Cystic Fibrosis Newborn Screening in Portugal: PAP Value in Populations with Stringent Rules for Genetic Studies

Abstract

Newborn screening (NBS) for cystic fibrosis (CF) has been shown to be advantageous for children with CF, and has thus been included in most NBS programs using various algorithms. With this study, we intend to establish the most appropriate algorithm for CF-NBS in the Portuguese population, to determine the incidence, and to contribute to elucidating the genetic epidemiology of CF in Portugal. This was a nationwide three-year pilot study including 255,000 newborns (NB) that were also screened for congenital hypothyroidism (CH) and 24 other metabolic disorders included in the Portuguese screening program. Most samples were collected in local health centers spread all over the country, between the 3rd and 6th days of life. The algorithm tested includes immunoreactive trypsinogen (IRT) determination, pancreatitis associated protein (PAP) as a second tier, and genetic study for cases referred to specialized clinical centers. Thirty-four CF cases were confirmed positive, thus indicating an incidence of 1:7500 NB. The p.F508del mutation was found in 79% of the alleles. According to the results presented here, CF-NBS is recommended to be included in the Portuguese NBS panel with a small adjustment regarding the PAP cutoff , which we expect to contribute to the improvement of the CF-NBS performance. According to our results, this algorithm is a valuable alternative for CF-NBS in populations with stringent rules for genetic studies.

Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT/IRT Versus IRT/PAP/IRT

“…The IRT/DNA strategy would have missed one case (P2) and the IRT/PAP/DNA protocol would have missed one case (P11). Although this study was carried out on a small cohort with only 14 CF cases detected, our results suggests that an IRT/PAP/IRT + SN strategy could be a good alternative for optimizing sensitivity, as opposed to what Marcao A. et al concluded in their study [32]. In this study, the IRT × PAP/IRT strategy, which was based on the study by Weidler, S. et al [35], clearly performed better.…”

“…We hypothesize that introducing PAP in the NBS algorithm could improve sensitivity if we decrease the initial IRT cutoff, but this premise could not be conclusively demonstrated in this study. PAP may also be a valuable tool for identifying CF newborns with meconium ileus whose IRT concentration may be normal [32]; we were not able to evaluate this hypothesis because we did not identify any cases with this clinical presentation during the study.…”

A comprehensive overview of the cystic fibrosis on the island of São Miguel (Azores, Portugal)

“…Cystic fibrosis occurs in all ethnicities (~70,000 patients worldwide), but the majority of patients are Caucasian of European descent [4]. In the present study, we observed an increased incidence of CF in São Miguel (1:3012 live births) when compared to recent Portuguese data (1:7500 live births) [6]. Although not corresponding to the same period of time analyzed and having been applied different methods for the estimation of incidence, we found that the incidence in São Miguel is approximately 2.5 folds the incidence estimated for Portugal.…”

“…The most common mutation is the CFTR:c.1521_1523delCTT (p.Phe508del), present in 85.8% of CF patients worldwide [4], with a higher frequency reported in Northern Europeans [5]. The incidence of CF in Portugal is estimated at 1 in 6000 newborns [2] but, in a three-year (end of 2013 to 2016) CF pilot study conducted in the scope of the national newborn screening program, this value was 1 in 7500 newborns [6]. Both values are lower than the ones observed in European Union population: 1 in 2000-3000 newborns [7].…”

Newborn Screening for CF across the Globe—Where Is It Worthwhile?

“…It is 1:2850 in Belgium [41], about 1:4500 in France [42], Germany [14], Italy [38,43,44], and Spain (where large regional variations are observed) [45], while it oscillates between 1:5200 and 1:6500 in Central Europe (Czech Republic [32], Denmark [46], Netherlands [47], Poland [48], Slovakia [49], and Sweden [50]). The incidence appears lower than 1:7000 in three European countries (Portugal [51], Norway [52], and Russia [40]) as well as in various regions of Spain [45]. In countries without NBS, the incidence ranges from 1:2000 (Romania [53]) to 1:25,000 (Finland [54]).…”