Celocentesis for early prenatal diagnosis of hemoglobinopathy

Abstract

Objective Celocentesis is an invasive technique that can provide prenatal diagnosis of single‐gene disorders, from as early as 7 weeks' gestation. The objective of this study was to examine the safety of celocentesis. Methods In this prospective study, celocentesis was performed for prenatal diagnosis of hemoglobinopathy in 402 singleton pregnancies in which both parents were carriers of β‐thalassemia or sickle cell disease trait. We assessed procedure‐related maternal discomfort or pain, success of sampling and obtaining results, pregnancy outcome and postnatal follow‐up. Results First, celocentesis was carried out at a median gestational age of 8.6 (range, 6.9–9.9) weeks and celomic fluid was successfully aspirated in 99.8% of cases. Second, 67% of women had no or only mild discomfort, 18% had moderate discomfort, 12% had mild‐to‐moderate pain and 3% had severe pain. Third, prenatal diagnosis from analysis of the celomic fluid was successful in 93.8% cases, and in the last 121 cases, it was always successful. Fourth, in all cases of successful sampling and analysis of celomic fluid, the diagnosis was concordant with results obtained from additional prenatal or postnatal testing. Fifth, in addition to diagnosis of hemoglobinopathy, quantitative fluorescence polymerase chain reaction analysis, which was performed to evaluate maternal contamination using several markers for chromosomes X, Y, 21, 18 and 13, led to the accurate diagnosis of chromosomal aneuploidy. Sixth, in all cases of an affected fetus diagnosed by celocentesis in which the parents chose termination of pregnancy, this was carried out < 10 weeks' gestation. Seventh, in 97.1% (298/307) of the continuing pregnancies there was live birth, in seven (2.3%) there was miscarriage and in two (0.7%) there was loss to follow‐up. Eighth, fetal abnormalities were diagnosed in three (1%) cases, including unilateral transverse amputation of the forearm, unilateral moderate hydronephrosis and small‐bowel duplication. All neonates were examined by a pediatrician and were found to be phenotypically normal, except for the three cases with a prenatally diagnosed defect. Conclusions Celocentesis can be used for early prenatal diagnosis of genetic abnormalities, and the procedure‐related risk of pregnancy complications appears to be low. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal diagnosis of single‐gene disorders: the earlier, the better?

“…The main reason why celocentesis has been approved by some researchers is that it can advance the time of prenatal diagnosis. For example, in the study of Makrydimas et al ., celocentesis was done at a median gestational age of 7–10 weeks, and affected pregnancies were terminated before 10 weeks 1 . However, hemoglobinopathies are a group of autosomal recessive diseases.…”

“…in clinical practice for prenatal testing of Mendelian disorders. Among these, Makrydimas et al carried out celocentesis at a median gestational age of 8.6 (range, 6.9-9.9) weeks in 402 singleton pregnancies at risk for hemoglobinopathy 1 . They achieved a technical success rate of 99.8% and a laboratory success rate of 93.8%.…”

“…Figure 1Theoretical outcome of 1000 pregnancies at risk for hemoglobinopathy undergoing celocentesis for early prenatal diagnosis. *Calculated using miscarriage rate of 3.2% and laboratory failure rate of 6.2%, as reported in study of Makrydimas et al1 .…”

Early prenatal diagnosis of hemoglobinopathy via celocentesis: Is it ready for use in routine clinical practice?

“…In a previous study, the authors' team performed celocentesis at a median gestational age of 8.6 (range, 6.9-9.9) weeks in 402 pregnant women at risk for fetal hemoglobinopathy. 3 They achieved a technical success rate of 99.8% and a laboratory success rate of 93.8%, but with a procedure-related miscarriage rate of 3.2%, and a laboratory failure rate of 6.2% due to maternal contamination. In other words, almost one out of every 10 patients either had a miscarriage or needed a repeat invasive procedure.…”

Reply

“…We thank Drs Li and Li for their comments on our paper 1 . Early prenatal diagnosis has been a longstanding objective in fetal medicine, and its acceptability inevitably depends on safety and accuracy.…”