Early Amniocentesis Versus Transabdominal Chorionic Villus Sampling for Early Invasive Prenatal Diagnosis: A 15-Year...

Two sampling routes are available when definitive genetic testing is required in the first trimester: early amniocentesis (EA) and transabdominal chorionic villus sampling (TA-CVS). Direct comparisons of the two at 11 to 14 weeks of gestation are, however, few. Our aim was to place the techniques side by side in terms of the genetic information they yield, the chromosomal abnormalities they uncover and the pregnancy outcomes that follow them.

This single-operator, prospective cohort study evaluated singleton pregnancies between 11 and 14 weeks of gestation across 15 years (2010-2024), comparing TA-CVS with EA. Fluid for EA was withdrawn by amniovacucentesis (3-5 mL of amniotic fluid) through a 22-gauge needle, while villus tissue was taken with a 20-gauge needle, both with the ultrasound image visible throughout. Color Doppler assessment of the uteroplacental and fetal vessels and of the fetal heart rate preceded and followed every procedure. Material obtained by either route underwent cytogenetic testing, and targeted copy-number variant (CNV) analysis was added whenever ultrasonography had shown a major structural abnormality.

Of 3238 singleton pregnancies, a cytogenetic result was achieved in 1611 of 1613 (99.9%) EA and in 1622 of 1625 (99.8%) TA-CVS cases. An abnormal chromosome finding was present in 138 cases (4.3%), while pathogenic CNVs emerged in 5 of 35 (14.3%) fetuses with structural abnormalities. Spontaneous abortion affected 4 of 1613 EA pregnancies (0.25%) and 3 of 1625 TA-CVS pregnancies (0.18%; difference 0.06%, 95% CI -0.32 to 0.47%; p = 0.73). Talipes occurred in two EA cases and none after TA-CVS, whereas hemangiomas occurred in two TA-CVS cases and none after EA. Premature rupture of membranes, preterm delivery, neonatal respiratory distress and neonatal anomalies did not differ between the groups. Doppler pulsatility indices were essentially unchanged after both procedures; small changes reached statistical significance only in the umbilical (p = 0.032) and middle cerebral (p < 0.001) arteries, and all were transient and unaccompanied by clinical complications.

Fetal-derived material adequate for first-trimester genetic diagnosis was obtained by both routes, with cytogenetic results in more than 99% of pregnancies. Beyond the conventional chromosomal abnormalities, targeted CNV analysis added clinically meaningful diagnoses in fetuses with structural anomalies. Invasive fetal sampling therefore retains a definite place in definitive prenatal genetic diagnosis in the era of NIPT.