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15
A Research Agenda to Investigate Preterm Birth

The purpose of this report has been to assess the state of the science on the causes of preterm birth; address the health, social-emotional, and economic consequences of preterm birth for children born preterm and their families; and establish a framework for action in addressing the range of priority issues, including a research and policy agenda for the future. The preceding chapters have provided an overview of the current knowledge on the measurement of maturity in infants; the range of causes of preterm birth; the diagnosis and treatment of preterm labor; the health and neurodevelopmental consequences for infants born preterm; and the impact of preterm birth on family, societal costs, and public programs.

The committee evaluated this evidence to identify gaps in knowledge and recommend areas for future research. In its review of the evidence, the committee finds that understanding of the conditions and the mechanisms that lead to preterm labor is limited and that despite the availability of several interventions that are designed to inhibit preterm labor, preterm birth remains a significant barrier to the health of newborns. It is clear that a variety of disciplines working in concert will be needed to address this problem.

Resolution of many of the complex questions about preterm birth will require large-scale, prospective studies. The National Children’s Study, a large-scale prospective study that has been proposed, has the potential to provide such data. The study will examine the effects of environmental influences on the health and development of more than 100,000 U.S. children and will monitor these children longitudinally from before birth to age 21. The environmental factors that will be assessed include natural and



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Preterm Birth: Causes, Consequences, and Prevention 15 A Research Agenda to Investigate Preterm Birth The purpose of this report has been to assess the state of the science on the causes of preterm birth; address the health, social-emotional, and economic consequences of preterm birth for children born preterm and their families; and establish a framework for action in addressing the range of priority issues, including a research and policy agenda for the future. The preceding chapters have provided an overview of the current knowledge on the measurement of maturity in infants; the range of causes of preterm birth; the diagnosis and treatment of preterm labor; the health and neurodevelopmental consequences for infants born preterm; and the impact of preterm birth on family, societal costs, and public programs. The committee evaluated this evidence to identify gaps in knowledge and recommend areas for future research. In its review of the evidence, the committee finds that understanding of the conditions and the mechanisms that lead to preterm labor is limited and that despite the availability of several interventions that are designed to inhibit preterm labor, preterm birth remains a significant barrier to the health of newborns. It is clear that a variety of disciplines working in concert will be needed to address this problem. Resolution of many of the complex questions about preterm birth will require large-scale, prospective studies. The National Children’s Study, a large-scale prospective study that has been proposed, has the potential to provide such data. The study will examine the effects of environmental influences on the health and development of more than 100,000 U.S. children and will monitor these children longitudinally from before birth to age 21. The environmental factors that will be assessed include natural and

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Preterm Birth: Causes, Consequences, and Prevention artificial environmental factors, geographic locations, physical surroundings, social factors, cultural and family influences and differences, behavioral influences and outcomes, biological and chemical factors, and genetics. The study will analyze the interactions of these factors and how they might affect children’s health. Many of these factors have been discussed in this report as potential causes of preterm birth. Such a cohort study will be of great value in helping to provide an understanding of the causes and consequences of preterm birth. Therefore, if the study is conducted, data should be collected in a manner consistent with the committee’s recommendations. This final chapter organizes the recommendations and findings presented in previous sections into a research agenda. The agenda is presented to help focus and direct research efforts. The recommendations are grouped and prioritized and therefore presented in a different sequence than they appear in the full report; however, their numeric designation remains the same. Priority areas are grouped as follows: Establish Multidisciplinary Research Centers Priority Areas for Research Better define the problem of preterm birth with improved data Recommendations included in this category pertain to the need for improved collection of surveillance and descriptive data in order to better define the nature and scope of the problem of preterm birth. Improve national data Study the economic outcomes for infants born preterm Conduct clinical and health services research investigations Recommendations in this category pertain to the need to examine and improve the clinical treatment of women who deliver preterm and infants born preterm and the health care systems that care for them. Improve the methods of identifying and treating women at risk for preterm labor Study the acute and the long-term outcomes for infants born preterm Study infertility treatments and institute guidelines to reduce the number of multiple gestations Improve the quality of care for women at risk for preterm labor and infants born preterm Investigate the impact of the health care delivery system on

