Preterm birth is a syndrome with many causes and phenotypes. We propose a classification that is based on clinical phenotypes that are defined by ≥1 characteristics of the mother, the fetus, the placenta, the signs of parturition, and the pathway to delivery. Risk factors and mode of delivery are not included. There are 5 components in a preterm birth phenotype: (1) maternal conditions that are present before presentation for delivery, (2) fetal conditions that are present before presentation for delivery, (3) placental pathologic conditions, (4) signs of the initiation of parturition, and (5) the pathway to delivery. This system does not force any preterm birth into a predefined phenotype and allows all relevant conditions to become part of the phenotype. Needed data can be collected from the medical records to classify every preterm birth. The classification system will improve understanding of the cause and improve surveillance across populations.
The epidemiologic factors, consequences, and suggested preventive strategies for preterm delivery have been reviewed extensively. In these and other articles, it is recognized increasingly that our understanding of preterm delivery has been limited by the failure to accept the idea that preterm birth is a syndrome with a number of etiologic factors and phenotypic characteristics, many of which are independent of each other. “What seems certain is that any progress in our understanding and prevention of preterm birth requires acknowledgement that it is not one disease with a single solution or cure, but rather the product of overlapping factors.”
See related editorial, page 99
As shown in the first 2 articles of this series, other than the categorization by gestational age, there are considerable challenges when one moves to classify cases of preterm birth by any system, including cause or phenotype. The authors of this series were brought together as a direct result of the Global Alliance to Prevent Prematurity and Stillbirth meeting in 2009 with instructions to determine the need for such a classification system, to define the issues that are related to creating a preterm birth classification system, and to present a prototype classification system. The aim of this article is to propose a classification system for clinical and research purposes for general consideration.
The preterm birth phenotype
A phenotype can be defined as “any observable characteristic or trait of an organism such as its morphology, development, biochemical or physiological properties, or behavior. Phenotypes of a disease result from the expression of an organism’s genes, as well as the influence of environmental factors and often interactions between the two.” In relationship to preterm birth, environmental factors might include exposure to infectious organisms, toxins, or stressful events. However, it is extremely unlikely that a single gene will be identified as responsible for more than a few cases of preterm birth. The inconsistencies that are reported in genetic studies could be explained by the involvement of multiple genes that leads to a wide range of phenotypic expression. Based on current knowledge, a specific cause is hard to discern for most cases of preterm birth. The authors therefore have decided that, at the present time, the most useful classification of preterm births would be by phenotype. However, because of its heterogeneous etiologic, pathophysiologic, and parturition event sequence, preterm birth is a “complex phenotype.” If and when specific phenotypes within the preterm birth syndrome are agreed on more universally, causes and appropriate preventive interventions can be developed for each preterm birth phenotype.
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