Based on a prospective cohort of 7929 pregnant women from the Quebec City metropolitan area, a nested case-control study was performed including 111 women who developed preeclampsia and 69 women with gestational hypertension matched with 338 normotensive women. Serum sFlt-1 and PlGF were measured between 20 and 32 weeks of gestation. The performance of the sFlt-1/ PlGF ratio, expressed as raw values and multiples of the median (MoM) for the prediction of early-onset, preterm and severe preeclampsia was evaluated. Results: Women who developed preeclampsia had significantly higher MoM sFlt-1/PlGF ratio (p < 0.001). In the early-onset preeclampsia group, the median of the MoM distribution was 24.0 and the area under the receiver operating characteristic curve (AUC) was 0.977, giving sensitivities of 77.8% and 88.9% at false-positive rates of 5% and 10%. Positive predictive values (PPV) were 2.5% and 1.5%, respectively. In a subset between 26 and 32 weeks of gestation, at a threshold of 30, the sFlt-1/PlGF ratio yielded 100% specificity and identified, respectively, 85.7% and 65.2% of women who developed early-onset and preterm preeclampsia. Conclusions: The sFlt-1/PlGF ratio has the potential to predict early-onset and preterm preeclampsia at midpregnancy in asymptomatic women. However, care must be paid to the prevalence of early-onset preeclampsia in the population since low prevalence reduces PPV and may hamper clinical utility.
Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pre... more Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women.
Journal of inborn errors of metabolism and screening, 2023
Screening newborns for genetic and other diseases is one of the most effective ways to improve he... more Screening newborns for genetic and other diseases is one of the most effective ways to improve health and reduce disease in a population. In developed countries, newborn screening has been a cornerstone of public health for decades. In many developing countries, however, newborn screening is still in its infancy. Many countries still lack screening programs. When a program is available, it generally lacks well-defined criteria on which decision-makers can justify the choice of diseases screened for and the methods used. One of the reasons put forward to understand this observation is the fact that little consideration is given by decision-makers to economic evaluations as a pillar of decision-making, as is the case in industrialized countries. This article provides a brief description of the challenges of using economic evaluation of newborn screening in developing countries. This will be illustrated by the example of the national newborn screening program in Vietnam.
Diabetes Research and Clinical Practice, Jun 1, 2018
Gestational diabetes mellitus (GDM) affects between 5 and 10% of all pregnancies in Canada and ca... more Gestational diabetes mellitus (GDM) affects between 5 and 10% of all pregnancies in Canada and can lead to adverse health outcomes in both the mother and fetus. Amino acids (AA) and acylcarnitines (AC) have been identified as early biomarkers of type 2 diabetes but their usefulness in screening for GDM has yet to be demonstrated. We conducted a nested case-control study involving 50 controls and 50 GDM cases diagnosed between the 24th and 28th week of gestation. Heparinized plasma samples were obtained during the first and early second trimester of pregnancy. Case and controls were matched according to date of recruitment, maternal age, gestational age at blood sampling as well as pre-pregnancy body mass index. Eight AA and eight AC were quantified using an ultra-high pressure liquid-chromatography quadrupole time-of-flight mass spectrometry platform. Conditional regression analyses adjusted for matching factors and smoking habits during pregnancy were performed to identify plasma metabolites associated with GDM risk. Odds ratio (OR) and 95% confidence interval (CI) for the prediction of GDM per one standard deviation increase of AA or AC in plasma levels were 0.25 (0.08-0.79) for butyrylcarnitine, 0.31 (0.12-0.79) for glutamic acid, 2.5 (1.2-5.3) for acetylcarnitine, 2.9 (1.3-6.8) for isobutyrylcarnitine and 5.3 (1.7-17.0) for leucine. These five metabolites were selected by stepwise conditional logistic regression to create a predictive model with an OR of 2.7 (1.5-4.9). Whether the identified metabolites can predict the risk of developing GDM requires additional studies in a larger sample of pregnant women.
Bjog: An International Journal Of Obstetrics And Gynaecology, Sep 1, 2014
Objectives: To evaluate the diagnostic value of urine microscopy in addition to dipstick analysis... more Objectives: To evaluate the diagnostic value of urine microscopy in addition to dipstick analysis for urinary tract infection (UTI). Methods: Results of 203 consecutive urine specimens submitted over a two-week period for culture, dipstick analysis and microscopy (done for leukocyte esterase and/or nitrite positive specimens; n = 147) were compared. Positive results were defined as follows: leukocyte esterase≥ trace, WBC count ≥ 5 cells/HPF and for culture ≥ 10 4 CFU/mL. Sensitivities and specificities of dipstick and microscopy were calculated against culture. Pre-test probability was based on a prevalence of UTI of 23%. Results: Conclusions: The addition of subsequent microscopic testing is most useful when used in cases in which the esterase alone is positive. In our setting, this occurs in 69% of submitted specimens. Application to different settings of practice with different pre-test probabilities may improve accuracy of diagnosis of urinary tract infection.
