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

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.

Public support for neonatal screening for Pompe disease, a broad-phenotype condition.

BACKGROUND: Neonatal screening for Pompe disease has been introduced in Taiwan and a few U.S. states, while other jurisdictions including some European countries are piloting or considering this screening. First-tier screening flags both classic infantile and late-onset Pompe disease, which challenges current screening criteria. Previously, advocacy groups have sometimes supported expanded neonatal screening more than professional experts, while neutral citizens' views were unknown. This study aimed to measure support for neonatal screening for Pompe disease in the general public and to compare it to support among (parents of) patients with this condition. The study was done in the Netherlands, where newborns are not currently screened for Pompe disease. Newborn screening is not mandatory in the Netherlands but current uptake is almost universal. METHODS: A consumer panel (neutral group) and (parents of) patients with Pompe disease (Pompe group) were sent information and a questionnaire. Responses were analyzed of 555 neutral and 58 Pompe-experienced informants who had demonstrated sufficient understanding. RESULTS: 87% of the neutral group and 88% of the Pompe group supported the introduction of screening (95% CI of difference -10 to 7%). The groups were similar in their moral reasoning about screening and acceptance of false positives, but the Pompe-experienced group expected greater benefit from neonatal detection of late-onset disease. Multivariate regression analysis controlling for demographics confirmed that approval of the introduction of screening was independent of having (a child with) Pompe disease. Furthermore, respondents with university education, regardless of whether they have (a child with) Pompe disease, were more likely to be reluctant about the introduction of screening than those with less education, OR for approval 0.29 (95% CI 0.18 to 0.49, p < 0.001). CONCLUSIONS: This survey suggests a rather high level of support for newborn screening for Pompe disease, not only among those who have personal experience of the disease but also among the general public in the Netherlands. Optional screening on the basis of informed parental consent is probably unrealistic, underlining the need for new guidelines to help policymakers in their consideration of newborn screening for broad phenotype conditions.

Neonatal screening for treatable and untreatable disorders: prospective parents' opinions.

OBJECTIVE: In the Netherlands, in 2007, the national newborn screening program was expanded from 3 to 17 disorders that met the World Health Organization's Wilson and Jungner screening criteria, especially regarding treatability. The decision of whether to add diseases to the program is generally based on experts' advice, whereas the opinion of those whom it concerns--prospective parents--remains unknown. In this study, we investigated the opinion of prospective parents concerning newborn screening for disorders that are incurable yet treatable to some extent or even untreatable. METHODS: A structured questionnaire that consisted of 3 parts in which similar questions were posed about treatable, less treatable, and untreatable childhood-onset disorders was posted on the Web site of a national pregnancy fair. RESULTS: A total of 1631 prospective parents filled out the questionnaire, 259 of whom were excluded. In contrast to current policy, respondents showed a positive attitude toward inclusion of less treatable (88%) or untreatable childhood-onset disorders (73%) within the national newborn screening program. Respondents who already had children at the time of completing the questionnaire were even more in favor of screening for especially untreatable disorders. The most important reason mentioned was to prevent a long diagnostic quest. Obtaining information to enable reproductive choices in future pregnancies was hardly mentioned. CONCLUSIONS: Prospective parents in the Dutch population seem interested in newborn screening for untreatable childhood-onset disorders; therefore, we argue that additional debate of pros and cons is needed among policy makers, health care professionals, and consumers.

Preconceptional ancestry-based carrier couple screening for cystic fibrosis and haemoglobinopathies: what determines the intention to participate or not and actual participation?

This paper explores determinants of the intention to participate or not and of actual participation in preconceptional ancestry-based carrier couple screening for cystic fibrosis (CF) and haemoglobinopathies (HbPs). In total, 9453 individuals from a multi-ethnic population were invited. Invitees who had a partner and who were planning a pregnancy were the target population (33-36%). Test participation was conditional on survey participation. Those who refrained from test participation were asked to participate in the survey only. The questionnaire was based on the Theory of Planned Behaviour, which explains behaviour through intention. It was completed by 418 survey participants: 171 who intended to participate in the testing, and 247 who refrained from test participation. Both test intenders and offer decliners generally had a positive attitude towards test participation, and perceived high behavioural control. This applied to Western and non-Western survey participants equally. Offer decliners, however, perceived less control in terms of the time and effort needed for participation. Still, 68% of them intended to participate in the future if the screening would be offered routinely. Test intenders more often would draw reproductive consequences from test results, perceived a higher risk of being a carrier, more benefits and less adverse psychological outcomes. Feelings of stigmatisation were not an important issue, but 14% thought that there would be discrimination against carriers: among them more were non-Western survey participants. Preconceptional ancestry-based CF and HbPs carrier screening was evaluated as positive and desirable among Western and non-Western survey participants. The effort and time needed for participation were important reasons for declining participation, which might be overcome by improving access to the screening.

Developing and optimizing a decisional instrument using self-reported ancestry for carrier screening in a multi-ethnic society.

PURPOSE: To develop a decisional instrument for ancestry-based cystic fibrosis and/or hemoglobinopathies carrier couple screening in The Netherlands. METHODS: A flowchart (Instrument A) and a questionnaire with maps of geographical areas with originally high cystic fibrosis and hemoglobinopathies carrier frequencies (Instrument B), were developed to support participants in self-assessing their eligibility as a couple for carrier screening for cystic fibrosis and/or hemoglobinopathies. The outcome was compared to the self-reported origin of both partners' ancestors during an in-depth interview. Furthermore, preference for Instrument A or B was determined. RESULTS: Of the 112 participants, 88% (99/112, 95% CI 82-94%) (Instrument A) and 91% (102/112, 95% CI 86-96%) (Instrument B), respectively, arrived at a decision in accordance with their ancestral origin, and 57% (64/112, 95% CI 48-66%) preferred Instrument B. A false negative proportion of 5.5% suggests that some carriers will exclude themselves from screening. Results might improve with minor changes in the instruments with regard to geographic specification, and availability of translated versions. CONCLUSION: A decisional instrument to assess ancestry-based eligibility for cystic fibrosis and/or hemoglobinopathies carrier screening, is now available and can with slight adaptations be used in other countries. The instrument also takes into account the possibility of mixed ancestry.