Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous aetiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top-associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft-susceptibility locus in our genome-wide association study (GWAS). Mega-analysis of the pooled individual data from the GWAS and replication study confirmed that common DLG1 variants are associated with the risk of nsCL/P. Two single nucleotide polymorphisms (SNPs), rs338217 and rs7649443, were statistically significant even at the genome-wide level (P = 9.70E-10 and P = 8.96E-09, respectively). Three other SNPs, rs9826379, rs6805920 and rs6583202, reached a suggestive genome-wide significance threshold (P < 1.00E-05). The location of the strongest individual SNP in the intronic sequence of the gene encoding DLG1 antisense RNA suggests that the true causal variant implicated in the risk of nsCL/P may affect the DLG1 gene expression level rather than structure of the encoded protein. In conclusion, we identified a novel cleft-susceptibility locus at chromosome 3q29 with a DLG1 as a novel candidate gene for this common craniofacial anomaly.

Background Although there have been some recent clinical trials on the effects of augmentation of labor with oxytocin, or augmentation of labor, there are no clinical guidelines to explain the variations in obstetric practice between countries and within countries. This retrospective case-control study from a single center in Warsaw, Poland aimed to evaluate the use and effects of augmentation of labor with oxytocin in 4350 women between 2015 and 2020. Material/Methods This was a single-center, retrospective, case-control study in which 29 455 cases were qualified for analysis. The study included the analysis of 2 groups: the study group consisted of 4382 patients who underwent stimulation of childbirth, and the control group consisted of 25 073 patients who did not undergo this obstetric procedure. Results Multivariate logistic regression analysis showed that the factors increasing the frequency of augmentation of labor were higher BMI ( P <0.05), preinduction ( P <0.05), epidural anesthesia ( P <0.05), and family present at birth ( P <0.05). Factors influencing reduction in the frequency of augmentation of labor were higher number of deliveries ( P <0.05), vaginal birth after cesarean ( P <0.05), and pre-pregnancy hypertension ( P <0.05). Conclusions This study from a single center in Poland showed that BMI, preinduction, epidural anesthesia, and family present at birth significantly increased the frequency of labor stimulation with oxytocin. However, a history of previous pregnancies, previous cesarean sections, and pre-pregnancy hypertension significantly reduced the frequency of augmentation of labor with oxytocin.

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Objective The etiology of non‐syndromic cleft lip with or without cleft palate (nsCL/P) is multifactorial, heterogeneous, and still not completely understood. The aim of the present study was to examine the associations between common and rare PAX7 nucleotide variants and the risk of this common congenital anomaly in a Polish population. Subjects and methods Eight top nsCL/P‐associated PAX7 variants identified in our cleft genome‐wide association study (GWAS) were selected for replication analysis in an independent group of patients and controls (n = 247 and n = 445, respectively). In addition, mutation screening of the PAX7 protein‐coding region was conducted. Results Analysis of the pooled data from the GWAS and replication study confirmed that common PAX7 nucleotide variants are significantly associated with the increased risk of nsCL/P. The strongest individual variant was rs1339062 (c.586 + 15617T > C) with a p‐value = 2.47E−05 (OR = 1.4, 95%CI: 1.20–1.64). Sequencing analysis identified a novel synonymous PAX7 substitution (c.87G > A, p.Val29Val) in a single patient with nsCLP. This transition located in the early exonic position was predicted to disrupt potential splice enhancer elements. Conclusion Our study confirmed that PAX7 is a strong candidate gene for nsCL/P. Nucleotide variants of this gene contribute to the etiology of nsCL/P in the homogenous Polish population.

Although the aetiology of non-syndromic cleft lip with or without cleft palate (nsCL/P) has been studied extensively, knowledge regarding the role of genetic factors in the pathogenesis of this common craniofacial anomaly is still limited. We conducted a follow-up association study to confirm that CDKAL1 nucleotide variants identified in our genome-wide association study (GWAS) for nsCL/P are associated with the risk of this anomaly. In addition, we performed a sequence analysis of the selected CDKAL1 exons. A mega-analysis of the pooled individual data from the GWAS and a replication study revealed that six out of thirteen CDKAL1 variants were positively replicated and reached the threshold of statistical significance (P < 3.85E-03). They represented a single association signal and were located within the fifth intron of CDKAL1. The strongest individual variant was rs9356746 with a P value = 5.71E-06 (odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.30-1.97). Sequencing analysis did not reveal any pathogenic mutations of this gene. This study provides the first evidence that chromosomal region 6p22.3 is a novel susceptibility locus for nsCL/P. The location of the risk variants within the CDKAL1 intronic sequence containing enhancer elements predicted to regulate the SOX4 transcription may suggest that SOX4, rather than CDKAL1, is a potential candidate gene for this craniofacial anomaly.