Neonatal mortality and morbidity in Down syndrome in the time of prenatal aneuploidy testing: a retrospective cohort study

Abstract

The total uptake of prenatal aneuploidy screening for Down syndrome (DS) is increasing worldwide. As a result of increasing prenatal diagnosis of DS and subsequent termination of pregnancy, livebirth prevalence of DS is decreasing. The aim of this study is to explore the impact of an increasing uptake of prenatal aneuploidy screening on the neonatal mortality and morbidity in DS. This is a retrospective cohort study of 253 neonates with DS born between 2012 and 2018 that were seen at the outpatient clinic of five hospitals in the Netherlands. The medical files were reviewed for maternal and neonatal characteristics and neonatal morbidities. The Dutch national birth registry (Perined) provided mortality numbers of neonates with DS. The results were interpreted in the context of other published studies. Neonatal mortality in DS remained stable, ranging from 1.4 to 3.6%. A congenital heart defect (CHD) was found in 138 of the 251 neonates (55.0%) with atrial septal defect, atrioventricular septal defect, and ventricular septal defect being the most common. The type of CHD in DS did not change over time. Gastro-intestinal defects were present in 22 of the 252 neonates with DS (8.7%), with duodenal atresia as the most reported anomaly. Persistent pulmonary hypertension of the neonate (PPHN) was found in 31 of the 251 infants (12.4%). Conclusions: Although uptake of prenatal aneuploidy screening increased, neonatal mortality and morbidity in DS appears to be stable. An increased incidence of PPHN was found. What is Known:• The total uptake of prenatal aneuploidy screening for Down syndrome is increasing worldwide.• As a result of increasing prenatal diagnosis of Down syndrome and subsequent termination of pregnancy, the livebirth prevalence of Down syndrome is decreasing. What is New:• Although uptake of prenatal aneuploidy screening increased, neonatal mortality and morbidity in Down syndrome appears to be stable.• An increased incidence of persistent pulmonary hypertension of the neonate was found.

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

“…For example, the authors report an increase in diagnoses of atrial and ventricular septal defects across 1992–2012 8 . This is similar to Dutch findings 10 and to our results of an increasing prevalence trend of non‐severe CHD and likely reflects expanded use and improved quality of echocardiography. Yet, we also observed a reduced proportion of children with Down syndrome diagnosed with non‐severe CHD in 2007, which speaks against the suggested improved diagnostics, but also supports our hypothesis of a milder phenotype.…”

“…However, in Sweden, this was the result of a decreased live birth prevalence of complex CHD (including atrioventricular septal defect [AVSD]) counteracted by an increased prevalence of atrial and ventricular septal defects 8 . A recent Dutch study similarly found the prevalence of atrial septal defect among newborns with Down syndrome to have increased following the introduction of first‐trimester combined screening (FTS) and non‐invasive prenatal testing, but, in contrast, reported the prevalence of AVSD to remain largely unchanged 10 . Potential temporal developments may be due to improved fetal echocardiography; however, a study from Hungary reported an unchanged prenatal detection rate of CHD in trisomy 21 fetuses from 1999–2008 to 2009–2018 11 .…”

Prevalence and Outcomes of Gastrointestinal Anomalies in Down Syndrome

“…1 It is caused by a nondisjunction type of trisomy of chromosome 21 (T21) in 95% of cases, and translocation or mosaicism in 5% of patients. 2,3 DS is associated with multiple congenital malformations including cardiac and gastrointestinal (GI) anomalies which can increase morbidity and mortality. 4 GI problems are common in children with DS, and the genetic imbalance resulting from the trisomy of chromosome 21 may cause developmental disorders of the enteric system, leading to functional GI disturbances.…”

“…7,8 However, the prevalence and predilection of concomitant small intestinal atresia (such as DA, jejunal atresia (JA), or ilial atresia (IA) with HD in DS infants) remain unknown, and there are currently no available reports on this association. This study aims to compare infants with and without DS for the following: (1) demographic and clinical characteristics, (2) prevalence of small intestinal atresia and HD, and (3) clinical outcomes when intestinal atresia and HD existed in infants of both groups. The investigators envision that the study findings may provide important insights into the potential risks and challenges associated with GI anomalies in DS infants, as well as the need for early screening and close monitoring to optimize outcomes and reduce complications.…”

“…1 It is caused by a nondisjunction type of trisomy of chromosome 21 (T21) in 95% of cases, and translocation or mosaicism in 5% of patients. 2 3…”