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NOVEL OXYTOCIN RECEPTOR VARIANTS IN LABORING WOMEN REQUIRING HIGH DOSES OF OXYTOCIN

Dr Sumaira Zareen, Dr Rabia Shaheen, Dr Hina Akram.

Abstract: To describe labor progression patterns with oxytocin for augmentation in women who achieve vaginal delivery; and to determine how long one should wait with effective uterine contraction before labor arrest can be diagnosed. It is a population-based retrospective cohort study. Term, nulliparous women requiring oxytocin doses of ≤4 milliunits/minute (low-dose requiring, n=83) or ≥20 milliunits/minute (high-dose requiring, n=104) for labor augmentation or induction were consented to a post-partum blood draw. Targeted-amplicon sequencing (coverage > 30X) was performed to discover variants in the coding exons of the oxytocin receptor gene. Baseline relevant clinical history, outcomes, demographics, and oxytocin receptor gene sequence variants and their allele frequencies were compared between low-dose-requiring and high-dose-requiring women. A P-value < 0.05 was considered statistically significant. The HDR (high-dose-requiring) women had higher rates of obesity and diabetes and were more likely to have undergone labor induction and required prostaglandins. Targeted sequencing of the oxytocin receptor gene in the total cohort (n=187). One novel variant was found in both the low- and high-dose-requiring groups. Three novel variants resulting in an amino acid substitution, loss of 9 amino acids, and a frame-shift stop mutation, respectively, were identified only in LDR (low-dose-requiring) women. Nine non-synonymous variants were unique to the high-dose-requiring group. There was no statistically significant association between the numbers of synonymous and non-synonymous substitutions in the patient groups. When oxytocin is just started for labor augmentation in early first stage, it may take up to 10 hours for the cervix to dilate by 1 cm. Labor induction and obesity were associated with the requirement for high doses of oxytocin. We did not identify significant differences in the prevalence of oxytocin receptor variants between low-dose-requiring and high-dose-requiring women, but novel oxytocin receptor variants were enriched in the high-dose-requiring women. Additionally, we found three oxytocin receptor variants (two novel, one known) that were predicted to damage oxytocin receptor function and would likely increase an individual’s risk for requiring a high oxytocin dose. Key Words: oxytocin receptor variant; requirement of oxytocin doses; labouring women.

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