scholarly journals A new customised placental weight standard redefines the relationship between maternal obesity and extremes of placental size and is more closely associated with pregnancy complications than an existing population standard

2019 ◽  
Vol 11 (4) ◽  
pp. 350-359
Author(s):  
Jacqueline M. Wallace ◽  
Joeleita P. Agard ◽  
Graham W. Horgan
Keyword(s):  
Pregnancy Complications ◽  
Maternal Obesity ◽  
Population Based ◽  
Multiple Regression Model ◽  
Placental Weight ◽  
Morbidly Obese ◽  
Obese Women ◽  
Entire Cohort ◽  
Multiparous Women ◽  
The Difference

AbstractPlacental weight is a valuable indicator of its function, predicting both pregnancy outcome and lifelong health. Population-based centile charts of weight-for-gestational-age and parity are useful for identifying extremes of placental weight but fail to consider maternal size. To address this deficit, a multiple regression model was fitted to derive coefficients for predicting normal placental weight using records from healthy pregnancies of nulliparous/multiparous women of differing height and weight (n = 107,170 deliveries, 37–43 weeks gestation). The difference between actual and predicted placental weight generated a z-score/individual centile for the entire cohort including women with pregnancy complications (n = 121,591). The association between maternal BMI and placental weight extremes defined by the new customised versus population-based standard was investigated by logistic regression, as was the association between low placental weight and pregnancy complications. Underweight women had a greater risk of low placental weight [<10thcentile, OR 1.84 (95% CI 1.66, 2.05)] and obese women had a greater risk of high placental weight [>90th centile, OR 1.98 (95% CI 1.88, 2.10)] using a population standard. After customisation, the risk of high placental weight in obese/morbidly obese women was attenuated [OR 1.17 (95% CI 1.09, 1.25)]/no longer significant, while their risk of low placental weight was 59%–129% higher (P < 0.001). The customised placental weight standard was more closely associated with stillbirth, hypertensive disease, placental abruption and neonatal death than the population standard. Our customised placental weight standard reveals higher risk of relative placental growth restriction leading to lower than expected birthweights in obese women, and a stronger association between low placental weight and pregnancy complications generally. Further, it provides an alternative tool for defining placental weight extremes with implications for the placental programming of chronic disease.

Obesity and oocyte quality: Significant implications for ART and Emerging mechanistic insights

2021 ◽  
Author(s):  
Macarena B Gonzalez ◽  
Rebecca L Robker ◽  
Ryan D Rose
Keyword(s):  
Pregnancy Complications ◽  
Maternal Obesity ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Live Birth Rate ◽  
Oocyte Quality ◽  
Reproductive Age ◽  
Developmental Competence ◽  
Obese Women ◽  
Increased Risk

Abstract The prevalence of obesity in adults worldwide, and specifically in women of reproductive age, is concerning given the risks to fertility posed by the increased risk of type 2 diabetes, metabolic syndrome and other non-communicable diseases. Obesity has a multi-systemic impact in female physiology that is characterized by the presence of oxidative stress, lipotoxicity, and the activation of pro-inflammatory pathways, inducing tissue-specific insulin resistance and ultimately conducive to abnormal ovarian function. A higher body mass is linked to Polycystic Ovary Syndrome, dysregulated menstrual cycles, anovulation, and longer time to pregnancy, even in ovulatory women. In the context of ART, compared to women of normal BMI, obese women have worse outcomes in every step of their journey, resulting in reduced success measured as live birth rate. Even after pregnancy is achieved, obese women have a higher chance of miscarriage, gestational diabetes, pregnancy complications, birth defects, and most worryingly, a higher risk of stillbirth and neonatal death. The potential for compounding effects of ART on pregnancy complications and infant morbidities in obese women has not been studied. There is still much debate in the field on whether these poorer outcomes are mainly driven by defects in oocyte quality, abnormal embryo development or an unaccommodating uterine environment, however the clinical evidence to date suggests a combination of all three are responsible. Animal models of maternal obesity shed light on the mechanisms underlaying the effects of obesity on the peri-conception environment, with recent findings pointing to lipotoxicity in the ovarian environment as a key driver of defects in oocytes that have not only reduced developmental competence but long-lasting effects in offspring health.

