Prenatal exposure to phthalates and phthalate replacements in relation to chorionic plate surface vasculature at delivery.

Pregnant people are ubiquitously exposed to endocrine-disrupting phthalates through consumer products and food. The placenta may be particularly vulnerable to the adverse effects of phthalates, with evidence from animal models suggesting impacts on placental development and vascularization. We translate this research to humans, examining gestational exposure to phthalates and phthalate replacements in relation to novel markers of chorionic plate surface vascularization.

Mediation Analysis using Semi-parametric Shape-Restricted Regression with Applications.

Often linear regression is used to estimate mediation effects. In many instances the underlying relationships may not be linear. Although, the exact functional form of the relationship may be unknown, based on the underlying science, one may hypothesize the shape of the relationship.

Urinary concentrations of phthalate metabolites in relation to preeclampsia and other hypertensive disorders of pregnancy in the environmental influences on child health outcomes (ECHO) program.

Background: Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking.

Objectives: To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP.

Methods: Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy.

Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York.

Background: Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human chorionic gonadotropin (hCG) is a dimeric glycoprotein hormone that can indicate placental toxicity.

Objectives: Our aim was to quantify the association of serum PFAS with placental hCG, measured as an intact molecule (hCG), as free alpha-() and beta-subunits (), and as a hyperglycosylated form (h-hCG), and evaluate effect measure modification by social determinants and by fetal sex.

Mediation Analysis using Semi-parametric Shape-Restricted Regression with Applications.

Often linear regression is used to perform mediation analysis. However, in many instances, the underlying relationships may not be linear, as in the case of placentalfetal hormones and fetal development. Although, the exact functional form of the relationship may be unknown, one may hypothesize the general shape of the relationship.

Prepregnancy obesity and risk of placental inflammation at term: a selection bias analysis.

Purpose: Placental histopathology is a resource for investigating obesity-associated pregnancy conditions. However, studies oversample adverse pregnancies, biasing findings. We examine the association between prepregnancy obesity (risk factor for inflammation) and histologic placental inflammation (correlated with impaired infant neurodevelopment) and how selection bias may influence the association.

Soluble CD137 and risk of hepatocellular carcinoma: nested case-control studies in cohorts in Shanghai and Singapore.

Background: The majority of hepatocellular carcinoma (HCC) cases occur in the presence of cirrhosis. Biomarkers of cirrhosis-associated immune dysfunction such as CD8+ T cell cytokines could aid HCC risk assessment.

Methods: CD8+ T cell cytokines were determined in pre-diagnostic serum in two studies including 315 HCC case-control pairs in the Shanghai Cohort Study (SCS) and 197 pairs in the Singapore Chinese Health Study (SCHS).

Application of 4-way decomposition to the analysis of placental-fetal biomarkers as intermediary variables between maternal body mass index and birthweight.

Human chorionic gonadotropin (hCG) is a placental hormone measured in pregnancy to predict individual level risk of fetal aneuploidy and other complications; yet may be useful in understanding placental origins of child development more generally. hCG was associated with maternal body mass index (BMI) and with birthweight. The primary aim here was to evaluate hCG as a mediator of maternal BMI effects on birthweight by causal mediation analysis.

Associations between Maternal Risk Factors and Intrinsic Placental and Fetal Brain Functional Properties in Congenital Heart Disease.

The relationship between maternal risk factors (MRFs) (particularly pre-gravid obesity, diabetes, and hypertension) and congenital heart disease (CHD) to placental and fetal brain outcomes is poorly understood. Here, we tested the hypothesis that MRF and CHD would be associated with reduced intrinsic placental and fetal brain function using a novel non-invasive technique. Pregnant participants with and without MRF and fetal CHD were prospectively recruited and underwent feto-placental MRI.

A study on the association of placental and maternal urinary phthalate metabolites.

Background: Phthalate exposure in pregnancy is typically estimated using maternal urinary phthalate metabolite levels. Our aim was to evaluate the association of urinary and placental tissue phthalates, and to explore the role of maternal and pregnancy characteristics that may bias estimates.

Methods: Fifty pregnancies were selected from the CANDLE Study, recruited from 2006 to 2011 in Tennessee.

Phthalate Exposures and Placental Health in Animal Models and Humans: A Systematic Review.

Phthalates are ubiquitous compounds known to leach from the plastic products that contain them. Due to their endocrine-disrupting properties, a wide range of studies have elucidated their effects on reproduction, metabolism, neurodevelopment, and growth. Additionally, their impacts during pregnancy and on the developing fetus have been extensively studied.

NAFLD polygenic risk score and risk of hepatocellular carcinoma in an East Asian population.

