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

Abstract

Objective: To determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome.

Design: Population-based prevalence study based on EUROCAT congenital anomaly registries.

Setting: Eight European countries.

Population: 14.8 million births 1990-2009; 2.89% multiple births.

Methods: DS 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 measures: Relative 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 analysis: Poisson and logistic regression stratified for maternal age, country and time.

Results: Overall, 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]).

Conclusions: The risk of DS per fetus/baby is lower in multiple than singleton pregnancies. These estimates can be used for genetic counselling and prenatal screening.

Keywords: Concordance; Down syndrome; monozygotic and dizygotic pregnancies; multiple births; pregnancy outcomes; twins.

Figure 1

Proportion (%) of mothers aged >35 by multiple/singleton birth status according to time period (1990–99, 2000–2007/9) and country.

Figure 2

Prevalence of DS per 10 000 singleton births and per 10 000 multiple births, 1990–99 and 2000–2009, by 5 years of maternal age for England and Wales and for the rest of Europe (nine registries) separately.

Figure 3

Prevalence of DS per per 10 000 singleton births and per 10 000 multiple births, 1990–99 and 2000–2009, by single year of maternal age, England and Wales.