American Journal of Obstetrics and Gynecology, 2017
cervical ripening or pitocin. Results were also examined by gestational age (GA) at the initiatio... more cervical ripening or pitocin. Results were also examined by gestational age (GA) at the initiation of delivery: 24-28 vs. 29-32 weeks. RESULTS: 471 pregnancies were analyzed; 200 (42%) had a pre-labor CD and 271 had IOL. The frequency of the MC (10.2% vs 21.1%) was significantly lower with IOL (aOR 0.46[0.24-0.88])(Table 2). The NC rates were not significantly different. The median duration of IOL was 13.9 hrs and the successful VD rate was 53%. VD success rate was lower at 24-28 weeks compared to 29-32 weeks (adjusted p¼0.01) (Table 1). Factors associated with an increased rate of VD were epidural (aOR 5.3 [2.6-11.1]), prior delivery (aOR 4.6 [2.2-9.4]), and Hispanic ethnicity (aOR 3.0 [1.0-8.5]); SGA infants were associated with a decreased rate of VD (aOR 0.3 [0.1-0.7]). CONCLUSION: In women with PAH requiring early preterm delivery, IOL is associated with a significantly lower risk of maternal but not neonatal morbidity compared with pre-labor CD. About half of women who undergo IOL have a successful VD and a median duration of IOL of 13.9 hours.
As per the Ministry of Health's mandate, newborn screening (NBS) for hemoglobinopathies started o... more As per the Ministry of Health's mandate, newborn screening (NBS) for hemoglobinopathies started on November 4th 2013 in Quebec, initially for the Greater Montreal area. The NBS laboratory is equipped with two high-performance liquid chromatography (HPLC) instruments for 1st tier testing, and abnormal results (2nd tier) are repeated using capillary electrophoresis (CE). To our knowledge, we are the first in America to implement a HPLC-CE design for newborn screening. Objectives: To illustrate the complementarity of HPLC and CE in the interpretation of results for hemoglobinopathy newborn screening. Methods: Newborn blood specimens from filter paper dried spots were first analyzed with the Biorad VARIANT™nbs System. Abnormal or indeterminate results were repeated using Sebia Capillarys 2 Neonatal Fast. Results: Analytical correlation between these technologies showed excellent results (n = 56). Three months after implementation, 18621 samples have been tested using HPLC, while 450 samples were retested using CE as 2nd tier. We identified 5 samples (0.03% of all samples, 1.1% of 2nd tier tests) for which initial interpretation by instruments software was not similar and needed further comparison of spectra to identify the appropriate hemoglobin variant. Conclusions: Despite a good correlation, we observed rare discrepancies in hemoglobin variant calls between both technologies, which have complementary strengths and limitations. Implementation of NBS using both HPLC and CE by the Quebec Newborn Blood Screening Program should help to improve sensitivity and specificity, and thus the overall performance of newborn screening for hemoglobinopathies.
Background: By 2050, an estimated 152 million people will be living with dementia. Prospective st... more Background: By 2050, an estimated 152 million people will be living with dementia. Prospective studies suggest that exposure to psychosocial stressors at work could be associated with a higher risk of mild cognitive impairment or dementia, but the evidence is still not clear. Method: This study aimed to evaluate the effect of cumulative exposure to psychosocial stressors at work on global cognitive function in a cohort followed for over 25 years. At baseline in 1991-1993 (T1), 9,188 white-collar workers were recruited. Two follow-ups were carried out in 1999-2001 (T2) and 2015-2019 (T3). This analysis was done among 5,728 participants working in T2, which participated in T3. Global cognitive function was evaluated with the validated Montreal Cognitive Assessment test (Nasreddine, 2005) and categorized in three groups according to standardized cutoffs. Psychosocial stressors at work were evaluated with the validated Job Content Questionnaire (Karasek, 1979) at each time. The effect of cumulative exposure to psychosocial stressors at work at T1 and T2 on cognitive function categories at T3 was estimated with marginal structural models using inverse probability of treatment and censoring weights. Each observation was weighted for the inverse of the probability of death and lost to follow-up and adjusted for potential confounders measured at T1 (age, sex, education, number of years in the same job, comorbidities, and lifestyle habits). Multiple imputation of missing data was performed. Result: Workers exposed to low job demand and those exposed to a passive job (low job demand combined with low job control) at both T1 and T2 were at higher risk of moderate to severe cognitive impairment than non-exposed workers (prevalence ratios (PR) and 95% confidence intervals (CI) of 1.34 (1.10;1.63), p=0.003, and 1.27 (1.05;1.54), p=0.012 respectively). Men, but not women, exposed to low job control at both T1 and T2 were at higher risk of moderate to severe cognitive impairment than non-exposed workers (PR and 95% CI: 1.38 (1.07;1.79), p=0.015). No statistically significant associations were observed with the risk of mild cognitive impairment. Conclusion: Primary prevention of cognitive impairment could be possible with the reduction of these frequent and modifiable psychosocial stressors at work.