scholarly journals Using the difference in actual and expected calf liveweight relative to its dam liveweight as a statistic for interherd and intraherd benchmarking and genetic evaluations1

2019 ◽  
Vol 97 (12) ◽  
pp. 4737-4745 ◽  
Author(s):  
Noirin McHugh ◽  
Ross D Evans ◽  
Donagh P Berry
Keyword(s):  
Genetic Variability ◽  
Production Systems ◽  
Management Strategies ◽  
Population Based ◽  
Multiple Regression Model ◽  
Residual Variance ◽  
Genetic Progress ◽  
The Difference ◽  
Simple Ratio ◽  
Maternal Heritability

Abstract The importance of improving the efficiency of beef production systems using both genetic and management strategies has long been discussed. Despite the contribution of the mature beef herd to the overall cost of production in the sector as a whole, most strategies for improving (feed) efficiency have focused on the growing animal. The objective of the present study was to quantify the phenotypic and genetic variability in several novel measures that relate the weight of a calf to that of its dam and vice versa. Two novel residual traits, representing the deviation in calf weight relative to its expectation from the population based on its dam’s weight (DIFFcalf) or the deviation in the weight of the dam relative to its expectation from the population based on its calf’s weight (DIFFdam), were calculated while simultaneously accounting for some nuisance factors in a multiple regression model. Four supplementary traits were also calculated, namely, 1) the deviation in calf weight from its expectation expressed relative to the weight of the dam (DIFFcalf_ratio), 2) the deviation in dam weight from its expectation relative to the weight of the dam (DIFFdam_ratio), 3) DIFFcalf-DIFFdam, and 4) the simple ratio of calf weight to its dam’s weight (RATIOcalfdam). Genetic and residual variance components for each of the 6 traits were estimated using animal–dam linear mixed models. The phenotypic SD for DIFFcalf was 42 kg and, when expressed relative to the weight of the dam (i.e., DIFFcalf_ratio), was 0.07. The genetic SD for DIFFcalf and DIFFcalf_ratio was 16.66 kg and 0.02, respectively. The direct and maternal heritability estimated for DIFFcalf was 0.28 (SE = 0.04) and 0.11 (SE = 0.02), respectively, and for DIFFcalf_ratio was 0.24 (SE = 0.04) and 0.17 (SE = 0.03), respectively. The genetic SD for DIFFdam was 47.09 kg; the direct heritability was 0.50 (SE = 0.03), and the dam repeatability was 0.75 (SE = 0.01). The genetic SD for RATIOcalfdam was 0.03; the direct and maternal heritability was 0.24 (SE = 0.04) and 0.24 (SE = 0.03), respectively. The suggested traits outlined in the present study provide useful metrics for benchmarking dam–calf efficiency; in addition, the genetic variability detected in these traits suggest genetic progress for more efficient dam–calf pairs is indeed possible.

scholarly journals Obese Women Exhibit Reduced Inhibin B and Estradiol SecretionFollowing Pulsatile Intravenous FSH Administration

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A734-A734
Author(s):  
Thanh Ha Luu ◽  
Katherine Kuhn ◽  
Andrew P Bradford ◽  
Rachel Johnson ◽  
Nichole Carlson ◽  
...  
Keyword(s):  
Linear Regression ◽  
Interim Analysis ◽  
Maternal Obesity ◽  
Ovarian Function ◽  
Normal Weight ◽  
Inhibin B ◽  
Blood Sampling ◽  
Obese Women ◽  
Early Results ◽  
The Difference

