Impact of a prenatal screening program on the Down syndrome phenotype: An interrupted time series analysis

• Published in: Acta obstetricia et gynecologica Scandinavica Vol. 102; no. 6; pp. 751 - 759
• Main Authors: Steffensen, Ellen Hollands, Pedersen, Lars Henning, Lou, Stina, Vogel, Ida
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-06-2023; John Wiley and Sons Inc
• Subjects: Adult; anthropometry; Biometrics; Body measurements; Cardiovascular disease; congenital abnormalities; Congenital diseases; congenital heart defect; Denmark - epidemiology; Down syndrome; Down Syndrome - diagnosis; Down Syndrome - epidemiology; Female; Fetal Medicine; first‐trimester combined screening; Genotype & phenotype; Heart; Heart Defects, Congenital - epidemiology; Humans; Infant, Newborn; Interrupted Time Series Analysis; Male; Original; phenotype; Pregnancy; Prenatal Diagnosis; prenatal ultrasonography; Program Evaluation; Time series; trisomy 21; Denmark; phenotype; first-trimester combined screening; congenital abnormalities; anthropometry; trisomy 21; prenatal ultrasonography; interrupted time series analysis; congenital heart defect
• ISSN: 0001-6349; 1600-0412
• DOI: 10.1111/aogs.14573

Introduction
We hypothesized that children with Down syndrome who were born after the implementation of first‐trimester combined screening for trisomy 13, 18, and 21 and a second‐trimester ultrasound scan in Denmark would show a milder syndrome phenotype. We investigated the birth biometry, prevalence of congenital malformations, and early childhood morbidity of children with Down syndrome before and after implementation of this screening program.
Material and methods
A nationwide register‐based study of all live born singletons with Down syndrome in Denmark from 1995 to 2018. In interrupted time series analyses, we studied the temporal developments in birth biometry, prevalence of congenital malformations, and early childhood morbidity related to the implementation of a national prenatal screening program.
Results
We included 602 singletons with Down syndrome born before and 308 after implementation of the screening program. Z‐scores of birthweight and head circumference increased over time before screening, but this temporal development changed after implementation by −0.05 (95% confidence interval [CI]: −0.11 to 0.01) and −0.05 (95% CI −0.12 to 0.02), respectively. Just after implementation, the prevalence of non‐severe congenital heart disease decreased (relative change in odds 0.48 [95% CI: 0.24–0.94]). For severe congenital heart disease, atrioventricular septal defect, and non‐heart malformations, this change was 1.16 (95% CI: 0.56–2.41), 0.95 (95% CI: 0.43–2.03), and 0.98 (95% CI: 0.33–2.76), respectively. For all malformations, pre‐existing temporal developments did not change following implementation of screening. The implementation was associated with higher odds of admission to a neonatal intensive care unit (relative change 1.98 [95% CI: 0.76–5.26]) and an increased risk of hearing impairment (risk difference 3.4% [95% CI: −0.4% to 7.1%]). In contrast, the implementation was not associated with the incidence of hospital admissions by 2 years of age or with the probability of a thyroid disorder.
Conclusions
After implementation of a national prenatal screening program, we did not observe a milder Down syndrome phenotype apart from an apparent reduction in the proportion of children with non‐severe congenital heart disease; this result is, however, limited by small numbers.
We hypothesized that children with Down syndrome would have a milder phenotype if born following the implementation of first‐trimester combined screening and second‐trimester ultrasonography in Denmark. Overall, this hypothesis was not supported by our results.