Prenatal genetic evaluation and outcomes in pregnancies with first-occurrence typical orofacial clefts

Background Orofacial clefts (OFCs) are among the most common birth defects. This study aimed to investigate the prenatal genetic evaluation and pregnancy outcomes of pregnancies with first-occurrence typical OFCs. Methods We retrospectively reviewed 205 first-occurrence OFCs pregnancies during 2010 and 2024, including cleft lip (CL, n = 42), cleft palate (CP, n = 31), and cleft lip and palate (CLP, n = 132). Based on the presence of additional malformations, cases were categorized as isolated (n = 153) or non-isolated (n = 52). Conventional karyotyping was used to detect chromosomal abnormalities, and single nucleotide polymorphism array (SNP array) analysis was performed in 138 cases to identify submicroscopic aberrations. Results The proportions of isolated cases for CL, CP, and CLP were 95.2% (40/42), 83.8% (26/31), and 65.9% (87/132), respectively. Conventional karyotyping identified chromosomal abnormalities in 24 cases (11.7%), with trisomy 13 being the most common (12 cases, 50.0%), followed by trisomy 18 (5 cases, 20.8%). All abnormalities were observed in the non-isolated group, where the chromosomal abnormality rate was 46.2% (24/52). In this group, the chromosomal abnormality rates for CL, CP, and CLP were 50.0% (1/2), 20.0% (1/5), and 48.9% (22/45), respectively. SNP array analysis in 138 cases revealed clinically significant submicroscopic aberrations in 4 karyotypically normal cases, with incremental detection rates of 2.0% (2/101) in the isolated group and 5.4% (2/37) in the non-isolated group (p > 0.05). The pregnancy termination rates were 25.5% (35/137) for the isolated group and 90.2% (46/51) for the non-isolated group. Among pregnancies with isolated OFCs and no clinically significant submicroscopic or microscopic chromosomal abnormalities, the termination rates were 11.8% (4/34) for CL, 3.8% (1/26) for CP, and 39.0% (30/77), respectively. Longitudinal follow-up of 46 cases with subsequent pregnancies revealed no recurrence of OFC. Conclusion Most fetal OFCs are isolated, presenting a very low risk of chromosomal abnormalities. For pregnancies with first-occurrence OFCs, the integration of karyotyping and SNP array analysis effectively evaluates the genetic etiology and provides essential guidance for prenatal counseling and future pregnancy management.