8 research outputs found
Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses
Background Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth.
Methods We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134.
Findings We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·91%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163 947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73–2·89]; I2=59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74–0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35–0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02–0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 μmol/L versus four (0·28%; 0·08–0·72) of 1412 cases with total bile acids of 40–99 μmol/L (hazard ratio [HR] 2·35 [95% CI 0·52–10·50]; p=0·26), and versus 18 (3·44%; 2·05–5·37) of 524 cases for bile acids of 100 μmol/L or more (HR 30·50 [8·83–105·30]; p<0·0001).
Interpretation The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 μmol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery.
Funding Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust
Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses
Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth.
We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134.
We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·83%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163 947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73-2·89]; I2=59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74-0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35-0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02-0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 μmol/L versus four (0·28%; 0·08-0·72) of 1412 cases with total bile acids of 40-99 μmol/L (hazard ratio [HR] 2·35 [95% CI 0·52-10·50]; p=0·26), and versus 18 (3·44%; 2·05-5·37) of 524 cases for bile acids of 100 μmol/L or more (HR 30·50 [8·83-105·30]; p<0·0001).
The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 μmol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery.
Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust
Assessing Measles and Rubella Infection and Immunity in Outbreak Settings in the Democratic Republic of the Congo
A Squaraine Derivative for Cost-Effective, Quick, and Highly Sensitive Determination of Mercury and Thiols and pH Sensing
The introduction of innovative sensing approaches is of increasing interest in the development of analytical platforms and methodologies for the colorimetric, fluorimetric, and/or optical detection of important analytes. Herein, the synthesis of a novel squaraine derivative is reported, as well as its successful utilization in the colorimetric and fluorimetric determination of thiols. The reported squaraine was also evaluated as a pH sensor. In addition, a promising paper-based colorimetric method for mercury detection was developed and evaluated. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei
Use of a rapid digital microfluidics-powered immunoassay for assessing measles and rubella infection and immunity in outbreak settings in the Democratic Republic of the Congo.
The Democratic Republic of the Congo (DRC) has a high measles incidence despite elimination efforts and has yet to introduce rubella vaccine. We evaluated the performance of a prototype rapid digital microfluidics powered (DMF) enzyme-linked immunoassay (ELISA) assessing measles and rubella infection, by testing for immunoglobulin M (IgM), and immunity from natural infection or vaccine, by testing immunoglobulin G (IgG), in outbreak settings. Field evaluations were conducted during September 2017, in Kinshasa province, DRC. Blood specimens were collected during an outbreak investigation of suspected measles cases and tested for measles and rubella IgM and IgG using the DMF-ELISA in the field. Simultaneously, a household serosurvey for measles and rubella IgG was conducted in a recently confirmed measles outbreak area. DMF-ELISA results were compared with reference ELISA results tested at DRC's National Public Health Laboratory and the US Centers for Disease Control and Prevention. Of 157 suspected measles cases, rubella IgM was detected in 54% while measles IgM was detected in 13%. Measles IgG-positive cases were higher among vaccinated persons (87%) than unvaccinated persons (72%). In the recent measles outbreak area, measles IgG seroprevalence was 93% overall, while rubella seroprevalence was lower for children (77%) than women (98%). Compared with reference ELISA, DMF-ELISA sensitivity and specificity were 82% and 78% for measles IgG; 88% and 89% for measles IgM; 85% and 85% for rubella IgG; and 81% and 83% for rubella IgM, respectively. Rubella infection was detected in more than half of persons meeting the suspected measles case definition during a presumed measles outbreak, suggesting substantial unrecognized rubella incidence, and highlighting the need for rubella vaccine introduction into the national schedule. The performance of the DMF-ELISA suggested that this technology can be used to develop rapid diagnostic tests for measles and rubella
Association of Adverse Perinatal Outcomes of Intrahepatic Cholestasis of Pregnancy With Biochemical Markers: Results of Aggregate and Individual Patient Data Meta-analyses
Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses
Background Intrahepatic cholestasis of pregnancy is associated with
adverse perinatal outcomes, but the association with the concentration
of specific biochemical markers is unclear. We aimed to quantify the
adverse perinatal effects of intrahepatic cholestasis of pregnancy in
women with increased serum bile acid concentrations and determine
whether elevated bile acid concentrations were associated with the risk
of stillbirth and preterm birth.