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Preterm Birth: Causes, Consequences, and Prevention preterm birth Conduct etiologic and epidemiologic investigations Recommendations in this category pertain to the need to examine the potential causes of preterm birth and its distribution in the population. Investigate the etiologies of preterm birth Study the multiple psychosocial, behavioral, and environmental risk factors associated with preterm birth simultaneously Investigate racial-ethnic and socioeconomic disparities in the rates of preterm birth Study and Inform Public Policy Recommendations in this final group pertain to the need to understand the impact of preterm birth on various public programs policies and how policies can be used to reduce rates of preterm birth. Categories under group II are not prioritized because the committee believes that they are actions that should occur simultaneously. However, recommendations within the categories are prioritized. The policy recommendations are listed last, as information resulting from previous recommendations will be needed in order to analyze and improve policies pertaining to preterm birth. The findings and recommendations presented in this report are intended to assist policy makers, academic researchers, funding agencies and organizations, insurers, and health care professionals with prioritizing research and to inform the public about the problem of preterm birth. The ultimate goal of the committee’s efforts is to work toward improved outcomes for the children who have been born preterm and their families. I. ESTABLISH MULTIDISCIPLINARY RESEARCH CENTERS The committee finds that there is need for a major focus on the problem of preterm birth. This will require the efforts of individuals from a broad spectrum of clinical, basic, and social science disciplines; the recruitment of more investigators; and increased funding. There are special barriers to the recruitment and participation of physician scientists who are trained in obstetrics and gynecology, such as a paucity of departments of intensive research in obstetrics and gynecology, the length of time required for combined clinical and research training, and the cost of liability insurance that is not proportional to clinical activity (Finding 13-1). Therefore, the committee recommends the establishment of multidisciplinary research centers to study preterm pregnancy and preterm infants.

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Preterm Birth: Causes, Consequences, and Prevention Recommendation V-1: The National Institutes of Health and private foundations should establish integrated multidisciplinary research centers. The objective of these centers will be to focus on understanding the causes of preterm birth and the health outcomes for women and their infants who were born preterm. Consistent with the Roadmap initiative of the National Institutes of Health, these activities should include the following: Basic, translational, and clinical research involving the clinical, basic, and behavioral and social science disciplines is needed. This research should include but not be limited to investigations covered by recommendations pertaining to the etiologies of preterm birth; the psychosocial, behavioral, sociodemographic, and environmental toxicant exposure-related risk factors associated with preterm birth; the disparities in the rates of preterm birth by race and ethnicity; the identification and treatment of women at risk of preterm labor; quality of health care provided to infants born preterm; and health services research. Sustained intellectual leadership of these research activities is essential to make progress in understanding and improving the outcomes for women and their infants who have been born preterm. Mentored research training programs should be integral parts of these centers. Fostering the development of basic and clinical researchers, including facilitating opportunities for funding and promotion, is critical. Funding agencies should provide ample and sustained funds to allow these centers to investigate the complex syndrome of preterm birth, analogous to programs developed to study cancer and cardiovascular disease. II. PRIORITY AREAS FOR RESEARCH Better Define the Problem of Preterm Birth with Improved Data The committee finds that there is a need to define more clearly the problem of preterm birth to better understand and study its causes and consequences. Two areas for research that can accomplish this are improved national data on preterm birth and studies of the economic outcomes for infants born preterm. 1. Improve National Data Birth weight is an incomplete surrogate for gestational age for determination of the risk of perinatal morbidity and mortality (Finding 2-1). The establishment of reliable gestational age estimates by ultrasound

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Preterm Birth: Causes, Consequences, and Prevention early in pregnancy facilitates both research and practice on the identification of multiple gestations; the diagnosis of preterm labor; the need for tocolysis, the administration of steroids, the elective induction of labor; determination of the mode of delivery, the hospital where the birth will take place, whether resuscitation will be needed in the delivery room; and the adequacy of fetal growth (Finding 2-2). Neither gestational age nor birth weight is a sufficient or complete indicator of the level of immaturity of a newborn (Finding 2-3). Recommendation I-1: Promote the collection of improved perina-tal data. The National Center for Health Statistics of the Centers for Disease Control and Prevention should promote and use a national mechanism to collect, record, and report perinatal data. The following key elements should be included: The quality of gestational age measurements in vital records should be evaluated. Vital records should indicate the accuracy of the gestational age determined by ultrasound early in pregnancy (less than 20 weeks of gestation). Birth weight for gestational age should be considered one measure of the adequacy of fetal growth. Perinatal mortality and morbidity should be reported by gestational age, birth weight, and birth weight for gestational age. A categorization or coding scheme that reflects the heterogeneous etiologies of preterm birth should be developed and implemented. Vital records should also state whether fertility treatments (including in vitro fertilization and ovulation promotion) were used. The committee recognizes that the nature of these data is private and sensitive. Recommendation I-2: Encourage the use of ultrasound early in pregnancy to establish gestational age. Because it is recognized that more precise measures of gestational age are needed to move the field forward, professional societies should encourage the use of ultrasound early in pregnancy (less than 20 weeks of gestation) to establish gestational age and should establish standards of practice and recommendations for the training of personnel to improve the reliability and the quality of ultrasound data. Recommendation I-3: Develop indicators of maturational age. Funding agencies should support and investigators should develop reliable and precise perinatal (prenatal and postnatal) standards as indicators of maturational age.

