Expanding the Danish Twin Registry into its Third Century: Secular Trends in Twin Births and Survival.

The Danish Twin Registry has been expanded several times since its establishment in 1954. Here we describe the inclusion of the Danish 2001-2021 twin birth cohorts and the merging with the Danish 1870-2000 twin birth cohorts that enabled us to analyze changes in both twin birth frequency and survival over three centuries. Through Danish nationwide registers, 22,680 twin pairs born in Denmark in the period 2001-2021 were identified and contacted. Response to an electronic questionnaire including similarity questions for zygosity classification was obtained from 15,005 pairs (66.2%). Genetic markers for a subsample revealed a zygosity misclassification rate of 5.3%. From the mid-19th to the mid-20th century, twinning rate was relatively stable followed by an unexplained one third reduction from 1950 to 1970. A doubling occurred from the 1980s to the 2000s due to increasing maternal age at birth and, most importantly, Medically Assisted Reproduction (MAR). Changes in MAR procedures have since resulted in a marked decline, bringing the contemporary twinning rate back to the level of the 19th century. In the 19th century, 43% of twins died before age 6; in the 1970s, the number was 5.4% and in the most recent 21st century cohorts, it was 2.0%. In all three centuries studied, the twin mortality before age 6 was 2-5 times higher in twins compared to singletons. However, large studies of the Danish and other Scandinavian twin cohorts suggest that twin-singleton differences generally vanish with age and, for more recent birth cohorts, are few and generally small after childhood.