Abstract Introduction: Maternal obesity is an independent risk factor for reduced reproductive fitness. Decreased secretion of FSH in women with obesity is well documented but poorly understood. Furthermore, obese women secrete less protein and steroid hormones from their ovaries. In mice, prior studies have demonstrated that pulsatile release of FSH enhances ovarian function and fertility. Hypothesis: We hypothesize that insufficient FSH pulsatility, as seen in women with obesity, results in inadequate folliculogenesis and reduced ovarian steroid production. We attempt to correct pulsatile FSH secretion in obese women by administering exogenous FSH to compensate for the suppressed circulating ovarian hormones. Our primary outcome is the change in peak inhibin B between pre- and post-treatment. We present results from our interim analysis. Methods: Reproductive aged, regularly menstruating, normal weight (NW) (BMI 18.5-24.9) and obese (OB) (BMI &gt;30) women were recruited for a 26hr study during the early follicular phase. Frequent blood sampling (q10min) for 10h was performed to obtain baseline hormone levels. At 10h, 3 mg of cetrorelix, a gonadotropin hormone antagonist, was given followed by a secondary dose (0.25mg) 6h later. At this time, hourly IV recombinant (r)FSH (30IU) was initiated and frequent blood sampling continued for 10h. LH, FSH, estradiol (E2) were measured by immunoassay (Advia Centaur XP, Siemens). Inhibin B was measured using an ELISA kit (Ansh labs). Differences between groups were modeled by linear regression, adjusted for age and cycle day (continuous). The relationship between change in peak inhibin B and change in peak E2 was estimated in a linear regression. Results: A total of 36 participants (19 NW and 17 OB) were included in our interim analysis. There were no differences in age, cycle day of study, race, and waist/hip ratio. Inhibin B and E2 rises following the intervention were statistically significant within each group. Peak Inhibin B and E2 levels following intervention were lower in obese women compared to normal weight (133.4 vs 202.5 pg/mL and 85.8 vs 126.4 pg/mL, respectively). The difference in pre and post peak inhibin B levels trended lower in the obese group (-40.1 (95%CI: -86.2, 6.1, p=0.087). No difference was seen in maximal E2 response. There was no relationship between inhibin B and E2 response [0.08 (95%CI -0.26, 0.42), p=0.634]. Conclusions: These early results suggest obese women may have a lower response to pulsatile rFSH as compared to normal weight counterparts even with intravenous administration. We speculate this may be due to decreased uptake of rFSH in obese patients or a sign of ovarian dysfunction in obese women. Additional subjects are recruited to detect these differences.

TUMOUR PATHOLOGY PREDICTS MICROSATELLITE INSTABILITY IN A POPULATION-BASED SERIES OF COLORECTAL CANCER CASES

2008 ◽  
Vol 31 (4) ◽  
pp. 12
Author(s):  
A J Hyde ◽  
D Fontaine ◽  
R C Green ◽  
M Simms ◽  
P S Parfrey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Population Based ◽  
Pathological Features ◽  
Predictive Tool ◽  
Entire Cohort ◽  
Dna Mismatch ◽  
Bethesda Guidelines ◽  
Revised Bethesda Guidelines

Background: Lynch Syndrome is an autosomal dominant trait that accounts forapproximately 3% of all cases of colorectal cancer (CRC). It is caused by mutations in DNA mismatch repair (MMR) genes, most commonly MLH1 or MSH2. These MMR defects cause high levels of microsatellite instability (MSI-H) in the tumours. MSI testing of all CRCs to identify potential Lynch Syndrome cases is not practical, so the Bethesda Guidelines, which use clinical and pathological features, were created to identify those tumours most likely to be MSI-H^1. In 2007 Jenkins et. al. created MsPath, a tool based on the pathological features described in the rarely used 3^rd Bethesda criterion, to improve prediction of MSI-H tumours among CRC cases diagnosed before age 60 years^2. Methods: We collected a population-based cohort of 716 CRC cases diagnosed before age 75 years in Newfoundland. For each of these cases we collected family history, performed MSI analysis, and scored a number of pathological features for the purpose of evaluating the accuracy of the Bethesda Criteria and MsPath at predicting MSI-H tumours. Results: Our work validates the MsPath tool in the Newfoundland population for the same age group used to create the tool. We found it identified MSI-H cases with a sensitivity of 95% and specificity of 35% in our population of CRCcases diagnosed before age 60 years (n=290). We also tested this tool on our older population of CRCcases, diagnosed at ages 60 to 74 years (n=426). We found it to be at least as predictive in this population,with a sensitivity of 95% and a specificity of 42%. We then used our entire cohort (N=716) to compare MsPath with the other Bethesda criteria.Bethesda criteria 1, 2, 4 and 5 together predicted MSI-H cases with a sensitivity of 67% and a specificity of 51%. MsPath was better at identifying these cases, with a sensitivity of 95% and a specificity of 39%. Conclusions: We conclude that MsPath can be extended to include patients diagnosed with CRC before age 75 years. As well, we have found that MsPath is a better predictive tool than the Revised Bethesda Guidelines for identifying MSI-H cases within a population-based setting of colorectal cancer. References: 1. Umar, A. et. al. J Natl Cancer Inst 2004;96:261-8 2.Jenkins, M.A. et. al. Gastroenterology 2007;133:48-56

