The impact of setting a pregnancy weight gain goal on total weight gain

Background: Expert groups recommend that women set a pregnancy weight gain goal with their care provider to optimise weight gain. Objective: Our aim was to describe the concordance between first-trimester personal and provider pregnancy weight gain goals with the Institute of Medicine (IOM) recommendations and to determine the association between these goals and total weight gain. Methods: We used data from 9353 women in the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be. In the first trimester, women reported their personal pregnancy weight gain goal and their provider weight gain goal, and we categorised personal and provider weight gain goals and total weight gain according to IOM recommendations. We used log-binomial or linear regression models to relate goals to total weight gain, adjusting for confounders including race/ethnicity, maternal age, education, smoking, marital status and planned pregnancy. Results: Approximately 37% of women reported no weight gain goals, while 24% had personal and provider goals, 31% had only a personal goal, and 8% had only a provider goal. Personal and provider goals were outside the recommended ranges in 12%-23% of normal-weight women, 31%-41% of overweight women and 47%-63% of women with obesity. Women with both personal and provider pregnancy weight gain goals were 6%-14% more likely than their counterparts to have a goal within IOM-recommended ranges. Having any goal or a goal within the IOM-recommended ranges was unrelated to pregnancy weight gain. Excessive weight gain occurred in approximately half of normal-weight or obese women and three-quarters of overweight women, regardless of goal setting group. Conclusions: These findings do not support the effectiveness of early-pregnancy personal or provider gestational weight gain goal setting alone in optimising weight gain. Multifaceted interventions that address a number of mediators of goal setting success may assist women in achieving weight gain consistent with their goals

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Identification of an enhancer that increases miR-200b~200a~429 gene expression in breast cancer cells

The miR-200b~200a~429 gene cluster is a key regulator of EMT and cancer metastasis, however the transcription-based mechanisms controlling its expression during this process are not well understood. We have analyzed the miR-200b~200a~429 locus for epigenetic modifications in breast epithelial and mesenchymal cell lines using chromatin immunoprecipitation assays and DNA methylation analysis. We discovered a novel enhancer located approximately 5.1kb upstream of the miR-200b~200a~429 transcriptional start site. This region was associated with the active enhancer chromatin signature comprising H3K4me1, H3K27ac, RNA polymerase II and CpG dinucleotide hypomethylation. Luciferase reporter assays revealed the upstream enhancer stimulated the transcription of the miR-200b~200a~429 minimal promoter region approximately 27-fold in breast epithelial cells. Furthermore, we found that a region of the enhancer was transcribed, producing a short, GC-rich, mainly nuclear, non-polyadenylated RNA transcript designated miR-200b eRNA. Over-expression of miR-200b eRNA had little effect on miR-200b~200a~429 promoter activity and its production did not correlate with miR-200b~200a~429 gene expression. While additional investigations of miR-200b eRNA function will be necessary, it is possible that miR-200b eRNA may be involved in the regulation of miR-200b~200a~429 gene expression and silencing. Taken together, these findings reveal the presence of a novel enhancer, which contributes to miR-200b~200a~429 transcriptional regulation in epithelial cells.Joanne L. Attema, Andrew G. Bert, Yat-Yuen Lim, Natasha Kolesnikoff, David M. Lawrence, Katherine A. Pillman, Eric Smith, Paul A. Drew, Yeesim Khew-Goodall, Frances Shannon, Gregory J. Goodal

Delayed Lactogenesis II and potential utility of antenatal milk expression in women developing late-onset preeclampsia: a case series

Abstract Background Preeclampsia is a multi-system, hypertensive disorder of pregnancy that increases a woman’s risk of later-life cardiovascular disease. Breastfeeding may counteract the negative cardiovascular sequela associated with preeclampsia; however, women who develop preeclampsia may be at-risk for suboptimal breastfeeding rates. In this case series, we present three cases of late-onset preeclampsia and one case of severe gestational hypertension that illustrate a potential association between hypertensive disorders of pregnancy and suboptimal breastfeeding outcomes, including delayed onset of lactogenesis II and in-hospital formula supplementation. Case presentation All cases were drawn from an ongoing pilot randomized controlled trial investigating the impact of antenatal milk expression versus an education control on breastfeeding outcomes. All study participants were healthy nulliparous women recruited at 34–366/7 gestational weeks from a hospital-based midwife practice. The variability in clinical presentation among the four cases suggests that any effect of hypertensive disorders on breastfeeding outcomes is likely multifactorial in nature, and may include both primary (e.g., preeclampsia disease course itself) and secondary (e.g., magnesium sulfate therapy, delayed at-breast feeding due to maternal-infant separation) etiologies. We further describe the use of antenatal milk expression (AME), or milk expression and storage beginning around 37 weeks of gestation, as a potential intervention to mitigate suboptimal breastfeeding outcomes in women at risk for preeclampsia and other hypertensive disorders of pregnancy. Conclusions Additional research is needed to address incidence, etiology, and interventions, including AME, for breastfeeding issues among a larger sample of women who develop hypertensive disorders of pregnancy