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Preterm Birth: Causes, Consequences, and Prevention 2. Study Economic Outcomes for Infants Born Preterm The medical costs of preterm birth during infancy, particularly during the neonatal period, are high and the medical needs are relatively well understood. The long-term medical, educational, productivity, and productivity costs borne by the individual, as well as by the family and society, are not well understood (Finding 12-1). The distribution of the costs of preterm birth between the public and the private sectors and among constituencies within these sectors has not been determined. Children born preterm may require a wide array of publicly supported services (Finding 14-1). The variance in the costs associated with preterm birth is large, even within gestational age groups. Sufficient knowledge about the factors that explain this variance is not available (Finding 12-2). Recommendation IV-2: Investigate the economic consequences of preterm birth. Researchers should investigate the gaps in understanding of the economic consequences of preterm birth to establish the foundation for accurate economic evaluation of the relative value of policies directed at prevention and guidelines for treatment. This research should assess the long-term educational, social, productivity, and medical costs associated with preterm birth, as well as the distributions of such costs; undertake multivariate modeling to refine the understanding of what drives the large variance of the economic burden, even by gestational age at birth; be ongoing to provide the basis for ongoing assessments; and establish the basis for refined economic assessment of policies and interventions that would reduce the economic burden. Conduct Clinical and Health Services Research Investigations The committee finds that in addition to improvements in data collection to obtain a better understanding of the scope and the nature of the problem of preterm birth, five clinical and health services areas warrant investigation: the identification and treatment of women at risk for preterm labor, study of acute and long-term outcomes for infants born preterm, study of and guidelines for infertility treatments, improvements in the quality of care for women at risk for preterm labor and infants born preterm, and investigation of the impact of the health care delivery system.

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Preterm Birth: Causes, Consequences, and Prevention 1. Improve the Methods of Identification and Treatment of Women at Risk for Preterm Labor Preterm parturition has heterogeneous origins that result in common biological pathways and that lead to relatively few clinical presentations (e.g., preterm labor, preterm rupture of membranes, and cervical insufficiency) (Finding 6-1). Current methods for the identification of women at risk for preterm birth by the use of demographic, behavioral, and biological risk factors have low sensitivities. Although the sensitivities increase as pathways and clinical syndromes are identified, the efficacies of interventions decline as the parturitional process progresses (Finding 9-2). Current methods for the diagnosis and treatment of women at risk of an imminent preterm birth are not sufficiently evidence based (Finding 9-4). The goal of prevention of preterm birth is subordinate to the goal of improved perinatal morbidity and mortality outcomes. This goal is important, because the continuation of pregnancy in women with preterm parturition in some instances may increase the health risk for the mother or the fetus, or both (Finding 9-5). Recommendation III-1: Improve methods for the identification and treatment of women at increased risk of preterm labor. Researchers should investigate ways to improve methods to identify and treat women with an increased risk of preterm labor. Specifically: The content and structure of prenatal care should include an assessment of the risk of preterm labor. Improved methods for the identification of women at increased risk of preterm labor both before pregnancy and in the first and second trimesters are needed. Combinations of known markers of preterm labor (e.g., a prior preterm birth, ethnicity, a short cervix, and biochemical and biophysical markers) and potential new markers (e.g., genetic markers) should be studied to allow the creation of an individualized composite assessment of risk. More accurate methods are needed to diagnose preterm labor, assess fetal health to identify women and fetuses that are and that are not candidates for the arrest of labor, and arrest labor.

