Prenatal diagnosis in 200 pregnancies with a 1-in-4 risk of cystic fibrosis

Abstract

Prenatal diagnosis of cystic fibrosis was performed in 200 pregnancies with a 1-in-4 risk, and was based on significant modifications in amniotic fluid taken at 17, 18, 19 weeks of pregnancy, of six enzymatic assays: gamma-glutamyl-transpeptidase, aminopeptidase M, and alkaline phosphatase (total and isoenzymes). On the basis of normal values, normal outcome was predicted in 135 pregnancies reaching term, all the babies were normal. On the basis of significantly abnormal enzymatic values, an affected fetus was predicted in 56 pregnancies, 53 were terminated, and 3 went to term; the infants were affected. There were discrepancies in enzymatic values in nine cases, in eight cases normal outcome was predicted, six babies were normal and two were affected; in one case an affected baby was predicted, the pregnancy went to term and the baby is normal. Criteria giving evidence for cystic fibrosis in fetuses have been described: macroscopic observation of a typical meconium ileus, significant increase of albumin content in the meconium, and PAS-positive mucus-like material in some pancreatic acini. Using these criteria, diagnosis of cystic fibrosis has been confirmed in all the examined fetuses. The recurrence rate of cystic fibrosis was 22.5% in 147 diagnoses in which the index case had cystic fibrosis without a history of meconium ileus at birth, but was 47.5% when the index case had meconium ileus. The results of the study suggest that prenatal diagnosis of cystic fibrosis can be performed with an accuracy of 98%.

Blood concentrations of pancreatitis associated protein in neonates: relevance to neonatal screening for cystic fibrosis

“…The incidence (1 in 4600) was in the expected range 7. PAP was significantly higher in CF than in non-CF babies, as expected from the observation that the CF pancreas is already damaged in utero 8. The two lowest PAP values in CF neonates (4.9 and 6.8 ng/ml) corresponded to genotypes associated with mild pancreatic phenotype,18 19 which corroborates the correlation between PAP expression and the severity of pancreatic damage 20.…”

“…The rationale for IRT testing is that duct obstructions by protein plugs develop in utero in the CF pancreas,8 leading to enzyme leakage into the blood. However, transient obstruction of the ducts of an otherwise healthy pancreas could also lead to increased blood IRT, so reducing the specificity of screening.…”

Glycaemic regulation and insulin secretion are abnormal in cystic fibrosis pigs despite sparing of islet cell mass

“…As in humans [7, 22, 34–36, 43–46], the exocrine pancreatic damage starts in utero in CF pigs [33] and progresses over time [29]. We have previously demonstrated that fetal CF pig pancreata (83–90 day, pig gestation is ~114 days) have patchy loss of zymogen-filled acini, inflammation and tissue destruction and these lesions progress into the newborn period [33].…”

“…At birth, CF pig pancreata have reduced number of acini, decreased cytoplasmic zymogen granules, and ectatic and plugged ducts surrounded by degenerative exocrine tissue. Over time, the exocrine pancreas is replaced by fat and fibrous tissue [29–33], as it occurs in humans with CF [8, 34–36]. With multi-organ disease and exocrine pancreatic disease that is similar to human disease, the CF pig model offers a unique opportunity to investigate the pathogenesis of CFRD.…”

Bayesian risk assessment for autosomal recessive diseases: fetal echogenic bowel with one or no detectable CFTR mutation

“…6 Another study determined the frequency of echogenic bowel among all fetuses with cystic fibrosis as about 0.55; however, echogenic bowel among fetuses without cystic fibrosis was not determined. 16 The criteria for echogenic bowel are somewhat subjective and vary among centres, and it is important that the same criteria for echogenic bowel are used for fetuses with cystic fibrosis and fetus carriers and non-carriers, so we used data from the single large study by Scotet et al for our calculations. 8 Generalised Bayesian analyses for genetic risk calculations Table 1 summarises various situations encountered in clinical settings.…”