Statistical analysis
Statistical analyses included all available stillbirth cases (n=9,404), controls (n=18,808) that were 2:1 matched with cases, and relatives of the parents of cases and controls. We compared maternal demographic characteristics of stillbirth cases to those of live birth controls using t-tests for continuous variables and chi-square tests for categorical variables.
Determination of stillbirth familial aggregation
We used the genealogical index,6 which considers all relationships in the UPDB, to identify pedigrees of stillbirth index cases (i.e., probands). To capture the maternally and paternally inherited risk of stillbirth, we designated the offspring rather than mothers as probands. We estimated the Familial Standardized Incidence Ratio (FSIR) to determine the level of stillbirth familial aggregation and identify high-risk pedigrees.23 The FSIR compares the observed incidence of stillbirth in a pedigree to its expected incidence in the UPDB population, weighting the familial risk contribution of each relative in a pedigree by the kinship coefficient (i.e., the probability that a relative shares an allele with the proband through a common ancestor).24 Our a priorispecified criteria for familial aggregation and a high-risk pedigree were pedigrees with FSIR ≥2 and P-value <0.05.23 We evaluated the skewness of FSIR among high-risk pedigrees by examining its distribution. We presented the top 10 high-risk pedigrees sorted by their FSIR and founders to eliminate any multiple founders claiming the same descendants through marriage.25 To avoid potential biased estimates of stillbirth familial aggregation due to multiple partnerships, we excluded multiple partnerships.