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Uptake of carrier testing in families after cystic fibrosis diagnosis through newborn screening.

ABSTRACT: Newborn screening (NBS) for cystic fibrosis (CF) provides the opportunity for cascade carrier testing of relatives. Uptake of testing by adult non-parent relatives of children diagnosed with CF through NBS has not been previously described, and this study describes uptake by both parents and adult non-parent relatives in Victoria, Australia. Pedigrees were taken from parents of children who were born in 2000-2004 and diagnosed with CF. A total of 40 families were eligible for the study and 30 (75%) were recruited. In all, 716 non-parent relatives were identified from the pedigrees as eligible for carrier testing, and 82 (adjusted uptake percentage: 11.8%; 95% confidence interval 8.0-15.7) have had carrier testing by March 2009. On average, 2.7 non-parent relatives per family had CF carrier testing after diagnosis through NBS. The odds of being tested were greater for females than males (adjusted odds ratio 1.61; 95% confidence interval 1.11-2.33; P=0.01) and greater for those more closely related to the child with CF (adjusted odds ratio 5.17; 95% confidence interval 2.38-11.24; P<0.001). Most relatives who undergo testing are tested immediately after the baby's diagnosis; however, some testing is undertaken up to 8 years later. These results indicate that in a clinical setting, the diagnosis of a baby with CF by NBS does not lead to carrier testing for the majority of the baby's non-parent relatives. We suggest re-contact with parents to offer cascade carrier testing.

SUBMITTER: McClaren BJ

PROVIDER: S-EPMC2987447 | biostudies-other | 2010 Oct

REPOSITORIES: biostudies-other

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Project description:Cystic fibrosis (CF) is the most common worldwide, life-shortening multisystem hereditary disease, with an autosomal recessive inheritance pattern caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The national newborn screening (NBS) program for CF has been initiated in Turkey since 2015. If the immunoreactive trypsinogen (IRT) is elevated (higher than 70 μg/L in the second control) and confirmed by sweat test or clinical findings, genetic testing is performed. The aims of this study are to emphasize the effect of NBS on the status of genetic diagnosis centers with the increasing numbers of molecular testing methods, and to determine the numbers and types of CFTR mutations in Turkey. The next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) results of 1595 newborns, who were referred to Cukurova University Adana Genetic Diseases Diagnosis and Treatment Center (AGENTEM) for molecular genetic testing, were evaluated with positive CF NBS program results since 2017. According to the results; 560 (35.1%) of the 1595 patients carried at least 1 (one) CF-related variant, while 1035 patients (64.9%) had no mutation. Compound heterozygosity for two mutations was the most common in patients, while two detected variants were homozygote in 14 patients. A total of 161 variants were detected in 561 patients with mutations. Fifteen novel variants that have not been previously reported were found. Moreover, p.L997F was identified as the most frequent pathogenic mutation that might affect the IRT measurements used for the NBS. The distribution of mutation frequencies in our study showed a difference from those previously reported; for example, the well-known p.F508del was the third most common (n = 42 alleles), rather than the first. The most striking finding is that 313 cases had a pathogenic variant together with the V470M variant, which might have a cumulative effect on CF perpetuation. This study is the first to determine the mutational spectrum of CFTR in correlation with the NBS program in the Turkish population. NBS for CF raises issues regarding screening in diverse populations, both medical and non-medical benefits, and carrier identification. Through the lens of NBS, we focused on the integrated diagnostic algorithms and their effect on the results of genetic testing.

Project description:Importance:Since the implementation of universal newborn screening (NBS) for cystic fibrosis (CF), the timing and magnitude of growth deficiency or its association with correlates of disease among infants with CF who underwent NBS has not been well described. Objective:To examine incremental weight gain, linear growth, and clinical features in the first year of life among infants with CF who underwent NBS. Design, Setting, and Participants:The Baby Observational and Nutrition Study (BONUS), a multicenter, longitudinal, observational cohort study, was conducted during regular CF clinic visits in the first 12 months of life at 28 US Cystic Fibrosis Foundation-accredited Care Centers from January 7, 2012, through May 31, 2015. Participants included 231 infants younger than 3.5 months who underwent NBS and had confirmed CF, with a gestational age of at least 35 weeks, birth weight of at least 2.5 kg, and toleration of full oral feeds. Of these, 222 infants (96.1%) had follow-up beyond 6 months of age and 215 (93.1%) completed 12 months of follow-up. Exposure:Cystic fibrosis. Main Outcome and Measures:Attained weight and length for age and World Health Organization normative z scores at ages 1 to 6 and 8, 10, and 12 months (defined a priori). Results:Of the 231 infants enrolled, 110 infants (47.6%) were female and 121 (52.4%) were male, with a mean (SD) age of 2.58 (0.69) months. BONUS infants had lower than mean birth weights (mean z score, -0.15; 95% CI, -0.27 to -0.04) and higher birth lengths (mean z score, 0.44; 95% CI, 0.26 to 0.62). They achieved normal weight by 12 months, a significant improvement over a prescreening cohort of newborns with CF from 20 years before the contemporary cohort (mean z score increase, 0.57; 95% CI, 0.37-0.77). However, length was lower than the mean at 12 months (mean z score, -0.56; 95% CI, -0.70 to -0.42). Only 30 infants (13.6%) were at less than the 10th percentile of weight for age, whereas 53 (23.9%) were at less than the 10th percentile of length for age at more than half their visits. Male sex, pancreatic insufficiency, meconium ileus, histamine blocker use, and respiratory Pseudomonas aeruginosa infection were associated with lower weight or length during the first year. Insulinlike growth factor 1 levels were significantly lower among low-length infants. Persistently low-weight infants consumed significantly more calories, and weight and length z scores were negatively correlated with caloric intake. Conclusions and Relevance:Since initiation of universal NBS for CF, significant improvement has occurred in nutritional status, with normalization of weight in the first year of life. However, length stunting remains common.

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Uptake of carrier testing in families after cystic fibrosis diagnosis through newborn screening.

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