Preterm Birth Projects

CDC scientists are collaborating with many partners, including states, university researchers, and health care professionals to understand why preterm births occur and what can be done to help prevent them. The following are brief descriptions of projects supported by CDC’s Division of Reproductive Health.

1. Perinatal Quality Collaboratives

   CDC launched a new multi-year initiative to support the advancement of state-based Perinatal Quality Collaboratives (PQC). PQCs are networks of hospitals, health care providers, and state health departments that improve maternal and infant outcomes through advancing evidence-based clinical practices and processes. These networks collect data in real time on health care practices and outcomes, and provide immediate feedback for quality improvement. These networks, consisting of hospitals, pediatricians and neonatologists, obstetricians and perinatologists, nurses and midwives, data managers, and state health department staff, use the best available methods to effect change and improve outcomes as efficiently as possible.

   The funded PQCs include the California Perinatal Quality Care Collaborative and California Maternal Quality Care Collaborative, the New York State Obstetrical and Neonatal Quality Collaborative, and the Ohio Perinatal Collaboration to Improve Birth Data and Prematurity Outcomes. 

   Outcomes: Activities of funded state-based PQCs will include reduction in elective inductions and cesarean sections without medical indication prior to 39 weeks gestation, use of antenatal steroids for preterm neonates, and reductions in blood stream infections among infants with central lines in the neonatal intensive care units. PQCs will also expand existing networks, document methods and barriers, and develop methods that can be used to expand capacity to other states and regions.

   Impact: Priority strategies will be implemented to improve outcomes of pregnant women and newborns.

2. Nested Case-Control Studies of 25-Hydroxyvitamin D and Preterm Birth

   Women who have low levels of Vitamin D may be at higher risk for problems during pregnancy, including preterm birth. Because this is a new and emerging idea, research is needed to clarify this association. Data from CDC’s National Health and Nutrition Examination Survey (NHANES) indicates that non-Hispanic pregnant black women have lower levels of Vitamin D compared to both non-Hispanic pregnant white women and Hispanic women. Non-Hispanic black mothers also have increased preterm delivery rates. CDC is conducting a study to examine Vitamin D status in completed group studies of preterm birth with stored blood samples. Participating group studies include the Omega Study in Seattle, Washington; the Pregnancy, Infection, and Nutrition Study (PINS) in North Carolina; and the Pregnancy Outcomes and Community Health (POUCH) Study in Michigan.

   Outcome: This study will assess the relative and attributable risks of preterm birth with deficient 25-hydroxyvitamin D levels. Variation in risks by race and ethnicity and other maternal factors including body mass index, immune status, and genetic variation also will be assessed.

   Impact: This study will determine if levels of maternal Vitamin D are associated with preterm birth in three groups.

3. Gestational Age Measurement: Quality and Sources of Information

   Birth certificates are the primary resource for learning about preterm birth rates in the United States. Accurate recording of gestational age on birth certificates is critical to calculate the rate of preterm delivery, better understand the impact of preterm birth, follow trends, and make recommendations about preventing preterm birth. CDC is sponsoring a set of pilot interviews with hospital personnel responsible for completing the birth certificate and their supervisors. The aims of this pilot study are to learn—

   • What pieces of information are used for gestational age estimates on the birth certificate (e.g., last menstrual period, ultrasound, etc.)?
   • Where is the information used for birth certificates obtained (e.g., prenatal record, hospital records, labor and delivery logs)?
   • What processes, if any, are in place to ensure that data for determining gestational age are collected according to the National Center for Health Statistics (NCHS) recommendations and transferred accurately to the birth certificate. 

   Outcome: Improve quality of gestational age data collected and entered into birth certificate records.

   Impact: Understanding the systems in place for reporting gestational age on the birth certificate may improve CDC’s ability to more accurately monitor trends in preterm birth and provide recommendations to prevent preterm birth. 

4. Immune System Gene Polymorphisms and Preterm Delivery

   Investigators at Michigan State University (MSU) and CDC are using data from the Pregnancy Outcomes & Community Health (POUCH) study to evaluate the socioeconomic, clinical, biologic, and genetic factors associated with preterm birth. The POUCH study is a multi-ethnic community-based study of women from 52 prenatal clinics in 5 Michigan communities.

   Outcome: Results from this study suggest that inflammatory-related maternal and fetal genotypes or other markers of inflammation and environmental exposures together may increase the risk of preterm delivery.

   Impact: Identifying the underlying causes for preterm delivery will help identify high-risk populations who may need special interventions.

   Publications:

   • Mijal RS, Holzman CB, Rana S, et al. Midpregnancy levels of angiogenic markers in relation to maternal characteristics. Am J Obstet Gynecol. 2011;204:244.e1–12.
   • Gargano J, Holzman C, Senagore P, Reuss M, Pathak D, Williams M, Fisher R. Evidence of placental haemorrhage and preterm delivery. BJOG. 2010;117:445–455.
   • Jones NM, Holzman C, Friderici KH, Jernigan K, Chung H, Wirth J, Fisher R. Interplay of cytokine polymorphisms and bacterial vaginosis in the etiology of preterm delivery. J Reprod Immunol. 2010;87(1–2):82–9. Epub 2010 Oct 20.
   • Xu J, Holzman CB, Arvidson CG, Chung H, Goepfert AR. Midpregnancy vaginal fluid defensins, bacterial vaginosis, and risk of preterm delivery. Obstet Gynecol. 2008;112(3):524–31.
5. From Science to Practice: 17-alpha hydroxyprogesterone caproate

   In 2005, the NIH Maternal Fetal Medicine Network published results of a clinical trial that found among women with a history of prior preterm birth, pregnant women who received weekly injections of 17-alpha hydroxyprogesterone caproate (17P) showed significant reductions in preterm birth. To identify ways to translate these findings into clinical practice, and public health programs, CDC is participating in cooperative research with the University of Cincinnati to evaluate factors associated with acceptance, use, and adherence to 17P in the context of routine obstetrical care. The study will also investigate progesterone receptor genes of mothers and infants to explore possible ways that 17P works.

