Newborn blood spot screening for cystic fibrosis with a four-step screening strategy in the Netherlands.

BACKGROUND: Newborn screening for cystic fibrosis (NBSCF) was introduced in the Dutch NBS program in 2011 with a novel strategy. METHODS: Dutch NBSCF consisted of four steps: immuno-reactive trypsin (IRT), Pancreatitis-associated Protein (PAP), DNA analysis by Inno-LiPa (35 mutations), extended gene analysis (EGA) as fourth step and as safety net. Only samples with two CFTR-variants were considered screen-positive, but samples with one disease-causing variant were considered also screen-positive from April 2013. The first 5 years of NBSCF were evaluated during a follow-up ranging from 2 to 6.8 years for sensitivity, specificity, positive predictive value (PPV), ratio of CF/Cystic Fibrosis Screen Positive infants with an Inconclusive Diagnosis (CFSPID) and median age at diagnosis, and were compared to other novel strategies for NBSCF and European Cystic Fibrosis Society (ECFS) Best Practice Standards of Care. RESULTS: NBSCF achieved a sensitivity of 90% (95% CI 82%-94%), specificity of 99.991% (95% CI 99.989%-99.993%), PPV of 63% (95% CI 55%-69%), CF/CFSPID ratio of 4/1, and median age at diagnosis of 22 days, if samples with two variants as well as samples with one disease-causing variant were considered screen-positive. CONCLUSION: The program achieved the goal to minimize the number of false positives and showed a favourable performance but sensitivity and CF/CFSPID ratio did not meet criteria of EFCS Best Standards of Care. Changed cut-off values for PAP and IRT and classification of R117H-7T/9T to non-pathogenic may improve sensitivity to ≥95% and CF/CFSPID ratio to 10/1. PPV is estimated to be around 60%.

Meconium-stained amniotic fluid is not a risk factor for otitis media.

It has recently been hypothesised that large amounts of amniotic fluid cellular content (AFCC) in the middle ear may lead to chronic inflammation and predispose young children to recurrent middle ear infections. Because children born with meconium-stained amniotic fluid (MSAF) have higher AFCC in the middle ear, we performed a retrospective cohort study to determine whether children born with MSAF had a higher risk of OM during infancy. Children born between May 1998 and April 2000 formed two groups based on the absence or presence of MSAF at birth as documented in the hospital birth records. In April 2002, home visits were made to take tympanometric measurements and administer a questionnaire on OM history and possible confounders. Logistic regression models were constructed to assess odds ratios (OR) as a measure of the effect of MSAF on OM and to adjust for potential confounders. There were no differences in the point prevalence of a type-B tympanogram at the home visit (OR 0.81; 95% confidence interval: 0.38-1.76). Also, no statistically significant association was found between the proportion of children with OM diagnosed in the 1st year of life (OR 0.86, 95% confidence interval: 0.27-2.73) and in the proportion of children that had ever been diagnosed with OM (OR 0.91, 95% confidence interval: 0.40-2.91). It can be concluded that children born with MSAF do not constitute a high-risk group for OM in early childhood. A long-term OM effect, especially in severe MSAF cases, cannot be excluded.