The Association Between Amniocentesis and Adverse Pregnancy Outcomes in Pregnancies with Normal/Reportable Test Results: An Indication-Based Comparison with Non-Invasive Prenatal Testing

<b>Background/Objectives</b>: To compare the maternal, fetal, and neonatal outcomes of pregnancies undergoing amniocentesis with those undergoing non-invasive prenatal testing (NIPT), within a cohort of women with comparable clinical indications, aiming to evaluate differences in adverse outcomes in a risk-indicated population. <b>Methods</b>: In this retrospective cohort study, pregnancy outcomes of 2044 pregnant women who underwent amniocentesis and 7668 pregnant women who underwent NIPT were evaluated using single-center data. The analysis was restricted to pregnancies with normal/reportable test results and without structural or genetic anomalies. Pregnancy loss outcomes were evaluated in the full cohort, while perinatal outcomes were analyzed among cases with available delivery data (377 amniocentesis and 2063 NIPT cases). Pregnancy and perinatal outcomes, including miscarriage, intrauterine fetal demise (IUD), preterm birth (PTB), pregnancy-induced hypertensive diseases (PIHDs), gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), low birth weight (LBW), small for gestational age (SGA), and low APGAR scores (<7), were evaluated. Multivariate logistic regression analysis was performed to adjust for potential confounding factors, and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were reported. <b>Results</b>: Amniocentesis was associated with a significantly higher risk of an adverse outcome compared to NIPT in this risk-indicated cohort. The likelihood of miscarriage was significantly higher in the amniocentesis group (aOR: 1.91, 95% CI: 1.17-3.14, <i>p</i> = 0.025), as was the risk of IUD (aOR: 4.10, 95% CI: 2.05-8.20, <i>p</i> < 0.001). PTB risk was also increased (aOR: 1.96, 95% CI: 1.53-2.51, <i>p</i> < 0.001). LBW was significantly more prevalent in the amniocentesis group (aOR: 7.73, 95% CI: 5.40-11.05, <i>p</i> < 0.001), and the likelihood of delivering a SGA neonate was also increased (aOR: 1.45, 95% CI: 1.02-2.06, <i>p</i> = 0.040). A 1st-minute APGAR score < 7 was also more frequent in the amniocentesis group (aOR: 1.51, 95% CI: 1.06-2.16, <i>p</i> = 0.022), although the association with 5th-minute APGAR scores < 7 did not reach statistical significance (aOR: 1.45, 95% CI: 0.83-2.52, <i>p</i> = 0.193). Overall, the risk of composite maternal and perinatal adverse outcomes (aOR: 1.77, 95% CI: 1.41-2.22, <i>p</i> < 0.001) as well as composite fetal and neonatal adverse outcomes (aOR: 1.97, 95% CI: 1.50-2.58, <i>p</i> < 0.001) was significantly higher in the amniocentesis group compared to the NIPT group. No significant association was observed for PIHD, GDM, or ICP. <b>Conclusions</b>: Our findings showed that, apart from fetal loss, amniocentesis may be associated with adverse perinatal outcomes such as PTB, LBW, SGA and low APGAR scores.