Biochemical Amniotic Fluid Pattern for Prenatal Diagnosis of Esophageal Atresia

Abstract

Prenatal diagnosis of esophageal atresia (EA) may improve the outcome of affected neonates by allowing optimization of both prenatal and postnatal care. Prenatal sonographic detection is based on polyhydramnios and/or nonvisualization of the fetal stomach bubble, two signs with a large number of etiologies. We evaluated a biochemical approach to improving diagnostic efficiency. We compared amniotic fluid biochemical markers in 44 EA cases with 88 polyhydramnios and 88 nonpolyhydramnios controls. Both matched for GA with cases. Total proteins, alpha-fetoprotein (AFP), and digestive enzyme activities were assayed, including gamma-glutamyl transpeptidase (GGTP). We defined an EA index (AFP multiplied by GGTP). A significant difference (p Ͻ 0.0001) was observed for total protein, AFP, GGTP, and EA index between the EA group and each of the two control groups. No statistical difference was observed for any marker between the two most frequent EA subgroups (type I and type III) or between the two control groups. Using a cutoff of 3 for the EA index, 98% sensitivity and 100% specificity were observed for amniotic fluid prenatal diagnosis of EA, whatever the anatomical type. A large prospective series is required to confirm these results.

Hyperechogenic kidneys and polyhydramnios associated with HNF1B gene mutation

“…Biochemical analysis of amniotic fluid was available only in one case. It did not show low alpha-fetoprotein and/or low proteins level as seen in Bartter syndrome [7], however, the compression of the stomach by the large multicystic kidney in that case may have modified the biochemical markers, leading to a suspicion of esophageal atresia [8]. That compression of the digestive tract may also have played a role in the development of the polyhydramnios in that case.…”

“…In one case (#4), therapeutic amnioreduction (removing 2 l of amniotic fluid) was performed at 32 weeks of gestation. Biochemical analysis of amniotic fluid was performed, but, surprisingly, showed a high gammaglutamyl transpeptidase, alpha-fetoprotein, and total protein levels as described in esophageal atresia [8]. The BBartterindex^ [7] was 8 (normal > 1.2).…”

“…However, approximately 50 % of cases of polyhydramnios remain unexplained [6]. Biochemical analysis of amniotic fluid may be helpful for prenatal diagnosis of Bartter syndrome [7] or esophageal atresia [8].…”

Specific biochemical amniotic fluid pattern of fetal isolated esophageal atresia

“…In a previous study (12), we demonstrated that the association of ultrasound scan screening and AF biochemistry showed 98% sensitivity and 100% specificity in EA diagnosis. However, no comprehensible and plausible pathophysiological explanation was provided for the specific biochemical AF-EA pattern we observed associating high GGTP and normal AMP activities.…”

“…Therefore, the suspicion of EA is usually based on these findings at ultrasound with, however, a high false-positive rate and a poor detection rate of ~50% (3,(8)(9)(10)(11). In a previous study based on a series of 44 cases of EA, we observed that amniotic fluid (AF) biochemistry had potential additional value in prenatal diagnosis, with a significant difference for total protein, α-fetoprotein, and γ-glutamyl transpeptidase (GGTP) between the EA group (whatever the anatomical type) and the control group (12). These markers are part of AF biochemical patterns used for prenatal diagnosis of different gastrointestinal diseases as previously described (13,14).…”