scholarly journals Effects of marital status on overall and cancer-specific survival in laryngeal cancer patients: a population-based study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhao Ding ◽  
Deshun Yu ◽  
Hefeng Li ◽  
Yueming Ding
Keyword(s):  
Marital Status ◽  
Cancer Patients ◽  
Laryngeal Cancer ◽  
Cox Regression ◽  
Group Analysis ◽  
Population Based ◽  
Cancer Specific Survival ◽  
Cox Regression Analysis ◽  
Prognostic Effect ◽  
The Difference

AbstractMarital status has long been recognized as an important prognostic factor for many cancers, however its’ prognostic effect for patients with laryngeal cancer has not been fully examined. We retrospectively analyzed 8834 laryngeal cancer patients in the Surveillance Epidemiology and End Results database from 2004 to 2010. Patients were divided into four groups: married, widowed, single, and divorced/separated. The difference in overall survival (OS) and cancer-specific survival (CSS) of the various marital subgroups were calculated using the Kaplan–Meier curve. Multivariate Cox regression analysis screened for independent prognostic factors. Propensity score matching (PSM) was also conducted to minimize selection bias. We included 8834 eligible patients (4817 married, 894 widowed, 1732 single and 1391 divorced/separated) with laryngeal cancer. The 5-year OS and CSS of married, widowed, single, and separated/divorced patients were examined. Univariate and multivariate analyses found marital status to be an independent predictor of survival. Subgroup survival analysis showed that the OS and CSS rates in widowed patients were always the lowest in the various American Joint Committee on Cancer stages, irrespective of sex. Widowed patients demonstrated worse OS and CSS in the 1:1 matched group analysis. Among patients with laryngeal cancer, widowed patients represented the highest-risk group, with the lowest OS and CSS.

Elevation of pulse pressure in middle age is associated with the risk of dementia: data from a population-based cohort

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Kim ◽  
H Jung ◽  
P.S Yang ◽  
H.T Yu ◽  
T.H Kim ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Pulse Pressure ◽  
Middle Age ◽  
Population Based ◽  
Entire Cohort ◽  
Incident Dementia ◽  
Increased Risk ◽  
Diagnosis Of Dementia ◽  
History Of ◽  
The Mean

Abstract Aims Pulse pressure (PP) is a well-known risk factor for cardiovascular disease. However, the association between the PP and dementia is not well identified. This study aimed to determine the effect of PP on the risk of dementia development in different age subgroups using a longitudinal, population-based, and stroke-free cohort from the general population. Methods The association of PP with the development of incident dementia was assessed from January 1, 2005, to December 31, 2013, in 433,154 participants without a history of dementia or stroke from the Korea National Health Insurance Service-Health Screening cohort. The diagnosis of dementia was defined using the 10th revision of the International Classification of Disease codes. Results The mean age of the cohort was 55.7±9.2 years, 45.7% were women. Hypertension was 23.6%. The mean systolic and diastolic blood pressure of the entire cohort were 125.9±16.6 and 78.4±10.7 mmHg, respectively. Mean PP was 47.5±10.9 mmHg. In the middle-age group (40 to 50 year-old), increasing of 10 mmHg of PP was associated with incident dementia after adjusting mean blood pressure and clinical variables with a hazard ratio (HR) of 1.21 (95% confidence interval [CI]: 1.19–1.23, p&lt;0.001). The association was still significant even after censoring for stroke (HR: 1.16, 95% CI: 1.08–1.22, p&lt;0.001). In the older population, elevation of PP was not associated with dementia development (HR: 0.98, 95% CI: 0.95–1.01, p=0.247) Conclusion PP was associated with increased risk of dementia only in middle-aged population beyond that of mean arterial pressure. Funding Acknowledgement Type of funding source: None

