Pre-pregnancy body mass index, gestational diabetes mellitus, and gestational weight gain: individual and combined effects on fetal growth.

Background: Pre-pregnancy body mass index (BMI), gestational diabetes mellitus (GDM), and gestational weight gain (GWG) are interlinked and may play a complex role in fetal growth. We aimed to examine the relationship between pre-pregnancy BMI, GDM, GWG, and fetal growth outcomes and explore the contribution of GDM and GWG to the relationship between Pre-pregnancy obesity/overweight and large-for-gestational-age (LGA) in a prospective cohort. Methods: We prospectively recruited women in the first trimester and having one-step GDM screened with a 75-g oral glucose tolerance test between 24 and 28 weeks of gestation (n = 802). Outcomes included LGA, small-for-gestational-age (SGA), and preterm birth. To assess the individual and cumulative associations between pre-pregnancy BMI, GDM, GWG, and these outcomes, we used multivariate logistic regression analysis. Furthermore, we employed structural equation modeling (SEM) to investigate the mediating role of GDM and excessive GWG in the correlation between pre-pregnancy overweight/obesity and LGA. Results: Pre-pregnancy obesity, GDM, and excessive GWG were all independently associated with increased odds of LGA. Inadequate GWG was associated with higher odds of preterm birth. Compared with women unexposed to pre-pregnancy overweight/obesity, GDM, or excessive GWG, women exposed any two conditions had higher odds for LGA (AOR 3.18, 95% CI 1.25-8.11) and women with coexistence of all had the highest odds for LGA (AOR 8.09, 95% CI 2.18-29.97). The mediation analysis showed that GDM explained 18.60% (p < 0.05) of the total effect of pre-pregnancy overweight/obesity on LGA, and GWG explained 17.44% (p < 0.05) of the total effect. Conclusion: Pre-pregnancy obesity/overweight, GDM, and excessive GWG are associated with higher odds of fetal growth disturbances as individual factors and when they co-exist. The effect of pre-pregnancy overweight/obesity on LGA is partially achieved through GDM and excessive GWG.

The implementation of target trial emulation for causal inference: a scoping review.

OBJECTIVES: We aim to investigate the implementation of Target Trial Emulation (TTE) for causal inference, involving research topics, frequently used strategies, and issues indicating the need for future improvements. STUDY DESIGN AND SETTING: We performed a scoping review by following the Joanna Briggs Institute (JBI) guidance and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. A health research-focused librarian searched multiple medical databases, and two independent reviewers completed screening and extraction within covidence review management software. RESULTS: Our search resulted in 1,240 papers, of which 96 papers were eligible for data extraction. Results show a significant increase in the use of TTE in 2018 and 2021. The study topics varied and focused primarily on cancer, cardiovascular and cerebrovascular diseases, and infectious diseases. However, not all papers specified well all three critical components for generating robust causal evidence: time-zero, random assignment simulation, and comparison strategy. Some common issues were observed from retrieved papers, and key limitations include residual confounding, limited generalizability, and a lack of reporting guidance that need to be improved. CONCLUSION: Uneven adherence to the TTE framework exists, and future improvements are needed to progress applications using causal inference with observational data.

The Shear Stress-Regulated Expression of Glypican-4 in Endothelial Dysfunction In Vitro and Its Clinical Significance in Atherosclerosis.

Retention of circulating lipoproteins by their interaction with extracellular matrix molecules has been suggested as an underlying mechanism for atherosclerosis. We investigated the role of glypican-4 (GPC4), a heparan sulfate (HS) proteoglycan, in the development of endothelial dysfunction and plaque progression; Expression of GPC4 and HS was investigated in human umbilical vein/artery endothelial cells (HUVECs/HUAECs) using flow cytometry, qPCR, and immunofluorescent staining. Leukocyte adhesion was determined in HUVECs in bifurcation chamber slides under dynamic flow. The association between the degree of inflammation and GPC4, HS, and syndecan-4 expressions was analyzed in human carotid plaques; GPC4 was expressed in HUVECs/HUAECs. In HUVECs, GPC4 protein expression was higher in laminar than in non-uniform shear stress regions after a 1-day or 10-day flow (p < 0.01 each). The HS expression was higher under laminar flow after a 1 day (p < 0.001). Monocytic THP-1 cell adhesion to HUVECs was facilitated by GPC4 knock-down (p < 0.001) without affecting adhesion molecule expression. GPC4 and HS expression was lower in more-inflamed than in less-inflamed plaque shoulders (p < 0.05, each), especially in vulnerable plaque sections; Reduced expression of GPC4 was associated with atherogenic conditions, suggesting the involvement of GPC4 in both early and advanced stages of atherosclerosis.

