The Massachusetts Department of Public Health, in collaboration with the Slone Epidemiology Center at Boston University, proposes to participate in the design and implementation of the Stillbirth Risk Factor Pilot Project and also to perform etiologic research studies focused on modifiable risk factors for stillbirths (SB) with and without birth defects (BD). Three SB experts have been added to our collaborative to increase our expertise in that area. Using the data and infrastructure of NBDPS we propose to conduct analyses to determine if BD risks differ between liveborn (LB) and SB subjects; we will also analyze risks for these outcomes associated with commonly-used medications. Medications will include two groups with a common mechanism of action (vasoactive, NSAIDs) and drugs for asthma that have been well-studied in BD among LB, but poorly studied among SB; risks will be estimated for these exposures among SB with BD relative to LB with BD. In BD-STEPS, we will repeat these analyses but expand them to include SB without BD and to include a disease-based approach involving asthma and the medications used in its treatment; we will also determine if risks differ between SB with and without BD. Because BD are a major risk factor for SB, we will evaluate the potential mediation of the association between exposures and SB through BD. This pilot study will serve as a model that, when expanded, will be useful to study less common exposures. Finally, we will use the NBDPS data to generate hypotheses for follow-up by screening risks for BD among LB and SB in relation to specific prescription and OTC drug use. In the BD-STEPS MA catchment area, we will incorporate SB without BD into the national study. MA is uniquely suited to contribute older mothers who are at high risk of SB, more likely to have an existing medical condition and use medications before or during pregnancy. MA women also have high rates of ART use and twinning, both germane to SB risk. An online SB survey, to be completed by subjects with SB with or without BD, will allow us to capture critical information for both pregnancy outcomes. We will enhance the information on asthma control with questions from the validated Asthma Control Test and extend the timeframe for these questions, as well as for medication use, to include the entire pregnancy, thus allowing us to distinguish whether risks are related to medications or to or to the degree of asthma control in different trimesters. Whereas the NBDPS analyses represent etiologic research, we consider this phase of our work a feasibility study, as the number of SB will be limited. Our overall goals are to identify modifiable causes of SB with and without BD and to develop research approaches that may be applied to future data collection and analysis to inform prevention messages and interventions to reduce the occurrence of SBs.
The project proposed in this application is designed to test or generate specific hypotheses of considerable etiologic and public health importance relevant to stillbirths with and without birth defects. The vast majority of pregnant women take medications, yet in regard to risks of birth defects, we know little about the risks and safety of most of these medicines, which include both prescription drugs and medicines available without a prescription. Given that critical knowledge gap, our proposed project will focus on detailed analyses of common maternal illnesses and commonly-used medications as risk factors for stillbirths with and without birth defects.
| Dukhovny, Stephanie; Van Bennekom, Carla M; Gagnon, David R et al. (2018) Metformin in the first trimester and risks for specific birth defects in the National Birth Defects Prevention Study. Birth Defects Res 110:579-586 |
| Werler, Martha M; Guéry, Esther; Waller, Dorothy K et al. (2018) Gastroschisis and Cumulative Stressor Exposures. Epidemiology 29:721-728 |
| Liberman, Rebecca F; Getz, Kelly D; Heinke, Dominique et al. (2017) Assisted Reproductive Technology and Birth Defects: Effects of Subfertility and Multiple Births. Birth Defects Res 109:1144-1153 |
| Louik, Carol; Werler, Martha; Anderka, Marlene et al. (2015) Application of data screening to drug exposure in large risk factor studies of birth defects. Birth Defects Res A Clin Mol Teratol 103:713-7 |
