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Section II
Causes of Preterm Birth

RECOMMENDATIONS

The committee finds that the lack of success of public health and clinical interventions to date is due, in large measure, to the limited understanding of the heterogeneous etiologies of preterm birth.


Recommendation II-1: Support research on the etiologies of preterm birth. Funding agencies should be committed to sustained and vigorous support for research on the etiologies of preterm birth to fill critical knowledge gaps.


Areas to be supported should include the following:


  • The physiological and pathologic mechanisms of parturition across the entire gestational period as well as the pregestational period should be studied.

  • The role of inflammation and its regulation during implantation and parturition should be studied. Specifically, perturbations to the immunologic and inflammatory pathways caused by bacterial and viral infections, along with the specific host responses to these pathogens, should be addressed.

  • Preterm birth should be defined as a syndrome of multiple patho-physiological pathways, with refinement of the phenotypes of preterm birth that recognizes and accurately reflects the heterogeneity of the underlying etiology.



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OCR for page 255
Preterm Birth: Causes, Consequences, and Prevention Section II Causes of Preterm Birth RECOMMENDATIONS The committee finds that the lack of success of public health and clinical interventions to date is due, in large measure, to the limited understanding of the heterogeneous etiologies of preterm birth. Recommendation II-1: Support research on the etiologies of preterm birth. Funding agencies should be committed to sustained and vigorous support for research on the etiologies of preterm birth to fill critical knowledge gaps. Areas to be supported should include the following: The physiological and pathologic mechanisms of parturition across the entire gestational period as well as the pregestational period should be studied. The role of inflammation and its regulation during implantation and parturition should be studied. Specifically, perturbations to the immunologic and inflammatory pathways caused by bacterial and viral infections, along with the specific host responses to these pathogens, should be addressed. Preterm birth should be defined as a syndrome of multiple patho-physiological pathways, with refinement of the phenotypes of preterm birth that recognizes and accurately reflects the heterogeneity of the underlying etiology.

OCR for page 255
Preterm Birth: Causes, Consequences, and Prevention Animal models, in vitro systems, and computer models of human implantation, placentation, parturition, and preterm birth should be studied. Simple genetic and more complex epigenetic causes of preterm birth should be studied. Gene-environment interactions and environmental factors should be considered broadly to include the physical and social environments. Biological targets and the mechanisms and biological markers of exposure to environmental pollutants should be studied. The committee finds that psychosocial, behavioral, and sociodemographic risk factors for preterm birth tend to cooccur; and the potentially powerful and complex interactions among these factors have been under-studied. When they are studied independently, each of these risk factors tends to have a weak and inconsistent association with the risk of preterm birth. The committee acknowledges that with each additional potential interaction sought, the sample size required to retain an adequate statistical power to reveal meaningful differences increases. Recommendation II-2: Study multiple risk factors to facilitate the modeling of the complex interactions associated with preterm birth. Public and private funding agencies should promote and researchers should conduct investigations of multiple risk factors for preterm birth simultaneously rather than investigations of the individual risk factors in isolation. These studies will facilitate the modeling of these complex interactions and aid with the development and evaluation of more refined interventions tailored to specific risk profiles. Specifically, these studies should achieve the following: Develop strong theoretical models of the pathways from psychosocial factors, including stress, social support, and other resilience factors, to preterm delivery as a basis for ongoing observational research. These frameworks should include plausible biological mechanisms. Comprehensive studies should include psychosocial, behavioral, medical, and biological data. Incorporate understudied exposures, such as the characteristics of employment and work contexts, including work-related stress; the effects of domestic or personal violence during pregnancy; racism; and personal resources, such as optimism, mastery and control, and pregnancy intendedness. These studies should also investigate the potential interactions of these exposures with exposure to environmental toxicants.

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Preterm Birth: Causes, Consequences, and Prevention Emphasize culturally valid measures in studies of stress and preterm delivery to consider the unique forms of stress that individuals in different racial and ethnic groups experience. Measurement of stress should also include specific constructs such as anxiety. Expand the study of neighborhood-level effects on the risk of preterm birth by including novel data in multilevel models. Data that address this information should be made more available to researchers for such activities. Interagency agreements for the sharing of data should be reached to support the development of cartographic modeling of neighborhoods. Work toward the development of primary strategies for the prevention of preterm birth. When there is evidence of modest effects of multiple causes, interventions that address all of these factors should be considered. Have designs that are common enough to allow for pooling of data and samples, and consider studying high-risk populations to increase the power of the study. Recommendation II-3: Expand research into the causes and methods for the prevention of the racial-ethnic and socioeconomic disparities in the rates of preterm birth. The National Institutes of Health and other funding agencies should expand current efforts in and expand support for research into the causes and methods for the prevention of the racial-ethnic and socioeconomic disparities in the rates of preterm birth. This research agenda should continue to prioritize efforts to understand factors contributing to the high rates of preterm birth among African-American infants and should also encourage investigation into the disparities among other racial-ethnic subgroups. Recommendation II-4: Investigate the causes of and consequences for preterm births that occur because of fertility treatments. The National Institutes of Health and other agencies, such as the Centers for Disease Control and Prevention and the Agency for Healthcare Research and Quality, should provide support for researchers to conduct investigations to obtain an understanding of the mechanisms by which fertility treatments, such as assisted reproductive technologies and ovulation promotion, may increase the risk for preterm birth. Studies should also be conducted to investigate the outcomes for mothers who have received fertility treatments and who deliver preterm and the outcomes for their infants. Specifically, those conducting work in this area should attempt to achieve the following:

OCR for page 255
Preterm Birth: Causes, Consequences, and Prevention Develop comprehensive registries for clinical research, with particular emphasis on obtaining data on gestational age and birth weight, whether the preterm birth was indicated or spontaneous, the outcomes for the newborns, and perinatal mortality and morbidity. These registries must distinguish multiple gestations from singleton gestations and link multiple infants from a single pregnancy. Conduct basic biological research to identify the mechanisms of preterm birth relevant to fertility treatments and the underlying causes of infertility or subfertility that may contribute to preterm delivery. Investigate the outcomes for preterm infants as well as all infants whose mothers received fertility treatments. Understand the impact of changing demographics on the use and outcomes of fertility treatments. Assess the short- and long-term economic costs of various fertility treatments. Investigate ways to improve the outcomes of fertility treatments, including ways to identify high-quality gametes and embryos to optimize success through the use of single embryos and improve ovarian stimulation protocols that lead to monofollicular development. Recommendation II-5: Institute guidelines to reduce the number of multiple gestations. The American College of Obstetricians and Gynecologists, the American Society for Reproductive Medicine, and state and federal public health agencies should institute guidelines that will reduce the number of multiple gestations. Particular attention should be paid to the transfer of a single embryo and the restricted use of superovulation drugs and other nonassisted reproductive technologies for infertility treatments. In addition to mandatory reporting to the Centers for Disease Control and Prevention by centers and individual physicians who use assisted reproductive technologies, the use of superovulation therapies should be similarly reported.