Placental structural adaptation to maternal physical activity and sedentary behavior: findings of the DALI lifestyle study
Authors: Zafaranieh Saghi , Siwetz Monika , Leopold-Posch Barbara , Kummer Daniel , Huppertz Berthold , Desoye Gernot , van Poppel Mireille ,   DALI Core Investigator Group, Desoye Gernot , Simmons David , Corcoy Rosa , Perez Juan M Adelantado , Kautzky-Willer Alexandra , Harreiter Jürgen , Damm Peter , Mathiesen Elizabeth , Jensen Dorte M , Andersen Lise Lotte T , Dunne Fidelma , Lapolla Annunziata , Dalfra Maria G , Bertolotto Alessandra , van Poppel Mireille , Jelsma Judith G M , Galjaard Sander , Wender-Oegowska Ewa , Zawiejska Agnieszka , Hill David J , Devlieger Roland , Snoek Frank J 
Published: May 2024

Abstract

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.