   Outcome: Results from this study will identify barriers to patient acceptance and adherence to progesterone therapy in routine clinical practice and genetic factors associated with ability to respond to progesterone therapy.

   Impact: Identifying barriers to patient acceptance and adherence to progesterone therapy can help develop strategies to improve obstetric care in women with a history of a prior preterm birth.

   Source: Meis PJ, Klebanoff M, et al. Does progesterone treatment influence risk factors for recurrent preterm delivery? Obstet Gynecol. 2005;106(3):557–561. PMID #16135587.

6. Functional Genomics and Proteomic Markers of Preterm Delivery

   Kansas University Medical Center, University of Tennessee, Memphis, and CDC are investigating oxygen independent and oxygen dependent defense mechanisms of the lower and upper genital tract and genes associated with regulating the inflammatory response.

   Outcome: Results from this study may identify potential cervico-vaginal biomarkers associated with altered immunity that may be associated with preterm birth.

   Impact: Knowledge about biomarkers can assist health care providers in early identification of women at risk for preterm delivery.

7. California Very Preterm Birth Study

   The vast majority of severe infant illness and death associated with preterm birth is due to very preterm birth (less than 32 weeks pregnant). Information from large, population-based group studies is needed to uncover genetic, clinical, and social reasons for both very preterm birth and racial disparities in maternal and infant health. CDC, in collaboration with California Department of Health Services, California Birth Defects and Monitoring Program, and the March of Dimes Foundation, is investigating the risk for very preterm birth using an existing bank of blood specimens obtained from routine testing of pregnant women and infant blood spots from newborn screening. This biobank is linked to clinical information from medical record review, birth certificate data, prenatal screening data, newborn screening data, and geocoded data on neighborhood stressors. Genomic investigations will focus on inflammatory, endocrine, and vascular pathway genes. In this way, social and biomedical factors and gene-environment interactions associated with very preterm birth among black, Hispanic, and white infants can be evaluated. The study identified 601 spontaneous very preterm births (less than 32 weeks for 207 whites and 217 Hispanics and less than 34 weeks for 177 blacks) and 796 controls identified from singleton live births born in southern California between 2000–2007. Investigators confirmed the association between 13 single nucleotide polymorphisms (SNPs) and spontaneous very preterm birth (P < 0.05) and also identified 48 additional polymorphisms that may be associated with preterm birth.

   Outcome: Results from this study may identify inflammatory, endocrine, and vascular pathway genes associated with very preterm birth and which genes may be specific for different racial and ethnic populations.

   Impact: Identifying maternal and infant genetic factors (risk alleles) in multiple racial and ethnic groups may allow for early detection of women at high risk of preterm birth.

8. Pregnancy to Early Life Longitudinally Linkage (PELL)

   Although 70% of preterm births are late preterm births (born at 34–36 weeks gestation), knowledge about the risk of short- and long-term outcomes among infant born late preterm is limited. CDC supports a surveillance system that links birth records, maternal, infant, and child hospitalization records, and other clinical and public health databases in Massachusetts. The surveillance system is known as the Pregnancy to Early Life Longitudinal Linkage (PELL) database.  Several analyses have been conducted or are underway to explore negative health outcomes associated with late preterm birth.  

   Outcome: Results from studies using the PELL database have shown that infants born late preterm (34–36 weeks) were 7 times more likely to have newborn illnesses than term infants. Also, infants born late preterm whose mothers had complications during pregnancy were especially vulnerable.

   Impact: Increased knowledge about the negative health consequences of late preterm birth has led to changes in obstetric and neonatal policies and practices.

9. Maternal Vitamin D Status and Preterm Birth

   Vitamin D deficiency is widespread among pregnant black women and is a lot less common among white women. Data indicate that vitamin D has direct and indirect influences on inflammation and other known pathways in the causes of preterm birth. Researchers at the University of Pittsburgh will conduct a study that will examine whether maternal vitamin D deficiency at less than 20 weeks gestation and maternal genotypic variation in the VDR gene are associated with risk of preterm birth. They will use samples from a cohort of 17,027 non-Hispanic white and 6,065 non-Hispanic black women who received prenatal screening and delivered singleton, live births with no fetal abnormalities at Magee-Women’s Hospital in Pittsburgh, Pennsylvania (1999–2010).

   Outcome: Results from this study will address some of the most urgent research recommendations from the 2010 Institute of Medicine (IOM) Committee on Dietary Reference Intakes for Calcium and Vitamin D, including exploring the role of vitamin D in non-skeletal health outcomes of pregnancy and explaining the effect of genetic variation, including variation among racial and ethnic groups.

   Impact: Improving maternal vitamin D status is safe, inexpensive, and straightforward, and could reduce racial disparities in birth outcomes.