Prevalence and risk of Down syndrome in monozygotic and dizygotic multiple pregnancies in Europe: implications for prenatal screening

Abstract

ObjectiveTo determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome.DesignPopulation-based prevalence study based on EUROCAT congenital anomaly registries.SettingEight European countries.Population14.8 million births 1990–2009; 2.89% multiple births.MethodsDS cases included livebirths, fetal deaths from 20 weeks, and terminations of pregnancy for fetal anomaly (TOPFA). Zygosity is inferred from like/unlike sex for birth denominators, and from concordance for DS cases.Main outcome measuresRelative risk (RR) of DS per fetus/baby from multiple versus singleton pregnancies and per pregnancy in monozygotic/dizygotic versus singleton pregnancies. Proportion of prenatally diagnosed and pregnancy outcome.Statistical analysisPoisson and logistic regression stratified for maternal age, country and time.ResultsOverall, the adjusted (adj) RR of DS for fetus/babies from multiple versus singleton pregnancies was 0.58 (95% CI 0.53–0.62), similar for all maternal ages except for mothers over 44, for whom it was considerably lower. In 8.7% of twin pairs affected by DS, both co-twins were diagnosed with the condition. The adjRR of DS for monozygotic versus singleton pregnancies was 0.34 (95% CI 0.25–0.44) and for dizygotic versus singleton pregnancies 1.34 (95% CI 1.23–1.46). DS fetuses from multiple births were less likely to be prenatally diagnosed than singletons (adjOR 0.62 [95% CI 0.50–0.78]) and following diagnosis less likely to be TOPFA (adjOR 0.40 [95% CI 0.27–0.59]).ConclusionsThe risk of DS per fetus/baby is lower in multiple than singleton pregnancies. These estimates can be used for genetic counselling and prenatal screening.

Prenatal screening for Down syndrome in twin pregnancies: Estimates of screening performance based on 61 affected and 7302 unaffected twin pregnancies

“…Each pregnancy was assigned a maternal age based on the 2014–2016 maternal age distribution of England and Wales . For each simulated monochorionic twin pregnancy, the risk of being affected with Down syndrome at term was calculated by multiplying the maternal age specific odds of having an affected singleton live birth, adjusted by the 66% reduction in risk of a pregnancy being affected if it is a monochorionic twin pregnancy compared with a singleton pregnancy, by the likelihood ratio for being affected (for the simulated set of marker values) calculated from the multivariate Gaussian distributions of marker levels in affected and unaffected pregnancies. For each simulated dichorionic twin pregnancy, the risk of being affected with Down syndrome at term was calculated by multiplying half the maternal age specific odds of having an affected singleton live birth, adjusted by the 34% increase in risk of at least one of the fetuses being affected in a dichorionic twin pregnancy compared with a singleton pregnancy, by the likelihood ratio for each NT MoM value, summing the two and then multiplying that by the likelihood ratio for the serum markers.…”

Second trimester maternal serum triple screening marker levels in normal twin and singleton pregnancies

“…It is well known that numerous maternal factors, such as weight and age, significantly influence the result of DS screening (12,13). A woman who is older at the time of delivery has a higher risk of having a child with DS.…”

Practice Bulletin No. 162

“…Recent data, however, suggest that such models may overestimate the risk of aneuploidy in twins. Data from a large European population registry indicated that the adjusted relative risk of Down syndrome per fetus from multiple gestations is only approximately one half of that of singletons (64).…”