Predictor characteristics necessary for building a clinically useful risk prediction model: a simulation study

Background: Compelled by the intuitive appeal of predicting each individual patient’s risk of an outcome, there is a growing interest in risk prediction models. While the statistical methods used to build prediction models are increasingly well understood, the literature offers little insight to researchers seeking to gauge a priori whether a prediction model is likely to perform well for their particular research question. The objective of this study was to inform the development of new risk prediction models by evaluating model performance under a wide range of predictor characteristics. Methods: Data from all births to overweight or obese women in British Columbia, Canada from 2004 to 2012 (n = 75,225) were used to build a risk prediction model for preeclampsia. The data were then augmented with simulated predictors of the outcome with pre-set prevalence values and univariable odds ratios. We built 120 risk prediction models that included known demographic and clinical predictors, and one, three, or five of the simulated variables. Finally, we evaluated standard model performance criteria (discrimination, risk stratification capacity, calibration, and Nagelkerke’s r2) for each model. Results: Findings from our models built with simulated predictors demonstrated the predictor characteristics required for a risk prediction model to adequately discriminate cases from non-cases and to adequately classify patients into clinically distinct risk groups. Several predictor characteristics can yield well performing risk prediction models; however, these characteristics are not typical of predictor-outcome relationships in many population-based or clinical data sets. Novel predictors must be both strongly associated with the outcome and prevalent in the population to be useful for clinical prediction modeling (e.g., one predictor with prevalence ≥20 % and odds ratio ≥8, or 3 predictors with prevalence ≥10 % and odds ratios ≥4). Area under the receiver operating characteristic curve values of >0.8 were necessary to achieve reasonable risk stratification capacity. Conclusions: Our findings provide a guide for researchers to estimate the expected performance of a prediction model before a model has been built based on the characteristics of available predictors.Medicine, Faculty ofNon UBCObstetrics and Gynaecology, Department ofReviewedFacult

Association between gestational age at delivery and indicator-specific severe maternal morbidity

Individuals who deliver preterm are disproportionately affected by severe maternal morbidity. Limited data suggest that indicator-specific maternal morbidity varies by gestational age at delivery. We sought to evaluate the relationship between gestational age at delivery and the incidence of severe maternal morbidity and indicator-specific severe maternal morbidity. We used a hospital administrative delivery database to identify all singleton deliveries between 16 and 42 weeks gestation from 2002 to 2018. We defined severe maternal morbidity as the presence of any International Classification of Disease diagnosis or procedure codes outlined by the Centers for Disease Control and Prevention, intensive care unit admission, and/or prolonged postpartum hospital length of stay. Indicator-specific severe maternal morbidity was based on the diagnosis and procedure codes and was characterized across gestational age epochs. We categorized gestational age into three epochs to capture extremely preterm birth (less than 28 weeks gestation), preterm birth (28-36 weeks gestation) and term birth (37 weeks gestation and above). Multivariable binomial regression was used to assess the association between categories of gestational age at delivery and severe maternal morbidity adjusting for confounders including age, race, body mass index (BMI), insurance status, and preexisting hypertension or diabetes. Severe maternal morbidity occurred in 2.5% of all deliveries. The unadjusted incidence of severe maternal morbidity by gestational age epoch was 12% at less than 28 weeks gestation, 8.4% at 28 to 36 weeks of gestation, and 1.7% at greater than or equal to 37 weeks gestation. After controlling for potential confounders the predicted probability of severe maternal morbidity was 16% (95% CI 14,17%) at 24 weeks compared to 2.2% (95% CI 2.1,2.3%) at 38 weeks. Sepsis, acute respiratory distress syndrome, mechanical ventilation, and shock were the most common diagnostic codes in deliveries less than 28 weeks gestation. Heart failure and cardiac arrhythmias were more common in patients with severe maternal morbidity delivering at term. A high proportion of severe maternal morbidity occurred in preterm patients, with the highest rates occurring at less than 28 weeks gestation. Individuals with severe maternal morbidity who deliver preterm had distinct indicators of morbidity compared to those who deliver at term.</p

Phenotypic comparison of wild-type (wt) and DNMT1o-deficient (mt) placentas at E12.5.

<p>(A) Measurements of wet placenta weight, (B) Spongiotrophoblast and Labyrinth central volume, and (C) the number of TGCs per slide of a cohort of wt and mt placentas are displayed as open and filled bars respectively. Data are plotted as mean +SEM. *(P<0.05) and **(P<0.005) denote significant differences between wt and mt averages by the Rank-sum test.</p

Histology of hematoxylin and eosin (H&E) stained labyrinth of one wild-type (wt) three DNMT1o-deficient low-<i>Peg10</i> gDMD methylation placentas.

<p>The scale bars for 50X, 100X and 200X magnification are 500, 200 and 100 μm respectively. Yellow lines in 50x and 100x magnification images outline the labyrinthine zone (LZ).</p