Introduction: The case-mother-control-mother design allows to study fetal and maternal genetic fa... more Introduction: The case-mother-control-mother design allows to study fetal and maternal genetic factors together with environmental exposures on early life outcomes. Mendelian constraints and conditional independence between child genotype and environmental factors enabled semiparametric likelihood methods to estimate logistic models with greater efficiency than standard logistic regression. Difficulties in child genotype collection require methods handling missing child genotype. Methods: We review a stratified retrospective likelihood and two semiparametric likelihood approaches: a prospective one and a modified retrospective one, the latter either modeling the maternal genotype as a function of covariates or leaving their joint distribution unspecified (robust version). We also review software implementing these modeling alternatives, compare their statistical properties in a simulation study, and illustrate their application, focusing on gene-environment interactions and partially missing child genotype. Results: The robust retrospective likelihood provides generally unbiased estimates, with standard errors only slightly larger than when modeling maternal genotype based on exposure. The prospective likelihood encounters maximization problems. In the application to the association of smallfor-gestational-age babies with CYP2E1 and drinking water disinfection by-products, the retrospective likelihood allowed a full array of covariates, while the prospective likelihood was limited to few covariates. Conclusion: We recommend the robust version of the modified retrospective likelihood.
International Journal of Environmental Research and Public Health
The identification of modifiable factors that could maintain cognitive function is a public healt... more The identification of modifiable factors that could maintain cognitive function is a public health priority. It is thought that some work-related psychosocial factors help developing cognitive reserve through high intellectual complexity. However, they also have well-known adverse health effects and are considered to be chronic psychosocial stressors. Indeed, these stressors could increase low-grade inflammation and promote oxidative stress associated with accelerated telomere shortening. Both low-grade inflammation and shorter telomeres have been associated with a cognitive decline. This study aimed to evaluate the total, direct, and indirect effects of work-related psychosocial factors on global cognitive function overall and by sex, through telomere length and an inflammatory index. A random sample of 2219 participants followed over 17 years was included in this study, with blood samples and data with cognitive function drawn from a longitudinal study of 9188 white-collar workers...
Where a licence is displayed above, please note the terms and conditions of the licence govern yo... more Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. Take down policy While the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive.
Using a series of keywords, we reviewed electronic databases (Medline, Embase, all records to May... more Using a series of keywords, we reviewed electronic databases (Medline, Embase, all records to May 2009) reporting the performance of biological and ultrasonographic markers to predict preeclampsia, both single markers and combinations of markers. We analyzed the data according to gestational age and risk levels of the studied populations. We evaluated the methodological quality of included publications using QUADAS (quality assessment of diagnostic accuracy studies). We identified 37 relevant studies that assessed 71 different combinations of biochemical and ultrasonographic markers. Most studies were performed during the second trimester on small-scale high-risk populations with few cases of preeclampsia. Combinations of markers generally led to an increase in sensitivity and/or specificity compared with single markers. In low-risk populations, combinations including placental protein 13 (PP13), pregnancy-associated plasma protein A (PAPP-A), a disintegrin and metalloprotease-12 (ADAM12), activin A, or inhibin Ameasured in first or early second trimester and uterine artery Doppler in second trimester appear promising (sensitivity 60%-80%, specificity &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 80%). In high-risk populations, the combination of PP13 and pulsatility index in first trimester showed 90% sensitivity and 90% specificity in a single study limited to severe preeclampsia. Combinations of biochemical and ultrasonographic markers improved the performance of early prediction of preeclampsia. From a perspective of integrative medicine, large population-based studies evaluating algorithms combining multiple markers are needed, if screening approaches are to be eventually implemented.
