Fetal Growth Restriction: Pathogenic Mechanisms

Abstract

Complex genetic and environmental mechanisms of maternal, fetal and placental origin regulate fetal growth and may contribute to fetal growth restriction (FGR). The somatotrophic regulatory factors include IGF-I, IGF-II, the IGF binding proteins (IGFBP) 1-6, IGF receptors 1 and 2, and the IGFBP specific proteases. Abnormal remodeling of utero-placental arteries and abnormal fetal-placental angiogenesis has also been implicated in FGR. The underlying molecular mediators include vascular endothelial growth factor (VEGF), placental growth factor (PlGF), VEGF receptors, VEGF binding proteins, and numerous other agents working through multiple pathways many of which still remain unknown. Expression of these major angiogenic factors appears to be regulated by local oxygen partial pressure. Future investigations may resolve many of these issues not only adding to the clarity of our understanding of the mechanisms of growth restriction but also improving clinical management.

Early onset fetal growth restriction

“…Numerous studies have also shown that some maternal biochemical markers (e.g. pregnancy associasted plasma protein-a, PAPP-A; alfa-fetoprotein, AFP; human chorionic gonadotropin, hCG; Inhibin A) are associated with placental function and fetal growth, and their levels are altered in SGA and FGR pregnancies [56]. A low level first trimester PAPP-A should be considered a major risk factor for delivering a SGA neonate; the combination of uterine artery Doppler and maternal serum markers appears promising for improving prediction of SGA fetus, although predictive values are still poor [57][58][59].…”

Angiogenic factors in placentas from pregnancies complicated by fetal growth restriction (Review)

“…Angiogenesis is a placental factor which plays an important role in the development of FGR (28)(29)(30)(31)(32). FGR occurs as a result of inadequate vascular transformation and terminal villus formation (28).…”

New aspect in management of fetal growth restriction

“…만삭 훨씬 전에 발생한 태아발육제한에서는 생물리학 계 수의 이상소견이 발생하기 전에 태반 순환의 부전, 혈류의 재분배 등이 일어나므로, 자궁동맥 및 제대 동맥 도플러 검사가 태반의 상태를 알아 보는 선별적 검사로 사용되고 있다 [28,29]. 많은 혈청 표지자들이 태아성장이나 태반기능과의 연관에 대해 보고 되고 있는데, 알파태아단백(alpha-fetoprotein), 임신-관련 혈청단백질-A (pregnancy-associated plasma protein-A), 융모성 성선자극 호르몬 (human chorionic gonadotrophin), 에스트리올(estriol), 인히빈-A (inhibin-A) 등은 염색체 이상뿐만 아니라 태아발육제한이나 임신 합병증과도 관련이 있다 [30][31][32]. 최근에는 vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), soluble human vascular endothelial growth factor receptor-1 (sVEGFR-1), soluble endoglin 등이 조발형 (early-onset) 태아발육제한과 연관이 있다고 보고되었다 [33][34][35].…”

“…최근에는 vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), soluble human vascular endothelial growth factor receptor-1 (sVEGFR-1), soluble endoglin 등이 조발형 (early-onset) 태아발육제한과 연관이 있다고 보고되었다 [33][34][35]. 이 러한 생화학적 지표와 임신 제2 삼분기에 임신부의 자궁동맥 도플러 검 사를 병행할 때 진단율이 더욱 향상될 수 있다 [32]. 하지만 임상적으로 유용할 정도의 민감도와 특이도를 갖기에는 더 많은 연구가 필요하다.…”