Effect of vitamin A on the relationship between maternal thyroid hormones in early pregnancy and fetal growth: A prospective cohort study.

Background: Fetal growth patterns are influenced by maternal thyroid function and vitamin A level during pregnancy. Vitamin A presents interactions with thyroid tissues and hormonal systems. We examined whether vitamin A status modified the associations of maternal thyroid hormones in early pregnancy and fetal growth outcomes among euthyroid pregnant women in a prospective cohort study (n = 637). Methods: We performed multiple linear regression and multinomial logistic regression analysis to investigate the effects of thyroid hormones in early pregnancy on fetal growth according to different levels of serum vitamin A based on median value. Results: A 1 pmol/L increase in maternal free triiodothyronine (FT3) levels was associated with an increased birth weight of 0.080 kg (p = 0.023) in women with lower maternal vitamin A levels in early pregnancy. Increased maternal free thyroxine (FT4) was associated with decreased odds for both small size for gestational age (SGA) [odds ratios (OR) = 0.66, 95% confidence interval (CI): 0.45-0.95] and large size for gestational age (LGA) (OR = 0.66, 95% CI: 0.45-0.98) in women with higher vitamin A level in early pregnancy after adjustment for maternal prepregnancy body mass index, gestational weight gain, maternal employed, parity, gestational week at sampling, and gestational diabetes mellitus. Conclusions: In Chinese pregnant women without overt thyroid dysfunction, maternal FT4 in early pregnancy was positively associated with optimal fetal growth among women with higher serum vitamin A concentrations.

The Impacts of Prenatal Mental Health Issues on Birth Outcomes during the COVID-19 Pandemic: A Scoping Review.

BACKGROUND: The severity of the COVID-19 pandemic is likely to exacerbate mental health problems during the prenatal period and increase the risk of adverse birth outcomes. This review assessed the published literature related to the impacts of prenatal mental health issues on birth outcomes during the COVID-19 pandemic. METHODS: This scoping review was conducted using PROSPERO, Cochrane Library, OVID Medline, Ovid EMBASE, OVID PsycInfo, EBSCO CINAHL, and SCOPUS. The search was conducted using controlled vocabulary and keywords representing the concepts "COVID19", "mental health" and "birth outcomes". The main inclusion criteria were peer-reviewed published articles from late 2019 to the end of July 2021. RESULTS AND DISCUSSION: After removing duplicates, 642 articles were identified, of which two full texts were included for analysis. Both articles highlighted that pregnant women have experienced increasing prenatal mental health issues during the COVID-19 pandemic and, further, increased the risk of developing adverse births. This scoping review highlighted that there is a lack of research on the impact of prenatal mental health issues on birth outcomes during the pandemic. CONCLUSION: Given the severity of the COVID-19 pandemic and the burdens of prenatal mental health issues and adverse birth outcomes, there is an urgent need to conduct further research.

Determinants of second pregnancy among pregnant women: a hospital-based cross-sectional survey in China.

OBJECTIVES: This study aimed to explore determinants of second pregnancy and underlying reasons among pregnant Chinese women. DESIGN: The study was a population-based cross-sectional survey. SETTING: 16 hospitals in 5 provinces of Mainland China were included. PARTICIPANTS: A total of 2345 pregnant women aged 18 years or above were surveyed face to face by investigators between June and August 2015. MAIN OUTCOME MEASURES: The pregnancy statuses (first or second pregnancy) and reasons for entering second pregnancy. RESULTS: A total of 1755 (74.8%) and 590 (25.2%) women in their respective first and second pregnancies were enrolled in this study. The most common self-reported reasons for entering second pregnancy among participants included the benefits to the first child (26.1%), love of children (25.8%), adoption of the 2-child policy (11.5%), concerns about losing the first child (7.5%) and suggestions from parents (7.5%). Pregnant women with low (prevalence ratio (PR) 1.96; 95% CI 1.62 to 2.36) and moderate education level (PR 1.97; 95% CI 1.65 to 2.36) were more likely to have a second pregnancy than their higher educated counterparts. Income was inversely associated with second pregnancy. However, unemployed participants (PR 0.79; 95% CI 0.66 to 0.95) were less likely to enter a second pregnancy than those employed. Women with moderate education were 3 times more likely to have a second child following the '2-child policy' than the low education level subgroup. CONCLUSIONS: 1 in every 4 pregnant women is undergoing a second pregnancy. The benefits of the firstborn or the love of children were the key drivers of a second pregnancy. Low socioeconomic status was positively associated with a second pregnancy as well. The new 2-child policy will have an influence on China's demographics.