Methods We did a systematic review by searching PubMed, Web of Science,
and Embase databases for studies published from database inception to
June 1, 2018, reporting perinatal outcomes for women with intrahepatic
cholestasis of pregnancy when serum bile acid concentrations were
available. Inclusion criteria were studies defining intrahepatic
cholestasis of pregnancy based upon pruritus and elevated serum bile
acid concentrations, with or without raised liver aminotransferase
concentrations. Eligible studies were case-control, cohort, and
population-based studies, and randomised controlled trials, with at
least 30 participants, and that reported bile acid concentrations and
perinatal outcomes. Studies at potential higher risk of reporter bias
were excluded, including case reports, studies not comprising cohorts,
or successive cases seen in a unit; we also excluded studies with high
risk of bias from groups selected (eg, a subgroup of babies with poor
outcomes were explicitly excluded), conference abstracts, and Letters to
the Editor without clear peer review. We also included unpublished data
from two UK hospitals. We did a random effects meta-analysis to
determine risk of adverse perinatal outcomes. Aggregate data for
maternal and perinatal outcomes were extracted from case-control
studies, and individual patient data (IPD) were requested from study
authors for all types of study (as no control group was required for the
IPD analysis) to assess associations between biochemical markers and
adverse outcomes using logistic and stepwise logistic regression. This
study is registered with PROSPERO, number CRD42017069134.
Findings We assessed 109 full-text articles, of which 23 studies were
eligible for the aggregate data meta-analysis (5557 intrahepatic
cholestasis of pregnancy cases and 165 136 controls), and 27 provided
IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth
occurred in 45 (0.83\%) of 4936 intrahepatic cholestasis of pregnancy
cases and 519 (0.32\%) of 163 947 control pregnancies (odds ratio {[}OR]
1.46 {[}95\% CI 0.73-2.89]; I-2 = 59.8\%). In singleton pregnancies,
stillbirth was associated with maximum total bile acid concentration
(area under the receiver operating characteristic curve {[}ROC AUC])
0.83 {[}95\% CI 0.74-0.92]), but not alanine aminotransferase (ROC AUC
0.46 {[}0.35-0.57]). For singleton pregnancies, the prevalence of
stillbirth was three (0.13\%; 95\% CI 0.02-0.38) of 2310 intrahepatic
cholestasis of pregnancy cases in women with serum total bile acids of
less than 40 mu mol/L versus four (0.28\%; 0.08-0.72) of 1412 cases with
total bile acids of 40-99 mu mol/L (hazard ratio {[}HR] 2.35 {[}95\% CI
0.52-10.50]; p=0.26), and versus 18 (3.44\%; 2.05-5.37) of 524 cases for
bile acids of 100 mu mol/L or more (HR 30.50 {[}8.83-105.30]; p<0.0001).
Interpretation The risk of stillbirth is increased in women with
intrahepatic cholestasis of pregnancy and singleton pregnancies when
serum bile acids concentrations are of 100 mu mol/L or more. Because
most women with intrahepatic cholestasis of pregnancy have bile acids
below this concentration, they can probably be reassured that the risk
of stillbirth is similar to that of pregnant women in the general
population, provided repeat bile acid testing is done until delivery.
Funding Tommy's, ICP Support, UK National Institute of Health Research,
Wellcome Trust, and Genesis Research Trust. Copyright (c) 2019 The
Author(s). Published by Elsevier Ltd. This is an Open Access article
under the CC BY 4.0 license