Placental structural adaptation to maternal physical activity and sedentary behavior: findings of the DALI lifestyle study.

STUDY QUESTION: Are maternal levels of moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) in obese pregnant women associated with placental structural adaptations for facilitating oxygen delivery to the fetus? SUMMARY ANSWER: Higher maternal MVPA and ST are associated with a higher density of villi, a proxy measure of placental surface area for oxygen delivery to the fetus, without further added placental vessels. WHAT IS KNOWN ALREADY: Physical activity during pregnancy intermittently reduces uterine blood flow, potentially limiting placental and fetal oxygen supply. The placenta can mount several adaptive responses, including enlargement of the surface area of villi and/or feto-placental vessels to accommodate fetal needs. Early research on the morphology and growth of the placenta with exercise interventions has shown inconsistencies and is lacking, particularly in non-lean pregnant women. STUDY DESIGN, SIZE, DURATION: This study is a secondary longitudinal analysis of the vitamin D and lifestyle intervention for gestational diabetes prevention (DALI) randomized controlled trial. The prospective study was conducted between 2012 and 2015 in nine European countries at 11 different sites. In this analysis, 92 pregnant women with a BMI ≥ 29 kg/m2 were combined into one cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: MVPA and percentage of time spent sedentary (% ST) were measured with accelerometers during gestation. Placental sections were immunostained for endothelial cell-specific CD34. Artificial intelligence (AI)-based stereology assessed villous density, number, and cross-sectional area of vessels on whole-slide images and in selected regions comprising peripheral villi only, where the majority of vascular adaptations occur. Expression of pro- and anti-angiogenic factors was quantified using molecular counting analysis. MAIN RESULTS AND THE ROLE OF CHANCE: In multivariable regression, higher levels of maternal MVPA (min/day) were associated with a higher density of villi in both whole-slide images (beta 0.12; 95% CI 0.05, 0.2) and selected regions (0.17; CI 0.07, 0.26). Unexpectedly, ST was also positively associated with density of villi (0.23; CI 0.04, 0.43). MVPA and ST were not associated with vessel count/mm2 villous area, vessel area, or pro- and anti-angiogenic factor mRNA expression. All estimates and statistical significance of the sensitivity analyses excluding smokers, women who developed gestational diabetes or pre-eclampsia and/or pregnancy-induced hypertension were similar in the main analysis. LIMITATIONS, REASONS FOR CAUTION: The placenta is a complex organ undergoing dynamic changes. While various adjustments were made to account for different maternal contributing factors, in addition to the outcome measures, various other factors could impact oxygen delivery to the fetus. WIDER IMPLICATIONS OF THE FINDINGS: For the first time, we evaluated the association between placental structures quantified using an AI-based approach with objectively measured physical activity and ST at multiple time points in pregnant women with obesity. The observed adaptations contribute to the advancement of our understanding of the hemodynamics and adaptations of the placental unit in response to MVPA and ST. However, our results might not be generalizable to lean pregnant women. STUDY FUNDING/COMPETING INTEREST(S): The DALI project has received funding from the European Community's 7th Framework Program (FP7/2007-2013) under grant agreement no. 242187. The funders had no role in study design, collection of data, analyses, writing of the article, or the decision to submit it for publication. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: ISRCTN70595832.

Automated stereological image analysis approach of the human placenta: Surface areas and vascularization.

Detecting and quantifying surface densities of placental villi and their vasculature adds important information on the development of the placenta under different exposures and pathological conditions. Today, a larger number of samples and tissue areas can be examined using automated Artificial Intelligence-based approaches. Although each image series calls for a particular approach, sharing the methods will help in facilitating reproducibility and comparability. Here we show the protocol of a software-based quantification of vessels (number and area) in villous tissues of human placentas, based on scanned images of full-size placental sections.

The Association of Physical Activity and Sedentary Behavior with Maternal and Cord Blood Anti-Oxidative Capacity and HDL Functionality: Findings of DALI Study.

Obesity is one of the most common health issues in pregnancy with short and long-term consequences for both mother and her offspring. Promoting moderate to vigorous physical activity (MVPA) and decreasing sedentary time (ST) could have a positive impact on weight and obesity management, and therefore adiposity-induced oxidative stress, inflammation, and atherogenesis. However, the effects of MVPA and ST on anti-oxidative and anti-atherogenic markers in pregnancy have not been studied to date. This study aimed to assess the association of longitudinally and objectively measured MVPA and ST in 122 overweight/obese women (BMI ≥ 29 kg/m2) with maternal and cord blood markers of oxidative stress measured by advanced oxidation protein products (AOPP), anti-oxidative capacity, as well as high-density lipoproteins (HDL) related paraoxonase-1 (PON-1) activity and cholesterol efflux. Linear regression models showed no associations of MVPA and ST with outcomes in maternal blood. In contrast, MVPA at <20 weeks and 24-28 weeks of gestation were positively associated with anti-oxidative capacity, as well as PON-1 activity of HDL in cord blood. MVPA at 35-37 weeks correlated with higher AOPP, as well as higher anti-oxidative capacity. ST <20 weeks was also positively associated with inhibition of oxidation in cord blood. We speculate that increasing MVPA of overweight/obese women during pregnancy attenuates the oxidative stress state in the new-born.

Physical Activity and Sedentary Time in Pregnancy: An Exploratory Study on Oxidative Stress Markers in the Placenta of Women with Obesity.

Regular moderate-to-vigorous physical activity (MVPA) and reduced sedentary time (ST) improve maternal glucose metabolism in pregnancy. More MVPA and less ST outside pregnancy increase antioxidant capacity, hence, are beneficial in preventing oxidative stress. The placenta is the first line of defense for the fetus from an adverse maternal environment, including oxidative stress. However, effects of MVPA and ST on oxidative stress markers in the placenta are unknown. The purpose of this study was to assess the association of MVPA and ST in pregnancy with oxidative stress markers in placentas of overweight/obese women (BMI ≥ 29 kg/m2). MVPA and ST were objectively measured with accelerometers at <20 weeks, 24−27 and 35−37 weeks of gestation. Using linear Bayesian multilevel models, the associations of MVPA and ST (mean and changes) with mRNA expression of a panel of 11 oxidative stress related markers were assessed in 96 women. MVPA was negatively correlated with HSP70 mRNA expression in a sex-independent manner and with GCLM expression only in placentas of female fetuses. ST was positively associated with HO-1 mRNA expression in placentas of male neonates. None of the other markers were associated with MVPA or ST. We speculate that increasing MVPA and reducing ST attenuates the oxidative stress state in placentas of obese pregnant women.