Amniotic fluid disaccharidases in the prenatal detection of cystic fibrosis

Abstract

Intestinal disaccharidases in amniotic fluid were studied in 41 pregnancies with a recurrence risk for cystic fibrosis (CF). In 11 out of 13 pregnancies with CF fetuses the maltase and sucrase activities were either below the control range (8 cases) or below the 10th percentile of control values (3 cases). Trehalase and lactase were slightly less informative indicators of CF. Of the other 28 pregnancies 3 had low amniotic fluid activities of several intestinal enzymes and were terminated, 12 resulted in the birth of a healthy child and 13 are continuing. The findings in fetal CF suggest an impairment of the defaecation of intestinal contents into the amniotic fluid. Reduced or low amniotic fluid disaccharidase activities were also found in other fetal disorders with demonstrated or presumed intestinal anomalies: e.g. anal atresia (2 cases), anencephaly (3 our of the 7 cases), trisomy 13 (5 cases), trisomy 18 (3 of the 5 cases) and trisomy 21 (19 of the 22 cases). Reduced amniotic fluid disaccharidase activities, although not specific for CF, are highly informative in pregnancies at high risk for CF. Using the 10th percentile of the normal range for amniotic fluid disaccharidase activities as an action line, the sensitivity of CF detection is estimated at 80 to 90 per cent, which could in high risk pregnancies reduce the risk of having another affected child from 1 in 4 to 1 in 20.

Congenital Abdominal Wall Defects: An Update

“…Ciftci et al [72] challenge this idea showing the meconium stain amniotic fluid is not related to meconium passage after distress but reflects impaired clearance of amniotic fluid, which already has meconium, caused by in utero physiologic defecation. The presence of intestinal enzymes in the amniotic fluid of healthy fetuses and its absence in fetuses with intestinal obstruction support the idea that meconium passage during fetal life is a normal physiologic event [73][74][75]. Proximal intestinal dilatation in fetuses with colonic atresia or anorectal malformations favors this theory.…”

An experimental study investigating the effects of intraperitoneal human neonatal urine and meconium on rat intestines

“…It has been suggested that these gastrointestinal enzymes enter the amniotic fluid as a result of fetal defecation, since the levels of these enzymes in amniotic fluid have been found to be either zero or significantly low in pregnancies complicated by fetal intestinal obstruction [14,18]. While the amniotic fluid of fetuses with intestinal and anal atresia was deficient in intestinal disaccharidases [18], the amniotic fluid disaccharidases levels were significantly low in pregnancies where fetuses were affected by cystic fibrosis [14]. On the other hand, anatomical study of meconium patterns in the intestines of human fetuses has demonstrated the presence of meconium in the anal canal [1].…”

“…Analysis of the human amniotic fluid of different gestational ages has shown that enzymes, such as disaccharidases, alkaline phosphatase and trypsin, are present in the human amniotic fluid [19,21,22]. It has been suggested that these gastrointestinal enzymes enter the amniotic fluid as a result of fetal defecation, since the levels of these enzymes in amniotic fluid have been found to be either zero or significantly low in pregnancies complicated by fetal intestinal obstruction [14,18]. While the amniotic fluid of fetuses with intestinal and anal atresia was deficient in intestinal disaccharidases [18], the amniotic fluid disaccharidases levels were significantly low in pregnancies where fetuses were affected by cystic fibrosis [14].…”

Prenatal detection of intestinal obstructions, aneuploidy syndromes, and cystic fibrosis by microvillar enzyme assays (disaccharidases, alkaline phosphatase, and glutamyltransferase) in amniotic fluid

“…Several authors have suggested that deficent amniotic fluid microvillar enzymes in pregnancies affected with cystic fibrosis is caused by impaired physiological extrusion of intestinal enzymes into the amniotic cavity due to the accumulation of viscous meconium Brock, 1983;Kleijer et al, 1985;Muller et al, 1985bl. Evidence of obstruction by thick meconium were already reported in CF abortuses [Muller et al, 1984b;Brock et al, 1985;Muller et al, 1985bl.…”

“…The deficiency of microvillar enzymes in pregnancies affected with cystic fibrosis (CF) has been confirmed by several laboratories in a large proportion of cases. On a research basis, the rnicrovillar enzymes are now used as a diagnostic test for pregnancies with a 25 % risk of an affected CF fetus [Kleijer et al, 1985;Muller et al, 1984a;Aitken et al, 1985;Schwartz and Brandt, 1985;Mulivor et al, 1985a;Beaudet et al, 19851. The reduced release of microvillar enzymes into amniotic fluid of affected fetuses seems related to the appearance of viscous meconium in the intestine causing an obstruction or decrease of the extrusion of membrane-bound intestinal enzymes in the amniotic fluid Brock et al, 1984;Muller et al, 1985;Kleijer et al, 19851.…”