Elsevier

Obstetrics & Gynecology

Volume 92, Issue 6, December 1998, Pages 1044-1055
Obstetrics & Gynecology

Review Articles
Current concepts of fetal growth restriction: part I. Causes, classification, and pathophysiology

https://doi.org/10.1016/S0029-7844(98)00328-7Get rights and content

Abstract

Objective: To update basic concepts and management strategies of fetal growth restriction (FGR).

Data source: An English literature search was conducted for pertinent articles related to FGR from 1976 to 1997. Original research articles, review articles, and book chapters were reviewed.

Methods of study selection: This study was divided into two parts. For this article, both human data and animal data pertinent to understanding causative factors, pathogenesis, clinical type, and pathophysiology were included. To perform a meaningful comparison, the concept of investigators and their methods of investigation were critically compared between the two study periods: 1976–1985 and 1986–1997.

Tabulation, integration, and results: Older concepts involving basic principles of FGR based on animal models during the first study period were integrated with new research findings obtained from human FGR during the second study period. By comparative analysis of older animal data and new human data, current concepts of FGR were synthesized.

Conclusion: Fetal growth restriction affects a heterogenous group of infants. Despite development of new technology for investigation, many older basic concepts related to FGR are still fundamentally sound. However, new investigations directly performed on human fetuses are a useful expansion of the older concepts.

Section snippets

Current definition of FGR

A growth-restricted fetus is one that has not reached its growth potential at a given gestational age due to one or more causative factors. Fetal growth restriction constitutes only a fraction of small for gestational age (SGA) newborn.12 Depending on an arbitrary cutoff level, 3 to 10% of neonates weigh below the normal adjusted value for gestational age.7, 9, 12, 14, 15 Up to 70% of SGA infants are small simply due to constitutional factors determined by maternal ethnicity, parity, weight, or

Classification of FGR

Fetal growth restriction can be classified according to cell growth dynamics and clinical types. The classification of cell growth dynamics was established during the first study period. Fetal growth was viewed as having three consecutive cell growth dynamic phases.18, 19 The first phase was referred to as the phase of cellular hyperplasia occurring during the first 16 weeks of gestation. During this phase, a rapid increase in cell number occurs. The second phase was known as the phase of

Causative factors of FGR

Fetal growth restriction can be caused by fetal, placental, maternal, and other factors listed in Table 1. During the first study period, many investigators mainly focused on factors responsible for mature FGR, such as high altitude, smoking, alcohol, maternal nutritional deprivation, etc. During the second study period, investigators turned their attention to preterm FGR, especially second trimester FGR, such as genetic causes, multiple gestations, antiphospholipid antibody related maternal

Pathophysiology of FGR

Basic concepts of pathophysiology of FGR are based on different levels of maternal supply, fetoplacental competitions, and fetal adaptations (Table 2). Uterine blood flow patterns in early sheep pregnancies cannot be distinguished from those in nonpregnant animals until day 17 of gestation.53 After day 60, the same level of uterine blood flow is maintained until term. The relative proportion of uterine blood flow distributed to the placental cotyledons is approximately 20 to 30% in early

Growth promoting hormones and FGR

Insulin is one of the determinants of fetal size through its action on nutrient uptake and utilization. Insulin in the fetus directs nutrients to insulin-sensitive tissues, such as skeletal muscle, liver, and adipose tissue, which promote glycogen and fat storage. Low insulin concentrations and a blunted insulin response to an intravenous glucose load have been described in fetuses with FGR.85 Since insulin increases placental glucose transfer, low insulin levels in fetuses with FGR might be an

Vasodilators, vasoconstrictors, and FGR

Pregnancies complicated by preeclampsia or by growth-restricted infants not only demonstrate inadequate maternal vascular response to placentation, but also are found to have extensive endothelial injury.94 Vasospasm causes resistance to blood flow and accounts for the development of arterial hypertension.

Studies during the first study period indicated that normal pregnant women are refractory to the pressor effects of infused angiotensin II.95 Gant et al96, 97 demonstrated that increased

Research in progress

Our knowledge of the basic features which regulate fetal growth is expanding. In this section we will briefly review three areas of current research which appear significant for understanding the development of FGR: genes involved in the regulation of the cell cycle; interaction between immunology and human placental implantation; and the control and function of growth factors.

The relationship between the fetal genome and genetic potential for growth, which as previously mentioned, is dependent

Conclusion

This review describes current concepts of pathogenesis and pathophysiology of FGR. The basic concept of FGR has been that there is an inadequate maternal-fetal supply of oxygen and nutrients which initiates fetal adaptation measures. Older investigations used well-controlled pregnant animal experiments. These established concepts from animal data are still useful today. Current investigations on human fetuses using new technologies have resulted in a greater understanding of the pathophysiology

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