Pre-pregnancy check-up of maternal vascular status and associated phenotype is crucial for the health of mother and offspring
Authors: Evsevieva Maria , Sergeeva Oksana , Mazurakova Alena , Koklesova Lenka , Prokhorenko-Kolomoytseva Irina , Shchetinin Evgenij , Birkenbihl Colin , Costigliola Vincenzo , Kubatka Peter , Golubnitschaja Olga 
Published: August 2022

Abstract
Cardiovascular disease remains the leading cause of disease burden globally with far-reaching consequences including enormous socio-economic burden to healthcare and society at large. Cardiovascular health is decisive for reproductive function, healthy pregnancy and postpartum. During pregnancy, maternal cardiovascular system is exposed to highly increased haemodynamic stress that significantly impacts health status of the mother and offspring. Resulting from sub-optimal maternal health conditions overlooked in pre-pregnancy time, progressive abnormalities can be expected during pregnancy and postpartum. Contextually, there are two main concepts to follow in the framework of predictive, preventive and personalised medicine, namely to develop:
1. advanced screening of sub-optimal health conditions in young populations to predict and prevent individual health risks prior to planned pregnancies
2. in-depth companion diagnostics during pregnancy to predict and prevent long-lasting postpartum health risks of the mother and offspring.
Data collected in the current study demonstrate group-specific complications to health of the mother and offspring and clinical relevance of the related phenotyping in pre-pregnant mothers. Diagnostic approach proposed in this study revealed its great clinical utility demonstrating important synergies between cardiovascular maladaptation and connective tissue dysfunction. Co-diagnosed pre-pregnancy low BMI of the mother, connective tissue dysfunction, increased stiffness of peripheral vessels and decreased blood pressure are considered a highly specific maternal phenotype useful for innovative screening programmes in young populations to predict and prevent severe risks to health of the mother and offspring. This crucial discovery brings together systemic effects characteristic, for example, for individuals with Flammer syndrome predisposed to the phenotype-specific primary vascular dysregulation, pregnancy-associated risks, normal tension glaucoma, ischemic stroke at young age, impaired wound healing and associated disorders. Proposed maternal phenotyping is crucial to predict and effectively protect both the mother and offspring against health-to-disease transition. Pre-pregnancy check-up focused on sub-optimal health and utilising here described phenotypes is pivotal for advanced health policy.

Plain English abstract
Cardiovascular health is decisive for reproductive function and healthy pregnancy. During pregnancy, maternal cardiovascular system may demonstrate health-to-disease transition relevant for the affected mother and offspring. Overlooked in pre-pregnancy time, progressive abnormalities can be expected during pregnancy and lifelong. Here we co-diagnosed maternal pre-pregnancy low bodyweight with systemic effects which may increase risks of pregnancy, eye and heart disorders and ischemic stroke at young age, amongst others. Innovative screening programmes focused on sub-optimal health in young populations to predict and to mitigate individual health risks prior to pregnancy is an essential innovation for health policy proposed.