Correlation between fetal nuchal translucency thickness and adverse pregnancy outcomes in the first trimester: a systematic review and meta-analysis

Abstract Introduction Nuchal translucency (NT) thickness is a useful marker for assessing the risk of genetic and congenital abnormalities during the first trimester (11–14 weeks). Increased NT levels are strongly linked to elevated risks of adverse pregnancy and fetal outcomes. In this study, we investigate the association between first-trimester NT thickness and the incidence of adverse maternal-fetal outcomes. Methods PubMed, EMBASE, Cochrane Library, and Web of Science (WOS) were searched from the inception of each database up to December 2025 for studies on NT thickness and maternal-fetal outcomes. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) for controlled cohort studies and the Joanna Briggs Institute (JBI) Case Series Checklist for uncontrolled single-arm cohort studies. For binary outcome measures, random-effects models were applied to calculate relative risks (RRs) with 95% confidence intervals (CIs). To evaluate model sensitivity, the restricted maximum likelihood (REML) approach was implemented. Results A total of 20 articles were included. Fetal NT thickness was categorized into four groups: 2.5–3.4 mm (reference group), 3.5–4.4 mm, 4.5–5.4 mm, and ≥ 5.5 mm. Compared with the reference group, the key results were as follows: Chromosomal abnormalities, cardiac malformations (in fetuses with normal karyotype), and structural malformations (in fetuses with normal karyotype) were significantly increased in all groups except the reference group. The NT ≥ 5.5 mm group had a significantly lower live birth rate (RR = 0.29; 95% CI: 0.15–0.54; P < 0.001). The live-birth rate in fetuses with normal karyotype was significantly decreased in the 3.5–4.4 mm group (RR = 0.92; 95% CI: 0.87–0.98; P = 0.005), and even lower in the 4.5–5.4 mm (RR = 0.80; 95% CI: 0.71–0.90; P < 0.001) and ≥ 5.5 mm (RR = 0.31; 95% CI: 0.24–0.40; P < 0.001) groups. No significant variations in termination of pregnancy (TOP) were observed within the 3.5–4.4 mm group. Conversely, the risk of TOP was significantly elevated in both the 4.5–5.4 mm (RR = 3.54; 95% CI: 1.84–6.80; P < 0.001) and ≥ 5.5 mm groups (RR = 3.39; 95% CI: 1.91–6.01; P < 0.001). Copy number variation (CNV) abnormalities (in fetuses with normal karyotype) were significantly increased only in the ≥ 5.5 mm group (RR = 6.52; 95% CI: 2.35–18.11; P < 0.001). No significant difference was observed in the risks of intrauterine fetal death (IUFD) or miscarriage across all groups except the reference group. Conclusions Increased NT thickness is associated with higher risks of adverse pregnancy outcomes, even in fetuses with normal karyotypes. We therefore used NT > 2.5 mm as an exploratory cutoff to investigate these outcomes. Although evidence is insufficient to define a clear clinical threshold for CNV testing among fetuses with ≥ 5.5 mm, the non-significant findings in the 2.5–3.4 mm and 3.5–5.4 mm strata come from sparse data and should not be interpreted as evidence against routine CNV testing in these subgroups. Accordingly, clinical recommendations should remain anchored in established guidelines and individualized counselling, and large-scale prospective validation is needed before the 2.5 mm cutoff is adopted in routine clinical practice.