Neonatal Morbidities of Fetal Growth Restriction: Pathophysiology and Impact

Fetal growth restriction (FGR) is a significant complication of pregnancy describing a fetus that does not grow to full potential due to pathological compromise. FGR affects 3-9% of pregnancies in high-income countries, and is a leading cause of perinatal mortality and morbidity. Placental insufficiency is the principal cause of FGR, resulting in chronic fetal hypoxia. This hypoxia induces a fetal adaptive response of cardiac output redistribution to favour vital organs, including the brain, and is in consequence called brain sparing. Despite this, it is now apparent that brain sparing does not ensure normal brain development in growth-restricted fetuses. In this review we have brought together available evidence from human and experimental animal studies to describe the complex changes in brain structure and function that occur as a consequence of FGR. In both humans and animals, neurodevelopmental outcomes are influenced by the timing of the onset of FGR, the severity of FGR, and gestational age at delivery. FGR is broadly associated with reduced total brain volume and altered cortical volume and structure, decreased total number of cells and myelination deficits. Brain connectivity is also impaired, evidenced by neuronal migration deficits, reduced dendritic processes, and less efficient networks with decreased long-range connections. Subsequent to these structural alterations, short- and long-term functional consequences have been described in school children who had FGR, most commonly including problems in motor skills, cognition, memory and neuropsychological dysfunctions.

Bronchopulmonary dysplasia and emphysema are significant global health problems at the extreme stages of life. Both are characterized by arrested alveolar development or loss of alveoli, respectively. Both lack effective treatment strategies. Knowledge about the genetic control of branching morphogenesis in mammals derives from investigations of the respiratory system in Drosophila, but mechanisms that regulate alveolar development remain poorly understood. Even less is known about regulation of the growth and development of the pulmonary vasculature. Understanding how alveoli and the underlying capillary network develop, and how these mechanisms are disrupted in disease states, are critical for developing effective therapies for lung diseases characterized by impaired alveolar structure. Recent observations have challenged old notions that the development of the blood vessels in the lung passively follows that of the airways. Rather, increasing evidence suggests that lung blood vessels actively promote alveolar growth during development and contribute to the maintenance of alveolar structures throughout postnatal life. Our working hypothesis is that disruption of angiogenesis impairs alveolarization, and that preservation of vascular growth and endothelial survival promotes growth and sustains the architecture of the distal airspace. Furthermore, the explosion of interest in stem cell biology suggests potential roles for endothelial progenitor cells in the pathogenesis or treatment of lung vascular disease. In this Pulmonary Perspective, we review recent data on the importance of the lung circulation, specifically examining the relationship between dysmorphic vascular growth and impaired alveolarization, and speculate on how these new insights may lead to novel therapeutic strategies for bronchopulmonary dysplasia.

To develop and test a new classification system for stillbirths to help improve understanding of the main causes and conditions associated with fetal death. Population based cohort study. West Midlands region. 2625 stillbirths from 1997 to 2003. Categories of death according to conventional classification methods and a newly developed system (ReCoDe, relevant condition at death). By the conventional Wigglesworth classification, 66.2% of the stillbirths (1738 of 2625) were unexplained. The median gestational age of the unexplained group was 237 days, significantly higher than the stillbirths in the other categories (210 days; P < 0.001). The proportion of stillbirths that were unexplained was high regardless of whether a postmortem examination had been carried out or not (67% and 65%; P = 0.3). By the ReCoDe classification, the most common condition was fetal growth restriction (43.0%), and only 15.2% of stillbirths remained unexplained. ReCoDe identified 57.7% of the Wigglesworth unexplained stillbirths as growth restricted. The size of the category for intrapartum asphyxia was reduced from 11.7% (Wigglesworth) to 3.4% (ReCoDe). The new ReCoDe classification system reduces the predominance of stillbirths currently categorised as unexplained. Fetal growth restriction is a common antecedent of stillbirth, but its high prevalence is hidden by current classification systems. This finding has profound implications for maternity services, and raises the question whether some hitherto "unexplained" stillbirths may be avoidable.