Use and Effects of Augmentation of Labor with Oxytocin: A Single-Center, Retrospective, Case-Control Study of 4350 Women in Warsaw, Poland, 2015-2020.

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 AND 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.

Retrospective Analysis of the Factors Affecting the Induction of Childbirth in 4350 Women from a Single Center in Warsaw, Poland.

Labor induction is one of the most common procedures performed during childbirth, on average in 20−30% of all pregnant women. The aim of this paper was to perform a retrospective analysis of the factors influencing the induction of childbirth. The data provide population-based evidence for Poland (Masovian Voivodeship). The electronic patient records of a hospital in Warsaw were used to create an anonymous retrospective database of all deliveries from 2015 to 2020. The study included an analysis of two groups of patients. The study group consisted of patients with labor induction­4350 cases, and the control group of patients with spontaneous contractions­20,345. The factors influencing the lower frequency of labor induction in the study group were previous cesarean section (OR = 0.73, 95% CI: 0.64−0.84, p < 0.05) and a higher number of deliveries (OR = 0.74, 95% CI: 0.68−0.80, p < 0.05). It is necessary to conduct further research about obstetric procedures used during childbirth, such as induction of childbirth, to reduce the risk of complications and improve the perinatal care of the mother and the neonate.

Identification of novel susceptibility genes for non-syndromic cleft lip with or without cleft palate using NGS-based multigene panel testing.

For non-syndromic cleft lip with or without cleft palate (ns-CL/P), the proportion of heritability explained by the known risk loci is estimated to be about 30% and is captured mainly by common variants identified in genome-wide association studies. To contribute to the explanation of the "missing heritability" problem for orofacial clefts, a candidate gene approach was taken to investigate the potential role of rare and private variants in the ns-CL/P risk. Using the next-generation sequencing technology, the coding sequence of a set of 423 candidate genes was analysed in 135 patients from the Polish population. After stringent multistage filtering, 37 rare coding and splicing variants of 28 genes were identified. 35% of these genetic alternations that may play a role of genetic modifiers influencing an individual's risk were detected in genes not previously associated with the ns-CL/P susceptibility, including COL11A1, COL17A1, DLX1, EFTUD2, FGF4, FGF8, FLNB, JAG1, NOTCH2, SHH, WNT5A and WNT9A. Significant enrichment of rare alleles in ns-CL/P patients compared with controls was also demonstrated for ARHGAP29, CHD7, COL17A1, FGF12, GAD1 and SATB2. In addition, analysis of panoramic radiographs of patients with identified predisposing variants may support the hypothesis of a common genetic link between orofacial clefts and dental abnormalities. In conclusion, our study has confirmed that rare coding variants might contribute to the genetic architecture of ns-CL/P. Since only single predisposing variants were identified in novel cleft susceptibility genes, future research will be required to confirm and fully understand their role in the aetiology of ns-CL/P.

PAX7 nucleotide variants and the risk of non-syndromic orofacial clefts in the Polish population.

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.

Association of CDKAL1 nucleotide variants with the risk of non-syndromic cleft lip with or without cleft palate.

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 (Ptrend < 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 Ptrend 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.

Whole-blood 3-hydroxyisovalerylcarnitine as a risk factor for orofacial clefts.

BACKGROUND/PURPOSE: In mice, biotin deficiency is one of the most potent clefting factors. Increased 3-hydroxyisovalerylcarnitine (C5OH) is regarded as a biomarker of biotin deficiency. This retrospective study was undertaken to determine whether increased C5OH in newborns is associated with orofacial clefts. MATERIALS AND METHODS: Seventy newborns with non-syndromic cleft lip with or without cleft palate and 140 control newborns without congenital anomalies were investigated. Whole-blood C5OH concentrations were measured using tandem mass spectrometry. RESULTS: The median (interquartile range, IQR) concentrations of C5OH in patients with clefts and controls were 0.16 (0.13-0.22)µmoll(-1) and 0.17 (0.13-0.20)µmoll(-1), respectively (p=0.90). The receiver operating characteristic analysis did not find out cut-off values for C5OH discriminating between cases and controls. CONCLUSION: There appears to be no association between biotin deficiency, as indexed by an increase of C5OH, and orofacial clefts in the investigated group of patients.