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Preterm Birth: Causes, Consequences, and Prevention The success of perinatal care during preterm birth should be based primarily on perinatal morbidity and mortality rates as well as the rate of preterm birth, the numbers of infants born with low birth weights, or neonatal morbidity and mortality. 2. Study Acute and Long-Term Outcomes for Infants Born Preterm The knowledge and beliefs of health care providers influence their attitudes toward and their management of mothers with threatened preterm delivery and their infants (Finding 9-6). Studies of intervention strategies for the prevention of preterm birth have had preterm birth as their only outcome variable. The study samples have not been large enough for sufficient investigations of morbidity, mortality, and neurological morbidity (Finding 9-3). Most studies of the outcomes of preterm birth use birth weight criteria for the selection of study participants. Few studies report on the outcomes for preterm infants by gestational age. In addition to infants born preterm, studies with samples of infants with birth weights less than 2,500 grams include full-term infants who are small for gestational age (Finding 11-1). There is tremendous variation in the outcomes reported for individuals born preterm. Much of this variation is due to a lack of uniformity in study sample selection criteria, the study methodologies used, the age of evaluation, and the measurement tools and cutoffs used (Finding 11-2). Few long-term studies of adolescents and adults born preterm have been conducted. Good indicators of the functional development of the central nervous system of preterm infants in neonatal intensive care units are lacking, and predictors of long-term neurodevelopmental and health outcomes are inadequate (Finding 11-3). Few postnatal intervention strategies that can be used to improve outcomes for children born preterm have been evaluated, and such intervention strategies are needed, especially for more immature preterm infants (Finding 10-1). Recommendation IV-1: Develop guidelines for the reporting of infant outcomes. The National Institutes of Health, the U.S. Department of Education, other funding agencies, and investigators should develop guidelines for determining and reporting outcomes for infants born preterm that better reflect their health, neurodevelopmental, educational, social, and emotional outcomes across the life span and conduct research to determine methods that can be used to optimize these outcomes.

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Preterm Birth: Causes, Consequences, and Prevention Specifically, Outcomes should be reported by gestational age categories, in addition to birth weight categories; and better methods of measuring fetal and infant maturity should be devised. Obstetrics-perinatology departments and pediatrics-neonatology departments should work together to establish guidelines to achieve a more uniform approach to evaluating and reporting outcomes, including ages of evaluation, measurement tools, and the minimum duration of follow-up. The measurement tools should cover a broad range of outcomes and should include quality of life and the elicitation of outcome preferences from adolescents and adults born preterm and their families. Long-term outcome studies should be conducted into adolescence and adulthood to determine the extent of recovery, if any, and to monitor individuals who were born preterm for the onset of disease during adulthood as a result of being born preterm. Research should identify better neonatal predictors of neurodevelopmental disabilities, functional outcomes, and other long-term outcomes. These will allow improved counseling of the parents, enhance the safety of trials of interventions for mothers and their infants by providing more immediate feedback on infant development, and facilitate planning for the use of comprehensive follow-up and early intervention services. Follow-up and outcome evaluations for infants involved in maternal trials of prenatal means of prevention or treatment of threatened preterm delivery and infant trials of means of prevention and treatment of organ injury not only should report the infant’s gestational age at delivery and any neonatal morbidity but also should include neurological and cognitive outcomes. Specific outcomes should be tailored to answer the study questions. Research should identify and evaluate the efficacies of postnatal interventions that improve outcomes. 3. Study Infertility Treatments and Institute Guidelines to Reduce the Number of Multiple Gestations Fertility treatments are a significant contributor to preterm birth among both multiple and singleton pregnancies (Finding 5-2). The mechanisms by which conditions of infertility, subfertility, and fertility treatments increase the risk of preterm birth, particularly among singleton pregnancies, are unknown. The mechanisms may be markedly different from the mechanisms suggested when racial and socioeconomic causes of preterm birth are considered (Finding 5-3). The prevalence of the use of superovulation with or without artificial

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Preterm Birth: Causes, Consequences, and Prevention insemination is unknown, and no systematic mechanisms are in place to collect these data (Finding 5-1). 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: 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 new-borns, 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