It is difficult to identify people with nonalcoholic fatty liver disease (NAFLD) who are at high risk for developing hepatocellular carcinoma (HCC). A polygenic risk score (PRS) for hepatic fat (HFC-PRS) derived from non-Asians has been reported to be associated with HCC risk in European populations. However, population-level data of this risk in Asian populations are lacking.

Shape Detection using Semi-parametric Shape-Restricted Mixed Effects Regression Spline with Applications.

Linear models are widely used in the field of epidemiology to model the relationship between placental-fetal hormone and fetal/infant outcome. When researchers suspect curvilinear relationship exists, some nonparametric techniques, including regression splines, smoothing splines and penalized regression splines, can be used to model the relationship (Korevaar et al. 2016; Wu and Zhang 2006).

Latent class analysis of placental histopathology: a novel approach to classifying early and late preterm births.

Background: Neonatal morbidity attributable to prematurity predominantly occurs among early preterm births (<32 weeks) rather than late preterm births (32 to <37 weeks). Methods to distinguish early and late preterm births are lacking given the heterogeneity in pathophysiology and risk factors, including maternal obesity. Although preterm births are often characterized by clinical presentation (spontaneous or clinically indicated), classifying deliveries by placental features detected on histopathology reports may help identify subgroups of preterm births with similar etiology and risk factors.

A pathway level analysis of PFAS exposure and risk of gestational diabetes mellitus.

Per- and polyfluoroalkyl substances (PFAS) have been found to be associated with gestational diabetes mellitus (GDM) development, a maternal health disorder in pregnancy with negative effects that can extend beyond pregnancy. Studies that report on this association are difficult to summarize due to weak associations and wide confidence intervals. One way to advance this field is to sharpen the biologic theory on a causal pathway behind this association, and to measure it directly by way of molecular biomarkers.

Second-Trimester Placental and Thyroid Hormones Are Associated With Cognitive Development From Ages 1 to 3 Years.

Adequate maternal thyroid hormone (TH) is necessary for fetal brain development. The role of placental human chorionic gonadotropin (hCG) in ensuring the production of TH is less well understood. The objective of the study was to evaluate 1) associations of placental hCG and its subunits, and maternal TH in the second trimester, and 2) the single and joint effects of TH and placental hormones on cognitive development and communication at ages 1 and 3 years.

A toolkit for the application of placental-fetal molecular biomarkers in epidemiologic studies of the fetal origins of chronic disease.

Purpose Of Review: In this review, we provide essential background knowledge and an analytical framework for the application of placental-fetal molecular biomarkers in fetal origins chronic disease epidemiology. The widely available and highly quantitative placental hormone human chorionic gonadotropin (hCG) is used as an example. hCG is currently used for diagnosing fetal genetic disorders; yet it can and should be expanded to understanding the fetal origins of chronic diseases.

First trimester mechanisms of gestational sac placental and foetal teratogenicity: a framework for birth cohort studies.

Background: The function of the gestational sac (GS) and the placenta in the closely related processes of embryogenesis and teratogenicity in the first trimester has been minimally described. The prevailing assumption is that direct teratogenic effects are mediated by the critical extraembryonic organ, the placenta, which either blocks or transfers exposures to the foetus. Placental transfer is a dominant mechanism, but there are other paradigms by which the placenta can mediate teratogenic effects.

An Investigation of the Single and Combined Phthalate Metabolite Effects on Human Chorionic Gonadotropin Expression in Placental Cells.

Background: Observational studies have reported associations between maternal phthalate levels and adverse outcomes at birth and in the health of the child. Effects on placental function have been suggested as a biologic basis for these findings.

Objective: We evaluated the effects of phthalates on placental function by measuring relevant candidate genes and proteins.

Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort.

Background: Prenatal urinary concentrations of phthalates in women participants in an urban birth cohort were associated with outcomes in their children related to neurodevelopment, autoimmune disease risk, and fat mass at 3,5,7, and 8 years of life. Placental biomarkers and outcomes at birth may offer biologic insight into these associations. This is the first study to address these associations with candidate genes from the phthalate and placenta literature, accounting for sex differences, and using absolute quantitation methods for mRNA levels.

IFPA meeting 2016 workshop report II: Placental imaging, placenta and development of other organs, sexual dimorphism in placental function and trophoblast cell lines.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops addressed challenges, strengths and limitations of techniques and model systems for studying the placenta, as well as future directions for the following areas of placental research: 1) placental imaging; 2) sexual dimorphism; 3) placenta and development of other organs; 4) trophoblast cell lines.

Placental Mechanics in the Zika-Microcephaly Relationship.

How the Zika virus (ZIKV) accesses the embryo remains unknown. In this issue, Quicke et al. (2016) use an in vitro model of the human placenta to show that placental macrophages are more permissive to ZIKV infection than trophoblasts, which may be refractory to infection (Bayer et al.