scholarly journals Maternal alcohol use, adverse neonatal outcomes and pregnancy complications in British Columbia, Canada: a population-based study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Svetlana Popova ◽  
Danijela Dozet ◽  
Graham O’Hanlon ◽  
Valerie Temple ◽  
Jürgen Rehm
Keyword(s):  
British Columbia ◽  
Risk Factor ◽  
Alcohol Use ◽  
Pregnancy Complications ◽  
Alcohol Exposure ◽  
Population Based ◽  
Neonatal Outcomes ◽  
Fiscal Year ◽  
Adverse Neonatal Outcomes ◽  
Icd 10

Abstract Background The current study aimed to estimate the prevalence of alcohol use identified as a risk factor during pregnancies by the antenatal care providers, resulting in live births in British Columbia (BC) and to examine associations between alcohol use, adverse neonatal outcomes, and pregnancy complications. Methods This population-based cross-sectional study utilized linked obstetrical and neonatal records within the BC Perinatal Data Registry (BCPDR), for deliveries that were discharged between January 1, 2015 and March 31, 2018. The main outcome measures were alcohol use identified as a risk factor during pregnancy, associated maternal characteristics, pregnancy complications, and adverse neonatal outcomes. Estimates for the period and fiscal year prevalence were calculated. Chi-square tests were used to compare adverse neonatal outcomes and pregnancy complications by alcohol use during pregnancy identified as a risk factor. Logistic regression was used to examine the association between alcohol use identified as a risk factor during pregnancy and adverse neonatal outcomes and pregnancy complications, after adjusting for identified risk factors. Results A total of 144,779 linked records within the BCPDR were examined. The period prevalence of alcohol use during pregnancy identified as a risk factor was estimated to be 1.1% and yearly prevalence was 1.1, 1.1, 1.3 and 0.9% from the 2014/2015 to 2017/2018 fiscal years, respectively. Alcohol use identified as a risk factor was associated with younger maternal age, fewer antenatal visits, being primiparous, a history of mental illness, substance use and smoking. Neonates with alcohol use during pregnancy identified as a risk factor had greater odds of being diagnosed with: “low birth weight (1000-2499g)” (ICD-10: P07.1; aOR = 1.25; 95% CI: 1.01, 1.53), “other respiration distress of newborn” (ICD-10: P22.8; aOR = 2.57; 95% CI: 1.52, 4.07), “neonatal difficulty in breastfeeding” (ICD-10: P92.5; aOR = 1.97; 95% CI: 1.27, 2.92) and “feeding problems, unspecified” (ICD-10: P92.9; aOR = 2.06; 95% CI: 1.31, 3.09). Conclusions The prevalence of alcohol use during pregnancy identified as a risk factor was comparable to previous estimates within the BCPDR. Identified prenatal alcohol exposure was associated with notable differences in maternal and neonatal characteristics and adverse neonatal outcomes. More consistent, thorough screening and prevention efforts targeting alcohol use in pregnancy are urgently needed in Canada.

scholarly journals Intravenous Immunoglobulin Treatment in Kawasaki Disease Decreases the Incidence of Myopia

2021 ◽  
Vol 10 (7) ◽  
pp. 1381
Author(s):  
Hun-Ju Yu ◽  
Meng-Ni Chuang ◽  
Chiao-Lun Chu ◽  
Pei-Lin Wu ◽  
Shu-Chen Ho ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Intravenous Immunoglobulin ◽  
Systemic Vasculitis ◽  
Age Distribution ◽  
Population Based ◽  
Research Database ◽  
Ocular Manifestations ◽  
Missing Data Treatment ◽  
The Difference ◽  
Age Range