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Preterm Birth: Causes, Consequences, and Prevention 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. 4. Improve the Quality of Care for Women at Risk for Preterm Labor and Infants Born Preterm Prenatal care was designed to address one complication of pregnancy; namely, preeclampsia. The proper timing of visits and the appropriate content of prenatal care for the detection or management of preterm delivery are not known (Finding 9-1). The literature on the environment for the perinatal and neonatal management of infants born preterm is evolving from a strict reliance on a limited characterization of levels of care to more clinically relevant responses to patient needs. However, the optimal deployment of resources for specific types of preterm delivery is not yet established (Finding 14-2). Substantial interinstitutional variations in the complication rates for infants born preterm have been documented, and some outcomes, like physical growth, remain suboptimal (Finding 10-2). Early childhood educational and other therapeutic research interventions have been demonstrated to improve outcomes for some infants born preterm; however, it is critical to determine the appropriate intensity, type of service, personnel, and curricula to achieve improvement in interventions (Finding 11-4). Recommendation V-2: Establish a quality agenda. Investigators, professional societies, state agencies, payors, and funding agencies should establish a quality agenda with the intent of maximizing outcomes with current technology for infants born preterm. This agenda should define quality across the full spectrum of providers who treat women delivering preterm and infants born preterm; identify efficacious interventions for preterm infants and identify the quality improvement efforts that are needed to incorporate these interventions into practice; and analyze variations in outcomes for preterm infants among institutions.

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Preterm Birth: Causes, Consequences, and Prevention 5. Investigate the Role of the Health Care Delivery System Recommendation V-3: Conduct research to understand the impact of the health care delivery system on preterm birth. The National Institutes of Health, the Agency for Healthcare Quality and Research, and private foundations should conduct and support research to understand the consequences of the organization and financing of the health care delivery system on access, quality, cost, and the outcomes of care as they relate to preterm birth throughout the full reproductive and childhood spectrum. Conduct Etiologic and Epidemiologic Investigations The committee highlights three specific research areas pertaining to the etiology and epidemiology of preterm birth: investigations that will provide an understanding of the etiology of preterm birth, studies of multiple risk factors, and studies that will provide a better understanding of the racialethnic and socioeconomic disparities in the rates of preterm birth. 1. Investigate the Etiologies of Preterm Birth 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

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Preterm Birth: Causes, Consequences, and Prevention that recognizes and accurately reflects the heterogeneity of the underlying etiology. 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. 2. Study the Multiple Psychosocial, Behavioral, Sociodemographic, and Environmental Risk Factors Associated with Preterm Birth Simultaneously 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 understudied. 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. Limited data suggest that some environmental pollutants, such as lead and tobacco smoke, and air pollution may contribute to the risk of preterm birth; but most environmental pollutants have not been investigated. In addition, the interactions between environmental toxicant exposures with other behavioral, psychosocial, and sociodemographic attributes have been understudied (Finding 8-1). Independent of the individual-level attributes that are risk factors for preterm birth, adverse neighborhood conditions such as poverty and crime are risk factors for preterm birth. These data suggest that intervention strategies may need to expand from focusing exclusively on the individual to including the contributions of social structural factors to the risk of preterm birth (Finding 4-2). 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 mod-

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Preterm Birth: Causes, Consequences, and Prevention eling 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. 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. 3. Investigate Racial-Ethnic and Socioeconomic Disparities in the Rates of Preterm Birth A particular focus of sociodemographic studies of preterm birth should be on disparities by race-ethnicity and socioeconomic condition, as significant differences in the rates of preterm birth by race-ethnicity and socioeconomic condition continue to exist in the United States. The causes of these persisting disparities remain largely unexplained (Finding 4-1).

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Preterm Birth: Causes, Consequences, and Prevention 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. This research should be guided by an integrative approach that takes into account the cooccurrence and interactions among the multiple determinants of disparities in preterm birth, including racism, which operates at multiple levels and across the life course. III. STUDY AND INFORM PUBLIC POLICY Finally, the committee finds that effective public policies that will reduce the rates of preterm birth and improve the outcomes for infants born preterm will require a better understanding of the determinants of preterm birth and the determinants of healthy outcomes for infants born preterm and better information on effective interventions. Preterm birth is associated with large expenditures across a wide range of public programs, including those for health care, education, and income support. Public investment in reducing the rate of preterm birth has the potential to result in large cost savings not only to society as a whole but also to the public sector (Finding 14-3). Recommendation V-4: Study the effects of public programs and policies on preterm birth. The National Institutes of Health, the Centers for Medicare and Medicaid Services, and private foundations should conduct and/or support research on the role of social programs and policies on the occurrence of preterm birth and the health of children born preterm. Recommendation V-5: Conduct research that will inform public policy. In order to formulate effective public policies to reduce preterm birth and assure healthy outcomes for infants, public and private funding agencies and organizations, state agencies, payors, professional societies, and researchers will need to work to imple-

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Preterm Birth: Causes, Consequences, and Prevention ment all of the previous recommendations. Research in the areas of better defining the problem of preterm birth, clinical investigations, and etiologic and epidemiologic investigations is critical to conduct before policy makers can create policies that will successfully address this problem.