Birth defects are an important public health issue because they are the leading cause of infant mortality, causing one in every five infant deaths. Multiple factors cause some birth defects, however, the etiology of nearly half of all birth defects is unknown. Several factors affect birth defects surveillance in the United States (US) such as birth defects case ascertainment methods, pregnancy outcomes and the nomenclature used for coding birth defects. We reviewed literature on the challenges of birth defects surveillance in the US. Then we implemented two epidemiological studies using data from Nevada Birth Outcomes Monitoring System, a statewide population-based birth defects surveillance system and live birth certificate data for the period 2005-2011 to investigate the relationship between interpregnancy and birth defects. In addition, we examined the spatial patterns of birth defects and used a spatial scan statistic to identify spatial birth defects clusters at ZIP Code level. After adjusting for demographics and other confounders, the results showed that a long interpregnancy interval was independently associated with birth defects. Other independent risk factors for birth defects were male infants, advancing maternal age, Black women, three or more previous births, smoking, and prescription drug use. Additionally, it was clear that birth defects prevalence varies widely within Nevada counties. Furthermore, a statistically significant (p<.0001) cluster of birth defects was identified at ZIP Code level in Clark County. The results highlight the need for maternal and child health programs and health care providers to include interpregnancy interval in the campaign of improving birth outcomes. In addition, further investigations at neighborhood level are needed to elucidate these disparities in order to guide targeted birth defects prevention efforts