Kawasaki disease (KD) is a systemic vasculitis that primarily affects children under the age of 5 years old. The most significant complication is coronary artery lesions, but several ocular manifestations have also been reported. Recently, one study revealed an increasing incidence of myopia among KD patients. Therefore, the aim of this study was to assess the difference in myopic incidence between Kawasaki disease (KD) patients treated with aspirin and intravenous immunoglobulin (IVIG). Materials and methods: We carried out a nationwide retrospective cohort study by analyzing the data of KD patients (ICD-9-CM code 4461) from Taiwan’s National Health Insurance Research Database (NHIRD) during the period of 1996–2013. Results: A total of 14,102 diagnosed KD were found in Taiwan during the study period. After excluded missing data, treatment strategy and age distribution, a total of 1446 KD patients were enrolled for analysis including 53 of which received aspirin (without IVIG) and 1393 of which were treated with IVIG. Patients who had myopia, astigmatism, glaucoma, cataract, etc. prior to their KD diagnosis were excluded. The age range was 0 to 6 years old. According to the cumulative curves, our results demonstrated that the myopic incidence in the IVIG group was significantly lower than the aspirin group (hazard ratio: 0.59, 95% confidence intervals: 0.36~0.96, p = 0.02). Treatment with IVIG for KD patients may have benefit for myopia control. Conclusion: Compared to aspirin, IVIG may decrease the myopic risk in KD patients. However, it needs further investigation including clinical vision survey of myopia due to the limitations of this population-based study.

scholarly journals A “Smart” Biosensor-Enabled Intravascular Catheter and Platform for Dynamic Delivery of Propofol to “Close the Loop” for Total Intravenous Anesthesia

2021 ◽  
Vol 186 (Supplement_1) ◽  
pp. 370-377
Author(s):  
Edward Chaum ◽  
Ernő Lindner
Keyword(s):  
Real Time ◽  
Drug Distribution ◽  
Population Based ◽  
Pharmacokinetic Data ◽  
Drug Infusion ◽  
Blood Concentrations ◽  
The Usa ◽  
The Difference ◽  
Automated Delivery

ABSTRACT Background Target-controlled infusion anesthesia is used worldwide to provide user-defined, stable, blood concentrations of propofol for sedation and anesthesia. The drug infusion is controlled by a microprocessor that uses population-based pharmacokinetic data and patient biometrics to estimate the required infusion rate to replace losses from the blood compartment due to drug distribution and metabolism. The objective of the research was to develop and validate a method to detect and quantify propofol levels in the blood, to improve the safety of propofol use, and to demonstrate a pathway for regulatory approval for its use in the USA. Methods We conceptualized and prototyped a novel “smart” biosensor-enabled intravenous catheter capable of quantifying propofol at physiologic levels in the blood, in real time. The clinical embodiment of the platform is comprised of a “smart” biosensor-enabled catheter prototype, a signal generation/detection readout display, and a driving electronics software. The biosensor was validated in vitro using a variety of electrochemical methods in both static and flow systems with biofluids, including blood. Results We present data demonstrating the experimental detection and quantification of propofol at sub-micromolar concentrations using this biosensor and method. Detection of the drug is rapid and stable with negligible biofouling due to the sensor coating. It shows a linear correlation with mass spectroscopy methods. An intuitive graphical user interface was developed to: (1) detect and quantify the propofol sensor signal, (2) determine the difference between targeted and actual propofol concentration, (3) communicate the variance in real time, and (4) use the output of the controller to drive drug delivery from an in-line syringe pump. The automated delivery and maintenance of propofol levels was demonstrated in a modeled benchtop “patient” applying the known pharmacokinetics of the drug using published algorithms. Conclusions We present a proof-of-concept and in vitro validation of accurate electrochemical quantification of propofol directly from the blood and the design and prototyping of a “smart,” indwelling, biosensor-enabled catheter and demonstrate feedback hardware and software architecture permitting accurate measurement of propofol in blood in real time. The controller platform is shown to permit autonomous, “closed-loop” delivery of the drug and maintenance of user-defined propofol levels in a dynamic flow model.

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