Clinical Chemistry and Laboratory Medicine, Mar 29, 2023
Objectives Placental growth factor (PlGF) is used for first-trimester preeclampsia screening and ... more Objectives Placental growth factor (PlGF) is used for first-trimester preeclampsia screening and could be combined with other biochemical markers for Down syndrome screening. We aim to estimate the predictive value of the combination of pregnancy-associated plasma protein (PAPP-A), free β-human chorionic gonadotropin (free β-hCG), placental growth factor (PlGF) and α-fetoprotein (AFP) with and without nuchal translucency. Methods Singleton pregnancies recruited at 11–14 weeks and followed until delivery. The four maternal markers were measured using Kryptor (ThermoFisher-BRAHMS) and adjusted for gestational age and maternal characteristics. The risk of Down syndrome was calculated using the Fetal Medicine Foundation algorithm and multivariate linear regression analyses in all cases and in 2,200 controls. Receiver-operator characteristic (ROC) curves were used to calculate the detection and false-positive rates. Results Twenty-six (0.2%) cases of Down syndrome were diagnosed among 13,386 participants. The combination of the four biomarkers could have detected 88% (95% CI: 72–97%) of the cases at a false-positive rate of 13% (95% CI: 12–15%). The addition of nuchal translucency would have increased the detection rate to 96% (95% CI: 82–99%) at a false-positive rate of 4% (95% CI: 4–5%) using a 1:300 cut-off and to 100% (95% CI: 89–100%) at a false-positive rate of 6% (95% CI: 5–8%) using a 1:500 cut-off. Conclusions First-trimester screening using biochemical markers allows the identification of approximately 88% of Down syndrome cases for a false-positive rate of 13%. The addition of nuchal translucency raises the detection rate above 95% with a false-positive rate below 5%.
Journal of obstetrics and gynaecology Canada, Dec 1, 2009
Objective: To evaluate the reproducibility of first-trimester, three-dimensional placental volume... more Objective: To evaluate the reproducibility of first-trimester, three-dimensional placental volume and vasculature evaluation by ultrasound in correlation with uterine artery Doppler flow studies. Method: We performed a prospective study of a cohort of pregnant women undergoing first-trimester ultrasound examination. Uterine artery Doppler and 3-D power Doppler angiography was performed. Placental volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were calculated three times by two independent observers using the virtual organ computer-aided analysis (VOCAL) software. Intra-and interobserver reproducibility was evaluated by Spearman's correlation test. All parameters between women with low (< 1.5 multiple of median) (MoM) and high (> 1.5 MoM) uterine artery Pourcelot index (PI) were compared by the Mann-Whitney test. Results: A total of 35 women between 11 and 14 weeks' gestation were recruited, including 26 who underwent uterine artery Doppler and six with elevated uterine artery PI. We found excellent intraand interobserver reproducibility (R 2 > 0.85) for all parameters. Women with elevated uterine artery PI had smaller placental volume, VI, FI, and VFI (P < 0.05). Conclusion: 3-D placental volume and vasculature evaluations during the first trimester are reproducible measures that inversely correlate with uterine artery PI.
Background: This study aims to evaluate the performance of the soluble Fms-like tyrosine kinase-1... more Background: This study aims to evaluate the performance of the soluble Fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio to predict early-onset, preterm and severe preeclampsia at mid-pregnancy in asymptomatic women. Methods: Based on a prospective cohort of 7929 pregnant women from the Quebec City metropolitan area, a nested case-control study was performed including 111 women who developed preeclampsia and 69 women with gestational hypertension matched with 338 normotensive women. Serum sFlt-1 and PlGF were measured between 20 and 32 weeks of gestation. The performance of the sFlt-1/ PlGF ratio, expressed as raw values and multiples of the median (MoM) for the prediction of early-onset, preterm and severe preeclampsia was evaluated. Results: Women who developed preeclampsia had significantly higher MoM sFlt-1/PlGF ratio (p < 0.001). In the early-onset preeclampsia group, the median of the MoM distribution was 24.0 and the area under the receiver operating characteristic curve (AUC) was 0.977, giving sensitivities of 77.8% and 88.9% at false-positive rates of 5% and 10%. Positive predictive values (PPV) were 2.5% and 1.5%, respectively. In a subset between 26 and 32 weeks of gestation, at a threshold of 30, the sFlt-1/PlGF ratio yielded 100% specificity and identified, respectively, 85.7% and 65.2% of women who developed early-onset and preterm preeclampsia. Conclusions: The sFlt-1/PlGF ratio has the potential to predict early-onset and preterm preeclampsia at midpregnancy in asymptomatic women. However, care must be paid to the prevalence of early-onset preeclampsia in the population since low prevalence reduces PPV and may hamper clinical utility.
Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pre... more Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women.
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Papers by Yves Giguere