BMC Public Health 2004, 4 http://www.biomedcentral.com/1471-2458/4/16 Table 5: Number of single familial households with 2 or 3 family members having the same condition 2 family members with the same condition 3 family members with the same condition Condition Spina Bifida and hydrocephalus Congenital anomalies of heart and circulatory system Other congenital anomalies of musculoskeletal system Asymmetry of Face Osteodystrophies Congenital scoliosis Clubfoot Flat foot/congenital fallen arches Musculoskeletal birth defects but different specific diagnoses Others Other condition due to sex chromosome anomalies Other specified anomalies (e.g. Marfan syndrome, Fragile X) Total results indicate that the NHIS provide limited useful information to be used in this manner. We used the Survey, particularly years 1994/1995, because it presented several advantages. The NHIS is a large, representative sample of all U.S. households with an annual response rate greater than 90 percent[13]. These data are collected through a personal household interview conducted by interviewers employed and trained by the U.S. Bureau of the Census according to pro- cedures specified by the National Center of Health Statis- tics and allows for the identification of households where one or more individuals with birth defects reside and the identification of individuals who have one or more than one birth defect. Furthermore, the addition of the Disabil- ity supplement in 1994/1995 resulted in specific birth defects on the condition lists unlike other versions of the survey. These data may also be used to identify various health problems, determine barriers to accessing and using appropriate health care, and to evaluate Federal health programs. Several limitations of the NHIS might have conspired against its usefulness for the stated objective. The accuracy of the birth defect information has not been validated, there are no objective measurements since data are self- reported or by proxy and isolated conditions can not be studied, since most birth defects are grouped by organ of affection. Also, since many of the questions in the NHIS are predicated on limitation of daily activities, identifica- tion of cases is problematic as birth defects cause a range of limitations. Issues around sampling also limit the usefulness of the NHIS in identifying informative families for genetic stud- ies. Estimates are based on a sample of the population, 2 5 - 3 - 5 3 13 5 - 2 1 39 - - - - 1 1 - - 3 - - - 5 thus are subject to sampling errors and the information on place of residence is limited to multi-state regions and not available at local levels such as states, counties, or dis- tricts. Also, since households were asked to identify con- ditions from specific grouped lists, we likely only identify families with two or more individuals with birth defects of the same class. Finally, several segments of the population are not included in the sample, such as patients in long- term care facilities, persons on active duty with the Armed Forces (though their dependents are included), and U.S. nationals living in foreign countries. Conclusions The difficulty to locate multiplex families using the NHIS suggests that population based ascertainment of families with two or more members with the same birth defect is an unrealistic strategy. Alternative strategies are needed to study the genetic contribution to most birth defects. One such strategy is to identify prospective participants in spe- cialty clinics. Another excellent source of data, albeit much more expensive than ascertainment through clinics, are the large, collaborative, multi-state or nationwide studies of birth defects, such as the National Birth Defects Prevention Study [14,15]. In addition to identifying fam- ilies of interest, these studies collect extensive epidemio- logical data and DNA samples from which genetic susceptibility and gene-environment interactions can be studied. List of abbreviations CHD: congenital heart defect C.I.: confidence interval CL/P: cleft lip with or without cleft palate Page 6 of 7 (page number not for citation purposes)