# From venous congestion to placental hypoxia: the underappreciated role of chronic venous disease in impaired placenta development and pregnancy health

**Authors:** Yang Zhang, Xiaotong Huang, Li Zou, Xiangwei Cheng, Xiaoxia Liu

PMC · DOI: 10.3389/fmed.2026.1753334 · Frontiers in Medicine · 2026-02-05

## TL;DR

This paper explores how chronic venous disease in pregnant women may affect placental development and pregnancy outcomes, highlighting the need for better understanding and management.

## Contribution

The paper reviews current literature to clarify the underappreciated role of chronic venous disease in pregnancy and identifies gaps in knowledge for future research.

## Key findings

- Chronic venous disease in pregnancy may lead to placental hypoxia and adverse outcomes.
- Current management strategies for CVD in pregnancy lack standardization.
- Emerging evidence suggests systemic effects of CVD beyond localized symptoms.

## Abstract

Chronic Venous Disease (CVD) is a common vascular disorder, primarily affecting the lower extremities, with a significantly higher incidence in women. Pregnant women represent a particularly high-risk population for CVD. Early screening and assessment of CVD severity and progression during pregnancy are imperative for preventing Venous Thromboembolism (VTE). Despite its high prevalence, CVD in pregnancy often remains underestimated, frequently being managed by clinicians as a localized and benign condition. However, emerging evidence suggests that CVD may exert broader systemic effects, potentially compromising placental development and fetal well-being through alterations in the maternal-placental-fetal circulation. Nevertheless, the precise correlations between CVD and a spectrum of adverse pregnancy outcomes remain unclear. Also, the standardized management strategies for CVD in pregnancies are yet to be established. This review synthesizes current literature to delineate the present understanding and identify persistent knowledge gaps in this field. Furthermore, it aims to underscore the clinical significance of CVD in pregnancy and to propose pertinent directions for future research, thereby advocating for heightened clinical awareness and more investigative efforts.

## Linked entities

- **Diseases:** Venous Thromboembolism (MONDO:0005399)

## Full-text entities

- **Genes:** STC1 (stanniocalcin 1) [NCBI Gene 6781] {aka STC}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, ILK (integrin linked kinase) [NCBI Gene 3611] {aka HEL-S-28, ILK-1, ILK-2, P59, p59ILK}, NOX1 (NADPH oxidase 1) [NCBI Gene 27035] {aka GP91-2, MOX1, NOH-1, NOH-1L, NOH1}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, PDCD6IP (programmed cell death 6 interacting protein) [NCBI Gene 10015] {aka AIP1, ALIX, DRIP4, HP95, MCPH29}, WNT1 (Wnt family member 1) [NCBI Gene 7471] {aka BMND16, INT1, OI15}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, AIF1 (allograft inflammatory factor 1) [NCBI Gene 199] {aka AIF-1, IBA1, IRT-1, IRT1}, FLT1 (fms related receptor tyrosine kinase 1) [NCBI Gene 2321] {aka FLT, FLT-1, VEGFR-1, VEGFR1}, PGF (placental growth factor) [NCBI Gene 5228] {aka D12S1900, PGFL, PIGF, PLGF, PlGF-2, SHGC-10760}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, HAT1 (histone acetyltransferase 1) [NCBI Gene 8520] {aka KAT1}, PDPN (podoplanin) [NCBI Gene 10630] {aka AGGRUS, D2-40, GP36, GP40, Gp38, HT1A-1}, CYBB (cytochrome b-245 beta chain) [NCBI Gene 1536] {aka AMCBX2, CGD, CGDX, GP91-1, GP91-PHOX, GP91PHOX}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, PAPPA (pappalysin 1) [NCBI Gene 5069] {aka ASBABP2, DIPLA1, IGFBP-4ase, PAPA, PAPP-A, PAPPA1}, PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175] {aka CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM}
- **Diseases:** Thromboembolic Disease (MESH:D013923), Constipation (MESH:D003248), stillbirth (MESH:D050497), fetal distress (MESH:D005316), CVD (MESH:D002908), immune dysregulation (OMIM:614878), VTE (MESH:D054556), hypertension (MESH:D006973), placental insufficiency syndromes (MESH:D010927), muscular cramps (MESH:D009120), abnormalities (MESH:D000014), vascular disorder (MESH:D002561), venous dilation (MESH:D002311), preterm birth (MESH:D047928), hypoxic placental injury (MESH:D010922), fatigue (MESH:D005221), venous congestion (MESH:D006940), venous (MESH:D014647), hypoxic (MESH:D002534), gestational diabetes (MESH:D016640), pruritus (MESH:D011537), hypoxia (MESH:D000860), ischemia (MESH:D007511), pain (MESH:D010146), venous obstruction (MESH:D006502), inflammatory (MESH:D007249), reflux (MESH:D005764), venous disease (MESH:D004194), fetal growth restriction (MESH:D005317), VV (MESH:D014648), telangiectasias (MESH:D013684), pigmentation (MESH:D010859), preeclampsia (MESH:D011225), edema (MESH:D004487), venous insufficiency (MESH:D014689), lymphedema (MESH:D008209), valvular incompetence (MESH:D006349)
- **Chemicals:** lipid (MESH:D008055), LMWH (MESH:D006495), ROS (MESH:D017382), coumarins (MESH:D003374), flavonoid compounds (-), aescin (MESH:D004928), progesterone (MESH:D011374), diosmin (MESH:D004145), cyanoacrylate (MESH:D003487)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12916620/full.md

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Source: https://tomesphere.com/paper/PMC12916620