Genetic Evaluation and Pregnancy Outcomes in Foetuses With Overgrowth at a Tertiary Referral Center

Fetal overgrowth is defined as one or more biometric parameters exceeding the 90th-97th percentile or 2 standard deviations above the mean for gestational age. This study aimed to evaluate genetic findings in foetuses diagnosed with sonographic overgrowth. We retrospectively analysed 78 singleton pregnancies that underwent invasive prenatal diagnosis between 2018 and 2024. Fetal overgrowth was defined based on biparietal diameter (BPD), head circumference (HC), and/or abdominal circumference (AC), and cases were categorized into three groups according to the pattern of enlargement: head enlargement (Group A, n = 49), abdominal enlargement (Group B, n = 12), and combined head and abdominal enlargement (Group C, n = 17). All foetuses underwent conventional karyotyping and single nucleotide polymorphism array analysis, and were further classified as isolated or non-isolated based on the presence of additional ultrasound findings. Chromosomal abnormalities were identified in 2 cases (2.6%) by karyotyping, including mosaic 47,XYY/45,X and 46,X,add(X)(p22)/45,X, while SNP array detected copy number variants involving chromosome 11 in 2 additional cases, one likely pathogenic and one variant of uncertain significance. Notably, all chromosomal abnormalities were observed in the non-isolated overgrowth group. Overall, 12 cases (15.4%) were classified as isolated and 66 (84.6%) as non-isolated. Associated ultrasound findings included structural anomalies in 18 cases, non-structural abnormalities in 12 cases, soft markers in 28 cases, and multiple coexisting abnormalities in 20 cases. Ventriculomegaly was the most common structural anomaly, particularly among foetuses with head enlargement, while polyhydramnios was the most frequent non-structural finding. Follow-up data were available for 76 cases, with 8 pregnancies resulting in stillbirth or termination and 68 in live births. Foetuses with combined head and abdominal enlargement had a significantly higher incidence of macrosomia compared with those with isolated head or abdominal enlargement (29.4% vs. 4.3% and 8.3%, respectively; p = 0.015). In conclusion, fetal overgrowth is predominantly non-isolated, and chromosomal abnormalities are mainly observed in this subgroup. Concurrent head and abdominal enlargement is associated with increased risks of structural anomalies and macrosomia. Prenatal genetic testing and macrosomia-specific management should be considered for head-abdominal enlargement foetuses.