Meta-analysis of 20 studies: thicker fetal nuchal translucency linked to lower live-birth rate
A meta-analysis of 20 studies found that first-trimester nuchal translucency above 2.5 mm is associated with higher risks of adverse outcomes, including in fetuses with normal karyotype.
A systematic review and meta-analysis by Chunsu Liao, Caiyan Yang and Lihong Pang, published in 2026 in BMC Pregnancy and Childbirth, examined how fetal nuchal translucency (NT) thickness at 11–14 weeks relates to pregnancy outcomes. It included 20 articles. According to the authors, increased NT is associated with higher risks of adverse pregnancy outcomes, even in fetuses with normal karyotype biomedcentral.com
BMC Pregnancy and Childbirthbiomedcentral.comOpen source ↗.
Search and NT groups
The authors searched PubMed, EMBASE, the Cochrane Library and Web of Science from the inception of each database to December 2025. Study quality was assessed with the Newcastle-Ottawa Scale for controlled cohort studies and the Joanna Briggs Institute Case Series Checklist for uncontrolled single-arm cohort studies. For binary outcomes, random-effects models were used to calculate relative risks (RR) with 95% confidence intervals (CI). Model sensitivity was evaluated with the restricted maximum likelihood approach.
Fetal NT thickness was divided into four groups: 2.5–3.4 mm (the reference group), 3.5–4.4 mm, 4.5–5.4 mm and ≥ 5.5 mm.
Outcomes by group
Chromosomal abnormalities, cardiac malformations (in fetuses with normal karyotype) and structural malformations (in fetuses with normal karyotype) were significantly more frequent in all groups except the reference group biomedcentral.com
BMC Pregnancy and Childbirthbiomedcentral.comOpen source ↗. The live-birth rate in the ≥ 5.5 mm group was significantly lower (RR = 0.29; 95% CI: 0.15–0.54). In fetuses with normal karyotype it was lower in the 3.5–4.4 mm group (RR = 0.92; 95% CI: 0.87–0.98), the 4.5–5.4 mm group (RR = 0.80; 95% CI: 0.71–0.90) and the ≥ 5.5 mm group (RR = 0.31; 95% CI: 0.24–0.40).
Termination of pregnancy did not differ significantly in the 3.5–4.4 mm group. Its risk was elevated in the 4.5–5.4 mm group (RR = 3.54; 95% CI: 1.84–6.80) and the ≥ 5.5 mm group (RR = 3.39; 95% CI: 1.91–6.01). Copy number variation 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). No significant differences in intrauterine fetal death or miscarriage were found across the groups other than the reference group.
The authors used NT > 2.5 mm as an exploratory cutoff. They state that the evidence is insufficient to define a clear clinical threshold for copy number variation testing in fetuses with NT ≥ 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 read as evidence against routine testing in these subgroups.
Clinical recommendations, the authors note, should remain anchored in established guidelines and individualized counselling. Large-scale prospective validation is needed before the 2.5 mm cutoff is adopted in routine clinical practice.
