COMPONENT A Three out of every 100 babies in the US are born with a structural birth defects. Birth defects are a leading cause of infant mortality in the US and worldwide. Children who survive with birth defects often experience a diminished quality of life and impose a substantial social and economic burden. Although birth defects pose a significant public health problem, clinical and public heath efforts to prevent most birth defects are limited. The lack of evidence regarding etiology of most nonsyndromic birth defects represents a major barrier in establishing prevention programs. In 1997, the National Birth Defects Prevention Study (NBDPS) was created to investigate these complex etiologies. With the phasing out of the NBDPS, the CDC initiated a new initiative building on the NBDPS findings -the Birth Defects STudy to Evaluate Pregnancy exposures (SD-STEPS). The Arkansas Center f~r Birth Defects Research and Prevention, a participant in the NBDPS for 16 years and a participant in 8D STEPS I, is dedicated to understani:ling the causes of birth defects and welcomes the opportunity to continue tocontribute to an evidence base that will facilitate development of effective prevention strategies. We are well positioned to build on the foundation of the Arkansas Center by identifying maternal exposures in early pregnancy that may be amenable to early prevention. The long-term goal of the Arkansas Center is to prevent or significantly reduce the occurrence of birth defects. We propose, therefore, to identify modifiable early pregnancy exposures that may decrease the occurrence of selected birth defects by participating in BO-STEPS II, discovering gene-environment interactions that lead to birth defects by supporting high-throughput genomic and epigenomlc analyses of biological samples collected from NBDPS and BO-STEPS participants, and helping develop future generations of birth-defect researchers by training and mentoring junior researchers in data analysis, manuscript preparation, and other study-related activities. Through our studies, we will maintain a leading role in establishing clinical and public health strategies to prevent birth defects. COMPONENTS Each year 32 million stillbirths occur globally. In the US and other developed countries, stillbirth is a largely under-studied perinatal outcome despite being one of the most common adverse pregnancy outcomes, accounting for one-half of all perinatal deaths. In 2006, the most recent data available for the US, stillbirths occurred In 6.05 of every 1,000 live births plus fetal deaths, much higher than many high-income countries and the US. Healthy People 2020 Objective of 5.6 (per 1,000 live births+ fetal deaths) for fetal mortality rates. Stillbirths are poorly ascertained in the US and most developed and developlng countries. The most recent national data available on stillbirth prevalence is from 2006 which underscores the insufficient infrastructure currently in place for ascertainment and monitoring of this understudied perinatal outcome. The Centers for Disease Control and Prevention (CDC) demonstrated through two pilot studies that expanding the current methods of existing birth defects registries for stillbirth surveillance is a viable and cost-effective method for surveillance of stillbirths. CDC announced an initiative, Birth Defects Study to Evaluate Pregnancy exposures (BO-STEPS) II Stillbirth study, which will focus on conducting a case-control study to elucidate modifiable risk factors for stillbirths, using the Centers for Birth Defects Research and Prevention infrastructure as the foundation for surveillance and research. The Arkansas Center's long-term goal is to prevent or significantly reduce the occurrence of birth defects and adverse pregnancy outcomes. We propose to utilize our population-based, active surveillance system of stillbirths in Arkansas to Identify novel modifiable pregnancy exposures that decrease the occurrence of stillbirths. Through our studies, we will maintain a leading role in establishing health strate1;1ies to prevent birth defects and stillbirths. RELEVANCE (See instructions): COMPONENT A: Birth defects are a leadlng cause of infant mortality. Three out of every 100 babies born in the US have a major structural birth defects, posing a significant public health problem. Building on our previous experience with the NBDPS and BD STEPS I, the Arkansas Center is positioned to continue Identifying maternal exposures in early pregnancy that may be amenable to early prevention, greatly reducing the occurrence of birth defects. Continuation of CDC Center funding will enable the Center to maintain a leading role in establishing clinical and public health strategies to prevent birth defects. COMPONENT B: Stillbirths account for half of all perinatal deaths, posing a significant public health problem. The cause of most stillbirths is unknown. Building on our previous experience with the NBDPS and BO-STEPS I, we will continue to identify maternal exposures in early pregnancy that may be amenable to early prevention and focus on greatly reducing the occurrence of stillbirths. Continuation of CDC Center funding will enable the Arkansas Center to maintain a leading role in establishing strategies to prevent stillbirths.

U01DD001285

2018-12-01

2023-08-31