Shared and disparate components of the pathophysiologies of fetal growth restriction and preeclampsia

Roberta B Ness1, Baha M Sibai

  • 1Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA 15261, USA. repro@pitt.edu

Intrauterine growth restriction (IUGR) and preeclampsia differ in their association with maternal disease but share a similar placental pathology. Moreover, mothers who have had pregnancies complicated by preeclampsia or IUGR are at elevated later-life cardiovascular risk. Why, then, do some women develop IUGR and others develop preeclampsia? In this clinical opinion, based on a review of the literature, we hypothesize that both women experiencing preeclampsia and IUGR enter pregnancy with some degree of endothelial dysfunction, a lesion that predisposes to shallow placentation. In our opinion, preeclampsia develops when abnormal placentation, through the mediator of elevated circulating cytokines, interacts with maternal metabolic syndrome, comprised of adiposity, insulin resistance/hyperglycemia, hyperlipidemia, and coagulopathy. IUGR develops in the absence of antenatal metabolic syndrome. Among these women, the baby is affected by shallow placentation but the mother does not develop clinically apparent disease. This conceptualization provides a testable framework for future etiologic studies of preeclampsia and IUGR.

Related Concept Videos

Pathophysiology of Diabetes01:20

Pathophysiology of Diabetes

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. The four categories of diabetes are type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes.
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility, suggesting a...
Teratogenicity01:07

Teratogenicity

The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
Hormonal Regulation01:33

Hormonal Regulation

The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Physiological Barriers01:25

Physiological Barriers

Physiological barriers are semi-permeable cellular structures restricting drug diffusion into intracellular compartments and tissues. There are six types of physiological barriers: blood endothelial, cell membrane, blood-brain, blood-cerebrospinal fluid (CSF), blood-placenta, and blood-testis barriers.
The blood endothelial barrier is the most porous of these. It allows all small ionized, un-ionized, and lipophilic molecules to pass through the endothelial lining into the interstitial space...
Factors Affecting Drug Distribution: Physiological Barriers01:23

Factors Affecting Drug Distribution: Physiological Barriers

Drug distribution in the body is intricately regulated by various physiological barriers that control the passage of substances. These include the capillary endothelial barrier, the blood-brain, blood-cerebrospinal fluid, blood-placental, and blood-testis barriers.
The capillary endothelial barrier allows only smaller molecules below 600 Da (Daltons) to pass through. It also restricts drugs like heparin that are bound to blood components, limiting their movement within the bloodstream.
The...